The efficacy and safety of thrombopoietin receptor agonists in patients with chronic liver disease undergoing elective procedures: a systematic review and meta-analysis.

Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. The majority of the included procedures were endoscopic. TPO-RAs were significantly more likely to result in a preoperative platelet count greater than 50 x 109/L (72.1% vs 15.6%, RR 4.8, 95% CI 3.6-6.4 p < .00001. NNT 1.8) and reduced the incidence of platelet transfusions (22.5% vs 67.8%, RR 0.33, 95% CI 0.3-0.4 p < .00001. NNT 2.2). Total periprocedural bleeding was decreased in patients who received TPO-RAs (11.6% vs 15.6%, RR 0.64, 95% CI 0.5-0.9 p = .01. NNT 24.7) and there was no increase in the rate of thrombosis (2.2% vs 1.8% RR 1.25, 95% CI 0.6-2.9 p = .60. NNH 211.1). In patients with CLD the use of preprocedural TPO-RAs resulted in significant increased platelet counts, and decreased the incidence of platelet transfusions as compared to placebo. TPO use likewise decreased the incidence of total periprocedural bleeding without increasing the rate of thrombosis.

Genomic view of bipolar disorder revealed by whole genome sequencing in a genetic isolate.

Bipolar disorder is a common, heritable mental illness characterized by recurrent episodes of mania and depression. Despite considerable effort to elucidate the genetic underpinnings of bipolar disorder, causative genetic risk factors remain elusive. We conducted a comprehensive genomic analysis of bipolar disorder in a large Old Order Amish pedigree. Microsatellite genotypes and high-density SNP-array genotypes of 388 family members were combined with whole genome sequence data for 50 of these subjects, comprising 18 parent-child trios. This study design permitted evaluation of candidate variants within the context of haplotype structure by resolving the phase in sequenced parent-child trios and by imputation of variants into multiple unsequenced siblings. Non-parametric and parametric linkage analysis of the entire pedigree as well as on smaller clusters of families identified several nominally significant linkage peaks, each of which included dozens of predicted deleterious variants. Close inspection of exonic and regulatory variants in genes under the linkage peaks using family-based association tests revealed additional credible candidate genes for functional studies and further replication in population-based cohorts. However, despite the in-depth genomic characterization of this unique, large and multigenerational pedigree from a genetic isolate, there was no convergence of evidence implicating a particular set of risk loci or common pathways. The striking haplotype and locus heterogeneity we observed has profound implications for the design of studies of bipolar and other related disorders.

The plant-specific protein FEHLSTART controls male meiotic entry, initializing meiotic synchronization in Arabidopsis.

Meiosis marks the transition from the sporophyte to the gametophyte generation in the life cycle of flowering plants, and creates genetic variations through homologous recombination. In most flowering plants, meiosis is highly synchronized within each anther, which is significant for efficient fertilization. To date, little is known about the molecular mechanisms of entry into meiosis and exit from it, and only a few genes in Arabidopsis have been characterized with a role in regulating meiotic progression. In this study, we report the functional characterization of a plant-specific basic helix-loop-helix (bHLH) protein, FEHLSTART (FST), a defect in which leads to premature meiotic entry and asynchronous meiosis, and results in decreased seed yield. Investigation of the time course of meiosis showed that the onset of leptotene, the first stage of prophase I, frequently occurred earlier in fst-1 than in the wild type. Asynchronous meiosis followed, which could manifest in the disruption of regular spindle structures and symmetric cell divisions in fst-1 mutants during the meiosis I/II transition. In accordance with frequently accelerated meiotic entry, whole-transcriptome analysis of fst-1 anthers undergoing meiosis revealed that 19 circadian rhythm genes were affected and 47 pollen-related genes were prematurely expressed at a higher level. Taken together, we propose that FST is required for normal meiotic entry and the establishment of meiotic synchrony.

