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1. A Wearable Open-Source electrical impedance tomography device

Author

Andrew Creegan, Joshua Bradfield, Samuel Richardson, Llewellyn Sims Johns, Kelly Burrowes, Haribalan Kumar, Poul M.F. Nielsen, and Merryn H. Tawhai

Subjects
Electrical impedance tomography, EIT, Medical imaging, Open source, Wearable, Science (General), Q1-390
Abstract

Electrical impedance tomography (EIT) is medical imaging technique in which small electrical signals are used to map the electrical impedance distribution within the body. It is safe and non-invasive, which make it attractive for use in continuous monitoring or outpatient applications, but the high cost of commercial devices is an impediment to its adoption. Over the last 10 years, many research groups have developed their own EIT devices, but few designs for open-source EIT hardware are available. In this work, we present a complete open-source EIT system that is designed to be suitable for monitoring the lungs of free breathing subjects. The device is low-cost, wearable, and is designed to comply with the industry accepted safety standard for EIT. The device has been tested in two regimes: Firstly in terms of measurement uncertainty as a voltage measurement system, and secondly against a set of measures that have been proposed specifically for EIT hardware. The voltage measurement uncertainty of the device was measured to be − 0.7 % ± 0.36 mV. The EIT specific performance was measured in a phantom test designed to be as physiologically representative as practicable, and the device performed similarly to other published devices. This work will contribute to increased accessibility of EIT for study and will contribute to consensus on testing methodology for EIT devices.

Published
2024
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2. A novel two-dimensional phantom for electrical impedance tomography using 3D printing

Author

Andrew Creegan, Poul M. F. Nielsen, and Merryn H. Tawhai

Subjects
Medicine, Science
Abstract

Abstract Electrical impedance tomography (EIT) is an imaging method that can be used to image electrical impedance contrasts within various tissues of the body. To support development of EIT measurement systems, a phantom is required that represents the electrical characteristics of the imaging domain. No existing type of EIT phantom combines good performance in all three characteristics of resistivity resolution, spatial resolution, and stability. Here, a novel EIT phantom concept is proposed that uses 3D printed conductive material. Resistivity is controlled using the 3D printing infill percentage parameter, allowing arbitrary resistivity contrasts within the domain to be manufactured automatically. The concept of controlling resistivity through infill percentage is validated, and the manufacturing accuracy is quantified. A method for making electrical connections to the 3D printed material is developed. Finally, a prototype phantom is printed, and a sample EIT analysis is performed. The resulting phantom, printed with an Ultimaker S3, has high reported spatial resolution of 6.9 µm, 6.9 µm, and 2.5 µm for X, Y, and Z axis directions, respectively (X and Y being the horizontal axes, and Z the vertical). The number of resistivity levels that are manufacturable by varying infill percentage is 15 (calculated by dividing the available range of resistivities by two times the standard deviation of the manufacturing accuracy). This phantom construction technique will allow assessment of the performance of EIT devices under realistic physiological scenarios.

Published
2024
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3. Changes in distribution, morphology and ultrastructure of chloride cell in Atlantic salmon during an AGD infection

Author

Yao-Chung Chang, Andrew Cree Preston, Tharangani Herath, Alexandra Adams, Jamie K. Downes, Jorge Del Pozo, Lynn Chalmers, Nilantha Sandaruwan Jayasuriya, Sean J. Monaghan, James E. Bron, Johanna L. Baily, Harry Hamlin-Wright, and Sophie Fridman

Subjects
0301 basic medicine, Gill, Gills, endocrine system, Pathology, medicine.medical_specialty, ionoregulatory cells, Veterinary (miscellaneous), salmonid, Salmo salar, Gene Expression, Aquatic Science, Biology, mitochondria‐rich cell, Epithelium, Lesion, 03 medical and health sciences, Fish Diseases, Microscopy, Electron, Transmission, transmission electron microscopy, medicine, Animals, 14. Life underwater, Na+/K+-ATPase, Salmo, Na+/K+‐ATPase, Amoebic gill disease, fungi, Histology, 04 agricultural and veterinary sciences, Amebiasis, biology.organism_classification, Immunohistochemistry, 030104 developmental biology, Neoparamoeba perurans, 040102 fisheries, Ultrastructure, 0401 agriculture, forestry, and fisheries, medicine.symptom
Abstract

Amoebic gill disease (AGD) is emerging as one of the most significant health challenges affecting farmed Atlantic salmon in the marine environment. It is caused by the amphizoic amoeba Neoparamoeba perurans, with infestation of gills causing severe hyperplastic lesions, compromising overall gill integrity and function. This study used histology, transmission electron microscopy (TEM), immunohistochemistry and transcript expression to relate AGD‐associated pathological changes to changes in the morphology and distribution of chloride cells (CCs) in the gills of Atlantic salmon (Salmo salar L.) showing the progression of an AGD infection. A marked reduction in numbers of immunolabelled CCs was detected, and a changing pattern in distribution and morphology was closely linked with the level of basal epithelial hyperplasia in the gill. In addition, acute degenerative ultrastructural changes to CCs at the lesion site were observed with TEM. These findings were supported by the early‐onset downregulation of Na+/K+‐ATPase transcript expression. This study provides supportive evidence that histological AGD lesion assessment was a good qualitative tool for AGD scoring and corresponded well with qPCR genomic Paramoeba perurans quantification. Ultrastructural changes induced in salmon CCs as a result of AGD are reported here for the first time.

Published
2019

4. Hemichordate genomes and deuterostome origins

Author

Shannon Dugan, Oleg Simakov, Ryo Koyanagi, Andrew Cree, Fuki Gyoja, Nicholas H. Putnam, Asao Fujiyama, Miyuki Kanda, Michael Holder, Geoffrey Okwuonu, Lynne V. Nazareth, Atsuko Sato, Christopher B. Cameron, Christopher J. Lowe, Jens H. Fritzenwanker, Yi Chih Chen, Therese Mitros, Paul Gonzalez, Daniel S. Rokhsar, Jireh Santibanez, Donna M. Muzny, Rui Chen, Kenneth W. Baughman, Jessen V. Bredeson, Shinichi Yamasaki, Hiroki Goto, Noriyuki Satoh, Nana Arakaki, Shalini N. Jhangiani, Richard A. Gibbs, Kanako Hisata, Takeshi Kawashima, Jia-Xing Yue, Jiaxin Qu, Donna Morton, Huyen Dinh, Christie Kovar, Jeremy Schmutz, Lora Lewis, Sandra L. Lee, Leonid Peshkin, Jerry Jenkins, Judith Levine, Stephen Richards, Kunifumi Tagawa, Kim C. Worley, John C. Gerhart, Robert Freeman, Manabu Fujie, Michael Wu, Yan Ding, Jr-Kai Yu, Marc W. Kirschner, Tom Humphreys, Ferdinand Marlétaz, Akane Sasaki, Andrew Gillis, Ariel M. Pani, Tomoe Hikosaka-Katayama, Eiichi Shoguchi, Yi-Hsien Su, Simakov, Oleg [0000-0002-3585-4511], Marlétaz, Ferdinand [0000-0001-8124-4266], Koyanagi, Ryo [0000-0002-9694-0288], Bredeson, Jessen [0000-0001-5489-8512], Yue, Jia-Xing [0000-0002-2122-9221], Fritzenwanker, Jens H [0000-0002-5201-4100], Richards, Stephen [0000-0001-8959-5466], Gillis, Andrew [0000-0003-2062-3777], Putnam, Nicholas H [0000-0002-1315-782X], Tagawa, Kunifumi [0000-0001-5634-9373], Worley, Kim C [0000-0002-0282-1000], Lowe, Christopher J [0000-0002-7789-8643], Rokhsar, Daniel S [0000-0002-8704-2224], and Apollo - University of Cambridge Repository

Subjects
0106 biological sciences, Evolution, General Science & Technology, Hemichordate, Synteny, 010603 evolutionary biology, 01 natural sciences, Article, Conserved sequence, Evolution, Molecular, 03 medical and health sciences, Chordata, Nonvertebrate, Transforming Growth Factor beta, Phylogenetics, Genetics, Animals, 14. Life underwater, Chordata, Phylogeny, Conserved Sequence, 030304 developmental biology, Comparative genomics, 0303 health sciences, Genome, Multidisciplinary, Deuterostome, biology, Phylum, Human Genome, Molecular, biology.organism_classification, Nonvertebrate, Multigene Family, Evolutionary developmental biology, Generic health relevance, Echinodermata, Signal Transduction
Abstract

Acorn worms, also known as enteropneust (literally, 'gut-breathing') hemichordates, are marine invertebrates that share features with echinoderms and chordates. Together, these three phyla comprise the deuterostomes. Here we report the draft genome sequences of two acorn worms, Saccoglossus kowalevskii and Ptychodera flava. By comparing them with diverse bilaterian genomes, we identify shared traits that were probably inherited from the last common deuterostome ancestor, and then explore evolutionary trajectories leading from this ancestor to hemichordates, echinoderms and chordates. The hemichordate genomes exhibit extensive conserved synteny with amphioxus and other bilaterians, and deeply conserved non-coding sequences that are candidates for conserved gene-regulatory elements. Notably, hemichordates possess a deuterostome-specific genomic cluster of four ordered transcription factor genes, the expression of which is associated with the development of pharyngeal 'gill' slits, the foremost morphological innovation of early deuterostomes, and is probably central to their filter-feeding lifestyle. Comparative analysis reveals numerous deuterostome-specific gene novelties, including genes found in deuterostomes and marine microbes, but not other animals. The putative functions of these genes can be linked to physiological, metabolic and developmental specializations of the filter-feeding ancestor.

Published
2015

5. Subaxial Injury Classification Scoring System Treatment Recommendations

Author

Stephen J. Ruff, Con Vasili, Sumant Samuel, Jiun-Lih Lin, Margaret M. Smith, Randolph Gray, Nathan Hartin, Ioannis G. Sergides, Jonathan R. Ball, and Andrew Cree

Subjects
Adult, Male, medicine.medical_specialty, Scoring system, MEDLINE, Test validity, Young Adult, Injury Severity Score, medicine, Humans, Orthopedics and Sports Medicine, Young adult, Aged, Retrospective Studies, business.industry, Reproducibility of Results, Retrospective cohort study, Injury classification, Evidence-based medicine, Middle Aged, Surgery, Spinal Injuries, Cervical Vertebrae, Physical therapy, Female, Neurology (clinical), business
Abstract

STUDY DESIGN Retrospective case series. OBJECTIVE To test validity of subaxial injury classification (SLIC) treatment recommendations. SUMMARY OF BACKGROUND DATA Although SLIC has been tested for reliability, external studies that test the validity of its treatment recommendations are lacking. METHODS The SLIC score was determined by reviewing imaging studies and clinical records in a consecutive series of 185 patients with subaxial cervical spine trauma presenting to a level 1 spinal injury referral center. Details including attending surgeon responsible for treatment decision, treatment received, and surgical approach were collected. RESULTS Treatment received matched SLIC guidelines in 93.6% nonsurgically managed patients and 96.3% surgically managed patients. The mean SLIC score of the surgically treated group of patients was significantly higher than that of the nonsurgical group (7.14 vs. 2.22; P

Published
2015

6. Tree Performance, Yield, and Fruit Quality of ‘Valencia’ Sweet Orange (Citrus sinensis L. Osbeck) Selections on New Poncirus trifoliata Rootstocks

Author

Tahir Khurshid, Andrew Creek, Graeme Sanderson, and Xiaochun Zhao

Subjects
total soluble solids, juice%, yield efficiency, alternate bearing index, trunk circumference, Plant culture, SB1-1110
Abstract

This study reports the performance of seven Valencia (Citrus sinensis) selections grafted to four Trifoliata (Poncirus trifoliata) rootstocks in the Riverina region of south-east Australia. Six of the Valencia selections (numbered as Valencia 1 to 6) were from orchards in the Riverina region, and the seventh was a standard commercial variety ‘Keenan’ (control). Three of the four Trifoliata rootstock selections (‘Zao Yang’, ‘Tanghe’, and ‘Donghai’) were imported from the People’s Republic of China, and the fourth was the ‘Tri22’ (control) selection used commercially in Australia. ‘Valencia 5’ produced the highest cumulative (162 kg/tree) yield over the five harvest seasons and increased levels of Total Soluble Solids (TSS, 1.7 °Brix) compared with the current industry standard, ‘Keenan’. Trees grafted to ‘Zao Yang’ produced higher yields than any of the other Trifoliata selections, again outperforming the current industry standard, ‘Tri22’. The new combination of ‘Valencia 5’ scion on ‘Zao Yang’ rootstock represents an opportunity to significantly improve orchard productivity, particularly for juice production. ‘Valencia 6’ on Zao Yang’ had the highest percentage (58%) of fruit >75 mm in diameter compared with other scion/rootstock combinations and creates an additional opportunity for fresh market production. Significant differences in tree size, growth rates, and productivity were identified. Results from this evaluation have resulted in the commercialisation of ‘Valencia 5’ and ‘Valencia 6’ scions and ‘Zao Yang’ rootstock as three new citrus varieties for sweet orange production in Australia.

Published
2024
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7. A comparison of disease susceptibility and innate immune response between diploid and triploid Atlantic salmon (Salmo salar) siblings following experimental infection with Neoparamoeba perurans, causative agent of amoebic gill disease

Author

Herve Migaud, John Taylor, Alexandra Adams, Andrew Cree Preston, William Roy, and Lynn Chalmers

Subjects
0301 basic medicine, Gills, Neoparamoeba perurans, endocrine system, triploid, Salmo salar, Disease, Aquaculture, amoebic gill disease, immune response, 03 medical and health sciences, Fish Diseases, AGD, Immune system, Immunity, Animals, Salmo, Amoeba, Amoebic gill disease, Innate immune system, biology, cohabitation, fungi, 04 agricultural and veterinary sciences, Amebiasis, biology.organism_classification, Diploidy, Triploidy, Immunity, Innate, 030104 developmental biology, Infectious Diseases, Immunology, 040102 fisheries, 0401 agriculture, forestry, and fisheries, Animal Science and Zoology, Parasitology, Disease Susceptibility, Ploidy, Research Article
Abstract

SUMMARYFew studies have focussed on the health and immunity of triploid Atlantic salmon and therefore much is still unknown about their response to commercially significant pathogens. This is important if triploid stocks are to be considered for full-scale commercial production. This study aimed to investigate and compare the response of triploid and diploid Atlantic salmon to an experimental challenge with Neoparamoeba perurans, causative agent of amoebic gill disease (AGD). This disease is economically significant for the aquaculture industry. The results indicated that ploidy had no significant effect on gross gill score or gill filaments affected, while infection and time had significant effects. Ploidy, infection and time did not affect complement or anti-protease activities. Ploidy had a significant effect on lysozyme activity at 21 days post-infection (while infection and time did not), although activity was within the ranges previously recorded for salmonids. Stock did not significantly affect any of the parameters measured. Based on the study results, it can be suggested that ploidy does not affect the manifestation or severity of AGD pathology or the serum innate immune response. Additionally, the serum immune response of diploid and triploid Atlantic salmon may not be significantly affected by amoebic gill disease.

