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1. CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

Author

Vennin, C, Melenec, P, Rouet, R, Nobis, M, Cazet, As, Murphy, Kj, Herrmann, D, Reed, Da, Lucas, Mc, Warren, Sc, Elgundi, Z, Pinese, M, Kalna, G, Roden, D, Samuel, M, Zaratzian, A, Grey, St, Da Silva, A, Leung, W, Mathivanan, S, Wang, Yx, Braithwaite, Aw, Christ, D, Benda, A, Parkin, A, Phillips, Pa, Whitelock, Jm, Gill, Aj, Sansom, Oj, Croucher, Dr, Parker, Bl, Pajic, M, Morton, Jp, Cox, Tr, Timpson, P, Johns, Al, Chantrill, La, Chou, A, Steinmann, A, Arshi, M, Dwarte, T, Froio, D, Pereira, B, Ritchie, S, Chambers, Cr, Metcalf, X, Waddell, N, Pearson, Jv, Patch, Am, Nones, K, Newell, F, Mukhopadhyay, P, Addala, V, Kazakoff, S, Holmes, O, Leonard, C, Wood, S, Grimmond, Sm, Hofmann, O, Christ, A, Bruxner, T, Samra, Js, Pavlakis, N, High, Ha, Asghari, R, Merrett, Nd, Pavey, D, Das, A, Cosman, Ph, Ismail, K, O'Connnor, C, Stoita, A, Williams, D, Spigellman, A, Lam, Vw, Mcleod, D, Kirk, J, Kench, Jg, Grimison, P, Cooper, Cl, Sandroussi, C, Goodwin, A, Mead, Rs, Tucker, K, Andrews, L, Texler, M, Forest, C, Epari, Kp, Ballal, M, Fletcher, Dr, Mukhedkar, S, Zeps, N, Beilin, M, Feeney, K, Nguyen, Nq, Ruszkiewicz, Ar, Worthley, C, Chen, J, Brooke-Smith, Me, Papangelis, V, Clouston, Ad, Barbour, Ap, O'Rourke, Tj, Fawcett, Jw, Slater, K, Hatzifotis, M, Hodgkinson, P, Nikfarjam, M, Eshleman, Jr, Hruban, Rh, Wolfgang, Cl, Lawlor, Rt, Beghelli, S, Corbo, V, Scardoni, M, Bassi, C, Biankin, Av, Dixon, J, Jamieson, Nb, and Chang, Dk

Subjects
0301 basic medicine, medicine.medical_treatment, Drug Resistance, General Physics and Astronomy, 02 engineering and technology, Mice, Cancer-Associated Fibroblasts, Cell Movement, lcsh:Science, Inbred BALB C, Cancer, education.field_of_study, Mice, Inbred BALB C, Multidisciplinary, Tumor, 021001 nanoscience & nanotechnology, 3. Good health, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, 0210 nano-technology, Pancreas, Signal Transduction, Cancer microenvironment, Cell biology, Science, Population, Perlecan, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Cell Line, 03 medical and health sciences, Pancreatic cancer, Cell Line, Tumor, medicine, Humans, Animals, Neoplasm Invasiveness, education, Cell Proliferation, Neoplastic, fungi, General Chemistry, Immunotherapy, medicine.disease, Pancreatic Neoplasms, 030104 developmental biology, Gene Expression Regulation, Drug Resistance, Neoplasm, Cancer cell, Cancer research, biology.protein, Neoplasm, lcsh:Q, Stromal Cells, Tumor Suppressor Protein p53, Heparan Sulfate Proteoglycans
Abstract

Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote and restrain disease progression. Here, we interrogate how cancer cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence of a p53-driven hierarchy, where cancer cells with a gain-of-function (GOF) mutant p53 educate a dominant population of CAFs that establish a pro-metastatic environment for GOF and null p53 cancer cells alike. We also demonstrate that CAFs educated by null p53 cancer cells may be reprogrammed by either GOF mutant p53 cells or their CAFs. We identify perlecan as a key component of this pro-metastatic environment. Using intravital imaging, we observe that these dominant CAFs delay cancer cell response to chemotherapy. Lastly, we reveal that depleting perlecan in the stroma combined with chemotherapy prolongs mouse survival, supporting it as a potential target for anti-stromal therapies in pancreatic cancer., Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.

Published
2019

2. Corrigendum

Author

Gryganskyi, AP, Golan, J, Dolatabadi, S, Mondo, S, Robb, S, Idnurm, A, Muszewska, A, Steczkiewicz, K, Masonjones, S, Liao, H-L, Gajdeczka, MT, Anike, F, Vuek, A, Anishchenko, IM, Voigt, K, de Hoog, GS, Smith, ME, Heitman, J, Vilgalys, R, and Stajich, JE

Subjects
Genetics
Published
2019

3. Corrigendum

Author

Gryganskyi, AP, Golan, J, Dolatabadi, S, Mondo, S, Robb, S, Idnurm, A, Muszewska, A, Steczkiewicz, K, Masonjones, S, Liao, H-L, Gajdeczka, MT, Anike, F, Vuek, A, Anishchenko, IM, Voigt, K, de Hoog, GS, Smith, ME, Heitman, J, Vilgalys, R, and Stajich, JE

Subjects
Genetics
Published
2019

4. Solid-state O-17 NMR of amino acids

Author

Pike, KJ, Lemaitre, V, Kukol, A, Anupold, T, Samoson, A, Howes, AP, Watts, A, Smith, ME, and Dupree, R

Abstract

17 O solid-state NMR from 14 amino acids is reported here, greatly increasing the number investigated. In most cases well-separated resonances from carbonyl and hydroxyl oxygens with distinct second-order quadrupolar line shapes are observed using a 600 MHz spectrometer with fast magic angle spinning (MAS). This is in contrast to the motionally averaged resonances usually seen from amino acids in solution. For amino acids double-angle rotation (DOR) produces a decrease in the line width by more than a factor of 40, providing very high resolution, ∼ 1 ppm, spectra. The oxygen lines in alanine and the carbonyl oxygens in L-glutamic acid hydrochloride are assigned using 1H-decoupled DOR. The NMR interaction parameters for amino acids show a wide variation of XQ, from 6.4 to 8.6 MHz, η from 0.0 to 0.9, and δiso from 83 to 353 ppm. The high quality of the MAS NMR line shapes obtained at 14.1 T means that even small changes in parameters can be very accurately deduced, offering the possibility of 17O NMR as a sensitive probe of structural changes in these and related compounds. The D- and L-forms of glutamic acid hydrochloride are shown to have the same NMR parameters to within error, which are very different from those reported in the literature for the D,L-form. A strong correlation (∼-1200 ppm/Å) is found between δiso and the C-O bond length of the carbonyl oxygens. On the basis of these data, enriching specific amino acids in more complex polypeptides and proteins could provide site-selective information about the bonding and functionality of different sites in biomolecules. An estimate is made of the possible detection limit for such species.

