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Context: The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness.Objective: To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression").Design: A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996.Setting: Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers.Intervention: Maintenance treatment with either sertraline hydrochloride (n = 77) in flexible doses up to 200 mg or placebo (n = 84).Patients: A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase.Main Outcome Measure: Time to recurrence of major depression.Results: Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P = .002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P = .001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P = .005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata.Conclusions: Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients. [ABSTRACT FROM AUTHOR]

There is little evidence supporting the management of depression in schizoaffective disorder, bipolar type. Managing bipolar depression can be a daunting task for clinicians. Most bipolar patients spend 80% of their time in the depressive phase of illness. In contrast with full-blown mania, patients and family frequently fail to recognize bipolar depression, which may interfere with early diagnosis and treatment. With only a few medications approved for bipolar depression, treatment becomes very challenging. There is evidence to support that schizoaffective depression has a worse outcome than psychotic depression and nonpsychotic depression. We report a patient with schizoaffective disorder, bipolar type with severe depression who responded to an adequate level of lithium and subsequently, on a combination of lithium and quetiapine. Finally, we emphasize the importance of measurement-based care. To our knowledge, this is the first case report focusing on the management of depression in schizoaffective disorder, bipolar type. [ABSTRACT FROM AUTHOR]

Abstract Background Establishing correct neuronal circuitry is crucial to proper function of the vertebrate nervous system. The abundance of chondroitin sulfate (CS) proteoglycans in embryonic neural environments suggests that matrix proteoglycans regulate axonal projections when fiber tracts have not yet formed. Among the early-born neurons, the vestibular nucleus (VN) neurons initiate commissural projections soon after generation at E12.5 and reach the contralateral target by E15.5 in the rat hindbrain. We therefore exploited 24-hour cultures (1 day in vitro (DIV)) of the rat embryos and chondroitinase ABC treatment of the hindbrain matrix to reveal the role of CS moieties in axonal initiation and projection in the early hindbrain. Results DiI tracing from the VN at E12.5(+1 DIV) showed contralaterally projecting fibers assuming fascicles that hardly reached the midline in the controls. In the enzyme-treated embryos, the majority of fibers were unfasciculated as they crossed the midline at 90°. At E13.5(+1 DIV), the commissural projections formed fascicles and crossed the midline in the controls. Enzyme treatment apparently did not affect the pioneer axons that had advanced as thick fascicles normal to the midline and beyond, towards the contralateral VN. Later projections, however, traversed the enzyme-treated matrix as unfasciculated fibers, deviated from the normal course crossing the midline at various angles and extending beyond the contralateral VN. This suggests that CSs also limit the course of the later projections, which otherwise would be attracted to alternative targets. Conclusions CS moieties in the early hindbrain therefore control the course and fasciculation of axonal projections and the timing of axonal arrival at the target.

Abstract Background Intermittent measurement of cardiac output may be performed using a lithium dilution technique (LiDCO). This can then be used to calibrate a pulse power algorithm of the arterial waveform which provides a continuous estimate of this variable. The purpose of this study was to examine the duration of accuracy of the pulse power algorithm in critically ill patients with respect to time when compared to measurements of cardiac output by an independent technique. Methods Pulse power analysis was performed on critically ill patients using a proprietary commercial monitor (PulseCO). All measurements were made using an in-dwelling radial artery line and according to manufacturers instructions. Intermittent measurements of cardiac output were made with LiDCO in order to validate the pulse power measurements. These were made at baseline and then following 1, 2, 4 and 8 hours. The LiDCO measurement was considered the reference for comparison in this study. The two methods of measuring cardiac output were then compared by linear regression and a Bland Altman analysis. An error rate for the limits of agreement (LOA) between the two techniques of less than 30% was defined as being acceptable for this study. Results 14 critically ill medical and surgical patients were enrolled over a three month period. At baseline patients showed a wide range of cardiac output (median 7.5 L/min, IQR 5.1 -9.0 L/min). The bias and limits of agreement between the two techniques was deemed acceptable for the first four hours of the study with percentage errors being 29%, 22%, and 285 respectively. The percentage error at eight hours following calibration increased to 36%. The ability of the PulseCo to detect changes in cardiac output was assessed with a similar analysis. The PulseCO tracked the changes in cardiac output with adequate accuracy for the first four hours with percentage errors being 20%, 24% and 25%. However at eight hours the error had increased to 43%. Conclusion The agreement between lithium dilution cardiac output and the pulse power algorithm in the PulseCO monitor remains acceptable for up to four hours in critically ill patients.

Abstract Background Studies suggest that Goal Directed Therapy (GDT) results in improved outcome following major surgery. However, there is concern that pre-emptive use of inotropic therapy may lead to an increased incidence of myocardial ischaemia and infarction. Methods Post hoc analysis of data collected prospectively during a randomised controlled trial of the effects of post-operative GDT in high-risk general surgical patients. Serum troponin T concentrations were measured at baseline and on day 1 and day 2 following surgery. Continuous ECG monitoring was performed during the eight hour intervention period. Patients were followed up for predefined cardiac complications. A univariate analysis was performed to identify any associations between potential risk factors for myocardial injury and elevated troponin T concentrations. Results GDT was associated with fewer complications, and a reduced duration of hospital stay. Troponin T concentrations above 0.01 μg l-1 were identified in eight patients in the GDT group and six in the control group. Values increased above 0.05 μg l-1 in four patients in the GDT group and two patients in the control group. There were no overall differences in the incidence of elevated troponin T concentrations. The incidence of cardiovascular complications was also similar. None of the patients, in whom troponin T concentrations were elevated, developed ECG changes indicating myocardial ischaemia during the intervention period. The only factor to be associated with elevated troponin T concentrations following surgery was end-stage renal failure. Conclusion The use of post-operative GDT does not result in an increased incidence of myocardial injury.