Published
2017

8. Surface feeding and aggressive behaviour of diploid and triploid brown trout Salmo trutta during allopatric pair-wise matchings

Author

Andrew Cree Preston, Herve Migaud, Colin E. Adams, and John Taylor

Subjects
biology, Ecology, fungi, food and beverages, Zoology, Aquatic Science, biology.organism_classification, Dominance hierarchy, Gammarus pulex, Trout, Brown trout, Dominance (ethology), Seasonal breeder, Ploidy, Salmo, reproductive and urinary physiology, Ecology, Evolution, Behavior and Systematics
Abstract

Diploid and triploid brown trout Salmo trutta were acclimated for 6 weeks on two feeding regimes (floating and sinking). Thereafter, aggression and surface feeding response were compared between pairs of all diploid, all triploid and diploid and triploid S. trutta in an experimental stream. In each pair-wise matching, fish of similar size were placed in allopatry and rank was determined by the total number of aggressive interactions recorded. Dominant individuals initiated more aggression than subordinates, spent more time defending a territory and positioned themselves closer to the surface food source (Gammarus pulex), whereas subordinates occupied the peripheries. In cross ploidy trials, diploid S. trutta were more aggressive than triploid, and dominated their sibling when placed in pair-wise matchings. Surface feeding, however, did not differ statistically between ploidy irrespective of feeding regime. Triploids adopted a sneak feeding strategy while diploids expended more time defending a territory. In addition, we also tested whether triploids exhibit a similar social dominance to diploids when placed in allopatry. Although aggression was lower in triploid pairs than in the diploid and triploid pairs, a dominance hierarchy was also observed between individuals of the same ploidy. Dominant triploid fish were more aggressive and consumed more feed items than subordinate individuals. Subordinate fish displayed a darker colour index than dominant fish suggesting increased stress levels. Dominant triploid fish, however, appeared to be more tolerant of subordinate individuals and did not display the same degree of invasive aggression as seen in the diploid and diploid or diploid and triploid matchings. These novel findings suggest that sterile triploid S. trutta feed similarly but are less aggressive than diploid trout. Future studies should determine the habitat choice of triploid S. trutta after release and the interaction between wild fish and triploids during the breeding season prior to utilization of triploids as an alternative management strategy within freshwater fisheries.

Published
2014

9. The common marmoset genome provides insight into primate biology and evolution

Author

San Juana Ruiz, Daniel Gerlach, Tomas Vinar, Brona Brejova, Saba Sajjadian, Miriam K. Konkel, Muthuswamy Raveendran, Yih Shin Liu, Paul Flicek, Lubomir Tomaska, Donna M. Muzny, Daniel R. Schrider, Megan C. Ranck, Kjersti Aagaard, Huyen Dinh, Jayantha B. Tennakoon, Lucinda Fulton, Lynne V. Nazareth, Brygg Ullmer, George M. Weinstock, Kim D. Delehaunty, Xose S. Puente, Charles E. Vejnar, Shyam Prabhakar, Matthew W. Hahn, J. Scott Moncrieff, Mark A. Batzer, Tina Graves, Catherine C. Fontenot, Carlos López-Otín, Corinna N. Ross, Catrina Fronick, Jeffrey Rogers, Nirmala Arul Rayan, Mario Ventura, Pieter J. De Jong, Elaine R. Mardis, Steve Searle, Christie LKovar, David Haig, Ngoc Nguyen, Shalini N. Jhangiani, Margaret Morgan, Crystal M. Warner, Mimi M. Chandrabose, Keith G. Mansfield, Vandita Joshi, Kathryn Beal, Saverio B. Capuano, Magali Ruffier, Ling Ling Pu, Jerilyn A. Walker, Marvin Diep Dao, John Lopez, Irene Newsham, Yuanqing Wu, Jan Hinnerk Vogel, Arian F.A. Smit, Javier Herrero, Andrew Cree, Tomas Marques-Bonet, Oronzo Capozzi, LaDeana W. Hillier, Robert S. Fulton, Claudio Casola, Mariano Rocchi, Benjamin Soibam, Suzette D. Tardif, Derek E. Wildman, Evgenia V. Kriventseva, Kim C. Worley, Baoli Zhu, Jennifer F. Hughes, Robert Hubley, Geoffrey Okwuonu, Jennifer Hume, Lora Lewis, Ricardo C.H. del Rosario, Devin P. Locke, Lora Perales, David Rio Deiros, David J. Witherspoon, Yi Han, Brian J. Raney, David Rodríguez, Stephen Fitzgerald, Jireh Santibanez, Albert J. Vilella, R. Gerald Fowler, Qing Wang, Belen Lorente-Galdos, Ramatu Ayiesha Gabisi, Víctor Quesada, Weimin Xiao, Nicoletta Archidiacono, Emre Karakor, Helen Skaletsky, R. Alan Harris, Evgeny M. Zdobnov, Richard A. Gibbs, Wesley C. Warren, Patrick Minx, Preethi H. Gunaratne, Rita A. Wright, Doriana Misceo, Jinchuan Xing, Evan E. Eichler, Lynn B. Jorde, Carolin Kosiol, Rick K. Wilson, Sandra L. Lee, University of St Andrews. School of Biology, University of St Andrews. Centre for Biological Diversity, National Human Genome Research Institute (US), National Institutes of Health (US), National Science Foundation (US), Howard Hughes Medical Institute, Louisiana State University, Cullen Foundation, European Research Council, Ministerio de Ciencia e Innovación (España), Instituto Nacional de Bioinformática (España), Gerlach, Daniel, Kriventseva, Evgenia, and Zdobnov, Evgeny

Subjects
endocrine system, animal structures, Evolució molecular, Evolution, QH301 Biology, animal diseases, Molecular Sequence Data, QH426 Genetics, Polymorphism, Single Nucleotide, Genome, Article, Evolution, Molecular, QH301, Phylogenetics, biology.animal, Genetics, Animals, ddc:576.5, Primate, Amino Acid Sequence, Polymorphism, QH426, Phylogeny, New World monkey, biology, Reproduction, Polimorfisme genètic, Callithrix/genetics, Molecular, Marmoset, Callithrix, Single Nucleotide, Sequence Analysis, DNA, biology.organism_classification, Reproduction/genetics, DNA/methods, body regions, MicroRNAs/genetics, MicroRNAs, Evolutionary biology, Female, Sequence Analysis
Abstract

The Marmoset Genome Sequencing and Analysis Consortium.-- Worley, Kim C. et al., We report the whole-genome sequence of the common marmoset (Callithrix jacchus). The 2.26-Gb genome of a female marmoset was assembled using Sanger read data (6×) and a whole-genome shotgun strategy. A first analysis has permitted comparison with the genomes of apes and Old World monkeys and the identification of specific features that might contribute to the unique biology of this diminutive primate, including genetic changes that may influence body size, frequent twinning and chimerism. We observed positive selection in growth hormone/insulin-like growth factor genes (growth pathways), respiratory complex I genes (metabolic pathways), and genes encoding immunobiological factors and proteases (reproductive and immunity pathways). In addition, both protein-coding and microRNA genes related to reproduction exhibited evidence of rapid sequence evolution. This genome sequence for a New World monkey enables increased power for comparative analyses among available primate genomes and facilitates biomedical research application. © 2014 Nature America, Inc., The marmoset genome project was funded by the National Human Genome Research Institute (NHGRI), including from grants U54 HG003273 (R.A. Gibbs) and U54 HG003079 (R.K.W.), with additional support from the US National Institutes of Health (NIH), including from grants R01 DK077639 (S.D.T.), R01 GM59290 (L.B.J. and M.A.B.), HG002385 (E.E.E.) and P51-OD011133 (Southwest NPRC), and support from the National Science Foundation (NSF BCS-0751508 to D.E.W.) and the VEGA grant agency: 1/0719/14 (T.V.) and 1/1085/12 (B.B.). C.C.F. and M.C.R. were supported in part by a Howard Hughes Medical Institute grant to Louisiana State University through the Undergraduate Biological Sciences Education program. J.X. was supported by NHGRI grant K99 HG005846. P.H.G. was supported by the Cullen Foundation. T.M.-B. was supported by European Research Council Starting Grant (260372) and MICINN (Spain) grant BFU2011-28549. B.L.-G. was supported by the Spanish National Institute of Bioinformatics (see URLs).

Published
2014

10. Optimisation of triploidy induction in brown trout (Salmo trutta L.)

Author

Pierre Bozzolla, Andrew Cree Preston, Herve Migaud, Brian Craig, David J. Penman, and John Taylor

Subjects
biology, media_common.quotation_subject, Fish farming, Hydrostatic pressure, Grayling, Aquatic Science, biology.organism_classification, Competition (biology), Fishery, Trout, Brown trout, Animal science, Stocking, Salmo, media_common
Abstract

Inland fisheries contribute substantially to the economies of England and Wales. Many trout fisheries rely partly or entirely on stocking to maintain catches. Given that farmed trout often differ genetically from their wild counterparts, wild trout could be at risk of reduced fitness due to interbreeding or competition with farmed fish. As a preventative measure, the UK Environment Agency has implemented the “National Trout and Grayling Strategy” which will only give consent to the stocking of rivers and some still waters with sterile, all-female triploid brown trout. In order to produce an optimised hydrostatic pressure induction protocol three experiments were conducted to (1) determine the optimal timing of application post-fertilisation, (2) define optimal pressure intensity and duration of the shock and (3) study the effect of temperature (6–12 °C) on triploid yield. Triploid rate was assessed using two different ploidy verification methods (blood smear and flow cytometry). Results indicated high survival to yolk sac absorption stage (69.2–93.6%) and high triploid yields (82.5–100%) from the range of treatments applied. Furthermore, no significant differences in triploid rates were shown when shock timings and durations were adjusted according to the temperature used. In all treatments deformity prevalence remained low (

Published
2013

11. Effects of temperature on feed intake and plasma chemistry after exhaustive exercise in triploid brown trout (Salmo trutta L)

Author

Andrew Cree Preston, John Taylor, Herve Migaud, Per Gunnar Fjelldal, and Thomas Willum Hansen

Subjects
Blood Glucose, 0106 biological sciences, Trout, Physiology, Blood chemistry, Brown trout, media_common.quotation_subject, Physical Exertion, Triploid, Aquatic Science, 01 natural sciences, Biochemistry, Article, Eating, Stocking, Animal science, Deformity, Animals, Aspartate Aminotransferases, Lactic Acid, Salmo, Exercise, media_common, biology, 010604 marine biology & hydrobiology, fungi, Temperature, Appetite, 04 agricultural and veterinary sciences, General Medicine, Anatomy, Alkaline Phosphatase, biology.organism_classification, Diploidy, Triploidy, Spine, Cholesterol, 040102 fisheries, 0401 agriculture, forestry, and fisheries, Alkaline phosphatase, Calcium, Ploidy
Abstract

The physiological effect of temperature on feed intake and haematological parameters after exhaustive swimming in diploid and triploid brown trout (Salmo trutta) was investigated. Trout were exposed to an incremental temperature challenge (2 degrees C/day) from ambient (6 degrees C) to either 10 or 19 degrees C. Feed intake profiles did not differ between ploidy at 10 degrees C; however, triploids had a significantly higher total feed intake at 19 degrees C. After 24 days, each temperature-ploidy group was exposed to exhaustive swimming for 10 min. The haematological response differed between ploidy, with the magnitude of the response affected by temperature and ploidy. Post-exercise, acid-base and ionic differences were observed. Plasma lactate increased significantly from rest for both temperature and ploidy groups, but glucose increased significantly at higher temperature. Post-exercise, triploids at 19 degrees C had significantly higher osmolality and cholesterol than diploids, but differences were resumed within 4 h. Elevated alkaline phosphatase (ALP) and aspartate aminotransferase (AST) in fish at higher temperature suggested greater tissue damage; however, both ploidy responded similarly. Despite no significant differences in deformity prevalence, the type and location of deformities observed differed between ploidy (decreased intervertebral space with higher prevalence in tail area and fin regions for diploids, while vertebral compression, fusion in cranial and caudal trunks for triploids). These results suggest triploids have greater appetite than diploids at elevated temperature and that triploids suffer similar blood disturbances after exercise as diploids. These findings have implications for the management of freshwater ecosystems and suggest that stocking triploid brown trout may offer an alternative to diploid brown trout.

Published
2016

12. Parr–smolt transformation in out-of-season triploid Atlantic salmon (Salmo salar L.)

Author

Derrick R Guy, Eric Leclercq, Herve Migaud, Andrew Cree Preston, and John Taylor

Subjects
Fishery, photoperiodism, biology, Spinal deformity, %22">Fish , Zoology, Atpase activity, Silvering, Ambient water, Aquatic Science, Salmo, biology.organism_classification, Smoltification
Abstract

article i nfo Article history: Keywords: Triploid Out-of-season Smoltification Photoperiod ATPase Atlantic salmon Production of sterile triploid Atlantic salmon (Salmo salar) would appear to be the best strategy to address the growing concerns on environmental impacts of escapees. However, the industry relies on a year round supply of smolts to ensure continual production and to date the production of out-of-season (S0+) triploid smolts has not been reported. The present study demonstrates that S0+ triploid smolts can be produced using an accelerated "square-wave" photoperiod (LL-LD 9.5:14.5-LL) under ambient water temperature. Such a regime advanced the timing of smoltification by 3 months (S0+) relative to their siblings under an ambient photoperiod (S1+) as observed through body silvering, fin darkening, decrease in condition and significantly increased gill Na + ,K + -ATPase activity. Importantly, triploid S0+ fish smolted 4 weeks earlier than their diploid siblings. In S1+ populations, no difference in smolt time was observed although triploid fish also achieved a higher weight. Furthermore, deformity prevalence was very low during the fresh (≤5%) and seawater (≤2.5%) stages within both ploidies mainly represented by spinal deformity and operculum shortening. Family effects for growth and condition were clear, however, no significant family/ploidy interactions were observed although this was based on only two full-sib crosses. These results are promising but there is still a long way to go before triploid can become a commercial reality. Further studies are required to optimize and refine husbandry protocols, define breeding strategies especially regarding family selection and overall better understand triploid salmon physiology.

Published
2012

13. Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes

Author

Helen Skaletsky, Shannon Dugan, Donna M. Muzny, Steve Rozen, Laura G. Brown, Jennifer F. Hughes, Joelle Veizer, Ting-Jan Cho, Donna Villasana, Tatyana Pyntikova, Colin Kremitzki, Laura Courtney, Tina Graves, David C. Page, Robert S. Fulton, Michael Holder, Yan Ding, Lynne V. Nazareth, Holland Kotkiewicz, Andrew Cree, Natalia Koutseva, Richard A. Gibbs, Qiaoyan Wang, Wesley C. Warren, Richard K. Wilson, Hua Shen, and Christian J. Buhay

Subjects
Male, Time Factors, Pan troglodytes, Molecular Sequence Data, Pseudoautosomal region, Biology, Y chromosome, Article, Chromosomal crossover, Evolution, Molecular, Y Chromosome, Animals, Humans, Gene family, Crossing Over, Genetic, Selection, Genetic, neoplasms, Conserved Sequence, In Situ Hybridization, Fluorescence, X chromosome, Genetics, Radiation Hybrid Mapping, Z chromosome, Bacterial artificial chromosome, Chromosomes, Human, Y, Multidisciplinary, Models, Genetic, Gene Amplification, myr, Macaca mulatta, digestive system diseases, Gene Deletion
Abstract

