Three Related Enzymes in Candida albicans Achieve Arginine- and Agmatine-Dependent Metabolism That Is Essential for Growth and Fungal Virulence

We thank Jane Usher (University of Exeter) for constructive criticism of the manuscript. We thank Valmik K. Vyas and Gerald R. Fink from the Whitehead Institute for Biomedical Research, Cambridge, United Kingdom, for providing the Candida CRISPR plasmid (CaCas9 Solo system pV1200 vector). N.A.R.G. acknowledges support provided by Wellcome as a Senior Investigator Award (101873/Z/13/Z), Collaborative Award (200208/A/15/Z), and Strategic Award (097377/Z11/Z) and by the MRC Centre for Medical Mycology (MR/N006364/2). R.M.A. acknowledges support from an EPSRC/BBSRC Interface Innovation Fellowship (EP/S001352/1). K.S., N.A.R.G., S.B., and J.W. conceived the study. N.A.R.G. was awarded the grant that served as a resource for this study. K.S., S.C., D.M.M., and S.B. performed experiments. K.S., N.A.R.G., S.B., and R.M.A. analyzed and interpreted results. K.S., N.A.R.G., and S.B. wrote the paper, and all of us provided comments.Peer reviewedPublisher PD

An evaluation of Bradfordizing effects

The purpose of this paper is to apply and evaluate the bibliometric method Bradfordizing for information retrieval (IR) experiments. Bradfordizing is used for generating core document sets for subject-specific questions and to reorder result sets from distributed searches. The method will be applied and tested in a controlled scenario of scientific literature databases from social and political sciences, economics, psychology and medical science (SOLIS, SoLit, USB Köln Opac, CSA Sociological Abstracts, World Affairs Online, Psyndex and Medline) and 164 standardized topics. An evaluation of the method and its effects is carried out in two laboratory-based information retrieval experiments (CLEF and KoMoHe) using a controlled document corpus and human relevance assessments. The results show that Bradfordizing is a very robust method for re-ranking the main document types (journal articles and monographs) in today’s digital libraries (DL). The IR tests show that relevance distributions after re-ranking improve at a significant level if articles in the core are compared with articles in the succeeding zones. The items in the core are significantly more often assessed as relevant, than items in zone 2 (z2) or zone 3 (z3). The improvements between the zones are statistically significant based on the Wilcoxon signed-rank test and the paired T-Test

Patient-Facing Mobile Apps to Treat High-Need, High-Cost Populations: A Scoping Review

BACKGROUND: Self-management is essential to caring for high-need, high-cost (HNHC) populations. Advances in mobile phone technology coupled with increased availability and adoption of health-focused mobile apps have made self-management more achievable, but the extent and quality of the literature supporting their use is not well defined. OBJECTIVE: The purpose of this review was to assess the breadth, quality, bias, and types of outcomes measured in the literature supporting the use of apps targeting HNHC populations. METHODS: Data sources included articles in PubMed and MEDLINE (National Center for Biotechnology Information), EMBASE (Elsevier), the Cochrane Central Register of Controlled Trials (EBSCO), Web of Science (Thomson Reuters), and the NTIS (National Technical Information Service) Bibliographic Database (EBSCO) published since 2008. We selected studies involving use of patient-facing iOS or Android mobile health apps. Extraction was performed by 1 reviewer; 40 randomly selected articles were evaluated by 2 reviewers to assess agreement. RESULTS: Our final analysis included 175 studies. The populations most commonly targeted by apps included patients with obesity, physical handicaps, diabetes, older age, and dementia. Only 30.3% (53/175) of the apps studied in the reviewed literature were identifiable and available to the public through app stores. Many of the studies were cross-sectional analyses (42.9%, 75/175), small (median number of participants=31, interquartile range 11.0-207.2, maximum 11,690), or performed by an app\u27s developers (61.1%, 107/175). Of the 175 studies, only 36 (20.6%, 36/175) studies evaluated a clinical outcome. CONCLUSIONS: Most apps described in the literature could not be located on the iOS or Android app stores, and existing research does not robustly evaluate the potential of mobile apps. Whereas apps may be useful in patients with chronic conditions, data do not support this yet. Although we had 2-3 reviewers to screen and assess abstract eligibility, only 1 reviewer abstracted the data. This is one limitation of our study. With respect to the 40 articles (22.9%, 40/175) that were assigned to 2 reviewers (of which 3 articles were excluded), inter-rater agreement was significant on the majority of items (17 of 30) but fair-to-moderate on others

Inhibition of microbial biofuel production in drought-stressed switchgrass hydrolysate

Additional file 2. Maps of significant gene ontology terms for chemical genomics data. Untreated biomass composition. Detailed hydrolysate composition

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Role of the Candida albicans MNN1 gene family in cell wall structure and virulence