Published
2016

6. Poly(gamma-glutamic acid)/Silica Hybrids with Calcium Incorporated in the Silica Network by Use of a Calcium Alkoxide Precursor

Author

Poologasundarampillai, G, Yu, B, Tsigkou, O, Wang, D, Romer, F, Bhakhri, V, Giuliani, F, Stevens, MM, McPhail, DS, Smith, ME, Hanna, JV, Jones, JR, and Engineering & Physical Science Research Council (EPSRC)

Subjects
Science & Technology, POLYGLUTAMIC ACID, Chemistry, Multidisciplinary, Biocompatible Materials, MECHANICAL-PROPERTIES, General Chemistry, NANOCOMPOSITES THIN-FILMS, ORGANIC-INORGANIC MATERIALS, ELABORATION, Silicon Dioxide, sol-gel process, SCAFFOLDS, CONDENSATION, Chemistry, poly(gamma-glutamic acid), bioactivity, REGENERATION, DISSOLUTION, poly(γ-glutamic acid), Physical Sciences, hybrid materials, Calcium, calcium methoxyethoxide, BIOACTIVE GLASS, 03 Chemical Sciences
Published
2014

7. PROTECTIVE SHIELD: A THEMATIC ANALYSIS OF THE EXPERIENCE OF HAVING AN ADULT SIBLING WITH INSULIN-DEPENDENT DIABETES MELLITUS

Author

Smith Me

Subjects
Adult, Male, Metaphor, media_common.quotation_subject, Protective shield, Nursing Methodology Research, Sibling relations, Middle Aged, Nuclear Family, Developmental psychology, Diabetes Mellitus, Type 1, Insulin dependent diabetes, Adaptation, Psychological, Chronic Disease, Humans, Sibling Relations, Female, Pshychiatric Mental Health, Thematic analysis, Sibling, Psychology, Attitude to Health, Stress, Psychological, media_common
Abstract

The purpose of this investigation was to describe the adult well sibling's experience of having grown up with a sibling who has insulin-dependent diabetes mellitus (IDDM). Using existential-phenomenological interview procedures, 14 participants were asked what it was like to have a chronically ill sibling. Analysis of participants' experiences was done using a hermeneutical approach. The thematic description of the experience of having lived with a chronically ill sibling with IDDM was divided into two interdependent and interrelated periods, the past and the present. The metaphor of a protective shield woven around the diabetic sibling by his or her family was taken from the words of a participant, and is seen by participants as occurring in the past and the present. The themes of the past provide the background for the themes of the present. Many of the themes of the past are moved forward to the present, but, because of the passage of time, are described differently by participants. Results of this study reinforce the fact that the stressors of chronic illness affect all family members, including the well siblings. It is imperative that nurses give care to the family, not just the designated patient. Nurses must be prepared to provide counseling, education, and anticipatory guidance to adults who have a sibling with a chronic illness.

Published
1998

8. RON is not a prognostic marker for resectable pancreatic cancer

Author

Tactacan, Carole M, Chang, David K, Cowley, Mark J, Humphrey, Emily S, Jianmin, Wu, Gill, Anthony J, Chou, Angela, Nones, Katia, Grimmond, Sean M, Sutherland, Robert L, Biankin, Andrew V, Daly, Roger J, Biankin, Av, Johns, Al, Mawson, A, Chang, Dk, Scarlett, Cj, Brancato, Ma, Rowe, Sj, Simpson, Sl, Martyn-Smith, M, Chantrill, La, Chin, Vt, Chou, A, Cowley, Mj, Caplan, W, Humphris, Jl, Jones, Md, Mead, R, Nagrial, Am, Pajic, M, Pettit, J, Pinese, M, Rooman, I, Wu, Jun, Daly, Rj, Musgrove, Ea, Sutherland, Rl, Grimmond, Sm, Waddell, N, Kassahn, Ks, Miller, Dk, Wilson, Pj, Patch, Am, Song, S, Harliwong, I, Idrisoglu, S, Nourse, C, Nourbakhsh, E, Manning, S, Wani, S, Gongora, M, Anderson, Michela, Holmes, O, Leonard, C, Taylor, D, Wood, JOHN STEPHAN, Xu, C, Nones, K, Fink, Julika, Christ, A, Bruxner, T, Cloonan, N, Newell, F, Pearson, Jv, Samra, Js, Gill, Aj, Nickpavlakis, Guminski, A, Toon, C, Asghari, R, Merrett, Nd, Pavey, Da, Das, A, Cosman, Ph, Ismail, K, O'Connor, C, Lam, Vw, Mcleod, D, Pleass, Hc, James, V, Kench, Jg, Cooper, Cl, Joseph, D, Sandroussi, C, Crawford, M, Texler, M, Forrest, C, Laycock, A, Epari, Kp, Ballal, M, Fletcher, Dr, Mukhedkar, S, Spry, Na, Deboer, B, Chai, M, Feeney, K, Zeps, N, Beilin, M, Nguyen, Nq, Ruszkiewicz, Ar, Worthley, C, Tan, Cp, Debrencini, T, Chen, J, Brooke-Smith, Me, Papangelis, V, Tang, H, Barbour, Ap, Clouston, Ad, Martin, P, O'Rourke, Tj, Chiang, A, Fawcett, Jw, Slater, K, Yeung, S, Hatzifotis, M, Hodgkinson, P, Christophi, C, Nikfarjam, M, Eshleman, Jr, Hruban, Rh, Maitra, A, Iacobuzio-Donahue, Ca, Schulick, Rd, Wolfgang, Cl, Morgan, Ra, Scarpa, A, Lawlor, Rt, Beghelli, S, Corbo, V, Scardoni, M, Bassi, C, Tempero, Ma., and Basic (bio-) Medical Sciences

Subjects
Oncology, Male, Receptor Protein-Tyrosine Kinases/analysis, Cancer Research, Receptor tyrosine kinase, Kaplan-Meier Estimate, Surgical oncology, 80 and over, Prospective cohort study, Pancreatic Neoplasms/metabolism, Biomarker, Gemcitabine, Chemotherapy, Adenocarcinoma, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Blotting, Western, Female, Humans, Immunohistochemistry, Middle Aged, Pancreatic Neoplasms, Prognosis, Proportional Hazards Models, Receptor Protein-Tyrosine Kinases, Tissue Array Analysis, Tumor, Blotting, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Adenocarcinoma/metabolism, CA19-9, Western, Research Article, medicine.drug, medicine.medical_specialty, lcsh:RC254-282, Biomarkers, Tumor/analysis, Breast cancer, Internal medicine, Pancreatic cancer, medicine, Genetics, business.industry, Cancer, medicine.disease, business, aged, 80 and over, Biomarkers
Abstract

Background The receptor tyrosine kinase RON exhibits increased expression during pancreatic cancer progression and promotes migration, invasion and gemcitabine resistance of pancreatic cancer cells in experimental models. However, the prognostic significance of RON expression in pancreatic cancer is unknown. Methods RON expression was characterized in several large cohorts, including a prospective study, totaling 492 pancreatic cancer patients and relationships with patient outcome and clinico-pathologic variables were assessed. Results RON expression was associated with outcome in a training set, but this was not recapitulated in the validation set, nor was there any association with therapeutic responsiveness in the validation set or the prospective study. Conclusions Although RON is implicated in pancreatic cancer progression in experimental models, and may constitute a therapeutic target, RON expression is not associated with prognosis or therapeutic responsiveness in resected pancreatic cancer.

Published
2012

9. Safe transfer of patients with brain injury

Author

M Power, I Johnston, S Cruickshank, E Moss, Ireland, B Matta, PA Farling, DK Whitaker, David K. Menon, Pjd Andrews, Smith Me, and MP Parris

Subjects
business.industry, Anesthesia, Medicine, business
Published
2006

11. Readerspeak

Author

Smith Me

Subjects
Advanced and Specialized Nursing, Chemistry
Published
1995

12. Nucleoside analogs plus ritonavir in stable antiretroviral therapy-experienced HIV-infected children - A randomized controlled trial

Author

Nachman, SA, Stanley, K, Yogev, R, Pelton, S, Wiznia, A, Lee, S, Mofenson, L, Fiscus, S, Rathore, M, Jimenez, E, Borkowsky, W, Pitt, J, Smith, ME, Wells, B, McIntosh, K, and University of Groningen