A transcriptomic approach to elucidate the physiological significance of human cytochrome P450 2S1 in bronchial epithelial cells.

BACKGROUND: Cytochrome P450 2S1 (CYP2S1) is an orphan P450 with an unknown biological function. Data from our laboratory and others suggest that CYP2S1 may have an important physiological role in modulating the synthesis and metabolism of bioactive lipids including prostaglandins and retinoids. CYP2S1 expression is elevated in multiple epithelial-derived cancers as well as in the chronic hyperproliferative disease psoriasis. Whether CYP2S1 expression in proliferative disease is protective, detrimental, or neutral to disease progression remains to be determined. Two human bronchial epithelial cells (BEAS-2B) were constructed to represent chronic depletion of CYP2S1 using short-hairpin RNA (shRNA) silencing directed toward the 3'UTR (759) and exon 3 (984) of the CYP2S1 gene and compared with a non-targeting shRNA control (SCRAM). Both CYP2S1 mRNA and protein were depleted by approximately 75% in stable cell lines derived from both targeted shRNA constructs (759 and 984). To elucidate the biological significance of CYP2S1, we analyzed transcriptome alterations in response to CYP2S1 depletion in human lung cells. RESULTS: RNA-sequencing (RNA-seq) analysis was performed to compare the transcriptome of the control (SCRAM) and the CYP2S1-depleted (759) BEAS-2B cell lines. Transcriptomes of the replicates from the two cell lines were found to be distinct populations as determined using Principal Component Analysis and hierarchical clustering. Approximately 1000 genes were differentially expressed in response to CYP2S1 depletion. Consistent with our previous phenotypes, DAVID analysis revealed altered regulation in key pathways implicated in cell proliferation and migration. Transcriptomic profiles were also consistent with the metabolism of proposed endogenous substrates. Pathway analysis also revealed significant expression changes within mTOR signaling, a critical pathway in cell growth. To determine whether these changes manifest as altered cell size, cell diameter and volume were calculated, revealing that CYP2S1 depletion promotes cell growth in BEAS-2B cells. CONCLUSIONS: These data suggest that pathway analysis of sequence-based gene expression is a powerful method to identify pathways and phenotypic alterations in response to changes in orphan enzyme expression. Our results suggest a novel role for CYP2S1-mediated metabolism in modulating BEAS-2B cell size. These findings warrant further studies on CYP2S1 regulated pathways to elucidate potential substrates of CYP2S1.

Transcriptome profiling of cytokinin and auxin regulation in tomato root.

Tomato is a model and economically important crop plant with little information available about gene expression in roots. Currently, there have only been a few studies that examine hormonal responses in tomato roots and none at a genome-wide level. This study examined the transcriptome atlas of tomato root regions (root tip, lateral roots, and whole roots) and the transcriptional regulation of each root region in response to the plant hormones cytokinin and auxin using Illumina RNA sequencing. More than 165 million 1×54 base pair reads were mapped onto the Solanum lycopersicum reference genome and differential expression patterns in each root region in response to each hormone were assessed. Many novel cytokinin- and auxin-induced and -repressed genes were identified as significantly differentially expressed and the expression levels of several were confirmed by qPCR. A number of these regulated genes represent tomato orthologues of cytokinin- or auxin-regulated genes identified in other species, including CKXs, type-A RRs, Aux/IAAs, and ARFs. Additionally, the data confirm some of the hormone regulation studies for recently examined genes in tomato such as SlIAAs and SlGH3s. Moreover, genes expressed abundantly in each root region were identified which provide a spatial distribution of many classes of genes, including plant defence, secondary metabolite production, and general metabolism across the root. Overall this study presents the first global expression patterns of hormone-regulated transcripts in tomato roots, which will be functionally relevant for future studies directed towards tomato root growth and development.

Characterization of a set of novel meiotically-active promoters in Arabidopsis.