This evolutionary decay was driven by a series of five ‘stratification’ events. Each event suppressed X–Y crossing over within a chromosome segment or ‘stratum’, incorporated that segment into the MSY and subjected its genes to the erosive forces that attend the absence of crossing over 2,6 . The last of these events occurred 30 million years ago, 5 million years before the human and Old World monkey lineages diverged. Although speculation abounds regarding ongoing decay and looming extinction of the human Y chromosome 7–10 , remarkably little is known about how many MSY genes were lost in the human lineage in the 25 million years that have followed its separation from the Old World monkey lineage. To investigate this question, we sequenced the MSY of the rhesus macaque, an Old World monkey, and compared it to the human MSY. We discovered that during the last 25 million years MSY gene loss in the human lineage was limited to the youngest stratum (stratum 5), which comprises three percent of the human MSY. In the older strata, which collectively comprise the bulk of the human MSY, gene loss evidently ceased more than 25 million years ago. Likewise, the rhesus MSY has not lost any older genes (from strata 1–4) during the past 25 million years, despite its major structural differences to the human MSY. The rhesus MSY is simpler, with few amplified gene families or palindromes that might enable intrachromosomal recombination and repair. We present an empirical reconstruction of human MSY evolution in which each stratum transitioned from rapid, exponential loss of ancestral genes to strict conservation through purifying selection. The human Y chromosome no longer engages in crossing over with its once-identical partner, the X chromosome, except in its pseudoautosomal regions. During evolution, X–Y crossing over was suppressed in five different chromosomal regions at five different times, each probably resulting from an inversion in the Y chromosome 2,3 . Each of these regions of the Y chromosome then began its own individual course of degeneration, experiencing deletions and gene loss. Comparison of the present-day X and Y chromosomes enables identification of these five evolutionary ‘strata’ in the MSY (and X chromosome); their distinctive degrees of X–Y differentiation indicate their evolutionary ages 2,3 . The oldest stratum (stratum 1) dates back over 240 million years (Myr) 2 and is the most highly differentiated, and the youngest stratum (stratum 5) originated only 30 Myr ago and displays the highest X–Y nucleotide sequence similarity within the MSY 3 . The five strata and their respective decay processes, over tens to hundreds of millions of years of mammalian evolution, offer replicate experiments of nature from which to reconstruct the trajectories and kinetics of gene loss in the MSY. Only the human and chimpanzee MSYs had been sequenced before the present study, and they are separated by just 6 Myr of evolution. We decided to examine the MSY of a much more distant relative, the rhesus macaque (Macaca mulatta), to enable us to reconstruct gene loss and conservation in the MSY during the past 25 Myr. We sequenced the rhesus MSY using bacterial artificial chromosome (BAC) clones and the SHIMS (single-haplotype iterative mapping and sequencing) strategy that has previously been used in the human and chimpanzee MSYs 4,11–13 as well as in the chicken Z chromosome 5 . The resulting sequence is comprised of 11.0 megabases (Mb), is complete aside from three small gaps and has an error rate of about one nucleotide per Mb. We ordered and oriented the finished sequence contigs by fluorescence in situ hybridization and radiation hybrid mapping (Supplementary Figs 1–6, Supplementary Table 1, Supplemen

Published
2012

14. A high-resolution map of human evolutionary constraint using 29 mammals

Author

Kerstin, Lindblad-Toh, Manuel, Garber, Or, Zuk, Michael F, Lin, Brian J, Parker, Stefan, Washietl, Pouya, Kheradpour, Jason, Ernst, Gregory, Jordan, Evan, Mauceli, Lucas D, Ward, Craig B, Lowe, Alisha K, Holloway, Michele, Clamp, Sante, Gnerre, Jessica, Alföldi, Kathryn, Beal, Jean, Chang, Hiram, Clawson, James, Cuff, Federica, Di Palma, Stephen, Fitzgerald, Paul, Flicek, Mitchell, Guttman, Melissa J, Hubisz, David B, Jaffe, Irwin, Jungreis, W James, Kent, Dennis, Kostka, Marcia, Lara, Andre L, Martins, Tim, Massingham, Ida, Moltke, Brian J, Raney, Matthew D, Rasmussen, Jim, Robinson, Alexander, Stark, Albert J, Vilella, Jiayu, Wen, Xiaohui, Xie, Michael C, Zody, Jen, Baldwin, Toby, Bloom, Chee Whye, Chin, Dave, Heiman, Robert, Nicol, Chad, Nusbaum, Sarah, Young, Jane, Wilkinson, Kim C, Worley, Christie L, Kovar, Donna M, Muzny, Richard A, Gibbs, Andrew, Cree, Huyen H, Dihn, Gerald, Fowler, Shalili, Jhangiani, Vandita, Joshi, Sandra, Lee, Lora R, Lewis, Lynne V, Nazareth, Geoffrey, Okwuonu, Jireh, Santibanez, Wesley C, Warren, Elaine R, Mardis, George M, Weinstock, Richard K, Wilson, Kim, Delehaunty, David, Dooling, Catrina, Fronik, Lucinda, Fulton, Bob, Fulton, Tina, Graves, Patrick, Minx, Erica, Sodergren, Ewan, Birney, Elliott H, Margulies, Javier, Herrero, Eric D, Green, David, Haussler, Adam, Siepel, Nick, Goldman, Katherine S, Pollard, Jakob S, Pedersen, Eric S, Lander, Manolis, Kellis, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Kellis, Manolis, Mag Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Ward, Lucas D., Jungreis, Irwin, and Rasmussen, Matthew D.

Subjects
Genome evolution, Genomics, Computational biology, Biology, Human accelerated regions, Genome, Article, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Coding region, Disease, Selection, Genetic, Gene, Phylogeny, 030304 developmental biology, Mammals, Genetics, 0303 health sciences, Multidisciplinary, Genome, Human, Molecular Sequence Annotation, Exons, Sequence Analysis, DNA, 3. Good health, Health, RNA, Human genome, Mobile genetic elements, Sequence Alignment, 030217 neurology & neurosurgery
Abstract

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ~4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ~60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease., National Human Genome Research Institute (U.S.), National Institute of General Medical Sciences (U.S.) (Grant number GM82901), National Science Foundation (U.S.). Postdoctural Fellowship (Award 0905968), National Science Foundation (U.S.). Career (0644282), National Institutes of Health (U.S.) (R01-HG004037), Alfred P. Sloan Foundation., Austrian Science Fund. Erwin Schrodinger Fellowship

Published
2011

15. Ploidy effects on hatchery survival, deformities, and performance in Atlantic salmon (Salmo salar)

Author

Andrew Cree Preston, John Taylor, Herve Migaud, and Derrick R Guy

Subjects
biology, business.industry, fungi, Hydrostatic pressure, food and beverages, Zoology, Aquatic Science, biology.organism_classification, Hatchery, Fishery, medicine.anatomical_structure, Aquaculture, medicine, Gamete, Ploidy, Salmo, business, Salmonidae, Fertilisation
Abstract

The production of sterile triploid Atlantic salmon (Salmo salar) may help address the increasing pressure on the industry to reduce potential breeding between farmed escapees and wild fish populations. However, many previous studies have observed poor performance at sea in triploid stocks (growth, survival, and deformity). This may result from poor early hatchery performance and a strong parental effect. Therefore, in the present study, two year classes (2007 and 2008) of mixed sex fish were created (10 males:10 females) to examine ploidy interactions on hatchery performance. Egg batches were divided in two at fertilisation with one group subjected to a hydrostatic pressure shock to induce triploidy. Triploid rate was confirmed at 100% in all groups, verified by red blood cell nucleus length measurements. Survival to hatch did not differ between ploidy. However, reduced survival was found to strongly correlate with gamete quality. During the hatchery phase ploidy significantly affected size at hatch, with diploids generally larger than triploids. Growth advantage of diploids over triploids was only maintained for 6 weeks post-first feeding, with triploids generally out-growing their diploid siblings by the end of the hatchery phase. Deformity prevalence in first feeding stages was generally low (mean

Published
2011

16. A full-length cDNA resource for the pea aphid, Acyrthosiphon pisum

Author

Takema Fukatsu, Richard A. Gibbs, Shuji Shigenobu, Stephen Richards, Mizue Morioka, Shin-ya Miyagishima, David L. Stern, Atsushi Nakabachi, Andrew Cree, and Toshiaki Kudo

Subjects
Genetics, Expressed sequence tag, biology, Gene prediction, food and beverages, Genomics, Genome project, biology.organism_classification, Acyrthosiphon pisum, Insect Science, Complementary DNA, Genomic library, Molecular Biology, Functional genomics
Abstract

Large collections of full-length cDNAs are important resources for genome annotation and functional genomics. We report the creation of a collection of 50 599 full-length cDNA clones from the pea aphid, Acyrthosiphon pisum. Sequencing from 5′ and 3′ ends of the clones generated 97 828 high-quality expressed sequence tags, representing approximately 9000 genes. These sequences were imported to AphidBase and are shown to play crucial roles in both automatic gene prediction and manual annotation. Our detailed analyses demonstrated that the full-length cDNAs can further improve gene models and can even identify novel genes that are not included in the current version of the official gene set. This full-length cDNA collection can be utilized for a wide variety of functional studies, serving as a community resource for the study of the functional genomics of the pea aphid.

Published
2010

17. Comprehensive genomic characterization defines human glioblastoma genes and core pathways

Author

Sandy Aronson, Leslie Cope, Michael L. Bittner, Daniel C. Koboldt, Alex E. Lash, W. K. Alfred Yung, Margaret Morgan, Devin Absher, Carl F. Schaefer, Roger E. McLendon, Michael D. Prados, Josh Gould, Ju Han, Stacey Gabriel, Scott R. VandenBerg, Ilana Perna, Troy Shelton, Junyuan Wu, Sacha Scott, Steve Scherer, Michael J. T. O’Kelly, Li Ding, Erin Hickey, Elizabeth J. Thomson, Bahram Parvin, Kim D. Delehaunty, Gi Choi Yoon, Mark D. Robinson, Oliver Bogler, Darrell D. Bigner, Michael R. Reich, Jianhua Zhang, Robert S. Fulton, Allan H. Friedman, Tammi L. Vickery, Amita Aggarwal, Subhashree Madhavan, Liuda Ziaugra, Yuan Qi, Vandita Joshi, Eric Van Name, Jane Wilkinson, W. Ruprecht Wiedemeyer, Xiaoqi Shi, Richard A. Gibbs, Lynda Chin, Jessica Chen, Stefano Monti, Erwin G. Van Meir, John Ngai, Amy Hawkins, Elizabeth Lenkiewicz, Brad Ozenberger, Shannon Dorton, Georgia Ren, John N. Weinstein, Gena M. Mastrogianakis, Asif T. Chinwalla, Scott L. Carter, Nicholas D. Socci, Rachel Abbott, Gavin Sherlock, Lucinda Fulton, Hyun Soo Kim, Fei Pan, Magali Cavatore, Gabriele Alexe, Francis S. Collins, Narayanan Sathiamoorthy, Lakshmi Jakkula, Brian H. Dunford-Shore, Jireh Santibanez, Tom Mikkelsen, Huy V. Nguyen, Levi A. Garraway, Christopher A. Miller, Jinghui Zhang, Ken Chen, Timothy Fennell, Robert Sfeir, James A. Robinson, Alexey Stukalov, Richard K. Wilson, Matthew Meyerson, Daniel J. Weisenberger, Mi Yi Joo, Yevgeniy Antipin, Anna Lapuk, Gerald V. Fontenay, Nicolas Stransky, Adam B. Olshen, Elizabeth Purdom, Josh Korn, Huyen Dinh, Sai Balu, Victoria Wang, James G. Herman, Christie Kovar, Kristian Cibulskis, Tisha Chung, Agnes Viale, Paul T. Spellman, Supriya Gupta, Melissa Parkin, Peter J. Park, Maddy Wiechert, John W. Wallis, Peter W. Laird, Nikolaus Schultz, James D. Brooks, David Nassau, Jun Li, John R. Osborne, Anna D. Barker, Peter Fielding, Boris Reva, Karen Vranizan, D. Neil Hayes, Aleksandar Milosavljevic, Lawrence A. Donehower, Won Kong Sek, Daniela S. Gerhard, Otis Hall, Rameen Beroukhim, Audrey Southwick, George M. Weinstock, Chris Markovic, Roel G.W. Verhaak, David Van Den Berg, Joe W. Gray, Yanru Ren, Ethan Cerami, Yiming Zhu, Amrita Ray, Yonghong Xiao, Kristin G. Ardlie, William L. Gerald, Michael S. Lawrence, Gerald R. Fowler, Mark S. Guyer, Isaac S. Kohane, Kornel E. Schuebel, Mitchel S. Berger, Jeffrey J. Olson, Gary W. Swift, Lora Lewis, Sheri Sanders, Norman L. Lehman, Eric S. Lander, Robert Penny, Liliana Villafania, John G. Conboy, Ari B. Kahn, Henry Marr, Heidi S. Feiler, Lynn Nazareth, David J. Dooling, Katherine A. Hoadley, Alicia Hawes, Marc Ladanyi, Aniko Sabo, Wendy Winckler, Vivian Peng, Barbara A. Weir, Daniel J. Brat, Scott Morris, Carolyn C. Compton, Todd R. Golub, Scott Abbott, Michael D. McLellan, Jiqiang Yao, Shalini N. Jhangiani, Michael D. Topal, Michael C. Wendl, Gad Getz, Jun Yao, Derek Y. Chiang, Larry Feng, Steffen Durinck, David A. Wheeler, Yuzhu Tang, Benjamin Gross, Barry S. Taylor, Kenneth Aldape, Craig Pohl, Rick Meyer, Peter J. Good, Ling Lin, Elaine R. Mardis, Robert C. Onofrio, Jane Peterson, Stephen B. Baylin, Li-Xuan Qin, Andrew Cree, Cameron Brennan, Charles M. Perou, William Courtney, Omar Alvi, Donna M. Muzny, Joseph G. Vockley, Jill P. Mesirov, Yan Shi, Alexei Protopopov, Jim Vaught, Craig H. Mermel, Scott Mahan, Laetitia Borsu, Heather Schmidt, Jennifer Baldwin, Tracie L. Miner, Toby Bloom, David E. Larson, Leander Van Neste, Nicholas J. Wang, Kenneth H. Buetow, Raju Kucherlapati, Anthony San Lucas, Martin L. Ferguson, Terence P. Speed, Venkatraman E. Seshan, Debbie Beasley, Carrie Sougnez, Carrie A. Haipek, Richard M. Myers, Chris Sander, Qing Wang Wei, Jon G. Seidman, Rob Nicol, Manuel L. Gonzalez-Garay, Shin Leong, Shannon T. Brady, and University of Groningen

Subjects
Male, Models, Molecular, DNA Repair, Gene Dosage, NEUROFIBROMATOSIS TYPE-1, MISMATCH REPAIR, Phosphatidylinositol 3-Kinases, 0302 clinical medicine, Genes, Tumor Suppressor, DNA Modification Methylases, Proneural Glioblastoma, Aged, 80 and over, Genetics, 0303 health sciences, Neurofibromin 1, Multidisciplinary, Brain Neoplasms, NF1 GENE, Genomics, Middle Aged, TUMORS, ALKYLATING-AGENTS, 3. Good health, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, DNA methylation, Female, DNA mismatch repair, Functional genomics, Signal Transduction, Adult, Adolescent, CELL-LINES, Oncogenomics, Biology, Article, 03 medical and health sciences, PIK3CA GENE, Humans, Epigenetics, Gene, Aged, Retrospective Studies, 030304 developmental biology, HIGH-FREQUENCY, Genome, Human, Tumor Suppressor Proteins, SOMATIC MUTATIONS, Genes, erbB-1, DNA Methylation, Protein Structure, Tertiary, MALIGNANT GLIOMAS, DNA Repair Enzymes, Mutation, Glioblastoma
Abstract

Human cancer cells typically harbour multiple chromosomal aberrations, nucleotide substitutions and epigenetic modifications that drive malignant transformation. The Cancer Genome Atlas ( TCGA) pilot project aims to assess the value of large- scale multi- dimensional analysis of these molecular characteristics in human cancer and to provide the data rapidly to the research community. Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas - the most common type of primary adult brain cancer - and nucleotide sequence aberrations in 91 of the 206 glioblastomas. This analysis provides new insights into the roles of ERBB2, NF1 and TP53, uncovers frequent mutations of the phosphatidylinositol- 3- OH kinase regulatory subunit gene PIK3R1, and provides a network view of the pathways altered in the development of glioblastoma. Furthermore, integration of mutation, DNA methylation and clinical treatment data reveals a link between MGMT promoter methylation and a hypermutator phenotype consequent to mismatch repair deficiency in treated glioblastomas, an observation with potential clinical implications. Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.