Subjects
VIRUS TYPE-1 RNA, IMMUNODEFICIENCY, PLASMA, ZIDOVUDINE, PROGRAM, DIDANOSINE
Abstract

Context Although protease inhibitors are used routinely in adults with human immunodeficiency virus (HIV) infection, the role of these drugs in the treatment of clinically stable HIV-infected children is not clear. Objective To evaluate the safety, tolerance, and virologic response produced by a change in antiretroviral therapy in HIV-infected children who were clinically and immunologically stable while receiving previous therapy. Design The Pediatric AIDS Clinical Trials Group 338, a multicenter, phase 2, randomized, open-label controlled trial conducted from February 6 to April 30, 1997 (patient entry period); patients were followed up for 48 weeks. Setting Pediatric HIV research clinics in the United States and Puerto Rico. Patients Two hundred ninety-seven antiretroviral-experienced, protease inhibitor-naive, clinically stable HIV-infected children aged 2 to 17 years. Interventions Children were randomized to receive zidovudine, 160 mg/m(2) 3 times per day, plus lamivudine, 4 mg/kg 2 times per day (n = 100); the same regimen plus ritonavir, 350 mg/m(2) 2 times per day (n = 100); or ritonavir, 350 mg/m(2) 2 times per day, and stavudine, 4 mg/kg 2 times per day (n = 97). Main Outcome Measure Plasma HIV-1 RNA levels at study weeks 12 and 48, compared among the 3 treatment groups. Results At study week 12, 12% of patients in the zidovudine-lamivudine group had undetectable plasma HIV RNA levels ( Conclusions In our study, change in antiretroviral therapy to a ritonavir-containing regimen was associated with superior virologic response at study week 12 compared with change to a dual nucleoside analog regimen. More children receiving ritonavir in combination with 2 compared with 1 nucleoside analog had undetectable HIV RNA levels at study week 48.

Published
2000

13. Groundwater drainage flow in a soil layer resting on an inclined leaky bed

Author

Koussis, AD Smith, ME Akylas, E Tombrou, M

Subjects
Physics::Fluid Dynamics
Abstract

We study subsurface storm flow from a planar hill slope, a problem that is similar hydraulically to lateral flow toward drains in landfills. Our analysis is based on the linearized one-dimensional Boussinesq equation (Dupuit-Forchheimer approximation), which is extended to allow for leakage through the underlying barrier. This linear advection-diffusion equation has a greater range of validity than the kinematic wave equation. Stating it in terms of the discharge, the variable of primary hydrologic interest, we integrate it numerically, using an adaptation of the Muskingum-Cunge routing scheme. A single-step computation of the outflow hydrograph, which combines the convenience of an analytical solution formula with acceptable accuracy, is proposed as a design tool and as a means of parameterization of drainage from hill slopes. Depth profiles are determined afterwards by a simple integration of Darcy’s law. Examples of the buildup and recession phases, with and without leakage, demonstrate the application of the computational method.

Published
1998

14. Short echo time proton MR spectroscopic imaging

Author

S. Posse, Schuknecht B, Norbert Herschkowitz, Smith Me, van Zijl Pc, and Moonen Ct

Subjects
Adult, Gadolinium DTPA, Male, Magnetic Resonance Spectroscopy, Multiple Sclerosis, Proton, Phosphorylcholine, Contrast Media, Gadolinium, Astrocytoma, Methylation, Choline, Spin–spin relaxation, Nuclear magnetic resonance, medicine, Image Processing, Computer-Assisted, Organometallic Compounds, Humans, Radiology, Nuclear Medicine and imaging, Aspartic Acid, Brain Diseases, medicine.diagnostic_test, business.industry, Brain Neoplasms, Multiple sclerosis, Brain, Water, Magnetic resonance imaging, Human brain, Glioma, Middle Aged, Pentetic Acid, medicine.disease, Lipids, Magnetic Resonance Imaging, Normal volunteers, medicine.anatomical_structure, Mr spectroscopic imaging, Lactates, Female, Protons, business, Short echo time
Abstract

Proton spectroscopic imaging at short TEs (20-30 ms) in human brain requires volume preselection inside the brain to suppress overwhelming lipid and water signals from surrounding tissue. In this article we discuss limitations of conventional volume preselection using stimulated echoes that lead to spectral contamination from surrounding tissue. Improved volume preselection was obtained by adding a complete outer volume suppression (presaturation). The performance of the method is illustrated on normal volunteers and on clinical cases with brain tumors and multiple sclerosis (MS) plaques. In normal human brain, we detected resonances with short T2 values and complex J-coupling, including rather broad methyl/methylene resonances in the chemical shift range between 0 and 2 ppm. Spectroscopic images obtained on patients with intracranial tumors and on one patient with several MS plaques demonstrate the possibility of detecting regional distributions of increased methyl/methylene resonances between 0 and 2 ppm in brain lesions.

Published
1993

15. A COMPARISON OF IMMUNE RESPONSES AGAINST AG-B AND NON-AG-B ANTIGENS, PRESENTED ALONE OR TOGETHER

Author

Smith Me, Sheila M. Sparshott, W.L. Ford, and Chisholm Pm

Subjects
Graft Rejection, Time Factors, Graft vs Host Reaction, Immune system, Antigen, Histocompatibility Antigens, Animals, Transplantation, Homologous, Cytotoxic T cell, Lymphocytes, Antigens, Cytotoxicity, Antibody-dependent cell-mediated cytotoxicity, Immunity, Cellular, Transplantation, Chemistry, Rats, Inbred Strains, Skin Transplantation, Cytotoxicity Tests, Immunologic, Acquired immune system, Molecular biology, Rats, Histocompatibility, B-1 cell, Lymphocyte Transfusion, Lymph Nodes
Abstract

By exploiting congenic rat strains (HO.B2 and PVG/c) cell-mediated immune responses against Ag-B antigens alone were measured and compared with responses against (1) non-Ag-B antigens and (2) Ag-B and non-Ag-B antigens in combination. It was confirmed that multiple non-Ag-B antigens provoke prompt first-set skin graft rejections, but are much weaker than Ag-B antigens in stimulating both graft-versus-host (GVH) and cytotoxic activity. No evidence of synergistic interaction was found between anti-Ag-B and anti-non-Ag-B responses either by GVH assay or in the generation of cytotoxic cells. Specific partitioning of cytotoxic cells on antigenic monolayers suggested that cytotoxic cells on antigenic monolayers suggested that cytotoxicity is predominantly directed against Ag-B antigens. The measurements of GVH activity consolidate previous work, which suggested that 4.5 to 12% of nonimmune T cells can respond to each Ag-B determined antigenic complex and eliminate the possibility that most of these cells were responding to non-Ag-B antigens. Two principles for measuring GVH activity were compared: (1) 3H-thymidine incorporation into donor lymphocytes at 24 hr after transfer to irradiated F1 hybrid recipients and (2) the popliteal lymph node assay, which depends on a secondary phase of host cell proliferation.

Published
1977

16. The effect of environment on sebum output and composition in cattle

Author

Noble Rc, Jenkinson Dm, and Smith Me

Subjects
body regions, Prolonged exposure, chemistry.chemical_compound, integumentary system, General Veterinary, chemistry, Warm environment, Linoleic acid, Myristic acid, Humidity, Composition (visual arts), Fatty acid composition, Food science
Abstract

In an investigation into the effect of short-term exposure to different temperatures and humidities on the sebaceous glands of Ayrshire calves it was concluded that temperature had no appreciable effect on sebum output or its fatty acid composition. At a low humidity, however, the cutaneous outputs of palmitic and myristic acids were higher. On prolonged exposure to a warm environment, a higher output of sebum occurred together with an increase in the percentage of linoleic acid in the sebum.