BACKGROUND: Homologous recombination, together with selection, laid the foundation for traditional plant breeding. The recombination process that takes place during meiotic cell division is crucial for the creation of novel variations of highly desired traits by breeders. Gaining control over this process is important for molecular breeding to achieve more precise, large-scale and quicker plant improvement. As conventional ubiquitous promoters are neither tissue-specific nor efficient in driving gene expression in meiocytes, promoters with high meiotic activities are potential candidates for manipulating the recombination process. So far, only a few meiotically-active promoters have been reported. Recently developed techniques to profile the transcriptome landscape of isolated meiocytes provided the means to discover promoters from genes that are actively expressed in meiosis. RESULTS: In a screen for meiotically-active promoters, we examined ten promoter sequences that are associated with novel meiotic candidate genes. Each promoter was tested by expressing a GFP reporter gene in Arabidopsis. Characterization of regulatory regions revealed that these meiotically-active promoters possessed conserved motifs and motif arrangement. Some of the promoters unite optimal properties which are invaluable for meiosis-directed studies such as delivering specific gene expression in early meiosis I and/or meiosis II. Furthermore, the examination of homologs of the corresponding genes within green plants points to a great potential of applying the information from Arabidopsis to other species, especially crop plants. CONCLUSIONS: We identified ten novel meiotically-active promoters; which, along with their homologs, are prime candidates to specifically drive gene expression during meiosis in plants and can thus provide important tools for meiosis study and crop breeding.

Genome-wide analyses of exonic copy number variants in a family-based study point to novel autism susceptibility genes.

The genetics underlying the autism spectrum disorders (ASDs) is complex and remains poorly understood. Previous work has demonstrated an important role for structural variation in a subset of cases, but has lacked the resolution necessary to move beyond detection of large regions of potential interest to identification of individual genes. To pinpoint genes likely to contribute to ASD etiology, we performed high density genotyping in 912 multiplex families from the Autism Genetics Resource Exchange (AGRE) collection and contrasted results to those obtained for 1,488 healthy controls. Through prioritization of exonic deletions (eDels), exonic duplications (eDups), and whole gene duplication events (gDups), we identified more than 150 loci harboring rare variants in multiple unrelated probands, but no controls. Importantly, 27 of these were confirmed on examination of an independent replication cohort comprised of 859 cases and an additional 1,051 controls. Rare variants at known loci, including exonic deletions at NRXN1 and whole gene duplications encompassing UBE3A and several other genes in the 15q11-q13 region, were observed in the course of these analyses. Strong support was likewise observed for previously unreported genes such as BZRAP1, an adaptor molecule known to regulate synaptic transmission, with eDels or eDups observed in twelve unrelated cases but no controls (p = 2.3x10(-5)). Less is known about MDGA2, likewise observed to be case-specific (p = 1.3x10(-4)). But, it is notable that the encoded protein shows an unexpectedly high similarity to Contactin 4 (BLAST E-value = 3x10(-39)), which has also been linked to disease. That hundreds of distinct rare variants were each seen only once further highlights complexity in the ASDs and points to the continued need for larger cohorts.

Axial spondyloarthritis patients have altered mucosal IgA response to oral and fecal microbiota.

