Conserved role for 14-3-3ϵ downstream of type I TGFβ receptors

AbstractSchistosoma mansoni receptor kinase-1 (SmRK1) is a divergent type I transforming growth factor β (TGFβ) receptor on the surface of adult parasites. Using the intracellular domain of SmRK1 as bait in a yeast two-hybrid screen we identified an interaction with S. mansoni 14-3-3ϵ. The interaction which is phosphorylation-dependent is not specific to schistosomes since 14-3-3ϵ also binds to TβRI, the human type I TGFβ receptor. 14-3-3ϵ enhances TGFβ-mediated signaling by TβRI and is the first TβRI-interacting non-Smad protein identified that positively regulates this receptor. The interaction of 14-3-3ϵ with schistosome and human TβRI suggests a conserved, but previously unappreciated, role for this protein in TGFβ signaling pathways

Factors associated with Anaplasma spp. seroprevalence among dogs in the United States

Background Dogs in the United States are hosts to a diverse range of ticks and tick-borne pathogens, including A. phagocytophilum, an important emerging canine and human pathogen. Previously, a Companion Animal Parasite Council (CAPC)-sponsored workshop proposed factors purported to be associated with the infection risk for tick-transmitted pathogens in dogs in the United States, including climate conditions, socioeconomic characteristics, local topography, and vector distribution. Methods Approximately four million test results from routine veterinary diagnostic tests from 2011–2013, which were collected on a county level across the contiguous United States, are statistically analyzed with the proposed factors via logistic regression and generalized estimating equations. Spatial prevalence maps of baseline Anaplasma spp. prevalence are constructed from Kriging and head-banging smoothing methods. Results All of the examined factors, with the exception of surface water coverage, were significantly associated with Anaplasma spp. prevalence. Overall, Anaplasma spp. prevalence increases with increasing precipitation and forestation coverage and decreases with increasing temperature, population density, relative humidity, and elevation. Interestingly, socioeconomic status and deer/vehicle collisions were positively and negatively correlated with canine Anaplasma seroprevalence, respectively. A spatial map of the canine Anaplasma hazard is an auxiliary product of the analysis. Anaplasma spp. prevalence is highest in New England and the Upper Midwest. Conclusions The results from the two posited statistical models (one that contains an endemic areas assumption and one that does not) are in general agreement, with the major difference being that the endemic areas model estimates a larger prevalence in Western Texas, New Mexico, and Colorado. As A. phagocytophilum is zoonotic, the results of this analysis could also help predict areas of high risk for human exposure to this pathogen

Measuring the humoral immune response in cats exposed to feline leukaemia virus

Retroviruses belong to an important and diverse family of RNA viruses capable of causing neoplastic disease in their hosts. Feline leukaemia virus (FeLV) is a gammaretrovirus that infects domestic and wild cats, causing immunodeficiency, cytopenia and neoplasia in progressively infected cats. The outcome of FeLV infection is influenced by the host immune response; progressively infected cats demonstrate weaker immune responses compared to regressively infected cats. In this study, humoral immune responses were examined in 180 samples collected from 123 domestic cats that had been naturally exposed to FeLV, using a novel ELISA to measure antibodies recognizing the FeLV surface unit (SU) glycoprotein in plasma samples. A correlation was demonstrated between the strength of the humoral immune response to the SU protein and the outcome of exposure. Cats with regressive infection demonstrated higher antibody responses to the SU protein compared to cats belonging to other outcome groups, and samples from cats with regressive infection contained virus neutralising antibodies. These results demonstrate that an ELISA that assesses the humoral response to FeLV SU complements the use of viral diagnostic tests to define the outcome of exposure to FeLV. Together these tests could allow the rapid identification of regressively infected cats that are unlikely to develop FeLV-related disease

Analytical validation of an ELISA for the measurement of feline pancreas-specific lipase and re-evaluation of the reference interval and decision threshold for diagnosing pancreatitis

BACKGROUND : The diagnosis of feline pancreatitis can be challenging. The clinical presentation often includes mild, nonspecific clinical signs, such as vomiting, anorexia, and weight loss. Measurement of feline pancreatic lipase immunoreactivity (fPLI) concentration in serum has been reported to be sensitive and specific for a diagnosis of pancreatitis in cats. However, analytical validation for a widely available commercial assay for the measurement of fPLI concentration has not been published. OBJECTIVE : We aimed to analytically validate the Spec fPL assay (IDEXX Laboratories, Westbrook, ME), a commercial ELISA for the measurement of fPLI concentration, and re-evaluate its reference interval and decision threshold for diagnosing pancreatitis in cats. METHODS : Dilutional linearity, accuracy, precision, and the effect of interfering substances were assessed. The upper limit of the reference interval was calculated based on the 95th percentile of results from clinically healthy cats (n = 107), and a decision threshold for diagnosing pancreatitis was calculated with an expected specificity of 99%. RESULTS : Analytical validation demonstrated good linearity, accuracy, and precision, as well as the absence of interference from lipemia, hemolysis, or icterus. The upper limit of the reference interval for Spec fPL was determined to be 4.4 μg/L, and the decision threshold (a theoretical cut-off) for diagnosing pancreatitis was determined to be 8.8 μg/L based on a desired specificity of 99%. CONCLUSIONS : The Spec fPL assay is analytically valid, and results suggest that a decision threshold of 8.8 μg/L would have high diagnostic specificity for excluding clinically healthy cats.http://www.wileyonlinelibrary.com/journal/vcphj2023Production Animal StudiesSDG-03:Good heatlh and well-bein