Abstract Background Lentiviral vectors have shown immense promise as vehicles for gene delivery to non-dividing cells particularly to cells of the central nervous system (CNS). Improvements in the biosafety of viral vectors are paramount as lentiviral vectors move into human clinical trials. This study investigates the packaging relationship between gene transfer (vector) and Gag-Pol expression constructs of HIV-1, HIV-2 and SIV. Cross-packaged vectors expressing GFP were assessed for RNA packaging, viral vector titre and their ability to transduce rat primary glial cell cultures and human neural stem cells. Results HIV-1 Gag-Pol demonstrated the ability to cross package both HIV-2 and SIV gene transfer vectors. However both HIV-2 and SIV Gag-Pol showed a reduced ability to package HIV-1 vector RNA with no significant gene transfer to target cells. An unexpected packaging relationship was found to exist between HIV-2 and SIV with SIV Gag-Pol able to package HIV-2 vector RNA and transduce dividing SV2T cells and CNS cell cultures with an efficiency equivalent to the homologous HIV-1 vector however HIV-2 was unable to deliver SIV based vectors. Conclusion This new non-reciprocal cross packaging relationship between SIV and HIV-2 provides a novel way of significantly increasing bio-safety with a reduced sequence homology between the HIV-2 gene transfer vector and the SIV Gag-Pol construct thus ensuring that vector RNA packaging is unidirectional.

Heavy-ion beam, a type of ionizing radiation, has been applied to plant breeding as a powerful mutagen and is a promising tool to induce large deletions and chromosomal rearrangements. The effectiveness of heavy-ion irradiation can be explained by linear energy transfer (LET; keV µm -1 ). Heavy-ion beams with different LET values induce different types and sizes of mutations. It has been suggested that deletion size increases with increasing LET value, and complex chromosomal rearrangements are induced in higher LET radiations. In this study, we mapped heavy-ion beam-induced deletions detected in Arabidopsis mutants to its genome. We revealed that deletion sizes were similar between different LETs (100 to 290 keV μm -1 ), that their upper limit was affected by the distribution of essential genes, and that the detected chromosomal rearrangements avoid disrupting the essential genes. We also focused on tandemly arrayed genes (TAGs), where two or more homologous genes are adjacent to one another in the genome. Our results suggested that 100 keV µm -1 of LET is enough to disrupt TAGs and that the distribution of essential genes strongly affects the heritability of mutations overlapping them. Our results provide a genomic view of large deletion inductions in the Arabidopsis genome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ishii, Kazama, Hirano, Fawcett, Sato, Hirai, Sakai, Shirakawa, Ohbu and Abe.)

Background: Plant genome information is fundamental to plant research and development. Along with the increase in the number of published plant genomes, there is a need for an efficient system to retrieve various kinds of genome-related information from many plant species across plant kingdoms. Various plant databases have been developed, but no public database covers both genomic and genetic resources over a wide range of plant species., Main Body: We have developed a plant genome portal site, Plant GARDEN (Genome And Resource Database Entry: https://plantgarden.jp/en/index ), to provide diverse information related to plant genomics and genetics in divergent plant species. Elasticsearch is used as a search engine, and cross-keyword search across species is available. Web-based user interfaces (WUI) for PCs and tablet computers were independently developed to make data searches more convenient. Several types of data are stored in Plant GARDEN: reference genomes, gene sequences, PCR-based DNA markers, trait-linked DNA markers identified in genetic studies, SNPs, and in/dels on publicly available sequence read archives (SRAs). The data registered in Plant GARDEN as of March 2023 included 304 assembled genome sequences, 11,331,614 gene sequences, 419,132 DNA markers, 8,225 QTLs, and 5,934 SNP lists (gvcf files). In addition, we have re-annotated all the genes registered in Plant GARDEN by using a functional annotation tool, Hayai-Annotation, to compare the orthologous relationships among genes., Conclusion: The aim of Plant GARDEN is to provide plant genome information for use in the fields of plant science as well as for plant-based industries, education, and other relevant areas. Therefore, we have designed a WUI that allows a diverse range of users to access such information in an easy-to-understand manner. Plant GARDEN will eventually include a wide range of plant species for which genome sequences are assembled, and thus the number of plant species in the database will continue to expand. We anticipate that Plant GARDEN will promote the understanding of genomes and gene diversity by facilitating comparisons of the registered sequences., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Common buckwheat, Fagopyrum esculentum, is an orphan crop domesticated in southwest China that exhibits heterostylous self-incompatibility. Here we present chromosome-scale assemblies of a self-compatible F. esculentum accession and a self-compatible wild relative, Fagopyrum homotropicum, together with the resequencing of 104 wild and cultivated F. esculentum accessions. Using these genomic data, we report the roles of transposable elements and whole-genome duplications in the evolution of Fagopyrum. In addition, we show that (1) the breakdown of heterostyly occurs through the disruption of a hemizygous gene jointly regulating the style length and female compatibility and (2) southeast Tibet was involved in common buckwheat domestication. Moreover, we obtained mutants conferring the waxy phenotype for the first time in buckwheat. These findings demonstrate the utility of our F. esculentum assembly as a reference genome and promise to accelerate buckwheat research and breeding., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Hyperdiverse tropical rainforests, such as the aseasonal forests in Southeast Asia, are supported by high annual rainfall. Its canopy is dominated by the species-rich tree family of Dipterocarpaceae (Asian dipterocarps), which has both ecological (e.g., supports flora and fauna) and economical (e.g., timber production) importance. Recent ecological studies suggested that rare irregular drought events may be an environmental stress and signal for the tropical trees. We assembled the genome of a widespread but near threatened dipterocarp, Shorea leprosula, and analyzed the transcriptome sequences of ten dipterocarp species representing seven genera. Comparative genomic and molecular dating analyses suggested a whole-genome duplication close to the Cretaceous-Paleogene extinction event followed by the diversification of major dipterocarp lineages (i.e. Dipterocarpoideae). Interestingly, the retained duplicated genes were enriched for genes upregulated by no-irrigation treatment. These findings provide molecular support for the relevance of drought for tropical trees despite the lack of an annual dry season., (© 2021. The Author(s).)