Published
1975

17. THE MIGRATION OF LYMPHOCYTES ACROSS SPECIALIZED VASCULAR ENDOTHELIUM

Author

Smith Me, W. L. Ford, S M Sparshott, and Sedgley M

Subjects
chemistry.chemical_classification, biology, Spleen, Cell Biology, General Medicine, Trypsin, Molecular biology, In vitro, Trypsinization, Vascular endothelium, Enzyme, medicine.anatomical_structure, chemistry, medicine, biology.protein, Neuraminidase, Perfusion, medicine.drug
Abstract

Lymphocytes were exposed in vitro to either trypsin or neuraminidase. The ability of the treated cells to migrate into tissues were measured (a) by i.v. injection into intact recipients and (b) by vascular perfusion through an isolated lymph-node preparation. The localization of trypsinized cells in the lymph-nodes of recipients was deficient when compared to untreated lymphocytes and there was a surplus of trypsinized cells in blood. Trypsinized cells migrated into the isolated nodes in reduced numbers. By contrast, neuraminidase treated lymphocytes were markedly deficient in the blood of recipients early after injection; their localization in the spleen and lymph-nodes was also deficient but they were in surplus in the liver. Moreover they migrated into the isolated nodes in slightly increased numbers. By 24 hr after injection the perturbed localization pattern produced by either enzyme was partly restored to normal. In conclusion, tryspin interfered with the capacity of lymphocytes to migrate into lymph-nodes but neuraminidase did not; the latter promoted the hepatic sequestration of cells and the reduced localization in the blood and tissues was a consequence of this. The hypothesis that lymphocytes adhere to specialized endothelia in lymph-nodes because of specific glycoside sequences on their surface lacks experimental support.

Published
1976

18. The Migration of Lymphocytes Across Specialized Vascular Endothelium

Author

W.L. Ford, Sheila M. Sparshott, and Smith Me

Subjects
Endothelium, biology, business.industry, Lymphocyte, Spleen, Cell Biology, General Medicine, In vitro, Pathology and Forensic Medicine, Vascular endothelium, medicine.anatomical_structure, Concanavalin A, Immunology, medicine, biology.protein, business, Molecular Biology
Abstract

Radioactively labelled rat lymphocytes were treated in vitro with concanavalin A (con A) and injected intravenously into syngeneic recipients. By examining the blood and tissues at intervals from 30 min to 48 h after injection, it was confirmed that con A altered the distribution of lymphocytes. Comparison was made with the localization of alternatively labelled untreated lymphocytes injected into the same recipients and with untreated lymphocytes injected into other recipients. Within 1 h of injection there was a surplus of treated cells in the lungs and liver and deficits (of equal magnitude) in the blood, spleen and lymphnodes. By 24 h after injection there was a twofold surplus of treated cells in the spleen but a persisting deficit in lymphnodes. These perturbations can be ascribed to the prolonged retention of lymphocytes in normal sites of localization; there is no evidence that con A either hinders the migration of lymphocytes from the blood or diverts them to abnormal sites. It is not clear whether the delay in the recipients’ tissues requires an active response to con A but, if so, then it does not proceed to blastic transformation.

Published
1977

19. Rubeosis Iridis and Primary Angle-Closure Glaucoma

Author

Smith Me and Ott Ft

Subjects
Ophthalmology, Rubeosis iridis, medicine.medical_specialty, business.industry, medicine, medicine.disease, business, Primary angle-closure glaucoma
Published
1971

20. Human infection with Moniliformis sp. in Rhodesia

Author

Fleming F, Goldsmith Jm, and Smith Me

Subjects
Zimbabwe, 030231 tropical medicine, Mebendazole, Helminthiasis, Physiology, Biology, Benzoates, Acanthocephala, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Pyrantel, medicine, Helminths, Humans, Adverse effect, Parasite Egg Count, Anthelmintics, Infant, Moniliformis, biology.organism_classification, Infectious Diseases, Immunology, Parasitology, Benzimidazoles, Female, Carbamates, medicine.drug
Published
1974

21. The stimulus to host cell proliferation in graft-versus-host reactions

Author

S. Fossum, Simon V. Hunt, B. Rolstad, Smith Me, S M Sparshott, and W. L. Ford

Subjects
B-Lymphocytes, biology, Host (biology), T-Lymphocytes, Immunology, Lymphocyte Cooperation, Rats, Inbred Strains, General Medicine, Stimulus (physiology), Major histocompatibility complex, Lymphocyte Activation, Molecular biology, Rats, Major Histocompatibility Complex, Graft vs Host Reaction, Phenotype, Graft versus host reactions, biology.protein, Animals, Popliteal Lymph Node, Parental strain, Crosses, Genetic
Abstract

Two experiments are described concerned with the mechanism of host cell activation in the rat popliteal lymph node (LN) undergoing a graft-versus-host (GVH) reaction. (1) Irradiated, F1 hybrid hosts (750 rad) mounted an impaired response to parental strain T cells. This was augmented by an intravenous injection of F1 hybrid lymphocytes but not by parental strain B lymphocytes syngeneic with the initiating T cells. When the donor T cells (footpad) and B lymphocytes (intravenous) were completely allogeneic the residual response of the irradiated F1 was completely inhibited. (2) The popliteal LN response in the semi-allogeneic situation of the type (A x C)F1 leads to (B x C)F1 was, if anything, weaker than in the allogeneic situation AA leads to BB. These results and other data are discussed in terms of a possible major histocompatibility complex (MHC) requirement for host cell activation. The sharing of an MHC haplotype between donor and host cells is unlikely to be a necessary or sufficient condition for host cell activation.

Published
1981

22. The architecture of rat lymph nodes. III. The lymph nodes and lymph-borne cells of the congenitally athymic nude rat (rnu)

Author

W.L. Ford, Smith Me, Bell Eb, and Sigbjørn Fossum

Subjects
Pathology, medicine.medical_specialty, Medullary cavity, Endothelium, medicine.drug_class, Immunology, Thymus Gland, Monoclonal antibody, Thoracic duct, Thoracic Duct, Peyer's Patches, Cell Movement, medicine, Thoracic duct lymph, Animals, business.industry, Germinal center, General Medicine, Organ Size, Rats, medicine.anatomical_structure, Mutation, Lymph, Interdigitating Cells, Lymph Nodes, business, Spleen
Abstract

The lymph nodes (LN) of the congenitally athymic nude rat(rnu) were compared with the LN of non-nude littermates. The mesenteric and coeliac LN were smaller in the rnu rats, but the axillary and the cervical LN were larger. Germinal centres were found in the LN of nude rats. They were scarce and often very small, but some were of normal structure, especially in the cervical LN. The endothelium of post-capillary venules in the LN or normal rats, was seen. The paracortex was extremely depleted of lymphocytes but remained a distinct area occupied predominantly by pale interdigitating cells. In some LN the medullary sinuses were distended and the cords engorged with plasma cells. The predominant cells in thoracic duct lymph were immunoglobulin-positive B lymphocytes. The hourly output of these cells was the same as that in non-nude littermates. However, small numbers of thoracic duct cells were positive for the markers identified by the monoclonal antibodies W3/13 and W3/25, although in normal rats these are not expressed on small B lymphocytes.

Published
1980

23. Fanconi's Anaemia

Author

Sinclair L, McCarthy Gt, Young De, M. E. J. Beard, Smith Me, Ronald Bodley Scott, Bateman Cj, and Franklin Aw

Subjects
Fetal hemoglobin determination, Fanconi anemia, business.industry, Partial response, medicine, General Medicine, Skin fibroblast, Symptom onset, Acquired aplastic anemia, Bioinformatics, medicine.disease, business, Fanconi's anaemia
Published
1973

24. The specific selection of recirculating lymphocytes by antigen in normal and preimmunized rats

Author

R. C. Atkins, Smith Me, D. A. Rowley, W. L. Ford, and J. L. Gowans

Subjects
Erythrocytes, Lymphocyte, Immunology, chemical and pharmacologic phenomena, In Vitro Techniques, Article, Thoracic Duct, Graft vs Host Reaction, Immune system, Antigen, medicine, Tetanus Toxoid, Immunology and Allergy, Animals, Lymphocytes, Antigens, Antibody-Producing Cells, Immunity, Cellular, Sheep, biology, Rats, Inbred Strains, Primary and secondary antibodies, Rats, Radiation Injuries, Experimental, medicine.anatomical_structure, Freund's adjuvant, Delayed hypersensitivity, Histocompatibility, Antibody Formation, biology.protein, gamma-Globulins, Antibody, Hapten, Haptens, Dinitrophenols, Spleen
Abstract