Published
2008

22. Evolutionary and Biomedical Insights from the Rhesus Macaque Genome

Author

Carolin Kosiol, Belinda Giardine, Janet A. Hopkins, Andrew G. Clark, Ryan D. Hernandez, Peng Wang, Peter D. Stenson, Yu-Hui Rogers, Aaron L. Halpern, Andrew D. Kern, Webb Miller, Kymberlie H. Pepin, Melissa J. Hubisz, Kimberly D. Delehaunty, Robert E. Palermo, Matthew W. Hahn, Erica Sodergren, Brian P. Walenz, Scott M. Smith, Sandra L. Lee, Xiang Qin, Yucheng Feng, Ewen F. Kirkness, Vandita Joshi, Xiaoqiu Huang, Amanda F. Svatek, Fan Yang, Young Ho Kim, Laura Clarke, John E. Karro, Courtney Sherell White, Jessica Kolb, David Glenn Smith, Clay Davis, Jian Ma, Shobha Patil, Todd Wylie, Arian F.A. Smit, Shalini N. Jhangiani, Michael G. Katze, Edward V. Ball, Jennifer Godfrey, Heather A. Lawson, Brian J. Raney, Michael Holder, Ross C. Hardison, Christian J. Buhay, Zhangwan Li, Alicia Hawes, Eric J. Vallender, David A. Wheeler, James C. Wallace, Galt P. Barber, Jinchuan Xing, Yufeng Shen, Kayla E. Smith, Marvin Diep Dao, Jeffrey Rogers, Evan E. Eichler, Cynthia Pfannkoch, Jireh Santibanez, Kateryna D. Makova, Kashif Hirani, Robert M. Kuhn, Yanru Ren, David Neil Cooper, David Haussler, Carlos Bustamante, Adam Siepel, Mimi N. Chandrabose, Xiaoming Liu, George M. Weinstock, Teresa Utterback, Jarret Glasscock, Tomas Vinar, R. Alan Harris, Anis Karimpour-Fard, San Juana Ruiz, Lucinda Fulton, Asif T. Chinwalla, Aniko Sabo, Xinwei She, Charles Addo-Quaye, David L. Nelson, Lora Lewis, Hui Ke, Eli Venter, Donna M. Muzny, Alison Marklein, Bruce T. Lahn, Grace Pai, Brian W. Schneider, Shannon Dugan-Rocha, Henry Xing-Zhi Song, Jeremiah D. Degenhardt, Kyudong Han, Huaiyang Jiang, Stephanie M. Moore, Ian Schenck, Dinh Ngoc Ngo, Michael J. Cox, Heidie A. Paul, Ann S. Zwieg, Kim C. Worley, Craig Pohl, Rui Chen, Robert L. Strausberg, Ling-Ling Pu, Donna Karolchik, Jonathan R. Pollack, Geoffrey Okwuonu, Jennifer Hume, Elaine R. Mardis, David N. Messina, W. James Kent, William E. O'Brien, Fan Hsu, Andrew R. Jackson, Huyen Dinh, Hui Wang, LaDeana W. Hillier, Richard A. Gibbs, Alexandra Denby, Wesley C. Warren, Brygg Ullmer, Laura J. Dumas, Yih-shin Liu, Tony Attaway, Richard K. Wilson, Patrick Minx, James M. Sikela, Lan Zhang, Sandra Hines, Steven J. M. Jones, Amit Indap, Ze Cheng, Karin A. Remington, Stephanie Bell, Jungnam Lee, Kelly E. Bernard, Sang-Gook Han, Mariano Rocchi, Judith Hernandez, Betsy Ferguson, Hildegard Kehrer-Sawatzki, Ziad Khan, Aleksandar Milosavljevic, Joanne O. Nelson, Jeffery P. Demuth, Richard Burhans, David A. Parker, Lynne V. Nazareth, Roger E. Bumgarner, Marco A. Marra, Robert Baertsch, Andrew Cree, Paul Havlak, J. Craig Venter, Kay Prüfer, Rasmus Nielsen, Ewan Birney, Miriam K. Konkel, Mark A. Batzer, Arthur M. Lesk, Jacqueline E. Schein, Granger G. Sutton, Yan Ding, Yue Liu, Andy Peng Xiang, Miklós Csürös, Selina Vattathil, John W. Wallis, R. Gerald Fowler, Shiaw-Pyng Yang, Ramatu Ayiesha Gabisi, and Toni T. Garner

Subjects
Male, Biomedical Research, Pan troglodytes, Macaque, Human accelerated regions, Genome, Evolution, Molecular, Species Specificity, Gene Duplication, biology.animal, Animals, Humans, Primate, Gene Rearrangement, Genetics, Whole genome sequencing, Multidisciplinary, biology, Genetic Diseases, Inborn, Genetic Variation, Sequence Analysis, DNA, Gene rearrangement, biology.organism_classification, Macaca mulatta, Rhesus macaque, Homo sapiens, Evolutionary biology, Multigene Family, Mutation, Female
Abstract

The rhesus macaque ( Macaca mulatta ) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineage-specific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

Published
2007

25. Effect of zoledronic acid in an L6–L7 rabbit spine fusion model

Author

Julie Briody, Richard J. Bransford, Andrew Cree, Negin Amanat, Elisabeth Goergens, and David G. Little

Subjects
medicine.medical_specialty, Bone density, medicine.medical_treatment, Urology, Lumbar vertebrae, Zoledronic Acid, Iliac crest, Bone Density, medicine, Animals, Orthopedics and Sports Medicine, Range of Motion, Articular, Lumbar Vertebrae, Bone Density Conservation Agents, Diphosphonates, business.industry, Imidazoles, medicine.disease, Biomechanical Phenomena, Surgery, Radiography, Pseudarthrosis, Spinal Fusion, medicine.anatomical_structure, Zoledronic acid, Spinal fusion, Distraction osteogenesis, Original Article, Rabbits, Range of motion, business, medicine.drug
Abstract

Previous studies have shown that zoledronic acid administration can increase mineral content and strength in distraction osteogenesis. Of the few studies that have examined the use of bisphosphonates in spinal arthrodesis, none have assessed the effect of single dose treatment. The objective of this study was to evaluate the feasibility of enhancing spinal fusion rate using single dose zoledronic acid (ZA) to increase fusion-mass size and mineral density. Forty-eight New Zealand white rabbits underwent an L6-L7 intertransverse process fusion. The L6-L7 model is more challenging than the more commonly used level of L5-L6. Animals were randomly allocated to one of three groups, one received iliac crest bone graft alone, one group received iliac crest bone graft with locally administered zoledronic acid, 20 microg, and one group received iliac crest bone graft with a single dose of systemically administered zoledronic acid, 0.1 mg/kg. ZA doses were administered at the time of surgery. Twenty-four rabbits were culled at 6 weeks and 24 rabbits were culled at 12 weeks. Success of spinal fusion was determined by manual palpation. Specimens were evaluated radiographically, underwent quantitative computerised tomography analysis and were tested biomechanically in flexion and extension. In the six-week group, only five of the 24 spines fused with no noticeable trend with respect to treatment. In the 12-week group there was a trend toward increased fusion in the systemically administered ZA group (63%) versus the other two groups (25%) but was not statistically significant (p = 0.15). Radiographically, the local ZA treatment group showed a delay in remodelling with the presence of unremodelled bone chips. The 12-week systemic ZA group exhibited an 86% increase in BMC, a 31% increase in vBMD and a 41% increase in the volume of the fusion-mass (p0.05). The 12-week local ZA group also showed significant increases in BMC (69%), vBMD (31%) and total fusion-mass volume (29%) (p0.05). Biomechanical testing showed that the range of motion in flexion decreased to 4.5 (+/-2.5) degrees and 4.8 (+/-4.7) degrees for the local and systemic groups respectively compared to 9.6 (+/-4.9) degrees for the control group (p0.05). This study has shown that zoledronic acid increased fusion-mass size and bone mineral content. Systemic ZA led to an increased fusion rate; however the fusion rate remained below 100%. We suggest that bisphosphonate treatment may require an anabolic conjunctive therapy to ensure enhanced successful fusion.

Published
2006

26. The DNA sequence, annotation and analysis of human chromosome 3

Author

Zhengdong D. Zhang, Jun Wang, Zhu Chen, Will Gillett, George M. Weinstock, Guoping Zhao, LaRonda Jackson, Christopher K. Raymond, Manuel L. Gonzalez-Garay, Yang Zhou, Judith Hernandez, Boqin Qiang, James B. Clendenning, Zhijian J. Chen, Shannon Dugan-Rocha, Andrew R. Jackson, Zhijian Yao, Yan Shen, R. Alan Harris, Ziad Khan, Margaret Morgan, Wei Dong, Sharon Wei, Dawn Garcia, Aleksandar Milosavljevic, Maynard V. Olson, Ruben Rodriguez, Kerstin P. Clerc-Blankenburg, Ryan J. Lozado, Ralf Sudbrak, Jun Gu, Jing Kun Zhang, Heather R. Draper, Mary J. Brown, Channakhone Saenphimmachak, M. Ali Ansari-Lari, Songnian Hu, Preethi H. Gunaratne, Donna M. Muzny, Shiran Pasternak, Xing Zhi Song, Oliver Delgado, Bailin Hao, Lesette Perez, Charles Q. Adams, Michael L. Metzker, Anne Hodgson, Daniel Verduzco, Bao Viet Nguyen, Susan H. Kelly, Xin He, Jing Wang, Runsheng Chen, Karen A. Phelps, Rajinder Kaul, Guan Chen, Wei Huang, Huyen Dinh, Lenee Waldron, Paul Havlak, George Miner, Qiaoyan Wang, Ye Yuan, Rachel Gill, Anthony Palmeiri, Mathew W. Wright, Kim C. Worley, Michael Kube, Jing Liu, Clay Davis, Christian J. Buhay, Zhangwan Li, Jun Yu, Alicia Hawes, Jing Lu, Steffen Hennig, David L. Nelson, Rui Chen, Leni S. Jacob, Huanming Yang, Bin Liu, Steven E. Scherer, Christie Kovar-Smith, Jian Wang, Manjula Maheshwari, Gabrielle A. Williams, Paul E. Tabor, David A. Wheeler, Hans Lehrach, Graham R. Scott, Farah J.H. Plopper, Erica Sodergren, Wen Liu, Mulu Ayele, Richard Reinhardt, Richard A. Gibbs, Eric Haugen, Lora Lewis, Hua Shen, Gang Fu, Jianling Zhou, Xiuqing Zhang, Stephen Ernst, Geoffrey Okwuonu, Susan L. Naylor, Jennifer Hume, Ruth Levy, Andrew Cree, Yan Ding, David Steffen, Lynne V. Nazareth, Jireh Santibanez, Sandhya Subramanian, and Gane Ka-Shu Wong

Subjects
Inversion, Chromosome, Genome evolution, DNA, Complementary, Pan troglodytes, Molecular Sequence Data, Biology, Synteny, Genome, Evolution, Molecular, Chimpanzee genome project, Contig Mapping, Chromosome 19, Human Genome Project, Animals, Humans, Expressed Sequence Tags, Genetics, Multidisciplinary, Base Sequence, Chromosome Breakage, Sequence Analysis, DNA, Genome project, Macaca mulatta, Chromosome Inversion, CpG Islands, Human genome, Chromosomes, Human, Pair 3, Chromosome 21, Reference genome
Abstract

Udgivelsesdato: 2006-Apr-27 After the completion of a draft human genome sequence, the International Human Genome Sequencing Consortium has proceeded to finish and annotate each of the 24 chromosomes comprising the human genome. Here we describe the sequencing and analysis of human chromosome 3, one of the largest human chromosomes. Chromosome 3 comprises just four contigs, one of which currently represents the longest unbroken stretch of finished DNA sequence known so far. The chromosome is remarkable in having the lowest rate of segmental duplication in the genome. It also includes a chemokine receptor gene cluster as well as numerous loci involved in multiple human cancers such as the gene encoding FHIT, which contains the most common constitutive fragile site in the genome, FRA3B. Using genomic sequence from chimpanzee and rhesus macaque, we were able to characterize the breakpoints defining a large pericentric inversion that occurred some time after the split of Homininae from Ponginae, and propose an evolutionary history of the inversion.

Published
2006

27. The DNA sequence of the human X chromosome

Author

Gernot Glöckner, Karen Thomas, Christine Lloyd, Huda Y. Zoghbi, Adrienne Hunt, Fiona Francis, Annemarie Poustka, George M. Weinstock, Xuehong Wei, Alan Tracey, Gabriele Nordsiek, Ines Müller, Graham Clarke, Oliver Beasley, John Sulston, Alfred Beck, Christian J. Buhay, Thomas Meitinger, Manjula Maheshwari, Yvonne Ramsey, Kirsten McLay, Shannon Dugan-Rocha, James G. R. Gilbert, Louisa Faulkner, Sidney Morris, Margaret Morgan, Huntington F. Willard, Leni S. Jacob, Hermela Loulseged, K M Porter, T. Daniel Andrews, Cordelia Langford, Paul Wray, Guan Chen, Juliane Ramser, Nigel P. Carter, Georgina Warry, Ruby Banerjee, Graeme Bethel, LaDeana W. Hillier, Anne Hodgson, Stephen M. J. Searle, K F Barlow, David R. Bentley, Paul E. Tabor, Kathryn L. Evans, Russell J. Grocock, Rebecca Woodmansey, Alex V Pearce, Christie Kovar-Smith, Angela Williamson, Dean Chavez, Roy Storey, Kevin L. Howe, Zhijian J. Chen, Lesette Perez, Richard A. Gibbs, Michele D'Urso, Karen N Bates, Jackie Bye, Shirin S. Joseph, Bernd Hinzmann, Paul Heath, Susan H. Kelly, Jennifer Hume, Paula E. Burch, David Buck, Mark T. Ross, David A. Wheeler, Matthew C. Jones, A K Babbage, Erica Sodergren, Sophie Palmer, Jie Ma, Elizabeth C. Sotheran, Margaret A. Leversha, Cerissa Hamilton, Hans Lehrach, Swaroop Aradhya, Michael L. Metzker, S. M. Clegg, Elizabeth J. Huckle, Audrey Fraser, Sarah Bray-Allen, C. D. Skuce, Petra Galgoczy, Richard K. Wilson, Patrick Minx, Richard E Connor, Tamsin Eades, Alfons Meindl, Michelle Smith, John M. Davis, André Rosenthal, Stuart McLaren, Geoffery Okwuonu, M. Vaudin, Laura Carrel, Ryan J. Lozado, Harminder Sehra, Richard Pandian, Sue Y Clark, Anna Kosiura, Wen Liu, Simon G. Gregory, A Tromans, Alexandra Emery-Cohen, Charles Shaw-Smith, Donna Villasana, Joseph Chako, Katja Heitmann, Robert G. David, Jennifer L. Ashurst, Craig Chinault, S Lawlor, Paul Havlak, Jane E. Loveland, Lucy Matthews, Jianling Zhou, S. Whitehead, Paul Hunt, E Sheridan, Richard Reinhardt, Tim Hubbard, Mary G. Schueler, Patrick Meidl, Helen Beasley, David Beare, Donna M. Muzny, Kerry A Ridler, Joanne C Chapman, Jennifer McDowall, Andrew Dunham, Anne Bridgeman, Gabrielle Williams, Amanda McMurray, Stefan Taudien, Matthew E. Hurles, Helen Williamson, Preethi H. Gunaratne, Alfredo Ciccodicola, R Ainscough, Alison J. Coffey, Charlotte G. Cole, Stephan Beck, Frances L Lovell, Alan Coulson, Qiaoyan Wang, Sally Jones, Charles A. Steward, Michael Hoffs, Kim C. Worley, Sarah Pelan, David Bonnin, David Schlessinger, Mathew N Whiteley, Graham Scott, Christopher N O'Dell, Tineace Taylor, Susan Rhodes, Anthony P. West, E. Hart, Ian P. Barrett, Andrea Thorpe, D. Pearson, Huyen Dinh, Susan M. Gribble, Andrew J Knights, Laurens G. Wilming, N Corby, Steven E. Scherer, Pawandeep Dhami, Gerald Nyakatura, J Lovell, M. Ali Ansari-Lari, Kerstin P. Clerc-Blankenburg, David Swarbreck, Sara Zorilla, Yanghong Gu, Karin Blechschmidt, Matthew Dunn, Andrew Brown, Kirsten M. Timms, Darren Grafham, Yan Ding, Elspeth A. Bruford, Leanne Williams, Melanie M. Wall, Hua Shen, Dina Patel, Joanne K Kershaw, Rachel Gill, Yuan Chen, Joy Davies, D C Burford, John Burton, Vicky Cobley, R I S Ashwell, Nicola Brady, Ellson Y. Chen, Ngoc Nguyen, Gaiping Wen, Gavin K. Laird, Julia E. Parrish, Carol Scott, C Griffiths, Ratna Shownkeen, Ralf Sudbrak, Denise R. DeShazo, Shiran Pasternak, Ireena Dutta, Brian Teague, Rachael Lyne, David Parker, Jane Rogers, Steve Dodsworth, Mary J. Brown, Gary E Barker, Steve Trevanion, Joanne Burgess, Jane E. Wilkinson, James T. Warren, Jen S. Conquer, R Mark Swann, Oliver Delgado, Heather R. Draper, Shailesh L Mistry, Chris Clee, Richard Durbin, Karen Clifford, John Frankland, Sarah E. Hunt, David Steffen, Christine Burrows, Daniel Verduzco, C Carder, Robert H. Waterston, Stephen Richards, Andrea Ballabio, Catherine M. Rice, David Willey, Helen Errington, Andrew Cree, K. James Durbin, Lora Lewis, D. M. Lloyd, Helen E. Steingruber, Adam Whittaker, K D Ambrose, Rhian Gwilliam, Adam Frankish, Robert S. Fulton, Judith Hernandez, Claire L Bagguley, Pieter J. de Jong, Jennifer Yen, Matthew Ellwood, Christine P. Bird, Rui Chen, Sarah Milne, Clay Davis, Alicia Hawes, Jing Lu, Sven Klages, David L. Nelson, Wayne Burrill, Jingkun Zhang, Judith Isherwood, Kathrin Reichwald, Lenee Waldron, Rebecca Deadman, Steffen Hennig, Ziad Khan, Sarah Ho, Matthias Platzer, Gareth R. Howell, Stephen Keenan, Petra Kioschis, Phillip J Howden, George Miner, David W. Johnson, and James C. Mullikin