In this paper, the scattering from a fluid-filled (infinite length) cylinder is considered. This cylinder, C, has a different interior sound speed and density than the surrounding water. Within the cylinder's interior, there are a number of smaller cylinders, inclusions, with yet other sound speeds and densities. The mean coherent field scattered from C is computed using Monte Carlo simulations with respect to the random realizations of the inclusion positions and compared to the results computed using an effective sound speed for C. An original formula for the effective sound speed is derived by equating the reflection coefficient for C (without inclusions) to the expected coherent scattered field from C with inclusions, assuming a single-scattering approximation. A single realization of inclusions is also considered with the backscattered spectra averaged azimuthally over the angle of the source/receiver pair. This result is then compared to the coherent fields predicted by the effective medium theory. This is performed for both spectra and the computed time series.

Many studies have reported that advancing age in broodmares has a negative impact on the reproductive performance of horses. However, although the ages at first and last mating vary among broodmares, it is unknown how this variation affects the correlation between age and reproductive performance in mares. Here, in order to examine the effects of the ages at first and last mating, we analyzed all recorded mating events for Thoroughbreds in Japan from 1997 to 2017. We found that the live foal birth rate of mares with a younger age at first mating indeed declined at an earlier age than those with an older age at first mating and that the number of years since the first mating also contributes to the decline in the birth rate. We also found that the live foal birth rate and mean earnings of the produced foals are much higher for mares with an older age at last mating compared with mares with a younger age at last mating. Our results should aid breeders in assessing the value of broodmares and designing breeding strategies., (©2021 The Japanese Society of Equine Science.)

Background: The complexity of health care data and workflow presents challenges to the study of usability in electronic health records (EHRs). Display fragmentation refers to the distribution of relevant data across different screens or otherwise far apart, requiring complex navigation for the user's workflow. Task and information fragmentation also contribute to cognitive burden., Objective: This study aims to define and analyze some of the main sources of fragmentation in EHR user interfaces (UIs); discuss relevant theoretical, historical, and practical considerations; and use granular microanalytic methods and visualization techniques to help us understand the nature of fragmentation and opportunities for EHR optimization or redesign., Methods: Sunburst visualizations capture the EHR navigation structure, showing levels and sublevels of the navigation tree, allowing calculation of a new measure, the Display Fragmentation Index. Time belt visualizations present the sequences of subtasks and allow calculation of proportion per instance, a measure that quantifies task fragmentation. These measures can be used separately or in conjunction to compare EHRs as well as tasks and subtasks in workflows and identify opportunities for reductions in steps and fragmentation. We present an example use of the methods for comparison of 2 different EHR interfaces (commercial and composable) in which subjects apprehend the same patient case., Results: Screen transitions were substantially reduced for the composable interface (from 43 to 14), whereas clicks (including scrolling) remained similar., Conclusions: These methods can aid in our understanding of UI needs under complex conditions and tasks to optimize EHR workflows and redesign., (©Yalini Senathirajah, David R Kaufman, Kenrick D Cato, Elizabeth M Borycki, Jaime Allen Fawcett, Andre W Kushniruk. Originally published in JMIR Human Factors (http://humanfactors.jmir.org), 21.10.2020.)

The domestication process of plants and animals typically involves intense inbreeding and directional selection for various traits. Here, we genotyped 370 Japanese Thoroughbred horses using the recently developed 670k SNP array and performed various genome-wide analysis also using genotype data of other horse breeds. We identified a number of regions showing interesting patterns of polymorphisms. For instance, the region containing the MC1R locus associated with chestnut coat color may have been targeted by selection for a different mutation much earlier on than the recent selection for chestnut color. We also identified regions that show signatures of selection specific to Thoroughbreds. In addition, we found that intense inbreeding early in the history of the Thoroughbred breed and also before the formation of the breed has a significant impact on the genomic architecture of modern Thoroughbreds. Our study demonstrates that the horse 670k array can be utilized to gain important insight into the domestication process of horses and to understand the genetic basis of the phenotypic diversity in horses., Competing Interests: FS is an employee of Hidaka Training and Research Center, Japan Racing Association; TT is an employee of Genetic Analysis Department, Laboratory of Racing Chemistry. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors declare that no competing interests exist.