Thoracic duct lymphocytes (TDL) from normal rats will restore a primary antibody response to sheep erythrocytes (SRBC) in irradiated recipients and cause a graft-versus-host reaction in F1 hybrid rats; lymphocytes from rats immunized with either tetanus toxoid or dinitrophenylated bovine gamma globulin (DNP BGG) will generate specific antibody after cell transfer and challenge. The ability of TDL to mediate each of these responses is severely depressed by giving a single intravenous dose of the specific antigen shortly before cannulation of the thoracic duct, although the lymphocyte donors themselves respond normally. The injection of antigen does not decrease the output of lymphocytes in the thoracic duct and the effect is specific for the antigen injected. The findings are most readily accounted for by assuming that small subpopulations of specific lymphocytes are selected from the recirculating pool by antigen which has localized in lymphoid tissue. The observation that passive antibody abolishes selection by SRBC supports this interpretation. The strong selection exerted by a subcutaneous injection of SRBC in Freund's complete adjuvant, which induces delayed hypersensitivity but little early antibody, suggests that a common cell type may be involved in the induction of both delayed hypersensitivity and antibody formation. The anti-DNP antibody response generated by TDL from rats immunized with DNP BGG was abolished by a selecting injection of the homologous conjugate. The response was depressed to a smaller degree by injections of either BGG or dinitrophenylated human serum albumin, suggesting that carrier-specific (T) and hapten-specific (B) lymphocytes could be separately selected from the recirculating pool. The regional selection of recirculating lymphocytes by antigen may explain a number of phenomena in which the prior injection of antigen has been found to inhibit a subsequent immune response.

Published
1972

25. Chemical synthesis and biological evaluation of 4′-thionucleosides

Author

Guinan, Mieke, Miller, GJ, and Smith, ME

Subjects
QD
Abstract

Nucleoside analogues have proven to be highly successful chemotherapeutic agents in the treatment of a wide variety of cancers and viruses. Several such compounds, including Sofosbuvir and Gemcitabine are the go-to option in first line treatments. However, these compoundss do have limitations (poor cellular uptake, low conversion to the active triphosphate metabolite, rapid degradation or clearance and development of resistance profiles in certain cell types) and the development of next generation compounds remains a topic of significant interest and necessity. This project broadly involves the chemical synthesis of thionucleoside analogues, a class of molecules which act as antimetabolites and are known to have antiproliferative activity against numerous cancers, viruses and bacteria. The thionucleoside targets herein are inspired by current nucleoside analogue drugs on the market, and they have potential for both greater potency and improved metabolic stability in vivo.