Subjects
Male, Genetic Linkage, Genetics, Medical, Centromere, HUMAN GENOME SEQUENCE, Biology, Y chromosome, Polymorphism, Single Nucleotide, Article, Evolution, Molecular, Contig Mapping, Chromosome 16, Antigens, Neoplasm, Dosage Compensation, Genetic, Sequence Homology, Nucleic Acid, Chromosome 19, Testis, Animals, Humans, Crossing Over, Genetic, X chromosome, Repetitive Sequences, Nucleic Acid, Genetics, Chromosomes, Human, X, Chromosomes, Human, Y, Multidisciplinary, INACTIVATION CENTER, LINKED MENTAL-RETARDATION, Genomics, Sequence Analysis, DNA, REPEAT HYPOTHESIS, MAMMALIAN Y-CHROMOSOME, Chromosome 4, Chromosome 3, RNA, Female, Chromosome 21, Chromosome 22
Abstract

The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence.

Published
2005

28. Pooled genomic indexing of rhesus macaque

Author

Aleksandar Milosavljevic, Erica Sodergren, Miklós Csürös, Richard A. Gibbs, Andrew Cree, Ken J. Kalafus, Andrew R. Jackson, Ronald A. Harris, George M. Weinstock, Anne Hodgson, Weilie Dai, Pieter J. de Jong, and Baoli Zhu

Subjects
Chromosome Aberrations, Genetic Markers, Genetics, Chromosomes, Artificial, Bacterial, Bacterial artificial chromosome, Genome, Genome, Human, Shotgun sequencing, Sequence analysis, DNA, Sequence Analysis, DNA, Biology, Macaca mulatta, DNA sequencing, Contig Mapping, Genetic marker, Methods, Animals, Humans, Human genome, Sequence Alignment, Genetics (clinical)
Abstract

Pooled genomic indexing (PGI) is a method for mapping collections of bacterial artificial chromosome (BAC) clones between species by using a combination of clone pooling and DNA sequencing. PGI has been used to map a total of 3858 BAC clones covering ∼24% of the rhesus macaque (Macaca mulatta) genome onto 4178 homologous loci in the human genome. A number of intrachromosomal rearrangements were detected by mapping multiple segments within the individual rhesus BACs onto multiple disjoined loci in the human genome. Transversal pooling designs involving shuffled BAC arrays were employed for robust mapping even with modest DNA sequence read coverage. A further innovation, short-tag pooled genomic indexing (ST-PGI), was also introduced to further improve the economy of mapping by sequencing multiple, short, mapable tags within a single sequencing reaction.

Published
2005

33. Gibbon genome and the fast karyotype evolution of small apes

Author

Nina V. Fuchs, Paul Flicek, Michael S. Campbell, Markus Brameier, Claudio Casola, Mark A. Batzer, Matthieu Muffato, Simon D. M. White, Michael F. Hammer, Michelle C Ward, Jeffrey Rogers, Stephen M. J. Searle, Gerald G. Schumann, Gabriella Skollar, LaDeana W. Hillier, Belen Lorente-Galdos, James M. Sikela, Boudewijn F.H. Ten Hallers, Fabio Anaclerio, Catrina Fronick, Krishna R. Veeramah, Robert Hubley, Marcos Fernandez-Callejo, Katherine S. Pollard, Zsuzsanna Izsvák, Donna M. Muzny, Sarah J. Wheelan, Giorgia Chiatante, Anis Karimpour-Fard, Javier Quilez, Duncan T. Odom, Dennis Kostka, Kathryn Beal, John Huddleston, Yue Liu, Antoine Blancher, Sante Gnerre, Christopher W. Whelan, Kimberly A. Nevonen, Daniel Barrell, Devin P. Locke, Mario Ventura, Kim C. Worley, Kemal Sonmez, Miriam K. Konkel, Richard A. Gibbs, Jessica Hernandez-Rodriguez, August E. Woerner, Lutz Walter, Nina G. Jablonski, Laura Dumas, Craig L. Bohrson, Gregg W.C. Thomas, Gut I, Lucinda Fulton, Wesley C. Warren, Brygg Ullmer, Lora Lewis, Christian Roos, Cornelia Ochis, Andrew Cree, Richard K. Wilson, Swapan Mallick, Lucia Carbone, Mariano Rocchi, Nathan H. Lazar, Lynne V. Nazareth, Pieter J. de Jong, Oronzo Capozzi, Bianca Ianc, Annette Damert, Thomas J. Meyer, Gut M, Evan E. Eichler, Tomas Marques-Bonet, Arian F.A. Smit, Javier Herrero, Sandra L. Lee, Matthew W. Hahn, Bronwen Aken, Elizabeth Terhune, Laurel Johnstone, Baoli Zhu, Carl Baker, Jeffrey D. Wall, Mark Yandell, Nicoletta Archidiacono, Majesta O'Bleness, David Reich, Larry J. Wilhelm, Fernando L. Mendez, Jerilyn A. Walker, and R. Alan Harris

Subjects
Arboreal locomotion, Genome, Structural variation, Evolutionary genetics, Next-generation sequencing, Retroelements, viruses, Karyotype, Molecular Sequence Data, Zoology, Chromosomal rearrangement, Evolution, Molecular, Hylobates, biology.animal, Mamífers -- Genètica, Animals, Humans, Primate, Selection, Genetic, Phylogeny, Multidisciplinary, biology, Human evolutionary genetics, Hominidae, Genètica evolutiva, biology.organism_classification, Nomascus leucogenys, Nomascus, Cardiovascular and Metabolic Diseases, Transcription Termination, Genetic
Abstract

Carbone, Lucia et al.-- This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported licence., Gibbons are small arboreal apes that display an accelerated rate of evolutionary chromosomal rearrangement and occupy a key node in the primate phylogeny between Old World monkeys and great apes. Here we present the assembly and analysis of a northern white-cheeked gibbon (Nomascus leucogenys) genome. We describe the propensity for a gibbon-specific retrotransposon (LAVA) to insert into chromosome segregation genes and alter transcription by providing a premature termination site, suggesting a possible molecular mechanism for the genome plasticity of the gibbon lineage. We further show that the gibbon genera (Nomascus, Hylobates, Hoolock and Symphalangus) experienced a near-instantaneous radiation ∼5 million years ago, coincident with major geographical changes in southeast Asia that caused cycles of habitat compression and expansion. Finally, we identify signatures of positive selection in genes important for forelimb development (TBX5) and connective tissues (COL1A1) that may have been involved in the adaptation of gibbons to their arboreal habitat.

Published
2014

34. Laminar screw fixation of the axis in the pediatric population: a series of eight patients

Author

Andrew Cree and Bhishampal Singh

Subjects
Male, medicine.medical_specialty, Adolescent, Vertebral artery, Screw fixation, Fixation (surgical), Fracture Fixation, Internal, Pedicle Screws, medicine.artery, medicine, Humans, Orthopedics and Sports Medicine, Child, Retrospective Studies, business.industry, Retrospective cohort study, Laminar flow, medicine.disease, Surgery, Stenosis, Spinal Fusion, Treatment Outcome, Atlanto-Axial Joint, Atlantoaxial instability, Child, Preschool, Cervical Vertebrae, Female, Neurology (clinical), business, Pediatric population
Abstract

Background context Instability of the atlantoaxial spine is a recognized problem in children. Safe passage of pedicle screws at C2 poses challenges because of the proximity to the vertebral artery, size of the pedicles, and variations in the location of the foramen transversarium. Purpose The C2 translaminar technique is a useful option and its stability is comparable to that offered by C2 pedicle screws. In this follow-up from our previously published study, we wanted to verify the safety and suitability of the C2 laminar screw in the treatment of cervical instability in the pediatric population. Study design/setting We present a case series of eight pediatric patients who underwent laminar screw fixation of the axis as part of their operative procedure. Patient sample There were five girls and three boys, with a mean age of 7 years (range 2–17 years) who underwent this procedure. Surgical indications included atlantoaxial instability, atlanto-occipital disassociation, multilevel cervical instability, and high cervical stenosis. Seven patients had underlying dysplastic syndromes. Outcome measures We studied the technical feasibility of passing laminar screws at C2 in eight consecutive patients, paying attention to screw length and diameter, vascular or neurologic complications, and stability of fixation. Methods This retrospective study was funded by our institution and there was no potential conflict of interest. All patients were placed prone. The posterior aspect of the cervical spine and craniocervical junction were exposed subperiosteally. We report our modification of the Wright technique, which allowed us to safely pass 3.5-mm screws into both laminae of the second cervical vertebra. Results A total of 15 laminar screws were passed at C2. The follow-up period ranged from 1 to 24 months (mean 8 months). There were no vascular or neurologic complications, no infection, and no instances of hardware failure either by lamina fracture or screw pullout. All patients maintained stable constructs on imaging studies at the last follow-up evaluation. Conclusion Children as young as 2 years can undergo safe and rigid fixation of the axis. The technique is especially valuable in patients with dysplastic bone and distorted anatomy where more traditional methods of C2 fixation cannot be safely used. To our knowledge, this is the largest reported series of C2 laminar screw fixation in a pediatric population.

Published
2014

35. Atlantoaxial and Craniocervical Arthrodesis in Children

Author

Fabio Ferri-de-Barros, Andrew Cree, David G. Little, John L. Cummine, and Corinne Bridge

Subjects
Male, medicine.medical_specialty, Arthrodesis, medicine.medical_treatment, Bone Screws, Screw fixation, Cohort Studies, Fixation (surgical), Neck injury, Humans, Trauma, Nervous System, Medicine, Orthopedics and Sports Medicine, Child, Orthodontics, Preoperative planning, business.industry, Background data, Internal Fixators, Fixation point, Surgery, Atlanto-Axial Joint, Child, Preschool, Cervical Vertebrae, Female, Neurology (clinical), Tomography, Tomography, X-Ray Computed, business
Abstract

Study Design. Analysis of C1–C2 tomographic anatomy in a cohort of healthy children. Objective. Compare suitability of C2 laminae and C2 pedicles for screw placement. Summary of Background Data. Surgeons have applied several techniques for craniocervical and atlantoaxial spondylodesis to address congenital or developmental abnormalities in children. Constructs with pedicle or transarticular screws are effective to stabilize the craniocervical junction; however, these fixation points are not suitable in all patients. Translaminar screw placement in C2 has been safely performed in children; yet, suitability of C2 laminae and C2 pedicles has not been systematically compared. Methods. Applying χ2 test, we compared suitability for screw placement in 46 C2 pedicles and 46 C2 laminae on digital images of axial reconstructions of cervical CT scans of 23 children who had been admitted to the same hospital due to head or neck injury. On the same scans, we estimated suitability for screw placement in 46 lateral masses of C1. Results. Twenty-four percent of C2 pedicles and 65% of C2 laminae were deemed suitable for 3.5-mm screw placement, and the difference was statistically significant (P ≤ 0.0001, χ2 15.88). Forty-one percent of C2 pedicles and 80% of C2 laminae were deemed suitable for 3.0-mm screw placement, and the difference was statistically significant (P ≤ 0.0001, χ2 14.78). Ninety-five percent of C1 lateral masses were deemed suitable for 3.5-mm screw placement. Conclusion. C2 laminae represent a viable fixation point for C1–C2 and craniocervical arthrodesis in children. This information can be useful for preoperative planning.

Published
2010

38. Operative treatment of chance injuries in the paediatric population

Author

Andrew Cree, Randolph Gray, Corrine Bridge, and Sean Suttor

Subjects
Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Lumbar vertebrae, Thoracic Vertebrae, medicine, Humans, Orthopedics and Sports Medicine, Child, Retrospective Studies, Lumbar Vertebrae, business.industry, Retrospective cohort study, Surgery, Single centre, medicine.anatomical_structure, Spinal Fusion, Treatment Outcome, Spinal fusion, Thoracic vertebrae, Spinal Fractures, Spine injury, Female, Original Article, Neurosurgery, business, Paediatric population
Abstract

Chance fractures are an uncommon spine injury in the paediatric population. As such there is a relative paucity of evidence in the literature to guide management decisions. We present our single centre experience in the operative management of these injuries.All patients presenting to a tertiary paediatric trauma centre between 2000 and 2008 were included. Retrospective analysis of clinical (SRS-22 and Oswestry) and radiological outcomes was undertaken.Twelve patients underwent operative stabilization of a Chance type injury. Radiological and clinical outcome measures demonstrated excellent outcomes in the majority of patients with no significant complications.Operative management of paediatric chance injuries with instrumentation results in excellent clinical and radiological outcomes.