Nature has found many ways to utilize transposable elements (TEs) throughout evolution. Many molecular and cellular processes depend on DNA-binding proteins recognizing hundreds or thousands of similar DNA motifs dispersed throughout the genome that are often provided by TEs. It has been suggested that TEs play an important role in the evolution of such systems, in particular, the rewiring of gene regulatory networks. One mechanism that can further enhance the rewiring of regulatory networks is nonallelic gene conversion between copies of TEs. Here, we will first review evidence for nonallelic gene conversion in TEs. Then, we will illustrate the benefits nonallelic gene conversion provides in rewiring regulatory networks. For instance, nonallelic gene conversion between TE copies offers an alternative mechanism to spread beneficial mutations that improve the network, it allows multiple mutations to be combined and transferred together, and it allows natural selection to work efficiently in spreading beneficial mutations and removing disadvantageous mutations. Future studies examining the role of nonallelic gene conversion in the evolution of TEs should help us to better understand how TEs have contributed to evolution., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

The current study evaluates changes in access as a result of the MyVA Access program-a system-wide effort to improve patient access in the Veterans Health Administration. Data on 20 different measures were collected, and changes were analyzed using t tests and Chow tests. Additionally, organizational health-how able a system is to create health care practice change-was evaluated for a sample of medical centers (n = 36) via phone interviews and surveys conducted with facility staff and technical assistance providers. An organizational health variable was created and correlated with the access measures. Results showed that, nationally, average wait times for urgent consults, new patient wait times for mental health and specialty care, and slot utilization for primary and specialty care patients improved. Patient satisfaction measures also improved, and patient complaints decreased. Better organizational health was associated with improvements in patient access.

Objectives: To present preliminary research using geographic information system (GIS) mapping as a tool that can be integrated into pharmacy practice to increase access to and utilization of pharmacy-based interventions, including the distribution of naloxone., Methods: Overdose death data was collected from medical examiner reports in an online database, and pharmacies carrying and distributing naloxone were determined by ZIP Code Tabulation Areas (ZCTAs) in Allegheny County, PA. The distribution of overdose death rates was analyzed in relation to naloxone-carrying pharmacies and all licensed pharmacies in the county with the use of GIS mapping., Results: Eighty-seven ZCTAs were included. Of 322 active licensed pharmacies, 28 pharmacies were confirmed to carry and distribute naloxone. The number of overdose deaths in ZCTAs that have naloxone-distributing pharmacies was significantly higher than the average number of deaths in all ZCTAs in Allegheny County: 7.38 deaths versus 4.84 deaths, respectively (P = 0.021)., Conclusion: This report illustrates the value of GIS mapping in monitoring the impact of overdose death prevention efforts, including the availability of naloxone in pharmacies. Analysis of these data over the next 5 years will provide valuable information on the potential impact of naloxone-distributing pharmacies on overdose rates, which, in turn, will inform pharmacists and pharmacy organizations on the value of carrying naloxone in pharmacies and inform local communities of its availability., (Copyright © 2017. Published by Elsevier Inc.)

Horses have substantial variation in coat color, and the genetic loci responsible for the coat color variations have been well investigated. It has been believed that some color variations should follow a single-locus Mendelian law. Examples include the Gray locus that causes the gray phenotype and the Extension locus that specifies the chestnut phenotype. We reevaluated the roles of the Gray and Extension loci by using a large number of mating records of Thoroughbred racing horses. We showed that the data indeed fits the Mendelian law extremely well for the two loci. Furthermore, we demonstrated that the Extension and Agouti loci might have an additional role in determining the degree of melanin that should distinguish bay, dark bay, and brown.

Many transposable element (TE) families show surprisingly high levels of similarity between distantly related species. This high similarity, coupled with a "patchy" phylogenetic distribution, has often been attributed to frequent horizontal transfers of TEs between species, even though the mechanistic basis tends to be speculative. Here, we studied the evolution of the Au SINE (Short INterspersed Element) family, in which high similarity between distantly related plant species has been reported. We were able to identify several copies present in orthologous regions of various species, including species that diverged ∼90 Ma, thereby confirming the presence of Au SINE at multiple evolutionary time points. We also found that the Au SINE has been degenerating and is en route to disappearing in many species, indicating that the loss of Au SINE is common. Our results suggest that the evolution of the Au SINE can be readily explained by a scenario of vertical transmission without having to invoke hypothetical scenarios of rampant horizontal transfers. The Au SINE was likely present in the common ancestor of all angiosperms and was retained in some lineages while lost from others. The high level of conservation is probably because the sequences were important for ensuring their transpositional activity. This model of TE evolution should provide a basic framework for understanding the evolution of TEs in general., (© The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

RADMAP, an open source program, allows for rapid analysis and visualization of the earliest stages of reactions between any molecule and a monoatomic probe (i.e., H*, H(+), H(-), Br*, or any other monoatomic species) using ab initio methods. This program creates non-planar potential energy surfaces of the initial interaction between a molecule of interest and the monoatomic probe. These surfaces can be used to both predict the site of addition as well as provide a qualitative estimate for the relative proportion of the formation of adducts; therefore, it gives insight into both the reactivity and the kinetic stability of a molecule. The program presents a way to quickly predict the number of signals anticipated in transverse field muon spin resonance spectra as well as their relative intensities., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The fission yeast Schizosaccharomyces pombe has been widely used as a model eukaryote to study a diverse range of biological processes. However, population genetic studies of this species have been limited to date, and we know very little about the evolutionary processes and selective pressures that are shaping its genome. Here, we sequenced the genomes of 32 worldwide S. pombe strains and examined the pattern of polymorphisms across their genomes. In addition to introns and untranslated regions (UTRs), intergenic regions also exhibited lower levels of nucleotide diversity than synonymous sites, suggesting that a considerable amount of noncoding DNA is under selective constraint and thus likely to be functional. A number of genomic regions showed a reduction of nucleotide diversity probably caused by selective sweeps. We also identified a region close to the end of chromosome 3 where an extremely high level of divergence was observed between 5 of the 32 strains and the remain 27, possibly due to introgression, strong positive selection, or that region being responsible for reproductive isolation. Our study should serve as an important starting point in using a population genomics approach to further elucidate the biology of this important model organism.