Axial spondyloarthritis (axSpA) is an inflammatory arthritis involving the spine and the sacroiliac joint with extra-articular manifestations in the eye, gut, and skin. The intestinal microbiota has been implicated as a central environmental component in the pathogenesis of various types of spondyloarthritis including axSpA. Additionally, alterations in the oral microbiota have been shown in various rheumatological conditions, such as rheumatoid arthritis (RA). Therefore, the aim of this study was to investigate whether axSpA patients have an altered immunoglobulin A (IgA) response in the gut and oral microbial communities. We performed 16S rRNA gene (16S) sequencing on IgA positive (IgA+) and IgA negative (IgA-) fractions (IgA-SEQ) from feces (n=17 axSpA; n=14 healthy) and saliva (n=14 axSpA; n=12 healthy), as well as on IgA-unsorted fecal and salivary samples. PICRUSt2 was used to predict microbial metabolic potential in axSpA patients and healthy controls (HCs). IgA-SEQ analyses revealed enrichment of several microbes in the fecal (Akkermansia, Ruminococcaceae, Lachnospira) and salivary (Prevotellaceae, Actinobacillus) microbiome in axSpA patients as compared with HCs. Fecal microbiome from axSpA patients showed a tendency towards increased alpha diversity in IgA+ fraction and decreased diversity in IgA- fraction in comparison with HCs, while the salivary microbiome exhibits a significant decrease in alpha diversity in both IgA+ and IgA- fractions. Increased IgA coating of Clostridiales Family XIII in feces correlated with disease severity. Inferred metagenomic analysis suggests perturbation of metabolites and metabolic pathways for inflammation (oxidative stress, amino acid degradation) and metabolism (propanoate and butanoate) in axSpA patients. Analyses of fecal and salivary microbes from axSpA patients reveal distinct populations of immunoreactive microbes compared to HCs using the IgA-SEQ approach. These bacteria were not identified by comparing their relative abundance alone. Predictive metagenomic analysis revealed perturbation of metabolites/metabolic pathways in axSpA patients. Future studies on these immunoreactive microbes may lead to better understanding of the functional role of IgA in maintaining microbial structure and human health.

Understanding exercise promotion in rheumatic diseases: A qualitative study among physical therapists.

Background: Physical therapists have unique expertise in planning, prescribing, and supporting exercise for patients with rheumatic diseases. Promoting exercise can be a challenge, but descriptions of physical therapists' experiences within the field of rheumatology are limited.Objective: The purpose of this study was to explore and describe ways of understanding exercise promotion among physical therapists working in rheumatology.Design and Method: A phenomenographic approach was used to analyze semi-structured interviews with 25 physical therapists working primarily within the field of rheumatology from eight different physical therapy departments at hospitals across Sweden.Results: Four ways of understanding exercise promotion were identified. These were named: exercise promotion as information and monitoring of the behavior, as facilitation of skills building, as co-creation of awareness, and as the development of independence and self-reflection.Conclusion: Physical therapists in rheumatology understand exercise promotion in various ways that differ with respect to comprehensiveness and patient-centeredness. The physical therapists' use of behavior change techniques serves different purposes in exercise promotion, varying from external control to self-management. The present results might thus be used to develop awareness, knowledge, and skills for more deliberate exercise promotion among physical therapists working with patients having rheumatic diseases.

Population-based study of genetic variation in individuals with autism spectrum disorders from Croatia.

BACKGROUND: Genome-wide studies on autism spectrum disorders (ASDs) have mostly focused on large-scale population samples, but examination of rare variations in isolated populations may provide additional insights into the disease pathogenesis. METHODS: As a first step in the genetic analysis of ASD in Croatia, we characterized genetic variation in a sample of 103 subjects with ASD and 203 control individuals, who were genotyped using the Illumina HumanHap550 BeadChip. We analyzed the genetic diversity of the Croatian population and its relationship to other populations, the degree of relatedness via Runs of Homozygosity (ROHs), and the distribution of large (>500 Kb) copy number variations. RESULTS: Combining the Croatian cohort with several previously published populations in the FastME analysis (an alternative to Neighbor Joining) revealed that Croatian subjects cluster, as expected, with Southern Europeans; in addition, individuals from the same geographic region within Europe cluster together. Whereas Croatian subjects could be separated from a sample of healthy control subjects of European origin from North America, Croatian ASD cases and controls are well mixed. A comparison of runs of homozygosity indicated that the number and the median length of regions of homozygosity are higher for ASD subjects than for controls (p = 6 × 10(-3)). Furthermore, analysis of copy number variants found a higher frequency of large chromosomal rearrangements (>2 Mb) in ASD cases (5/103) than in ethnically matched control subjects (1/197, p = 0.019). CONCLUSIONS: Our findings illustrate the remarkable utility of high-density genotype data for subjects from a limited geographic area in dissecting genetic heterogeneity with respect to population and disease related variation.