Published
2012

39. Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development

Author

Joshua Y Shen, Yoko Kuroki, Lynne V. Nazareth, Shafagh Al Nadaf, Terence P. Speed, Katherine Belov, Kevin R. Nicholas, James Lindsay, Yoshiyuki Sakaki, Anthony T. Papenfuss, Arthur Hsu, Stephen Frankenberg, Hannah V. Siddle, Shalini N. Jhangiani, Fremiet Lara, Jireh Santibanez, Thomas N. Heider, Jixin Deng, Margaret Morgan, Xing-Zhi Henry Song, Rebecca Thornton, Benjamin James Lansdell, Frank W. Nicholas, A. Men, Carmen Troon, Shinji Kondo, William A O'Hara, Christophe Lefevre, Susan M. Forrest, San Juana Ruiz, Geoffrey Okwuonu, Chenwei Wang, Andrew Cree, Yanqiu Hu, Matthew Wakefield, Kyall R. Zenger, Rachel J. O’Neill, Donna M. Muzny, Benjamin G. Cocks, Huyen Dinh, Kaighin A. McColl, Geoff Shaw, Kim C. Worley, Hongshi Yu, Jennifer A. Marshall Graves, Asao Fujiyama, Andrew J Pask, Keng Yih Chew, Janine E. Deakin, Lankesha Yapa, Elizabeth Kuczek, Tanya Levchenko, George M. Weinstock, Kirsty R. Short, Malcolm A. Ferguson-Smith, Yutaka Suzuki, Mehlika Hazar-Rethinam, Chyn Jing, Yuichiro Nishida, Gerald R. Fowler, Paul D. Waters, Lora Lewis, Elizabeth A. Pharo, Timothy A. Hore, Nanette Y. Schneider, Susan Fairley, Danielle Hickford, Zhi-Ping Feng, Annette McGrath, Vandita Joshi, Willem Rens, Jianghui Wang, Javier Herrero, Desmond W. Cooper, Christie Kovar, Kathryn Beal, Daniel Thomas, Yogi Sundaravadanam, Stephen M. J. Searle, David L. A. Wood, Marilyn B. Renfree, Yue-E Liu, Dawn M. Carone, A Mohammadi, Amber E. Stephens, Shoji Tatsumoto, Jessica M Stringer, John Davis, Allison Hall, Sumio Sugano, Peter A Wilson, Margaret L. Delbridge, Atsushi Toyoda, Paul Flicek, Emily S. W. Wong, Lei Chen, Ion Mandiou, Shunsuke Suzuki, Brandon R. Menzies, Richard A. Gibbs, Janette Edson, Sarah E. Williams, Chen-Chen Wu, Ferguson-Smith, Malcolm [0000-0001-9372-1381], and Apollo - University of Cambridge Repository

Subjects
0106 biological sciences, Molecular Sequence Data, wallaby, Sequence assembly, Zoology, Genomics, Genome, 010603 evolutionary biology, 01 natural sciences, DNA sequencing, Mammalian reproduction, symbols.namesake, 03 medical and health sciences, Genomic Imprinting, 0302 clinical medicine, Tammar wallaby, Marsupial, Animals, Macropus, In Situ Hybridization, Fluorescence, 030304 developmental biology, Genetics, Sanger sequencing, Whole genome sequencing, Macropodidae, 0303 health sciences, biology, Research, Reproduction, Australia, Correction, Chromosome Mapping, Sequence Analysis, DNA, biology.organism_classification, Research Highlight, Biological Evolution, Chromosomes, Mammalian, kangaroo, MicroRNAs, Gene Expression Regulation, symbols, Female, Transcriptome, Sequence Alignment, 030217 neurology & neurosurgery
Abstract

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution.

Published
2011

40. Subaxial Injury Classification (SLIC) Scoring System Treatment Recommendations for Cervical Spine Trauma: Retrospective Review of 193 Patients

Author

Margaret M. Smith, Sumant Samuel, Andrew Cree, Con Vasili, Randolph Gray, Nathan Hartin, and Jiun-lih J. Lin

Subjects
Retrospective review, medicine.medical_specialty, Scoring system, business.industry, Physical therapy, Medicine, Surgery, Orthopedics and Sports Medicine, Injury classification, Neurology (clinical), business, Cervical spine
Published
2014

41. A catalog of reference genomes from the human microbiome

Author

Dirk Gevers, Doyle V. Ward, Sean M. Sykes, Justin Johnson, Michael Fitzgerald, Jessica B. Hostetler, Sarah Young, Dianhui Zhu, Jason R. Miller, Chinnappa D. Kodira, Aaron M. Berlin, Erica Sodergren, Michael G. Surette, Matthew D. Pearson, Asif T. Chinwalla, Ashlee M. Earl, Michael Feldgarden, Kim C. Worley, Christian J. Buhay, Lisa Hemphill, Manolito Torralba, Xiang Qin, Jonathan H. Badger, Clint Howarth, Marcus Gillis, Candace N. Farmer, Karen E. Nelson, Bruce W. Birren, Richard A. Gibbs, Sandra W. Clifton, Mike Holder, Aye Wollam, Carsten Russ, Wesley C. Warren, Brian J. Haas, Michelle G. Giglio, Qiang Xu, Richard K. Wilson, Patrick Minx, Scott Durkin, Chad Nusbaum, Craig Pohl, Robert S. Fulton, Steve Ferriera, Chandri N. Yandava, Sharvari Gujja, Qiandong Zeng, Ramana Madupu, Victor Markowitz, Joshua Orvis, Andrew Cree, Chad Tomlinson, Donna M. Muzny, Vandita Joshi, Amrita Pati, Christie Kovar, Theresa A. Hepburn, Nikos C. Kyrpides, Kymberlie H. Pepin, Douglas B. Rusch, Granger G. Sutton, Amr Abouellleil, Konstantinos Liolios, Sarah K. Highlander, Yan Ding, Jamison McCorrison, George M. Weinstock, Kris A. Wetterstrand, Emma Allen-Vercoe, Teena Mehta, Lucinda Fulton, Katarzyna Wilczek-Boney, Makedonka Mitreva, Lei Chen, Joseph F. Petrosino, Heather Huot Creasy, Shannon Dugan, Lan Zhang, Owen White, Robert L. Strausberg, Jennifer R. Wortman, Jonathan Crabtree, and Barbara A. Methé

Subjects
Sequence analysis, Respiratory System, Urogenital System, Biology, Genome, Article, Bacterial Proteins, Phylogenetics, Genome, Archaeal, Databases, Genetic, Humans, Microbiome, Gene, Phylogeny, Skin, Genetics, Mouth, Multidisciplinary, Bacteria, Human microbiome, Computational Biology, Genetic Variation, Biodiversity, Sequence Analysis, DNA, Gastrointestinal Tract, Metagenomics, Genes, Bacterial, Metagenome, Peptides, Genome, Bacterial, Reference genome
Abstract

The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (approximately 97%) were unique. In addition, this set of microbial genomes allows for approximately 40% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented.