In this paper, a Boundary Integral Equation Method (BIEM) is described for the computation of scattering from a finite, rigid, cylinder near a pressure release interface. The cylinder lies parallel or tilted with respect to the interface plane so that the azimuthal symmetry of the problem is destroyed. The scattering solution is first described in terms of an azimuthally symmetric free space solution. The multiple interactions of the scattered field with the interface are accounted for by an azimuthal-conversion matrix. In Sec. III, the method of this paper is benchmarked using wavefield superposition for a sphere near a pressure-release surface. Computed scattered spectra are shown for a finite cylinder, parallel and tilted with respect to the interface, and for a variety of source/receiver geometries. The differences resulting from not including multiple target/interface interactions (single scatter solution) and from including all interactions are presented. The problem of irregular frequencies for the single-scatter and the fully coupled BIEM are discussed and numerically examined.

Meiotic chromosome architecture called 'axis-loop structures' and histone modifications have been shown to regulate the Spo11-dependent formation of DNA double-strand breaks (DSBs) that trigger meiotic recombination. Using genome-wide chromatin immunoprecipitation (ChIP) analyses followed by deep sequencing, we compared the genome-wide distribution of the axis protein Rec8 (the kleisin subunit of meiotic cohesin) with that of oligomeric DNA covalently bound to Spo11, indicative of DSB sites. The frequency of DSB sites is overall constant between Rec8 binding sites. However, DSB cold spots are observed in regions spanning ±0.8 kb around Rec8 binding sites. The axis-associated cold spots are not due to the exclusion of Spo11 localization from the axis, because ChIP experiments showed that substantial Spo11 persists at Rec8 binding sites during DSB formation. Spo11 fused with Gal4 DNA binding domain (Gal4BD-Spo11) tethered in close proximity (≤0.8 kb) to Rec8 binding sites hardly forms meiotic DSBs, in contrast with other regions. In addition, H3K4 trimethylation (H3K4me3) remarkably decreases at Rec8 binding sites. These results suggest that reduced histone H3K4me3 in combination with inactivation of Spo11 activity on the axis discourages DSB hot spot formation., (© 2014 The Authors Genes to Cells © 2014 by the Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.)

Patients with post-traumatic stress disorder (PTSD) are frequently symptomatic despite being on medications currently approved by the US Food and Drug Administration for PTSD. There is evidence to support the notion that prazosin is effective for PTSD nightmares. However, PTSD-related nightmares often do not resolve completely on a low dose of prazosin. The capacity of prazosin to treat daytime symptoms of PTSD which are distressing to patients has not been well studied. Clinicians are reluctant to increase the dose of prazosin due to side effect concerns. To date, the highest reported dose of prazosin used for PTSD is 16 mg daily. We illustrate two case reports using high-dose (up to 30 and 45 mg) prazosin for PTSD with comorbid treatment-resistant mood disorders. We report that high-dose prazosin was safe, tolerable and effective for PTSD in adults. To our knowledge, this is the first case series to highlight the importance of using high-dose prazosin for the treatment of PTSD. In patients with partial response to currently available medications for PTSD, greater utilization of high-dose prazosin for the management of PTSD may lead to better outcomes.

Genes involved in the transition from wild to cultivated crop species should be of great agronomic importance. Population genomic approaches utilizing genome resequencing data have been recently applied for this purpose, although it only reports a large list of candidate genes with no biological information. Here, by resequencing more than 30 genomes altogether of wild rice Oryza rufipogon and cultivated rice O. sativa, we identified a number of regions with clear footprints of selection during the domestication process. We then focused on identifying candidate domestication genes in these regions by utilizing the wealth of QTL information in rice. We were able to identify a number of interesting candidates such as transcription factors that should control key domestication traits such as shattering, awn length, and seed dormancy. Other candidates include those that might have been related to the improvement of grain quality and those that might have been involved in the local adaptation to dry conditions and colder environments. Our study shows that population genomic approaches and QTL mapping information can be used together to identify genes that might be of agronomic importance.