Published
2022

26. Defining the role of common variation in the genomic and biological architecture of adult human height

Author

Wood, Ar, Esko, T, Yang, J, Vedantam, S, Pers, Th, Gustafsson, S, Chu, Ay, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, Ml, Croteau Chonka DC, Day, Fr, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, Au, Karjalainen, J, Lo, Ks, Locke, Ae, Mägi, R, Mihailov, E, Porcu, E, Randall, Jc, Scherag, A, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Workalemahu, T, Zhao, Jh, Absher, D, Albrecht, E, Anderson, D, Baron, J, Beekman, M, Demirkan, A, Ehret, Gb, Feenstra, B, Feitosa, Mf, Fischer, K, Fraser, Rm, Goel, A, Gong, J, Justice, Ae, Kanoni, S, Kleber, Me, Kristiansson, K, Lim, U, Lotay, V, Lui, Jc, Mangino, M, Mateo Leach, I, Medina Gomez, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Pasko, D, Pechlivanis, S, Prokopenko, I, Ried, Js, Ripke, S, Shungin, D, Stancáková, A, Strawbridge, Rj, Sung, Yj, Tanaka, T, Teumer, A, Trompet, S, van der Laan SW, van Setten, J, Van Vliet Ostaptchouk JV, Wang, Z, Yengo, L, Zhang, W, Afzal, U, Arnlöv, J, Arscott, Gm, Bandinelli, S, Barrett, A, Bellis, C, 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S, Mclaren, Pj, Menni, C, Merger, S, Milani, L, Moayyeri, A, Monda, Kl, Morken, Ma, Müller, G, Müller Nurasyid, M, Musk, Aw, Narisu, N, Nauck, M, Nolte, Im, Nöthen, Mm, Oozageer, L, Pilz, S, Rayner, Nw, Renstrom, F, Robertson, Nr, Rose, Lm, Roussel, R, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, Fr, Schunkert, H, Scott, Ra, Sehmi, J, Seufferlein, T, Shi, J, Silventoinen, K, Smit, Jh, Smith, Av, Smolonska, J, Stanton, Av, Stirrups, K, Stott, Dj, Stringham, Hm, Sundström, J, Swertz, Ma, Syvänen, Ac, Tayo, Bo, Thorleifsson, G, Tyrer, Jp, van Dijk, S, van Schoor NM, van der Velde, N, van Heemst, D, van Oort FV, Vermeulen, Sh, Verweij, N, Vonk, Jm, Waite, Ll, Waldenberger, M, Wennauer, R, Wilkens, Lr, Willenborg, C, Wilsgaard, T, Wojczynski, Mk, Wong, A, Wright, Af, Zhang, Q, Arveiler, D, Bakker, Sj, Beilby, J, Bergman, Rn, Bergmann, S, Biffar, R, Blangero, J, Boomsma, Di, Bornstein, Sr, Bovet, P, Brambilla, P, Brown, Mj, Campbell, H, Caulfield, Mj, Chakravarti, A, Collins, R, Collins, Fs, Crawford, Dc, Cupples, La, Danesh, J, de Faire, U, den Ruijter HM, Erbel, R, Erdmann, J, Eriksson, Jg, Farrall, M, Ferrannini, Eleuterio, Ferrières, J, Ford, I, Forouhi, Ng, Forrester, T, Gansevoort, Rt, Gejman, Pv, Gieger, C, Golay, A, Gottesman, O, Gudnason, V, Gyllensten, U, Haas, Dw, Hall, As, Harris, Tb, Hattersley, At, Heath, Ac, Hengstenberg, C, Hicks, Aa, Hindorff, La, Hingorani, Ad, Hofman, A, Hovingh, Gk, Humphries, Se, Hunt, Sc, Hypponen, E, Jacobs, Kb, Jarvelin, Mr, Jousilahti, P, Jula, Am, Kaprio, J, Kastelein, Jj, Kayser, M, Kee, F, Keinanen Kiukaanniemi SM, Kiemeney, La, Kooner, Js, Kooperberg, C, Koskinen, S, Kovacs, P, Kraja, At, Kumari, M, Kuusisto, J, Lakka, Ta, Langenberg, C, Le Marchand, L, Lehtimäki, T, Lupoli, S, Madden, Pa, Männistö, S, Manunta, P, Marette, A, Matise, Tc, Mcknight, B, Meitinger, T, Moll, Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Nelis, M, Ohlsson, C, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pasterkamp, G, Peters, A, Pramstaller, Pp, Price, Jf, Qi, L, Raitakari, Ot, Rankinen, T, Rao, Dc, Rice, Tk, Ritchie, M, Rudan, I, Salomaa, V, Samani, Nj, Saramies, J, Sarzynski, Ma, Schwarz, Pe, Sebert, S, Sever, P, Shuldiner, Ar, Sinisalo, J, Steinthorsdottir, V, Stolk, Rp, Tardif, Jc, Tönjes, A, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, Mc, Electronic Medical Records, Genomics, Consortium, Migen, Consortium, Pagege, Consortium, LifeLines Cohort Study, Amouyel, P, Asselbergs, Fw, Assimes, Tl, Bochud, M, Boehm, Bo, Boerwinkle, E, Bottinger, Ep, Bouchard, C, Cauchi, S, Chambers, Jc, Chanock, Sj, Cooper, Rs, de Bakker PI, Dedoussis, G, Ferrucci, L, Franks, Pw, Froguel, P, Groop, Lc, Haiman, Ca, Hamsten, A, Hayes, Mg, Hui, J, Hunter, Dj, Hveem, K, Jukema, Jw, Kaplan, Rc, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, Ng, März, W, Melbye, M, Moebus, S, Munroe, Pb, Njølstad, I, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Perola, M, Pérusse, L, Peters, U, Powell, Je, Power, C, Quertermous, T, Rauramaa, R, Reinmaa, E, Ridker, Pm, Rivadeneira, F, Rotter, Ji, Saaristo, Te, Saleheen, D, Schlessinger, D, Slagboom, Pe, Snieder, H, Spector, Td, Strauch, K, Stumvoll, M, Tuomilehto, J, Uusitupa, M, van der Harst, P, Völzke, H, Walker, M, Wareham, Nj, Watkins, H, Wichmann, He, Wilson, Jf, Zanen, P, Deloukas, P, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, Thorsteinsdottir, U, Barroso, I, Fox, Cs, North, Ke, Strachan, Dp, Beckmann, Js, Berndt, Si, Boehnke, M, Borecki, Ib, Mccarthy, Mi, Metspalu, A, Stefansson, K, Uitterlinden, Ag, van Duijn CM, Franke, L, Willer, Cj, Price, Al, Lettre, G, Loos, Rj, Weedon, Mn, Ingelsson, E, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, T. M., Isotope Research, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Research Institute for Asthma and COPD (GRIAC), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Ehret, Georg Benedikt, Wood, A, Esko, T, Yang, J, Vedantam, S, Pers, T, Gustafsson, S, Chu, A, Estrada, K, Luan, J, Kutalik, Z, Amin, N, Buchkovich, M, Croteau Chonka, D, Day, F, Duan, Y, Fall, T, Fehrmann, R, Ferreira, T, Jackson, A, Karjalainen, J, Lo, K, Locke, A, Mägi, R, Mihailov, E, Porcu, E, Randall, J, Scherag, A, Vinkhuyzen, A, Westra, H, Winkler, T, 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Epstein, SE., Scheffold, T., Berger, K., Huge, A., Martinelli, N., Olivieri, O., Corrocher, R., König, I., Hólm, H., Thorleifsson, G., Thorsteinsdottir, U., Stefansson, K., Do, R., Xie, C., Siscovick, D., Matise, T., Buyske, S., Higashio, J., Williams, R., Nato, A., Ambite, JL., Deelman, E., Manolio, T., Hindorff, L., North, KE., Heiss, G., Taylor, K., Franceschini, N., Avery, C., Graff, M., Lin, D., Quibrera, M., Cochran, B., Kao, L., Umans, J., Cole, S., MacCluer, J., Person, S., Pankow, J., Gross, M., Boerwinkle, E., Fornage, M., Durda, P., Jenny, N., Patsy, B., Arnold, A., Buzkova, P., Haines, J., Murdock, D., Glenn, K., Brown-Gentry, K., Thornton-Wells, T., Dumitrescu, L., Jeff, J., Bush, WS., Mitchell, SL., Goodloe, R., Wilson, S., Boston, J., Malinowski, J., Restrepo, N., Oetjens, M., Fowke, J., Zheng, W., Spencer, K., Pendergrass, S., Le Marchand£££Loïc£££ L., Wilkens, L., Park, L., Tiirikainen, M., Kolonel, L., Lim, U., Cheng, I., Wang, H., Shohet, R., Haiman, C., Stram, D., Henderson, B., Monroe, K., Schumacher, F., Kooperberg, C., Peters, U., Anderson, G., Prentice, R., LaCroix, A., Wu, C., Carty, C., Gong, J., Rosse, S., Young, A., Haessler, J., Kocarnik, J., Lin, Y., Jackson, R., Duggan, D., Kuller, L., Psychiatry, Epidemiology and Data Science, EMGO - Lifestyle, overweight and diabetes, Wood, Ar, Pers, Th, Chu, Ay, Buchkovich, Ml, CROTEAU CHONKA, Dc, Day, Fr, Jackson, Au, Locke, Ae, Randall, Jc, Vinkhuyzen, Aa, Westra, Hj, Winkler, Tw, Zhao, Jh, Ehret, Gb, Feitosa, Mf, Fraser, Rm, Justice, Ae, Kleber, Me, Lui, Jc, MATEO LEACH, I, MEDINA GOMEZ, C, Nalls, Ma, Nyholt, Dr, Palmer, Cd, Strawbridge, Rj, Sung, Yj, VAN DER LAAN, Sw, VAN SETTEN, J, VAN VLIET OSTAPTCHOUK, Jv, Arnlöv, J, Arscott, Gm, Bennett, Aj, Bolton, Jl, Boyd, Ha, Buckley, Bm, Caspersen, Ih, CLAUDI BOEHM, S, Daw, Ew, DE JONG, Pa, Denny, Jc, DHONUKSHE RUTTEN, R, Garcia, Me, Grammer, Tb, DE GROOT, Lc, Groves, Cj, Hartman, Ca, HEARD COSTA, Nl, Henders, Ak, Hillege, Hl, Hlatky, Ma, HOUWING 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Fl, Montgomery, Gw, Morris, Ad, Morris, Ap, Murray, Jc, Oldehinkel, Aj, Ong, Kk, Ouwehand, Wh, Pramstaller, Pp, Price, Jf, Raitakari, Ot, Rao, Dc, Rice, Tk, Samani, Nj, Sarzynski, Ma, Schwarz, Pe, Shuldiner, Ar, Stolk, Rp, Tardif, Jc, Vohl, Mc, ELECTRONIC MEDICAL RECORDS AND GENOMICS, Consortium, Migen, Consortium, Page, Consortium, LIFELINES COHORT, Study, Asselbergs, Fw, Assimes, Tl, Boehm, Bo, Bottinger, Ep, Chambers, Jc, Chanock, Sj, DE BAKKER, Pi, Franks, Pw, Groop, Lc, Haiman, Ca, Hayes, Mg, Hunter, Dj, Jukema, Jw, Kaplan, Rc, Martin, Ng, Munroe, Pb, Oostra, Ba, Palmer, Cn, Pedersen, Nl, Powell, Je, Ridker, Pm, Rotter, Ji, Saaristo, Te, Slagboom, Pe, Spector, Td, VAN DER HARST, P, Wareham, Nj, Wichmann, He, Wilson, Jf, Heid, Im, Lindgren, Cm, Mohlke, Kl, Speliotes, Ek, North, Ke, Strachan, Dp, Berndt, Si, Borecki, Ib, Mccarthy, Mi, Uitterlinden, Ag, VAN DUIJN, Cm, Willer, Cj, Price, Al, Loos, Rj, Weedon, Mn, O'Connell, Jr, Abecasis, Gr, Chasman, Di, Goddard, Me, Visscher, Pm, Hirschhorn, Jn, Frayling, Tm, Epidemiology, Surgery, Public Health, Internal Medicine, Erasmus MC other, Genetic Identification, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Biological Psychology, AIMMS, Functional Genomics, EMGO+ - Lifestyle, Overweight and Diabetes, Wood, AR, Vadantam, S, Hypponen, Elina, Frayling, TM, Wood A.R., Esko T., Yang J., Vedantam S., Pers T.H., Gustafsson S., Chu A.Y., Estrada K., Luan J., Kutalik Z., Amin N., Buchkovich M.L., Croteau-Chonka D.C., Day F.R., Duan Y., Fall T., Fehrmann R., Ferreira T., Jackson A.U., Karjalainen J., Lo K.S., Locke A.E., Magi R., Mihailov E., Porcu E., Randall J.C., Scherag A., Vinkhuyzen A.A.E., Westra H.-J., Winkler T.W., Workalemahu T., Zhao J.H., Absher D., Albrecht E., Anderson D., Baron J., Beekman M., Demirkan A., Ehret G.B., Feenstra B., Feitosa M.F., Fischer K., Fraser R.M., Goel A., Gong J., Justice A.E., Kanoni S., Kleber M.E., Kristiansson K., Lim U., Lotay V., Lui J.C., Mangino M., Leach I.M., Medina-Gomez C., Nalls M.A., Nyholt D.R., Palmer C.D., Pasko D., Pechlivanis S., Prokopenko I., Ried J.S., Ripke S., Shungin D., Stancakova A., Strawbridge R.J., Sung Y.J., Tanaka T., Teumer A., Trompet S., Van Der Laan S.W., Van Setten J., Van Vliet-Ostaptchouk J.V., Wang Z., Yengo L., Zhang W., Afzal U., Arnlov J., Arscott G.M., Bandinelli S., Barrett A., Bellis C., Bennett A.J., Berne C., Bluher M., Bolton J.L., Bottcher Y., Boyd H.A., Bruinenberg M., Buckley B.M., Buyske S., Caspersen I.H., Chines P.S., Clarke R., Claudi-Boehm S., Cooper M., Daw E.W., De Jong P.A., Deelen J., Delgado G., Denny J.C., Dhonukshe-Rutten R., Dimitriou M., Doney A.S.F., Dorr M., Eklund N., Eury E., Folkersen L., Garcia M.E., Geller F., Giedraitis V., Go A.S., Grallert H., Grammer T.B., Grassler J., Gronberg H., De Groot L.C.P.G.M., Groves C.J., Haessler J., Hall P., Haller T., Hallmans G., Hannemann A., Hartman C.A., Hassinen M., Hayward C., Heard-Costa N.L., Helmer Q., Hemani G., Henders A.K., Hillege H.L., Hlatky M.A., Hoffmann W., Hoffmann P., Holmen O., Houwing-Duistermaat J.J., Illig T., Isaacs A., James A.L., Jeff J., Johansen B., Johansson A., Jolley J., Juliusdottir T., Junttila J., Kho A.N., Kinnunen L., Klopp N., Kocher T., Kratzer W., Lichtner P., Lind L., Lindstrom J., Lobbens S., Lorentzon M., Lu Y., Lyssenko V., Magnusson P.K.E., Mahajan A., Maillard M., McArdle W.L., McKenzie C.A., McLachlan S., McLaren P.J., Menni C., Merger S., Milani L., Moayyeri A., Monda K.L., Morken M.A., Muller G., Muller-Nurasyid M., Musk A.W., Narisu N., Nauck M., Nolte I.M., Nothen M.M., Oozageer L., Pilz S., Rayner N.W., Renstrom F., Robertson N.R., Rose L.M., Roussel R., Sanna S., Scharnagl H., Scholtens S., Schumacher F.R., Schunkert H., Scott R.A., Sehmi J., Seufferlein T., Shi J., Silventoinen K., Smit J.H., Smith A.V., Smolonska J., Stanton A.V., Stirrups K., Stott D.J., Stringham H.M., Sundstrom J., Swertz M.A., Syvanen A.-C., Tayo B.O., Thorleifsson G., Tyrer J.P., Van Dijk S., Van Schoor N.M., Van Der Velde N., Van Heemst D., Van Oort F.V.A., Vermeulen S.H., Verweij N., Vonk J.M., Waite L.L., Waldenberger M., Wennauer R., Wilkens L.R., Willenborg C., Wilsgaard T., Wojczynski M.K., Wong A., Wright A.F., Zhang Q., Arveiler D., Bakker S.J.L., Beilby J., Bergman R.N., Bergmann S., Biffar R., Blangero J., Boomsma D.I., Bornstein S.R., Bovet P., Brambilla P., Brown M.J., Campbell H., Caulfield M.J., Chakravarti A., Collins R., Collins F.S., Crawford D.C., Cupples L.A., Danesh J., De Faire U., Den Ruijter H.M., Erbel R., Erdmann J., Eriksson J.G., Farrall M., Ferrannini E., Ferrieres J., Ford I., Forouhi N.G., Forrester T., Gansevoort R.T., Gejman P.V., Gieger C., Golay A., Gottesman O., Gudnason V., Gyllensten U., Haas D.W., Hall A.S., Harris T.B., Hattersley A.T., Heath A.C., Hengstenberg C., Hicks A.A., Hindorff L.A., Hingorani A.D., Hofman A., Hovingh G.K., Humphries S.E., Hunt S.C., Hypponen E., Jacobs K.B., Jarvelin M.-R., Jousilahti P., Jula A.M., Kaprio J., Kastelein J.J.P., Kayser M., Kee F., Keinanen-Kiukaanniemi S.M., Kiemeney L.A., Kooner J.S., Kooperberg C., Koskinen S., Kovacs P., Kraja A.T., Kumari M., Kuusisto J., Lakka T.A., Langenberg C., Le Marchand L., Lehtimaki T., Lupoli S., Madden P.A.F., Mannisto S., Manunta P., Marette A., Matise T.C., McKnight B., Meitinger T., Moll F.L., Montgomery G.W., Morris A.D., Morris A.P., Murray J.C., Nelis M., Ohlsson C., Oldehinkel A.J., Ong K.K., Ouwehand W.H., Pasterkamp G., Peters A., Pramstaller P.P., Price J.F., Qi L., Raitakari O.T., Rankinen T., Rao D.C., Rice T.K., Ritchie M., Rudan I., Salomaa V., Samani N.J., Saramies J., Sarzynski M.A., Schwarz P.E.H., Sebert S., Sever P., Shuldiner A.R., Sinisalo J., Steinthorsdottir V., Stolk R.P., Tardif J.-C., Tonjes A., Tremblay A., Tremoli E., Virtamo J., Vohl M.-C., Amouyel P., Asselbergs F.W., Assimes T.L., Bochud M., Boehm B.O., Boerwinkle E., Bottinger E.P., Bouchard C., Cauchi S., Chambers J.C., Chanock S.J., Cooper R.S., De Bakker P.I.W., Dedoussis G., Ferrucci L., Franks P.W., Froguel P., Groop L.C., Haiman C.A., Hamsten A., Hayes M.G., Hui J., Hunter D.J., Hveem K., Jukema J.W., Kaplan R.C., Kivimaki M., Kuh D., Laakso M., Liu Y., Martin N.G., Marz W., Melbye M., Moebus S., Munroe P.B., Njolstad I., Oostra B.A., Palmer C.N.A., Pedersen N.L., Perola M., Perusse L., Peters U., Powell J.E., Power C., Quertermous T., Rauramaa R., Reinmaa E., Ridker P.M., Rivadeneira F., Rotter J.I., Saaristo T.E., Saleheen D., Schlessinger D., Slagboom P.E., Snieder H., Spector T.D., Strauch K., Stumvoll M., Tuomilehto J., Uusitupa M., Van Der Harst P., Volzke H., Walker M., Wareham N.J., Watkins H., Wichmann H.-E., Wilson J.F., Zanen P., Deloukas P., Heid I.M., Lindgren C.M., Mohlke K.L., Speliotes E.K., Thorsteinsdottir U., Barroso I., Fox C.S., North K.E., Strachan D.P., Beckmann J.S., Berndt S.I., Boehnke M., Borecki I.B., McCarthy M.I., Metspalu A., Stefansson K., Uitterlinden A.G., Van Duijn C.M., Franke L., Willer C.J., Price A.L., Lettre G., Loos R.J.F., Weedon M.N., Ingelsson E., O'Connell J.R., Abecasis G.R., Chasman D.I., Goddard M.E., Visscher P.M., Hirschhorn J.N., and Frayling T.M.