Published
2010

44. The Genome of the Sea Urchin Strongylocentrotus purpuratus

Author

Amro Hamdoun, Virginia Brockton, Huyen Dinh, Qiang Tu, Richard O. Hynes, Maria Ina Arnone, Wratko Hlavina, L. Courtney Smith, Mariano A. Loza, David R. Burgess, Matthew P. Hoffman, Florian Raible, Qiu Autumn Yuan, Geoffrey Okwuonu, Mark Y. Tong, Jennifer Hume, Donna Maglott, Manisha Goel, Olivier Fedrigo, Manuel L. Gonzalez-Garay, Celina E. Juliano, Judith Hernandez, Gary M. Wessel, William F. Marzluff, Audrey J. Majeske, Christian Gache, Louise Duloquin, Xingzhi Song, François Lapraz, Fowler J, Alexandre Souvorov, Jared V. Goldstone, Georgia Panopoulou, Sandra Hines, Kyle M. Judkins, Clay Davis, Christine G. Elsik, Paul Kitts, Mariano Loza-Coll, Greg Wray, Taku Hibino, Eric Röttinger, Allison M. Churcher, Annamaria Locascio, Arcady Mushegian, Masashi Kinukawa, Anna Reade, Katherine M. Buckley, I. R. Gibbons, Bert Gold, Aleksandar Milosavljevic, David Epel, Victor D. Vacquier, Ling Ling Pu, Vincenzo Cavalieri, Erin L. Allgood, Lan Zhang, Lynne V. Nazareth, Constantin N. Flytzanis, Ian Bosdet, Yi-Hsien Su, Zeev Pancer, Matthew L. Rowe, Robert C. Angerer, David R. McClay, William H. Klein, Rachel F. Gray, Julian L. Wong, Shunsuke Yaguchi, Robert Bellé, Aaron J. Mackey, Herath Jayantha Gunaratne, Karl Frederik Bergeron, Bruce P. Brandhorst, Greg Murray, Avis H. Cohen, Stephanie Bell, Kristin Tessmar-Raible, Ian K. Townley, Bertrand Cosson, Thomas D. Glenn, Jongmin Nam, Cynthia A. Bradham, Michael Dean, Joseph Chacko, Anthony J. Robertson, Margherita Branno, Valeria Matranga, K. James Durbin, Esther Miranda, Lili Chen, Eran Elhaik, Robert D. Burke, Rita A. Wright, Paola Oliveri, Sandra L. Lee, Gary W. Moy, Alexander E Primus, Shawn S. McCafferty, Cristina Calestani, David A. Garfield, Erica Sodergren, Karen Wilson, Joel Smith, Marco A. Marra, Cynthia Messier, Julia Morales, Kim D. Pruitt, Rachel Thorn, Rachel Gill, John S. Taylor, Mark E. Hahn, Victor Sapojnikov, Meredith Howard-Ashby, Lynne M. Angerer, Maurice R. Elphick, Kathy R. Foltz, Anne Marie Genevière, Justin T. Reese, Blanca E. Galindo, Kim C. Worley, Andrew Leone, Glen Humphrey, Kevin Berney, Olga Ermolaeva, George Miner, David P. Terwilliger, Elly Suk Hen Chow, Lora Lewis, Dan Graur, C. Titus Brown, Gerard Manning, Kevin J. Peterson, Angela Jolivet, Michele K. Anderson, Francesca Rizzo, Ekaterina Voronina, Thierry Lepage, Giorgio Matassi, Antonio Fernandez-Guerra, Mamoru Nomura, Charles A. Whittaker, James R.R. Whittle, James A. Coffman, George M. Weinstock, Mohammed M. Idris, Ashlan M. Musante, Sebastian D. Fugmann, Katherine D. Walton, Sorin Istrail, Shu-Yu Wu, Cerrissa Hamilton, Jonah Cool, Jacqueline E. Schein, Stacey M. Curry, Athula Wikramanayke, Seth Carbonneau, Blair J. Rossetti, Christopher E. Killian, Melissa J. Landrum, Amanda P. Rawson, Jenifer C. Croce, Ryan C. Range, Rahul Satija, John J. Stegeman, Yufeng Shen, Cavit Agca, Terry Gaasterland, Rocky Cheung, Takae Kiyama, Nikki Adams, Jonathan P. Rast, Robert Piotr Olinski, Andrew Cree, Mark Scally, Shuguang Liang, David A. Parker, Rebecca Thomason, Gretchen E. Hofmann, Michelle M. Roux, Ronghui Xu, Robert A. Obar, Enrique Arboleda, Odile Mulner-Lorillon, Shannon Dugan-Rocha, David J. Bottjer, Gabriele Amore, Manoj P. Samanta, Waraporn Tongprasit, Véronique Duboc, La Ronda Jackson, Fred H. Wilt, Viktor Stolc, Anna T. Neill, Michael Raisch, Pei Yun Lee, Jia L. Song, Margaret Morgan, Brian T. Livingston, Sofia Hussain, Zheng Wei, Bryan J. Cole, Tonya F. Severson, Victor V. Solovyev, Finn Hallböök, Donna M. Muzny, Christine A. Byrum, Albert J. Poustka, Xiuqian Mu, Andrew R. Jackson, Shin Heesun, Euan R. Brown, Nansheng Chen, Patrick Cormier, Ralph Haygood, Pedro Martinez, R. Andrew Cameron, D. Wang, Wendy S. Beane, Eric H. Davidson, Christie Kovar, Hemant Kelkar, Charles A. Ettensohn, Sham V. Nair, Robert L. Morris, Stefan C. Materna, Michael C. Thorndyke, Richard A. Gibbs, Dan O Mellott, Department of Physiology and Biophysics, Stony Brook University [The State University of New York] ( SBU ), Astronomy Unit ( AU ), Queen Mary University of London ( QMUL ), Urban and Industrial Air Quality Group, CSIRO Energy Technology, Commonwealth Scientific and Industrial Research Organisation Energy Technology ( CSIRO Energy Technology ), Commonwealth Scientific and Industrial Research Organisation, Center for Polymer Studies ( CPS ), Boston University [Boston] ( BU ), Physics Department [Boston] ( BU-Physics ), Max Planck Institute for Psycholinguistics, Max-Planck-Institut, Department of Biology [Norton], Wheaton College [Norton], Mathematical Institute [Oxford] ( MI ), University of Oxford [Oxford], Centre for the Analysis of Time Series ( CATS ), London School of Economics and Political Science ( LSE ), Thomas Jefferson National Accelerator Facility ( Jefferson Lab ), Thomas Jefferson National Accelerator Facility, Laboratoire d'Energétique et de Mécanique Théorique Appliquée ( LEMTA ), Université de Lorraine ( UL ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Evolution, Génomes et Spéciation ( LEGS ), Centre National de la Recherche Scientifique ( CNRS ), Department of Geology, University of Illinois at Urbana-Champaign [Urbana], Department of Electrical and Computer Engineering [Portland] ( ECE ), Portland State University [Portland] ( PSU ), Saint-Gobain Crystals [USA], SAINT-GOBAIN, Institute for Animal Health ( IAH ), Biotechnology and Biological Sciences Research Council, Center for Agricultural Resources Research, Chinese Academy of Sciences [Changchun Branch] ( CAS ), Ipsen Inc. [Milford] ( Ipsen ), IPSEN, Department of Physics [Berkeley], University of California [Berkeley], Institute for Climate and Atmospheric Science [Leeds] ( ICAS ), University of Leeds, Chung-Ang University ( CAU ), Chung-Ang University [Seoul], Antarctic Climate and Ecosystems Cooperative Research Center ( ACE-CRC ), Institute of Aerodynamics and Fluid Mechanics ( AER ), Technische Universität München [München] ( TUM ), Mer et santé ( MS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Imperial College London, Radio and Atmospheric Sciences Division, National Physical Laboratory [Teddington] ( NPL ), International Research Institute for Climate and Society ( IRI ), Earth Institute at Columbia University, Columbia University [New York]-Columbia University [New York], Soils Group, The Macaulay Institute, Department of Haematology, University of Cambridge [UK] ( CAM ), School of Biology and Biochemistry, Queen's University, Leslie Hill Institute for Plant Conservation ( PCU ), University of Cape Town, Institute for Microelectronics and Microsystems/ Istituto per la Microelettronica e Microsistemi ( IMM ), Consiglio Nazionale delle Ricerche ( CNR ), Laboratoire d'acoustique de l'université du Mans ( LAUM ), Le Mans Université ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Interactive Systems Labs ( ISL ), Carnegie Mellon University [Pittsburgh] ( CMU ), Dalian Institute of Chemical Physics ( DICP ), Architectures, Languages and Compilers to Harness the End of Moore Years ( ALCHEMY ), Laboratoire de Recherche en Informatique ( LRI ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de Recherche en Informatique et en Automatique ( Inria ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ) -Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique ( Inria ), Clean Air Task Force ( CATF ), Clean Air Task Force, Space Physics Laboratory, Indian Space Research Organisation ( ISRO ), Centre d'études et de recherches appliquées à la gestion ( CERAG ), Université Pierre Mendès France - Grenoble 2 ( UPMF ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Microbiology and Immunology, College of Medicine and Health Sciences-Sultan Qaboos University, European Molecular Biology Laboratory [Heidelberg] ( EMBL ), Department of Biostatistics, University of Michigan [Ann Arbor], Department of Radiation Oncology [Michigan] ( Radonc ), Department of Physics and Astronomy [Leicester], University of Leicester, Informatique, Biologie Intégrative et Systèmes Complexes ( IBISC ), Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Institut für Meteorologie und Klimaforschung ( IMK ), Karlsruher Institut für Technologie ( KIT ), Physics Department [UNB], University of New Brunswick ( UNB ), Laboratoire Parole et Langage ( LPL ), Centre National de la Recherche Scientifique ( CNRS ) -Aix Marseille Université ( AMU ), Institut des Sciences Chimiques de Rennes ( ISCR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Ecole Nationale Supérieure de Chimie de Rennes-Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Biogéosciences [Dijon] ( BGS ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), Bioprojet, Laboratoire de Matériaux à Porosité Contrôlée ( LMPC ), Université de Haute-Alsace (UHA) Mulhouse - Colmar ( Université de Haute-Alsace (UHA) ) -Ecole Nationale Supérieure de Chimie de Mulhouse-Centre National de la Recherche Scientifique ( CNRS ), School of Information Engineering [USTB] ( SIE ), University of Science and Technology Beijing [Beijing] ( USTB ), Laboratory for Atmospheric and Space Physics [Boulder] ( LASP ), University of Colorado Boulder [Boulder], Department of Applied Mathematics [Sheffield], University of Sheffield [Sheffield], School of Mathematics and Statistics [Sheffield] ( SoMaS ), Laboratoire de Mécanique de Lille - FRE 3723 ( LML ), Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Centre National de la Recherche Scientifique ( CNRS ), Computer Science Department [UCLA] ( CSD ), University of California at Los Angeles [Los Angeles] ( UCLA ), Développement et évolution ( DE ), Université Paris-Sud - Paris 11 ( UP11 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie du Développement de Villefranche sur mer ( LBDV ), Laboratoire Pierre Aigrain ( LPA ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Department of Mathematics and Statistics [Mac Gill], McGill University, Departamento de Botánica [Comahue], Universidad nacional del Comahue, Bioénergétique Cellulaire et Pathologique ( BECP ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Environnements et Paléoenvironnements OCéaniques ( EPOC ), Observatoire aquitain des sciences de l'univers ( OASU ), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ) -École pratique des hautes études ( EPHE ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Jacques Monod ( IJM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratori Nazionali del Sud ( LNS ), National Institute for Nuclear Physics ( INFN ), Departament de Matemàtiques [Barcelona], Universitat Autònoma de Barcelona [Barcelona] ( UAB ), Max-Planck-Institut für Kohlenforschung (coal research), Institute of Oceanology [CAS] ( IOCAS ), National Chiao Tung University ( NCTU ), Department of Hydrology and Water Resources ( HWR ), University of Arizona, Centre for Educational Technology, Environment Department [York], University of York [York, UK], State Key Laboratory of Nuclear Physics and Technology ( SKL-NPT ), Peking University [Beijing], Department of Physics and Astronomy [Iowa City], University of Iowa [Iowa], NASA Ames Research Center ( ARC ), Department of Materials, Digital Language & Knowledge Contents Research Association ( DICORA ), Hankuk University of Foreign Studies, Department of Physics [Coventry], University of Warwick [Coventry], Space Science and Technology Department [Didcot] ( RAL Space ), STFC Rutherford Appleton Laboratory ( RAL ), Science and Technology Facilities Council ( STFC ) -Science and Technology Facilities Council ( STFC ), Institut de biologie et chimie des protéines [Lyon] ( IBCP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), H M Nautical Almanac Office [RAL] ( HMNAO ), Rutherford Appleton Laboratory, United Kingdom Met Office [Exeter], University College of London [London] ( UCL ), Department of Pathology and Laboratory Medicine [UCLA], University of California at Los Angeles [Los Angeles] ( UCLA ) -School of Medicine, School of Earth and Environmental Sciences [Seoul] ( SEES ), Seoul National University [Seoul], Department of Chemistry, Seoul Women's University, MicroMachines Centre ( MMC ), Nanyang Technological University [Singapour], Regroupement Québécois sur les Matériaux de Pointe ( RQMP ), École Polytechnique de Montréal ( EPM ) -Université de Sherbrooke [Sherbrooke]-McGill University-Université de Montréal-Fonds Québécois de Recherche sur la Nature et les Technologies ( FQRNT ), Département de Physique [Montréal], Université de Montréal, School of Earth and Environment [Leeds] ( SEE ), Centre for Ecology and Hydrology ( CEH ), Natural Environment Research Council ( NERC ), Norwegian Institute for Water Research ( NIVA ), Norwegian Institute for Water Research, Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY), Astronomy Unit [London] (AU), Queen Mary University of London (QMUL), Commonwealth Scientific and Industrial Research Organisation Energy Technology (CSIRO Energy Technology), Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Department of Biochemistry and Molecular Biology [Houston], The University of Texas Medical School at Houston, Mathematical Institute [Oxford] (MI), University of Oxford, Centre for the Analysis of Time Series (CATS), London School of Economics and Political Science (LSE), Thomas Jefferson National Accelerator Facility (Jefferson Lab), Laboratoire Énergies et Mécanique Théorique et Appliquée (LEMTA ), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Evolution, Génomes et Spéciation (LEGS), Centre National de la Recherche Scientifique (CNRS), University of Illinois System-University of Illinois System, Department of Electrical and Computer Engineering [Portland] (ECE), Portland State University [Portland] (PSU), Saint-Gobain, Institute for Animal Health (IAH), Biotechnology and Biological Sciences Research Council (BBSRC), Chinese Academy of Sciences [Changchun Branch] (CAS), Ipsen Inc. [Milford] (Ipsen), University of California [Berkeley] (UC Berkeley), University of California (UC)-University of California (UC), Institute for Climate and Atmospheric Science [Leeds] (ICAS), School of Earth and Environment [Leeds] (SEE), University of Leeds-University of Leeds, Chung-Ang University (CAU), Antarctic Climate and Ecosystems Cooperative Research Centre (ACE-CRC), Institute of Aerodynamics and Fluid Mechanics (AER), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Mer et santé (MS), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), National Physical Laboratory [Teddington] (NPL), International Research Institute for Climate and Society (IRI), Macaulay Institute, University of Cambridge [UK] (CAM), Queen's University [Kingston, Canada], Leslie Hill Institute for Plant Conservation (PCU), Istituto per la Microelettronica e Microsistemi [Catania] (IMM), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Laboratoire d'Acoustique de l'Université du Mans (LAUM), Le Mans Université (UM)-Centre National de la Recherche Scientifique (CNRS), Interactive Systems Labs (ISL), Carnegie Mellon University [Pittsburgh] (CMU), Dalian Institute of Chemical Physics (DICP), Architectures, Languages and Compilers to Harness the End of Moore Years (ALCHEMY), Laboratoire de Recherche en Informatique (LRI), Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Clean Air Task Force (CATF), Indian Space Research Organisation (ISRO), Centre d'études et de recherches appliquées à la gestion (CERAG), Université Pierre Mendès France - Grenoble 2 (UPMF)-Centre National de la Recherche Scientifique (CNRS), Sultan Qaboos University (SQU)-College of Medicine and Health Sciences [Baylor], Baylor University-Baylor University, European Molecular Biology Laboratory [Heidelberg] (EMBL), University of Michigan System-University of Michigan System, Department of Radiation Oncology [Michigan] (Radonc), Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Institute for Meteorology and Climate Research (IMK), Karlsruhe Institute of Technology (KIT), University of New Brunswick (UNB), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] (BGS), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Matériaux à Porosité Contrôlée (LMPC), Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS), School of Information Engineering [USTB] (SIE), University of Science and Technology Beijing [Beijing] (USTB), Laboratory for Atmospheric and Space Physics [Boulder] (LASP), University of Colorado [Boulder], School of Mathematics and Statistics [Sheffield] (SoMaS), Laboratoire de Mécanique de Lille - FRE 3723 (LML), Université de Lille, Sciences et Technologies-Centrale Lille-Centre National de la Recherche Scientifique (CNRS), Computer Science Department [UCLA] (CSD), University of California [Los Angeles] (UCLA), Développement et évolution (DE), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie du Développement de Villefranche sur mer (LBDV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Pierre Aigrain (LPA), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Department of Mathematics and Statistics [Montréal], McGill University = Université McGill [Montréal, Canada], Departamento de Botánica [Bariloche], Centro Regional Universitario Bariloche [Bariloche] (CRUB), Universidad Nacional del Comahue [Neuquén] (UNCOMA)-Universidad Nacional del Comahue [Neuquén] (UNCOMA), Bioénergétique Cellulaire et Pathologique (BECP), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Environnements et Paléoenvironnements OCéaniques (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratori Nazionali del Sud (LNS), Istituto Nazionale di Fisica Nucleare (INFN), Departament de Matemàtiques [Barcelona] (UAB), Universitat Autònoma de Barcelona (UAB), Max-Planck-Institut für Kohlenforschung (Coal Research), Max-Planck-Gesellschaft, CAS Institute of Oceanology (IOCAS), Chinese Academy of Sciences [Beijing] (CAS), National Chiao Tung University (NCTU), Department of Hydrology and Water Resources (HWR), State Key Laboratory of Nuclear Physics and Technology (SKL-NPT), University of Iowa [Iowa City], NASA Ames Research Center (ARC), Digital Language & Knowledge Contents Research Association (DICORA), Space Science and Technology Department [Didcot] (RAL Space), STFC Rutherford Appleton Laboratory (RAL), Science and Technology Facilities Council (STFC)-Science and Technology Facilities Council (STFC), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), H M Nautical Almanac Office [RAL] (HMNAO), University College of London [London] (UCL), University of California (UC)-University of California (UC)-School of Medicine, School of Earth and Environmental Sciences [Seoul] (SEES), Seoul National University [Seoul] (SNU), MicroMachines Centre (MMC), Regroupement Québécois sur les Matériaux de Pointe (RQMP), École Polytechnique de Montréal (EPM)-Université de Sherbrooke (UdeS)-McGill University = Université McGill [Montréal, Canada]-Université de Montréal (UdeM)-Fonds Québécois de Recherche sur la Nature et les Technologies (FQRNT), Université de Montréal (UdeM), Centre for Ecology and Hydrology (CEH), Natural Environment Research Council (NERC), Norwegian Institute for Water Research (NIVA), SEA URCHIN GENOME SEQUENCING CONSORTIUM, SODERGREN E, WEINSTOCK GM, DAVIDSON EH, CAMERON RA, GIBBS RA, ANGERER RC, ANGERER LM, ARNONE MI, BURGESS DR, BURKE RD, COFFMAN JA, DEAN M, ELPHICK MR, ETTENSOHN CA, FOLTZ KR, HAMDOUN A, HYNES RO, KLEIN WH, MARZLUFF W, MCCLAY DR, MORRIS RL, MUSHEGIAN A, RAST JP, SMITH LC, THORNDYKE MC, VACQUIER VD, WESSEL GM, WRAY G, ZHANG L, ELSIK CG, ERMOLAEVA O, HLAVINA W, HOFMANN G, KITTS P, LANDRUM MJ, MACKEY AJ, MAGLOTT D, PANOPOULOU G, POUSTKA AJ, PRUITT K, SAPOJNIKOV V, SONG X, SOUVOROV A, SOLOVYEV V, WEI Z, WHITTAKER CA, WORLEY K, DURBIN KJ, SHEN Y, FEDRIGO O, GARFIELD D, HAYGOOD R, PRIMUS A, SATIJA R, SEVERSON T, GONZALEZ-GARAY ML, JACKSON AR, MILOSAVLJEVIC A, TONG M, KILLIAN CE, LIVINGSTON BT, WILT FH, ADAMS N, BELLE R, CARBONNEAU S, CHEUNG R, CORMIER P, COSSON B, CROCE J, FERNANDEZ-GUERRA A, GENEVIERE AM, GOEL M, KELKAR H, MORALES J, MULNER-LORILLON O, ROBERTSON AJ, GOLDSTONE JV, COLE B, EPEL D, GOLD B, HAHN ME, HOWARD-ASHBY M, SCALLY M, STEGEMAN JJ, ALLGOOD EL, COOL J, JUDKINS KM, MCCAFFERTY SS, MUSANTE AM, OBAR RA, RAWSON AP, ROSSETTI BJ, GIBBONS IR, HOFFMAN MP, LEONE A, ISTRAIL S, MATERNA SC, SAMANTA MP, STOLC V, TONGPRASIT W, TU Q, BERGERON KF, BRANDHORST BP, WHITTLE J, BERNEY K, BOTTJER DJ, CALESTANI C, PETERSON K, CHOW E, YUAN QA, ELHAIK E, GRAUR D, REESE JT, BOSDET I, HEESUN S, MARRA MA, SCHEIN J, ANDERSON MK, BROCKTON V, BUCKLEY KM, COHEN AH, FUGMANN SD, HIBINO T, LOZA-COLL M, MAJESKE AJ, MESSIER C, NAIR SV, PANCER Z, TERWILLIGER DP, AGCA C, ARBOLEDA E, CHEN N, CHURCHER AM, HALLBOOK F, HUMPHREY GW, IDRIS MM, KIYAMA T, LIANG S, MELLOTT D, MU X, MURRAY G, OLINSKI RP, RAIBLE F, ROWE M, TAYLOR JS, TESSMAR-RAIBLE K, WANG D, WILSON KH, YAGUCHI S, GAASTERLAND T, GALINDO BE, GUNARATNE HJ, JULIANO C, KINUKAWA M, MOY GW, NEILL AT, NOMURA M, RAISCH M, READE A, ROUX MM, SONG JL, SU YH, TOWNLEY IK, VORONINA E, WONG JL, AMORE G, BRANNO M, BROWN ER, CAVALIERI, V, DUBOC V, DULOQUIN L, FLYTZANIS C, GACHE C, LAPRAZ F, LEPAGE T, LOCASCIO A, MART, University of California-University of California, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Le Mans Université (UM), Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Biogéosciences [UMR 6282] [Dijon] (BGS), Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Ecole Nationale Supérieure de Chimie de Mulhouse-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), University of California-University of California-School of Medicine, Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), University of Manchester Institute of Science and Technology (UMIST), Condensed Matter Physics and Materials Science Department, Brookhaven National Laboratory, Brookhaven National Laboratory [Upton, NY] (BNL), UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY)-U.S. Department of Energy [Washington] (DOE)-UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), State University of New York (SUNY)-State University of New York (SUNY)-U.S. Department of Energy [Washington] (DOE), Baylor College of Medicine (BCM), Baylor University, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Modélisation et Simulation Multi Echelle (MSME), Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Duke University [Durham], Instituto Andaluz de Geofísica y Prevención de Desastres Sísmicos [Granada] (IAGPDS), Universidad de Granada (UGR), Laboratoire d'Ingénierie des Matériaux de Bretagne (LIMATB), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO), University of New South Wales [Sydney] (UNSW), Celera Genomics (CRA), Celera Genomics, Paléobiodiversité et paléoenvironnements, Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma Tor Vergata [Roma], Unité de recherches forestières (BORDX PIERR UR ), Institut National de la Recherche Agronomique (INRA), Deptartment of Neuroscience, Uppsala University, State Key Laboratory of Palaeobiology and Stratigraphy, Nanjing Institute of Geology and Palaeontology (NIGPAS-CAS), Chinese Academy of Sciences [Nanjing Branch]-Chinese Academy of Sciences [Nanjing Branch], Institut Méditerranéen d'Ecologie et de Paléoécologie (IMEP), Université Paul Cézanne - Aix-Marseille 3-Université de Provence - Aix-Marseille 1-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Key Laboratory of Ocean Circulation and Waves, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China, Université Paris Diderot - Paris 7 (UPD7), Department of Physical and Environmental Sciences [Toronto], University of Toronto at Scarborough, inconnu temporaire UPEMLV, Inconnu, Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Department of Atmospheric Sciences [Seattle], University of Washington [Seattle], National Institute of Advanced Industrial Science and Technology (AIST), Department of Pharmacy, Università degli studi di Genova = University of Genoa (UniGe), Interdisciplinary Arts and Sciences Department, St. Vincent's Hospital, Sydney, Laboratoire des Sciences de l'Environnement Marin (LEMAR) (LEMAR), Institut de Recherche pour le Développement (IRD)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Department of Electrical Engineering (DEE-POSTECH), Pohang University of Science and Technology (POSTECH), Centre Suisse d'Electronique et de Microtechnique SA [Neuchatel] (CSEM), Centre Suisse d'Electronique et Microtechnique SA (CSEM), Human Genome Sequencing Center [Houston] (HGSC), Brookhaven National Laboratory, Meteorological Service of Canada, 4905 Dufferin Street, Université européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris-Est Marne-la-Vallée (UPEM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherches Forestières, Department of Physical and Environmental Sciences, University of Toronto [Scarborough, Canada], National Institute for Nuclear Physics (INFN), University of Genoa (UNIGE), Institut de Recherche pour le Développement (IRD)-Institut Universitaire Européen de la Mer (IUEM), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Universidad de Granada = University of Granada (UGR), Laboratoire d'Energétique et de Mécanique Théorique Appliquée (LEMTA ), Technische Universität München [München] (TUM), Queen's University [Kingston], Centre National de la Recherche Scientifique (CNRS)-Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Grenoble Alpes (UGA), Institut für Meteorologie und Klimaforschung (IMK), Karlsruher Institut für Technologie (KIT), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Rennes-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Université de Lille, Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Universitat Autònoma de Barcelona [Barcelona] (UAB), École Polytechnique de Montréal (EPM)-Université de Sherbrooke [Sherbrooke]-Université de Montréal [Montréal]-McGill University-Fonds Québécois de Recherche sur la Nature et les Technologies (FQRNT), Université de Montréal [Montréal], U.S. Department of Energy [Washington] (DOE)-UT-Battelle, LLC-Stony Brook University [SUNY] (SBU), Université de Bretagne Sud (UBS)-Institut Brestois du Numérique et des Mathématiques (IBNM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université Paul Cézanne - Aix-Marseille 3-Centre National de la Recherche Scientifique (CNRS)-Avignon Université (AU)-Université de Provence - Aix-Marseille 1, Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS)-Université de Brest (UBO), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, Sciences et Technologies-Ecole Centrale de Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS), École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: Signal Transduction, MESH: Sequence Analysis, DNA, MESH : Transcription Factors, MESH : Calcification, Physiologic, Genome, MESH : Proteins, 0302 clinical medicine, MESH : Embryonic Development, MESH: Gene Expression Regulation, Developmental, Innate, MESH: Embryonic Development, Developmental, Nervous System Physiological Phenomena, MESH: Animals, MESH: Proteins, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Complement Activation, ComputingMilieux_MISCELLANEOUS, MESH: Evolution, Molecular, MESH : Strongylocentrotus purpuratus, Genetics, 0303 health sciences, MESH: Nervous System Physiological Phenomena, Multidisciplinary, biology, Medicine (all), MESH: Immunologic Factors, Gene Expression Regulation, Developmental, Genome project, MESH: Transcription Factors, MESH : Immunity, Innate, MESH : Complement Activation, MESH: Genes, Bacterial artificial chromosome (BAC)DeuterostomesStrongylocentrotus purpuratusVertebrate innovations, Echinoderm, MESH : Nervous System Physiological Phenomena, embryonic structures, MESH: Cell Adhesion Molecules, MESH : Genes, MESH: Immunity, Innate, Sequence Analysis, Signal Transduction, MESH: Computational Biology, Genome evolution, MESH: Complement Activation, Sequence analysis, Evolution, MESH: Strongylocentrotus purpuratus, MESH : Male, Embryonic Development, MESH : Immunologic Factors, Article, MESH: Calcification, Physiologic, Calcification, MESH : Cell Adhesion Molecules, Evolution, Molecular, 03 medical and health sciences, Calcification, Physiologic, Animals, Immunologic Factors, MESH: Genome, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Evolution, Molecular, Physiologic, Gene, Strongylocentrotus purpuratus, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, MESH : Signal Transduction, Bacterial artificial chromosome, Immunity, Molecular, Computational Biology, Proteins, Cell Adhesion Molecules, Genes, Immunity, Innate, Transcription Factors, Sequence Analysis, DNA, DNA, biology.organism_classification, MESH: Male, Gene Expression Regulation, MESH : Animals, MESH : Gene Expression Regulation, Developmental, MESH : Genome, 030217 neurology & neurosurgery, MESH : Computational Biology, MESH : Sequence Analysis, DNA
Abstract