Hotspots of non-allelic homologous recombination (NAHR) have a crucial role in creating genetic diversity and are also associated with dozens of genomic disorders. Recent studies suggest that many human NAHR hotspots have been preserved throughout the evolution of primates. NAHR hotspots are likely to remain active as long as the segmental duplications (SDs) promoting NAHR retain sufficient similarity. Here, we propose an evolutionary model of SDs that incorporates the effect of gene conversion and compare it with a null model that assumes SDs evolve independently without gene conversion. The gene conversion model predicts a much longer lifespan of NAHR hotspots compared with the null model. We show that the literature on copy number variants (CNVs) and genomic disorders, and also the results of additional analysis of CNVs, are all more consistent with the gene conversion model., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The broadband scattering characteristics of a target may be used to distinguish its echoes from those of clutter. In a shallow water situation, the echo from the target will consist of a sequence of pulses corresponding to the various coherent combinations of incident and backscattered multipath arrivals. Thus, the interference effects of the waveguide propagation can have a significant effect upon the received echo and thus also affect the classification of the target from the echo. In addition, the target may be moving, in which case the received echo is also Doppler-shifted. The purpose of this paper is to investigate the simultaneous determination of a spherical target's position (range and depth) within a waveguide, its radial speed, its radius, its shell thickness, and the elastic parameters of the shell. It will be shown that many of these parameters can be accurately estimated from a single wideband echo, even in the presence of significant noise. The marginal probability distributions of the parameter values will also be investigated. It will be seen that the positional and speed parameters of the sphere can be determined to high precision. The other parameters are determined with varying degrees of precision.

The number of introns varies considerably among different organisms. This can be explained by the differences in the rates of intron gain and loss. Two factors that are likely to influence these rates are selection for or against introns and the mutation rate that generates the novel intron or the intronless copy. Although it has been speculated that stronger selection for a compact genome might result in a higher rate of intron loss and a lower rate of intron gain, clear evidence is lacking, and the role of selection in determining these rates has not been established. Here, we studied the gain and loss of introns in the two closely related species Arabidopsis thaliana and A. lyrata as it was recently shown that A. thaliana has been undergoing a faster genome reduction driven by selection. We found that A. thaliana has lost six times more introns than A. lyrata since the divergence of the two species but gained very few introns. We suggest that stronger selection for genome reduction probably resulted in the much higher intron loss rate in A. thaliana, although further analysis is required as we could not find evidence that the loss rate increased in A. thaliana as opposed to having decreased in A. lyrata compared with the rate in the common ancestor. We also examined the pattern of the intron gains and losses to better understand the mechanisms by which they occur. Microsimilarity was detected between the splice sites of several gained and lost introns, suggesting that nonhomologous end joining repair of double-strand breaks might be a common pathway not only for intron gain but also for intron loss.

The spider mite Tetranychus urticae is a cosmopolitan agricultural pest with an extensive host plant range and an extreme record of pesticide resistance. Here we present the completely sequenced and annotated spider mite genome, representing the first complete chelicerate genome. At 90 megabases T. urticae has the smallest sequenced arthropod genome. Compared with other arthropods, the spider mite genome shows unique changes in the hormonal environment and organization of the Hox complex, and also reveals evolutionary innovation of silk production. We find strong signatures of polyphagy and detoxification in gene families associated with feeding on different hosts and in new gene families acquired by lateral gene transfer. Deep transcriptome analysis of mites feeding on different plants shows how this pest responds to a changing host environment. The T. urticae genome thus offers new insights into arthropod evolution and plant-herbivore interactions, and provides unique opportunities for developing novel plant protection strategies., (©2011 Macmillan Publishers Limited. All rights reserved)

An exact integral equation approach to solving scattering from a finite section of roughness in an otherwise infinitely flat surface was described in DeSanto and Martin [J. Acoust. Soc. Am. 102, 67-77]. In this letter, the details of a numerical implementation of this approach are presented for a rough pressure release surface. An example comparing the results from this method to those from a standard, truncated integral approach is given.

We report the 207-Mb genome sequence of the North American Arabidopsis lyrata strain MN47 based on 8.3× dideoxy sequence coverage. We predict 32,670 genes in this outcrossing species compared to the 27,025 genes in the selfing species Arabidopsis thaliana. The much smaller 125-Mb genome of A. thaliana, which diverged from A. lyrata 10 million years ago, likely constitutes the derived state for the family. We found evidence for DNA loss from large-scale rearrangements, but most of the difference in genome size can be attributed to hundreds of thousands of small deletions, mostly in noncoding DNA and transposons. Analysis of deletions and insertions still segregating in A. thaliana indicates that the process of DNA loss is ongoing, suggesting pervasive selection for a smaller genome. The high-quality reference genome sequence for A. lyrata will be an important resource for functional, evolutionary and ecological studies in the genus Arabidopsis.

Gene conversion is one of the major mutational mechanisms involved in the DNA sequence evolution of duplicated genes. It contributes to create unique patters of DNA polymorphism within species and divergence between species. A typical pattern is so-called concerted evolution, in which the divergence between duplicates is maintained low for a long time because of frequent exchanges of DNA fragments. In addition, gene conversion affects the DNA evolution of duplicates in various ways especially when selection operates. Here, we review theoretical models to understand the evolution of duplicates in both neutral and non-neutral cases. We also explain how these theories contribute to interpreting real polymorphism and divergence data by using some intriguing examples.

Previous literature reporting gait parameters in the MS population has largely focused on preferred walking speed without the use of an assistive device. However, these data may not fully represent daily activity, as individuals with MS vary their speed or use a cane when walking. In this exploratory study, 11 MS participants and 13 controls walked at both maximal and preferred speed for a distance of 25-feet. Participants with MS that used a cane daily (n=6) were asked to complete additional trials with their cane. When walking unassisted at both speeds, MS participants displayed significantly reduced velocity, cadence, stride length, step length ratio, single support and swing time, as well as increased double support and stance time compared to controls. Cane use resulted in significantly higher velocities when walking at maximal speeds, and showed significantly improved variability, gait asymmetry, and bilateral coordination at preferred walking speed. In conclusion, the use of a cane may significantly improve gait for individuals with MS. Furthermore, gait parameters should be measured at both maximal and preferred speeds, with and without a cane, as its use may mask underlying gait impairment., (Published by Elsevier B.V.)