Subjects
Netherlands Twin Register (NTR), BIO/12 - BIOCHIMICA CLINICA E BIOLOGIA MOLECOLARE CLINICA, Electronic Medical Records and Genomics (eMEMERGEGE) Consortium, Medizin, Genome-wide association study, Adult, Analysis of Variance, Body Height/genetics, European Continental Ancestry Group/genetics, Genetic Variation/genetics, Genetics, Population, Genome-Wide Association Study/methods, Humans, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide/genetics, heritability, 0302 clinical medicine, Genome-wide, SNPS, snps, Genetics & Heredity, ddc:616, Genetics, Medical And Health Sciences, 0303 health sciences, education.field_of_study, variants, GENETIC-VARIATION, Biological Sciences, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], body height, genetic-variation, Life Sciences & Biomedicine, Single Nucleotide/genetics, Human, European Continental Ancestry Group, Population, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, NO, complex traits, 03 medical and health sciences, Genetic variation, heritability, adult, height, Polymorphism, Human height, PAGEGE Consortium, education, Gene, VLAG, 030304 developmental biology, Global Nutrition, Wereldvoeding, genome-wide association study, Science & Technology, Whites, Oligonucleotide Array Sequence Analysi, MUTATIONS, COMPLEX TRAITS, ta1184, Klinisk medicin, population genetics, Genetic Variation, Heritability, ta3121, mutations, Genetic architecture, Body Height, genetic variation, MIGen Consortium, Inflammatory diseases Radboud Institute for Health Sciences [Radboudumc 5], Clinical Medicine, 030217 neurology & neurosurgery, height, LifeLines Cohort Study, Developmental Biology, Genome-Wide Association Study
Abstract