Background The Candida albicans cell wall is the first point of contact with the host, and its outer surface is heavily enriched in mannoproteins modified through the addition of N- and O-mannan. Previous work, using mutants with gross defects in glycosylation, has clearly identified the importance of mannan in the host-pathogen interaction, immune recognition and virulence. Here we report the first analysis of the MNN1 gene family, which contains six members predicted to act as α-1,3 mannosyltransferases in the terminal stages of glycosylation. Findings We generated single null mutants in all members of the C. albicans MNN1 gene family, and disruption of MNN14 led to both in vitro and in vivo defects. Null mutants in other members of the family demonstrated no phenotypic defects, suggesting that these members may display functional redundancy. The mnn14Δ null mutant displayed hypersensitivity to agents associated with cell wall and glycosylation defects, suggesting an altered cell wall structure. However, no gross changes in cell wall composition or N-glycosylation were identified in this mutant, although an extension of phosphomannan chain length was apparent. Although the cell wall defects associated with the mnn14Δ mutant were subtle, this mutant displayed a severe attenuation of virulence in a murine infection model. Conclusion Mnn14 plays a distinct role from other members of the MNN1 family, demonstrating that specific N-glycan outer chain epitopes are required in the host-pathogen interaction and virulence

Genome-Wide Detection of Allele Specific Copy Number Variation Associated with Insulin Resistance in African Americans from the HyperGEN Study

African Americans have been understudied in genome wide association studies of diabetes and related traits. In the current study, we examined the joint association of single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the HyperGEN study, a family based study with proband ascertainment for hypertension. This analysis is restricted to 1,040 African Americans without diabetes. We generated allele specific CNV genotypes at 872,243 autosomal loci using Birdsuite, a freely available multi-stage program. Joint tests of association for SNPs and CNVs were performed using linear mixed models adjusting for covariates and familial relationships. Our results highlight SNPs associated with fasting insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10−7≤P≤1.1*10−5) near ATPase, class V, type 10A (ATP10A), and the L Type voltage dependent calcium channel (CACNA1D, rs1401492, P≤5.2*10−6). ATP10A belongs to a family of aminophospholipid-transporting ATPases and has been associated with type 2 diabetes in mice. CACNA1D has been linked to pancreatic beta cell generation in mice. The two most significant copy variable markers (rs10277702 and rs361367; P<2.0*10−4) were in the beta variable region of the T-cell receptor gene (TCRVB). Human and mouse TCR has been shown to mimic insulin and its receptor and could contribute to insulin resistance. Our findings differ from genome wide association studies of fasting insulin and other diabetes related traits in European populations, highlighting the continued need to investigate unique genetic influences for understudied populations such as African Americans

Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study

<p>Abstract</p> <p>Background</p> <p>Aortic root diameter is a clinically relevant trait due to its known relationship with the pathogenesis of aortic regurgitation and risk for aortic dissection. African Americans are an understudied population despite a particularly high burden of cardiovascular diseases. We report a genome-wide association study on aortic root diameter among African Americans enrolled in the HyperGEN study. We invoked a two-stage, mixed model procedure to jointly identify SNP allele and copy number variation effects.</p> <p>Results</p> <p>Results suggest novel genetic contributors along a large region between the <it>CRCP </it>and <it>KCTD7 </it>genes on chromosome 7 (p = 4.26 × 10^<b>-7</b>); and the <it>SIRPA </it>and <it>PDYN </it>genes on chromosome 20 (p = 3.28 × 10^<b>-8</b>).</p> <p>Conclusions</p> <p>The regions we discovered are candidates for future studies on cardiovascular outcomes, particularly in African Americans. The methods we employed can also provide an outline for genetic researchers interested in jointly testing SNP and CNV effects and/or applying mixed model procedures on a genome-wide scale.</p

Language development after cochlear implantation: an epigenetic model

Growing evidence supports the notion that dynamic gene expression, subject to epigenetic control, organizes multiple influences to enable a child to learn to listen and to talk. Here, we review neurobiological and genetic influences on spoken language development in the context of results of a longitudinal trial of cochlear implantation of young children with severe to profound sensorineural hearing loss in the Childhood Development after Cochlear Implantation study. We specifically examine the results of cochlear implantation in participants who were congenitally deaf (N = 116). Prior to intervention, these participants were subject to naturally imposed constraints in sensory (acoustic–phonologic) inputs during critical phases of development when spoken language skills are typically achieved rapidly. Their candidacy for a cochlear implant was prompted by delays (n = 20) or an essential absence of spoken language acquisition (n = 96). Observations thus present an opportunity to evaluate the impact of factors that influence the emergence of spoken language, particularly in the context of hearing restoration in sensitive periods for language acquisition. Outcomes demonstrate considerable variation in spoken language learning, although significant advantages exist for the congenitally deaf children implanted prior to 18 months of age. While age at implantation carries high predictive value in forecasting performance on measures of spoken language, several factors show significant association, particularly those related to parent–child interactions. Importantly, the significance of environmental variables in their predictive value for language development varies with age at implantation. These observations are considered in the context of an epigenetic model in which dynamic genomic expression can modulate aspects of auditory learning, offering insights into factors that can influence a child’s acquisition of spoken language after cochlear implantation. Increased understanding of these interactions could lead to targeted interventions that interact with the epigenome to influence language outcomes with intervention, particularly in periods in which development is subject to time-sensitive experience