We report a high-quality draft genome sequence of the domesticated apple (Malus × domestica). We show that a relatively recent (>50 million years ago) genome-wide duplication (GWD) has resulted in the transition from nine ancestral chromosomes to 17 chromosomes in the Pyreae. Traces of older GWDs partly support the monophyly of the ancestral paleohexaploidy of eudicots. Phylogenetic reconstruction of Pyreae and the genus Malus, relative to major Rosaceae taxa, identified the progenitor of the cultivated apple as M. sieversii. Expansion of gene families reported to be involved in fruit development may explain formation of the pome, a Pyreae-specific false fruit that develops by proliferation of the basal part of the sepals, the receptacle. In apple, a subclade of MADS-box genes, normally involved in flower and fruit development, is expanded to include 15 members, as are other gene families involved in Rosaceae-specific metabolism, such as transport and assimilation of sorbitol.

Flowering plants contain many genes, most of which were created during the past 200 or so million years through small- and large-scale duplications. Paleo-polyploidy events, in particular, have been the subject of much recent research. There is a growing consensus that one or more genome doubling or merging events occurred early during the evolution of the flowering plants, and that many lineages have since undergone additional, independent and more recent duplication events. Here, we review the difficulties in determining the number of genome duplications and discuss how the completion of some additional genome sequences of species occupying key phylogenetic positions has led to a better understanding of the timing of certain duplication events. This is important if we want to demonstrate the significance of genome duplications for the evolution and radiation of (different groups of) flowering plants.

The US Food and Drug Administration warnings that psychotropic medications may increase the risk of suicidality have generated concern about prescribing these agents to patients with psychiatric disorders, many of whom are already at increased risk for suicide. To effectively prevent suicidal behaviors and suicide in clinical practice, clinicians must understand the dangers and benefits associated with psychotropic medications. In addition, they must learn how to identify and manage suicidal risk during treatment., (Copyright 2009 Physicians Postgraduate Press, Inc.)

Most flowering plants have been shown to be ancient polyploids that have undergone one or more whole genome duplications early in their evolution. Furthermore, many different plant lineages seem to have experienced an additional, more recent genome duplication. Starting from paralogous genes lying in duplicated segments or identified in large expressed sequence tag collections, we dated these youngest duplication events through penalized likelihood phylogenetic tree inference. We show that a majority of these independent genome duplications are clustered in time and seem to coincide with the Cretaceous-Tertiary (KT) boundary. The KT extinction event is the most recent mass extinction caused by one or more catastrophic events such as a massive asteroid impact and/or increased volcanic activity. These events are believed to have generated global wildfires and dust clouds that cut off sunlight during long periods of time resulting in the extinction of approximately 60% of plant species, as well as a majority of animals, including dinosaurs. Recent studies suggest that polyploid species can have a higher adaptability and increased tolerance to different environmental conditions. We propose that polyploidization may have contributed to the survival and propagation of several plant lineages during or following the KT extinction event. Due to advantages such as altered gene expression leading to hybrid vigor and an increased set of genes and alleles available for selection, polyploid plants might have been better able to adapt to the drastically changed environment 65 million years ago.

In this paper a simplified approach is described for the computation of scattering from finite length rough surfaces. In an earlier paper [Fawcett, J. Acoust. Soc. 118, 1348-1357 (2005)], it was described how to solve such problems by considering a scattering chamber and using the method of wavefield superposition to satisfy the various boundary and continuity conditions. In this paper, a form of the field in the interior of the scattering chamber is assumed and the solution to the scattering problem is reduced to solving a system of equations just along the rough surface. The solution to this system of equations can then be used to compute the scattered or total fields anywhere in the half-space. The results of this approach are compared to those obtained by other methods.

We report the draft genome sequence of the model moss Physcomitrella patens and compare its features with those of flowering plants, from which it is separated by more than 400 million years, and unicellular aquatic algae. This comparison reveals genomic changes concomitant with the evolutionary movement to land, including a general increase in gene family complexity; loss of genes associated with aquatic environments (e.g., flagellar arms); acquisition of genes for tolerating terrestrial stresses (e.g., variation in temperature and water availability); and the development of the auxin and abscisic acid signaling pathways for coordinating multicellular growth and dehydration response. The Physcomitrella genome provides a resource for phylogenetic inferences about gene function and for experimental analysis of plant processes through this plant's unique facility for reverse genetics.