A qualitative exploration of chiropractic and physiotherapy teachers' experiences and conceptualizations of the educational environment.

OBJECTIVE: There has been increasing scholarly interest in the role of environments in health care professional education, and the value of these has been widely acknowledged as an influential factor in educational quality. However, little is known about how teachers experience the environment, and there is a recognizable absence of a perspective from chiropractic and physiotherapy faculties. The aim of this study was to explore and contrast chiropractic and physiotherapy teachers' experiences and conceptualizations of the meaning of the educational environment. METHODS: In this qualitative study, we performed semistructured interviews with 14 teachers, purposefully selected to obtain richness, variation, and breadth in the data. The data were analyzed using inductive qualitative content analysis. RESULTS: The most noteworthy findings were, first, that chiropractic teachers experienced the meaning of the environment as motivating a vocational practice and modeling ideal, supporting and managing stressed students, and including students in the community of chiropractors. Physiotherapy teachers experienced the meaning of the environment as putting the pedagogical vision into practice, balancing students' expectations, and providing the prerequisites to grow within the profession. Second, both groups of teachers held common conceptualizations of the constituents of the environment as physical, organizational, relational, communicational, and pedagogical; however, they attached different connotations to these dimensions. CONCLUSION: The findings conveyed a variance in the experience of the meaning of the educational environment that can be attributed to contextual and cultural differences.

Physiotherapy students' professional identity on the edge of working life.

Market expectations of physiotherapists reflect changing demands of health care for client centred, community based management of chronic disease in an ageing population. This study forms a component part of a longitudinal study of students' socialization throughout their education programme examining the outcome of professional identity throughout professional socialization processes. The aim of this study was to explore characteristics of graduating physiotherapy students' professional identity before leaving the University. An interview guide, agreed between the Swedish and UK researchers, was used to focus the semi-structured interviews. The phenomenon of professional identity of 18 students was studied through their perceptions of their role, practice, vision, beliefs and scope of practice as physiotherapists. A phenomenographic approach was taken to analysis and identified three qualitatively different categories of professional identity as a physiotherapist which are described as the Empowerer, the Educator and the Treater. A variation of concepts in professional identity at graduation questions the extent to which educators consider how they guide the development of professional identities which fit the expectations of stakeholders and which are able to respond to promotion and development of the profession of physiotherapy in the changing fields of health care over future years.

Development pathways in learning to be a physiotherapist.

BACKGROUND AND PURPOSE: Few studies have examined the experiences of students' professional socialization in physiotherapy. This international longitudinal study aimed to study experiences of situated learning and change in a student cohort during a physiotherapy education programme. METHOD: A phenomenographic design with semi-structured interviews was carried out with a cohort of physiotherapy students from two sites, strategically selected for variation in gender, age, educational background, work experience and academic level. Interviews were carried out after each of the first five semesters in the programme by a team of researchers. Seventy-six interviews explored students' learning experiences. Analysis identified the variation in experiences seen as important to becoming a physiotherapist. RESULTS: Distinct perceptions of professional growth and progression are identified in four pathways of development: 'Reflecting on Practice'; 'Communicating with Others'; 'Performing Skills'; and 'Searching Evidence'. These pathways demonstrate qualitative differences in the focus of learning experiences and preferred learning context, and include learning in a context which supports reflection, learning as agreed by others in a context with patients and other professionals, learning physiotherapy skills in a practice context and learning formal knowledge in a context where theory can be linked with practice. CONCLUSIONS: In a cohort of students professional growth can be seen in a variety of development pathways. Each shows progress of professional growth in the 'what' as changes in experiences and the 'how' as ways of learning from them. In addition, the pattern of pathways in a cohort may change from one semester to another suggesting individuals may adopt different learning pathways throughout their education. Teaching staff are challenged to consider how they recognize a variation in development pathways in their student cohorts and how they purposefully ensure experiences to guide students through different learning pathways in socialization to become a physiotherapist.