We report the sequence and analysis of the 814-megabase genome of the sea urchin Strongylocentrotus purpuratus , a model for developmental and systems biology. The sequencing strategy combined whole-genome shotgun and bacterial artificial chromosome (BAC) sequences. This use of BAC clones, aided by a pooling strategy, overcame difficulties associated with high heterozygosity of the genome. The genome encodes about 23,300 genes, including many previously thought to be vertebrate innovations or known only outside the deuterostomes. This echinoderm genome provides an evolutionary outgroup for the chordates and yields insights into the evolution of deuterostomes.

Published
2006

45. The finished DNA sequence of human chromosome 12

Author

Steven E, Scherer, Donna M, Muzny, Christian J, Buhay, Rui, Chen, Andrew, Cree, Yan, Ding, Shannon, Dugan-Rocha, Rachel, Gill, Preethi, Gunaratne, R Alan, Harris, Alicia C, Hawes, Judith, Hernandez, Anne V, Hodgson, Jennifer, Hume, Andrew, Jackson, Ziad Mohid, Khan, Christie, Kovar-Smith, Lora R, Lewis, Ryan J, Lozado, Michael L, Metzker, Aleksandar, Milosavljevic, George R, Miner, Kate T, Montgomery, Margaret B, Morgan, Lynne V, Nazareth, Graham, Scott, Erica, Sodergren, Xing-Zhi, Song, David, Steffen, Ruth C, Lovering, David A, Wheeler, Kim C, Worley, Yi, Yuan, Zhengdong, Zhang, Charles Q, Adams, M Ali, Ansari-Lari, Mulu, Ayele, Mary J, Brown, Guan, Chen, Zhijian, Chen, Kerstin P, Clerc-Blankenburg, Clay, Davis, Oliver, Delgado, Huyen H, Dinh, Heather, Draper, Manuel L, Gonzalez-Garay, Paul, Havlak, Laronda R, Jackson, Leni S, Jacob, Susan H, Kelly, Li, Li, Zhangwan, Li, Jing, Liu, Wen, Liu, Jing, Lu, Manjula, Maheshwari, Bao-Viet, Nguyen, Geoffrey O, Okwuonu, Shiran, Pasternak, Lesette M, Perez, Farah J H, Plopper, Jireh, Santibanez, Hua, Shen, Paul E, Tabor, Daniel, Verduzco, Lenee, Waldron, Qiaoyan, Wang, Gabrielle A, Williams, Jingkun, Zhang, Jianling, Zhou, Carlana C, Allen, Anita G, Amin, Vivian, Anyalebechi, Michael, Bailey, Joseph A, Barbaria, Kesha E, Bimage, Nathaniel P, Bryant, Paula E, Burch, Carrie E, Burkett, Kevin L, Burrell, Eliana, Calderon, Veronica, Cardenas, Kelvin, Carter, Kristal, Casias, Iracema, Cavazos, Sandra R, Cavazos, Heather, Ceasar, Joseph, Chacko, Sheryl N, Chan, Dean, Chavez, Constantine, Christopoulos, Joseph, Chu, Raynard, Cockrell, Caroline D, Cox, Michelle, Dang, Stephanie R, Dathorne, Robert, David, Candi Mon'Et, Davis, Latarsha, Davy-Carroll, Denise R, Deshazo, Jeremy E, Donlin, Lisa, D'Souza, Kristy A, Eaves, Amy, Egan, Alexandra J, Emery-Cohen, Michael, Escotto, Nicole, Flagg, Lisa D, Forbes, Abdul M, Gabisi, Melissa, Garza, Cerissa, Hamilton, Nicholas, Henderson, Omar, Hernandez, Sandra, Hines, Marilyn E, Hogues, Mei, Huang, DeVincent G, Idlebird, Rudy, Johnson, Angela, Jolivet, Sally, Jones, Ryan, Kagan, Laquisha M, King, Belita, Leal, Heather, Lebow, Sandra, Lee, Jaclyn M, LeVan, Lakeshia C, Lewis, Pamela, London, Lorna M, Lorensuhewa, Hermela, Loulseged, Demetria A, Lovett, Alice, Lucier, Raymond L, Lucier, Jie, Ma, Renita C, Madu, Patricia, Mapua, Ashley D, Martindale, Evangelina, Martinez, Elizabeth, Massey, Samantha, Mawhiney, Michael G, Meador, Sylvia, Mendez, Christian, Mercado, Iracema C, Mercado, Christina E, Merritt, Zachary L, Miner, Emmanuel, Minja, Teresa, Mitchell, Farida, Mohabbat, Khatera, Mohabbat, Baize, Montgomery, Niki, Moore, Sidney, Morris, Mala, Munidasa, Robin N, Ngo, Ngoc B, Nguyen, Elizabeth, Nickerson, Ogechi O, Nwaokelemeh, Stanley, Nwokenkwo, Melissa, Obregon, Maryann, Oguh, Njideka, Oragunye, Rodolfo J, Oviedo, Bridgette J, Parish, David N, Parker, Julia, Parrish, Kenya L, Parks, Heidie A, Paul, Brett A, Payton, Agapito, Perez, William, Perrin, Adam, Pickens, Eltrick L, Primus, Ling-Ling, Pu, Maria, Puazo, Miyo M, Quiles, Juana B, Quiroz, Dina, Rabata, Kacy, Reeves, San Juana, Ruiz, Hongmei, Shao, Ida, Sisson, Titilola, Sonaike, Richard P, Sorelle, Angelica E, Sutton, Amanda F, Svatek, Leah Anne, Svetz, Kavitha S, Tamerisa, Tineace R, Taylor, Brian, Teague, Nicole, Thomas, Rachel D, Thorn, Zulma Y, Trejos, Brenda K, Trevino, Ogechi N, Ukegbu, Jeremy B, Urban, Lydia I, Vasquez, Virginia A, Vera, Donna M, Villasana, Ling, Wang, Stephanie, Ward-Moore, James T, Warren, Xuehong, Wei, Flower, White, Angela L, Williamson, Regina, Wleczyk, Hailey S, Wooden, Steven H, Wooden, Jennifer, Yen, Lillienne, Yoon, Vivienne, Yoon, Sara E, Zorrilla, David, Nelson, Raju, Kucherlapati, George, Weinstock, and Richard A, Gibbs

Subjects
Pan troglodytes, Molecular Sequence Data, Biology, Synteny, Linkage Disequilibrium, Evolution, Molecular, Chromosome 16, Chromosome 19, Animals, Humans, Sequence Deletion, Short Interspersed Nucleotide Elements, Genetics, Chromosome 7 (human), Expressed Sequence Tags, Base Composition, Multidisciplinary, Chromosomes, Human, Pair 12, Sequence Analysis, DNA, Chromosome 17 (human), Mutagenesis, Insertional, Chromosome 4, Chromosome 3, Genes, Evolutionary biology, CpG Islands, Chromosome 21, Chromosome 22, Microsatellite Repeats
Abstract

Human chromosome 12 contains more than 1,400 coding genes and 487 loci that have been directly implicated in human disease. The q arm of chromosome 12 contains one of the largest blocks of linkage disequilibrium found in the human genome. Here we present the finished sequence of human chromosome 12, which has been finished to high quality and spans approximately 132 megabases, representing approximately 4.5% of the human genome. Alignment of the human chromosome 12 sequence across vertebrates reveals the origin of individual segments in chicken, and a unique history of rearrangement through rodent and primate lineages. The rate of base substitutions in recent evolutionary history shows an overall slowing in hominids compared with primates and rodents.

Published
2005

46. Diagnostic biomarkers in Alzheimer’s disease

Author

Emerlee Andersen, Bryce Casteigne, William Daniel Chapman, Andrew Creed, Forrest Foster, Allison Lapins, Rhonna Shatz, and Russell P. Sawyer

Subjects
Alzheimer's disease, Biomarkers, Amyloid PET, Cerebrospinal fluid, Tau PET, FDG PET, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

In this review article we examine the various types of diagnostic biomarkers which are used in the early detection of Alzheimer’s disease. This review summerizes the A/T/N classification system for Alzheimer’s biomarkers and its use in the biomarker-based diagnosis of Alzheimer’s disease. Furthermore we review the use of structural MRI, 18F-FDG PET, Amyloid PET, Tau PET, cerebrospinal fluid biomarkers, and the emerging role of plasma biomarkers in the diagnosis of Alzheimer’s disease. In doing so we discuss each biomarkers correlation with pathologic findings, ability to distinguish Alzheimer’s disease from healthy aging, ability to distinguish Alzheimer’s disease from other neurodegenerative diseases, role in A/T/N classification system, and limitations of each biomarker.

Published
2021
Full Text
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47. Effect of Sex-Specific Running Shoes on Female Recreational Runners

Author

Spencer Rasmussen, Baker Wilkes, Lily Poulton, Megan Roser, Shane Draper, Andrew Creer, and Tyler Standifird

Subjects
sex-specific footwear, joint kinetics, joint kinematics, lower limb mechanics, running biomechanics, ground reaction force, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

Alterations in running shoe design have been studied and used in the prevention of injury and enhancement of performance allowing running shoe companies to market to a variety of runners based on skill level, foot-strike pattern, and even sex. These alterations have been shown to affect biomechanical and physiological variables associated with running. Some shoe companies have designed shoes specifically for biological female runners due to the morphological differences found between male and female feet. The purpose of this study is to determine if sex-specific running shoes can alter female runner biomechanics or physiology. Female runners were asked to run in the male and female models of the Altra Torin 4 Plush shoe to determine if there were differences in ground reaction forces (GRFs), sagittal plane joint angles and moments, oxygen consumption (VO2), respiratory exchange ratio (RER), and perceived level of comfort while running; There were no significant differences in GRFs, sagittal joint angles and moments, VO2, RER, or perceived comfort; There were no differences in measured biomechanical or physiological variables between the female and male version of the shoes suggesting that the alterations made to the female-specific shoe do not provide any additional benefit to female recreational runners.

Published
2022
Full Text
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48. Evaluating drug prices, availability, affordability, and price components: implications for access to drugs in Malaysia.

Author

Zaheer Ud Din Babar, Mohamed Izham Mohamed Ibrahim, Harpal Singh, Nadeem Irfan Bukahri, and Andrew Creese

Subjects
Medicine
Abstract

BACKGROUND: Malaysia's stable health care system is facing challenges with increasing medicine costs. To investigate these issues a survey was carried out to evaluate medicine prices, availability, affordability, and the structure of price components. METHODS AND FINDINGS: The methodology developed by the World Health Organization (WHO) and Health Action International (HAI) was used. Price and availability data for 48 medicines was collected from 20 public sector facilities, 32 private sector retail pharmacies and 20 dispensing doctors in four geographical regions of West Malaysia. Medicine prices were compared with international reference prices (IRPs) to obtain a median price ratio. The daily wage of the lowest paid unskilled government worker was used to gauge the affordability of medicines. Price component data were collected throughout the supply chain, and markups, taxes, and other distribution costs were identified. In private pharmacies, innovator brand (IB) prices were 16 times higher than the IRPs, while generics were 6.6 times higher. In dispensing doctor clinics, the figures were 15 times higher for innovator brands and 7.5 for generics. Dispensing doctors applied high markups of 50%-76% for IBs, and up to 316% for generics. Retail pharmacy markups were also high-25%-38% and 100%-140% for IBs and generics, respectively. In the public sector, where medicines are free, availability was low even for medicines on the National Essential Drugs List. For a month's treatment for peptic ulcer disease and hypertension people have to pay about a week's wages in the private sector. CONCLUSIONS: The free market by definition does not control medicine prices, necessitating price monitoring and control mechanisms. Markups for generic products are greater than for IBs. Reducing the base price without controlling markups may increase profits for retailers and dispensing doctors without reducing the price paid by end users. To increase access and affordability, promotion of generic medicines and improved availability of medicines in the public sector are required.

Published
2007
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