Background: Worldwide, grapes and their derived products have a large market. The cultivated grape species Vitis vinifera has potential to become a model for fruit trees genetics. Like many plant species, it is highly heterozygous, which is an additional challenge to modern whole genome shotgun sequencing. In this paper a high quality draft genome sequence of a cultivated clone of V. vinifera Pinot Noir is presented., Principal Findings: We estimate the genome size of V. vinifera to be 504.6 Mb. Genomic sequences corresponding to 477.1 Mb were assembled in 2,093 metacontigs and 435.1 Mb were anchored to the 19 linkage groups (LGs). The number of predicted genes is 29,585, of which 96.1% were assigned to LGs. This assembly of the grape genome provides candidate genes implicated in traits relevant to grapevine cultivation, such as those influencing wine quality, via secondary metabolites, and those connected with the extreme susceptibility of grape to pathogens. Single nucleotide polymorphism (SNP) distribution was consistent with a diffuse haplotype structure across the genome. Of around 2,000,000 SNPs, 1,751,176 were mapped to chromosomes and one or more of them were identified in 86.7% of anchored genes. The relative age of grape duplicated genes was estimated and this made possible to reveal a relatively recent Vitis-specific large scale duplication event concerning at least 10 chromosomes (duplication not reported before)., Conclusions: Sanger shotgun sequencing and highly efficient sequencing by synthesis (SBS), together with dedicated assembly programs, resolved a complex heterozygous genome. A consensus sequence of the genome and a set of mapped marker loci were generated. Homologous chromosomes of Pinot Noir differ by 11.2% of their DNA (hemizygous DNA plus chromosomal gaps). SNP markers are offered as a tool with the potential of introducing a new era in the molecular breeding of grape.

In this paper, an approach for modeling the scattering from azimuthally symmetric bathymetric features is described. These features are useful models for small mounds and indentations on the seafloor at high frequencies and seamounts, shoals, and basins at low frequencies. A bathymetric feature can be considered as a compact closed region, with the same sound speed and density as one of the surrounding media. Using this approach, a number of numerical methods appropriate for a partially buried target or facet problem can be applied. This paper considers the use of wavefield superposition and because of the azimuthal symmetry, the three-dimensional solution to the scattering problem can be expressed as a Fourier sum of solutions to a set of two-dimensional scattering problems. In the case where the surrounding two half spaces have only a density contrast, a semianalytic coupled mode solution is derived. This provides a benchmark solution to scattering from a class of penetrable hemispherical bosses or indentations. The details and problems of the numerical implementation of the wavefield superposition method are described. Example computations using the method for a simple scattering feature on a seabed are presented for a wide band of frequencies.

Background: Analyses of complete genomes and large collections of gene transcripts have shown that most, if not all seed plants have undergone one or more genome duplications in their evolutionary past., Results: In this study, based on a large collection of EST sequences, we provide evidence that the haploid moss Physcomitrella patens is a paleopolyploid as well. Based on the construction of linearized phylogenetic trees we infer the genome duplication to have occurred between 30 and 60 million years ago. Gene Ontology and pathway association of the duplicated genes in P. patens reveal different biases of gene retention compared with seed plants., Conclusion: Metabolic genes seem to have been retained in excess following the genome duplication in P. patens. This might, at least partly, explain the versatility of metabolism, as described for P. patens and other mosses, in comparison to other land plants.

The distribution and evolution of Au SINE in plants were examined. Au SINE is a short interspersed element first identified in Aegilops umbellulata, a close relative of wheat. The Au SINE was previously found in species such as wheat, maize, tobacco, and tomato, but not in rice. In this study, we first searched public databases, and next examined the presence of Au in a broad range of plant species by PCR using internal primers of Au. Although Au is likely to be absent from many species including rice, it was identified in many Gramineae, Solanaceae, and Fabaceae species, and also in a basal angiosperm species, Asimina triloba. Phylogenetic studies suggest that Au SINE originated before the divergence of monocots and eudicots. Au SINE sequences of Asimina, Triticum, Zea, Nicotiana, Lotus, Medicago, and Glycine were aligned and compared. Although sequences of Au were highly conserved among distantly related species, every Au element in Glycine had a 16 bp deletion and its 3' end differed from sequences of other species. This type of Au could only be found in G. max, and not in other species including other Fabaceae species such as M. truncatula and L. japonicus. This is the first report of a plant SINE family present in multiple lineages, and the evolution of Au SINE in the plant kingdom, especially in Gramineae and Fabaceae is discussed.

This Task Force report by the American College of Neuropsychopharmacology evaluates the safety and efficacy of selective serotonin reuptake inhibitor (SSRIs) antidepressants for depressed youth under 18 years. The report was undertaken after regulatory agencies in the United States and United Kingdom raised concerns in 2003 about the possibility that treatment of depression in children and adolescents with SSRIs may increase the risk of suicidal thinking or suicide attempts.

In this paper the integrals which arise in target/seabed scattering problems are examined. These are the integrals which express the propagation of a spherical harmonic term in a fluid above or below a half-space and the integrals which compute the conversion coefficients of outgoing spherical harmonics into incident spherical harmonics after a seabed reflection. A very efficient and accurate method of computing these integrals, using the method of complex images, is derived. Numerical comparisons with the exact integral expressions show the accuracy of this approach.

In this paper, the issue of using higher-order finite difference schemes to handle the azimuthal derivative term in a three-dimensional parabolic equation based model is addressed. The three-dimensional penetrable wedge benchmark problem is chosen to illustrate the accuracy and efficiency of the proposed schemes. Both point source and modal initializations of the pressure field are considered. For each higher-order finite difference scheme used in azimuth, the convergence of the numerical solution with respect to the azimuth is investigated and the CPU times are given. Some comparisons with solutions obtained from another 3-D model [J. A. Fawcett, J. Acoust. Soc. Am. 93, 2627-2632 (1993)] are presented. The numerical simulations show that the use of a higher-order scheme in azimuth allows one to reduce the required number of points in the azimuthal direction while still obtaining accurate solutions. The higher-order schemes have approximately the same efficiency as a FFT-based approach (in fact, may outperform it slightly); however, the finite difference approach has the advantage that it may be more flexible than the FFT approach for various PE approximations.