Experiences of participation in rhythm and movement therapy after stroke.

PURPOSE: The aim of this study was to investigate how persons with stroke experience participation in rhythm and music therapy. METHODS: To gain knowledge of the qualitatively different ways persons with stroke experience participation in Ronnie Gardiner Rhythm and Music (RGRM) therapy, a phenomenographic approach was chosen. Interviews with 17 persons with stroke were done. Selection criteria were set to capture the variations in how the phenomenon appeared to the informants. RESULTS: Two qualitatively different ways of experiencing the RGRM therapy were identified: (A) challenge leading to connection with the body and (B) being able. A feeling of being connected to the body was achieved as a result of the challenging tasks. By gaining a feeling of body awareness joy, energy and desire to do things increased. Learning new skills was promoted by having to be concentrated during therapy sessions and a sense of being able to carry out difficult tasks was achieved. CONCLUSIONS: Participation in RGRM seems to have helped the persons come to terms with their changed bodies, leading to feelings of being connected with their bodies. A feeling of change in competence occurred when an ability to carry out the tasks was simultaneously achieved. IMPLICATIONS FOR REHABILITATION: Stroke may cause considerable functional limitations with needs of rehabilitation services as a consequence. Participation in rhythm and movement activities may help persons who have had a stroke come to terms with their "new" bodies. The rhythm and movement activities were considered demanding and helped return to a meaningful life.

Exploring perceptions of the educational environment among undergraduate physiotherapy students.

OBJECTIVE: The aim of this study was to explore areas of strength and weakness in the educational environment as perceived by undergraduate physiotherapy students and to investigate these areas in relation to the respondents' demographic characteristics. METHODS: This study utilized a cross-sectional study design and employed the Dundee Ready Education Environment Measure, a 50-item, self-administered inventory relating to a variety of topics directly pertinent to educational environments. Convenience sampling was used, and the scores were compared across demographic variables. All undergraduate physiotherapy students in their first five terms of the programme in a major Swedish university were invited to participate in the study. RESULTS: A total of 222 students (80%) completed the inventory. With an overall score of 150/200 (75%), the students rated the educational environment in this institution as "more positive than negative". Two items consistently received deprived scores - authoritarian teachers and teaching with an overemphasis on factual learning. Students in term 4 differed significantly from others, and students with earlier university education experience perceived the atmosphere more negatively than their counterparts. There were no significant differences with regards to other demographic variables. CONCLUSIONS: This study provides valuable insight into how undergraduate physiotherapy students perceive their educational environment. In general, students perceived that their educational programme fostered a sound educational environment. However, some areas require remedial measures in order to enhance the educational experience.

Draft Genome Sequences of Vancomycin-Susceptible Staphylococcus aureus Related to Heterogeneous Vancomycin-Intermediate S. aureus.

We report the draft genome sequences of three vancomycin-susceptible methicillin-resistant Staphylococcus aureus strains. S. aureus strain MV8 is a sequence type 8 (ST-8) staphylococcal cassette chromosome mec element type IV (SCCmec IV) derivative, while the other two strains (S. aureus MM25 and MM61) are ST-5 SCCmec II strains. MM61 is also closely related to the heterogeneous vancomycin-intermediate S. aureus strain MM66.

Draft Genomes of Heterogeneous Vancomycin-Intermediate Staphylococcus aureus Strain MM66 and MM66 Derivatives with Altered Vancomycin Resistance Levels.

The draft genomes of heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) strain MM66 and MM66 isolates demonstrating altered vancomycin resistance levels were produced in an effort to provide information on mutations contributing to the vancomycin resistance levels observed in these strains.