Chromosome-Biased Binding and Gene Regulation by the Caenorhabditis elegans DRM Complex

DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we describe new aspects of DRM binding and function revealed through genome-wide analyses of the Caenorhabditis elegans DRM subunit LIN-54. We show that LIN-54 DNA-binding activity recruits DRM to promoters enriched for adjacent putative E2F/DP and LIN-54 binding sites, suggesting that these two DNA–binding moieties together direct DRM to its target genes. Chromatin immunoprecipitation and gene expression profiling reveals conserved roles for DRM in regulating genes involved in cell division, development, and reproduction. We find that LIN-54 promotes expression of reproduction genes in the germline, but prevents ectopic activation of germline-specific genes in embryonic soma. Strikingly, C. elegans DRM does not act uniformly throughout the genome: the DRM recruitment motif, DRM binding, and DRM-regulated embryonic genes are all under-represented on the X chromosome. However, germline genes down-regulated in lin-54 mutants are over-represented on the X chromosome. We discuss models for how loss of autosome-bound DRM may enhance germline X chromosome silencing. We propose that autosome-enriched binding of DRM arose in C. elegans as a consequence of germline X chromosome silencing and the evolutionary redistribution of germline-expressed and essential target genes to autosomes. Sex chromosome gene regulation may thus have profound evolutionary effects on genome organization and transcriptional regulatory networks.National Institutes of Health (U.S.) (grant GM24663)National Institutes of Health (U.S.) (grant DK068429)National Institutes of Health (U.S.) (grant GM082971)National Institutes of Health (U.S.) (grant GM076378

Genetic associations with micronutrient levels identified in immune and gastrointestinal networks

The discovery of vitamins and clarification of their role in preventing frank essential nutrient deficiencies occurred in the early 1900s. Much vitamin research has understandably focused on public health and the effects of single nutrients to alleviate acute conditions. The physio- logical processes for maintaining health, however, are complex systems that depend upon interactions between multiple nutrients, environmental factors, and genetic makeup. To analyze the relationship between these factors and nutritional health, data were obtained from an observational, community-based participatory research program of children and teens (age 6–14) enrolled in a summer day camp in the Delta region of Arkansas. Assessments of erythrocyte S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), plasma homocysteine (Hcy) and 6 organic micronutrients (retinol, 25-hydroxy vitamin D3, pyridoxal, thiamin, riboflavin, and vitamin E), and 1,129 plasma proteins were performed at 3 time points in each of 2 years. Genetic makeup was analyzed with 1 M SNP genotyping arrays, and nutrient status was assessed with 24-h dietary intake questionnaires. A pattern of metabolites (met_PC1) that included the ratio of erythro- cyte SAM/SAH, Hcy, and 5 vitamins were identified by principal component analysis. Met_PC1 levels were sig- nificantly associated with (1) single-nucleotide polymor- phisms, (2) levels of plasma proteins, and (3) multilocus genotypes coding for gastrointestinal and immune func- tions, as identified in a global network of metabolic/pro- tein–protein interactions. Subsequent mining of data from curated pathway, network, and genome-wide association studies identified genetic and functional relationships that may be explained by gene–nutrient interactions. The sys- tems nutrition strategy described here has thus associated a multivariate metabolite pattern in blood with genes involved in immune and gastrointestinal functions

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Communication: Making Connections

Updated in a new 8th edition, Communication: Making Communications is a popular, comprehensive introduction to speech communication that skillfully blends theory, current research and skills, while emphasizing the connections between communication and our daily lives. Unique in its integrated “connections” theme and streamlined pedagogy, this book introduces the basic principles of public speaking, interpersonal communication and group communication. The constant application of a solid theoretical foundation to everyday communication through relevant examples, thought-provoking questions and boxed features stress Communication Competence. Communication has new and strengthened pedagogy highlights and reinforces the “connections” theme throughout the book, demonstrating how communication connects us to each other in a variety of contexts: the workplace, family, friends, community, school, public communication settings, the Internet and across cultures. -- Provided by publisherhttps://scholarworks.uni.edu/facbook/1251/thumbnail.jp

Communication: making connections

Lively, clear, and geared to students\u27 needs, Communication: Making Connections directs students on the path to become more skilled, educated, and competent communicators in their everyday lives. Centered on the authors\u27 belief that communication is about connecting, linking, sharing, participating, bonding, coupling, and joining with others, this text introduces students to the skills and theory of communication. It combines student-oriented case studies, exercises, examples, and the authors\u27 conversational style to draw students into the text and motivate them to learn and understand the basic principles of communication. An integrated emphasis on technology-both in the text itself and in the supplements package-helps students learn about its relationship to communication. -- Provided by publisherhttps://scholarworks.uni.edu/facbook/1272/thumbnail.jp