Item does not contain fulltext Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated approximately 2,000, approximately 3,700 and approximately 9,500 SNPs explained approximately 21%, approximately 24% and approximately 29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Published
2014

27. Global diversity and geography of soil fungi

Author

R. Henrik Nilsson, Luis Villarreal Ruiz, Sandra E. Abell, Helery Harend, André Ledoux Njouonkou, Sergei Põlme, Luiza Majuakim, Jordan R. Mayor, Karin Pritsch, Kentaro Hosaka, Gregory Bonito, Rein Drenkhan, Cherdchai Phosri, John Dearnaley, Tan Dang, Nourou S. Yorou, József Geml, Su S ee Lee, Xin Chen, D. Jean Lodge, Leho Tedersoo, Kessy Abarenkov, Francis Q. Brearley, Miguel Rosas, Meike Piepenbring, Alessandro Saitta, Marko Peterson, Urmas Kõljalg, Eveli Otsing, Kadri Põldmaa, Sten Anslan, Terry W. Henkel, Franz Buegger, Genevieve Gates, Karl-Henrik Larsson, Cathy Sharp, Taavi Riit, Aída M. Vasco-Palacios, Luis N. Morgado, Eduardo Nouhra, Matthew E. Smith, Ravi L. C. Wijesundera, Chris W. Dunk, Ave Suija, André De Kesel, Gwen Grelet, Kaarin Parts, Liang-Dong Guo, Tom W. May, Pham Q uang Thu, Erki Saluveer, Petr Kohout, Kadri Pärtel, W. Dunstan, Alina Greslebin, Indrek Hiiesalu, Mohammad Bahram, David A. Ratkowsky, Tedersoo, L, Bahram, M, Põlme, S, Kõljalg, U, Yorou, NS, Wijesundera, R, Villareal Ruiz, L, Vasco-Palacios, AM, Quang Thu, P, Suija, A, Smith, ME, Sharp, C, Saluveer, E, Saitta, A, Rosas, M, Riit, T, Ratkowsky, D, Pritsch, K, Põldma, K, Piepenbring, M, Phosri, C, Peterson, M, Parts, K, Pärtel, K, Otsing, E, Nouhra, E, Njouonkou, A L, Nilsson, RH, Morgado, LN, Mayor, J, May, TW, Majuakim, L, Lodge, DJ, Lee, SS, Larsson, K-H, Kohout, P, Hosaka, K, Hiiesalu, I, Henkel, TW, Harend, H, Guo, L-d, Greslebin, A, Grelet, G, Geml, J, Gates, G, Dunstan, W, Dunk, C, Drenkhan, R, Dearnaley, J, De Kesel, A, Dang, T, Chen, X, Buegger, F, Brearley, F Q, Bonito, G, Anslan, S, Abell, S, and Abarenkov, K

Subjects
media_common.quotation_subject, Biodiversity, DIVERSITY, fungi, diversity, Biology, PHYLOGEOGRAPHY, Ciencias Biológicas, METABARCODING, Ecosystem, Macroecology, media_common, Multidisciplinary, Ecology, Settore BIO/02 - Botanica Sistematica, fungi, FUNGI, Global change, Edaphic, Ecología, Species richness, Micología, Soil microbiology, human activities, CIENCIAS NATURALES Y EXACTAS, Diversity (politics)
Abstract

Fungi play integral roles in soil nutrient cycling, but the determinants of fungal diversity and biogeographic patterns of key functional groups remain poorly understood. By using pyrosequencing data from hundreds of globally distributed soil samples, we demonstrated fungal diversity that expands upon the taxonomic and molecular diversity recorded so far. Except for ectomycorrhizal symbionts, fungal functional group richness was unrelated to plant diversity and plant-to-fungus richness ratio declined exponentially towards the poles. Climatic factors, followed by edaphic and spatial variables, constituted the best predictors of fungal richness and community composition at the global scale. Fungi follow general biogeographic patterns and latitudinal diversity gradients with several exceptions. Fil: Tedersoo, Leho. University Of Tartu.; Estonia Fil: Bahram, Mohammad. University Of Tartu.; Estonia Fil: Põlme, Sergei. University Of Tartu.; Estonia Fil: Kõljalg, Urmas. University Of Tartu.; Estonia Fil: Yorou, Nourou. Université de Parakou. Faculté d′Agronomie; Benín Fil: Nouhra, Eduardo Ramon. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina Fil: Greslebin, Alina Gabriela. Universidad Nacional de la Patagonia; Argentina Fil: Kohout, Petr. University Of Tartu.; Estonia Fil: Hosaka, Kentaro. National Museum of Nature and Science. Department of Botany; Japón Fil: Hiiesalu, Indrek. University Of Tartu.; Estonia Fil: Henkel, Terry W.. Humboldt State University. Department of Biological Sciences; Estados Unidos Fil: Harend, Helery. University Of Tartu.; Estonia Fil: Guo, Liang-dong. Chinese Academy of Sciences. Institute of Microbiology. State Key Laboratory of Mycology; China Fil: Geml, József. Fil: Grelet, Gwen. Landcare Research. Ecosystems and Global Change Team; Nueva Zelanda Fil: Gates, Genevieve. Tasmanian Institute of Agriculture; Australia Fil: Dunstan, William. Murdoch University. School of Veterinary and Life Sciences; Australia Fil: Dunk, Chris. Swedish University of Agricultural Sciences. Department of Forest Ecology and Management; Suecia Fil: Drenkhan, Rein. Estonian University of Life Sciences. Institute of Forestry and Rural Engineering; Estonia Fil: Dearnaley, John. University of Southern Queensland. Faculty of Health, Engineering and Sciences; Australia Fil: De Kesel, André. Botanic Garden Meise; Bélgica Fil: Dang,Tan. Vietnamese Academy of Forest Sciences; Vietnam Fil: Chen, Xin. Zhejiag University. College of Life Sciences; China Fil: Buegger, Franz. Helmholtz Zentrum München. Institute of Soil Ecology; Alemania Fil: Brearley, Francis Q.. Manchester Metropolitan University. School of Science and the Environment; Reino Unido Fil: Bonito, Gregory. Royal Botanic Gardens Melbourne; Australia Fil: Anslan, Sten. University Of Tartu.; Estonia Fil: Abell, Sandra. James Cook University. School of Marine and Tropical Biology; Australia Fil: Abarenkov, Kessy. University Of Tartu.; Estonia

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