Comparative genome analysis of non-toxigenic non-O1 versus toxigenic O1 Vibrio cholerae.

Pathogenic strains of Vibrio cholerae are responsible for endemic and pandemic outbreaks of the disease cholera. The complete toxigenic mechanisms underlying virulence in Vibrio strains are poorly understood. The hypothesis of this work was that virulent versus non-virulent strains of V. cholerae harbor distinctive genomic elements that encode virulence. The purpose of this study was to elucidate genomic differences between the O1 serotypes and non-O1 V. cholerae PS15, a non-toxigenic strain, in order to identify novel genes potentially responsible for virulence. In this study, we compared the whole genome of the non-O1 PS15 strain to the whole genomes of toxigenic serotypes at the phylogenetic level, and found that the PS15 genome was distantly related to those of toxigenic V. cholerae. Thus we focused on a detailed gene comparison between PS15 and the distantly related O1 V. cholerae N16961. Based on sequence alignment we tentatively assigned chromosome numbers 1 and 2 to elements within the genome of non-O1 V. cholerae PS15. Further, we found that PS15 and O1 V. cholerae N16961 shared 98% identity and 766 genes, but of the genes present in N16961 that were missing in the non-O1 V. cholerae PS15 genome, 56 were predicted to encode not only for virulence-related genes (colonization, antimicrobial resistance, and regulation of persister cells) but also genes involved in the metabolic biosynthesis of lipids, nucleosides and sulfur compounds. Additionally, we found 113 genes unique to PS15 that were predicted to encode other properties related to virulence, disease, defense, membrane transport, and DNA metabolism. Here, we identified distinctive and novel genomic elements between O1 and non-O1 V. cholerae genomes as potential virulence factors and, thus, targets for future therapeutics. Modulation of such novel targets may eventually enhance eradication efforts of endemic and pandemic disease cholera in afflicted nations.

Transcriptome analysis of cytokinin response in tomato leaves.

Tomato is one of the most economically and agriculturally important Solanaceous species and vegetable crops, serving as a model for examination of fruit biology and compound leaf development. Cytokinin is a plant hormone linked to the control of leaf development and is known to regulate a wide range of genes including many transcription factors. Currently there is little known of the leaf transcriptome in tomato and how it might be regulated by cytokinin. We employ high throughput mRNA sequencing technology and bioinformatic methodologies to robustly analyze cytokinin regulated tomato leaf transcriptomes. Leaf samples of two ages, 13d and 35d were treated with cytokinin or the solvent vehicle control dimethyl sulfoxide (DMSO) for 2 h or 24 h, after which RNA was extracted for sequencing. To confirm the accuracy of RNA sequencing results, we performed qPCR analysis of select transcripts identified as cytokinin regulated by the RNA sequencing approach. The resulting data provide the first hormone transcriptome analysis of leaves in tomato. Specifically we identified several previously untested tomato orthologs of cytokinin-related genes as well as numerous novel cytokinin-regulated transcripts in tomato leaves. Principal component analysis of the data indicates that length of cytokinin treatment and plant age are the major factors responsible for changes in transcripts observed in this study. Two hour cytokinin treatment showed a more robust transcript response indicated by both greater fold change of induced transcripts and the induction of twice as many cytokinin-related genes involved in signaling, metabolism, and transport in young vs. older leaves. This difference in transcriptome response in younger vs. older leaves was also found to a lesser extent with an extended (24 h) cytokinin treatment. Overall data presented here provides a solid foundation for future study of cytokinin and cytokinin regulated genes involved in compound leaf development or other developmental processes in tomato.

Genome Sequence of Non-O1 Vibrio cholerae PS15.

The draft genome sequence of a non-O1 Vibrio cholerae strain, PS15, organized into 3,512 open reading frames within a 3.9-Mb genome, was determined. The PS15 genome sequence will allow for the study of the evolution of virulence and environmental adaptation in V. cholerae.