Carlsenchristie7270

may be influenced by alterations of the microbiome that occur during infection. To explore this notion, we took a two-pronged approach. First, we studied a cohort of dogs naturally infected with various enteric parasites and found a strong association between parasite infection and altered gut microbiota composition. Giardia, one of the most prevalent parasite infections globally, had a particularly large impact on the microbiome. Second, we took a database-driven strategy to integrate microbiome data with clinical data from large human field studies and found that Giardia infection is also associated with marked alteration of the gut microbiome of children, suggesting a possible explanation for why Giardia has been reported to be associated with protection from moderate to severe diarrhea.Regulation of epidermal growth factor (EGF) receptor (EGFR) signaling is critical for the replication of human cytomegalovirus (HCMV) as well as latency and reactivation in CD34+ hematopoietic progenitor cells. HCMV microRNAs (miRNAs) provide a means to modulate the signaling activated by EGF through targeting components of the EGFR signaling pathways. Here, we demonstrate that HCMV miR-US5-2 directly downregulates the critical EGFR adaptor protein GAB1 that mediates activation and sustained signaling through the phosphatidylinositol 3-kinase (PI3K) and MEK/extracellular signal-regulated kinase (ERK) pathways and cellular proliferation in response to EGF. Expression of HCMV UL138 is regulated by the transcription factor early growth response gene 1 (EGR1) downstream of EGFR-induced MEK/ERK signaling. We show that by targeting GAB1 and attenuating MEK/ERK signaling, miR-US5-2 indirectly regulates EGR1 and UL138 expression, which implicates the miRNA in critical regulation of HCMV latency.IMPORTANCE Human cytomrole during reactivation from latency by reducing proliferation and UL138 expression.Spore-forming bacteria of the orders Bacillales and Clostridiales play a major role in food spoilage and foodborne diseases. When environmental conditions become favorable, these spores can germinate as the germinant receptors located on the spore's inner membrane are activated via germinant binding. This leads to the formation of vegetative cells via germination and subsequent outgrowth and potential deleterious effects on foods. Bafilomycin A1 The present report focuses on analysis of the synthesis of the MalS (malic enzyme) protein during Bacillus subtilis spore germination by investigating the dynamics of the presence and fluorescence level of a MalS-GFP (MalS-green fluorescent protein) fusion protein using time-lapse fluorescence microscopy. Our results show an initial increase in MalS-GFP fluorescence intensity within the first 15 min of germination, followed by a discernible drop and stabilization of the fluorescence throughout spore outgrowth as reported previously (L. Sinai, A. Rosenberg, Y. Smith, E. Segev, and S.to a very low level of core water content and a phase-bright state of spores. The present report, focusing on proteins MalS and PdhD (pyruvate dehydrogenase subunit D) and complementary to our companion report published in this issue, aims to shed light on a major dilemma in the field, i.e., whether protein synthesis, in particular that of MalS, takes place in phase-bright spores. Clustered MalS-GFP in dormant spores diffuses throughout the spore as germination proceeds. However, fluorescence intensity measurements, supported by Western blot analysis and SILAC proteomics, confirm that there is no new MalS protein synthesis in bright-phase dormant spores.Bacillus subtilis spores can reactivate their metabolism through germination upon contact with germinants and can develop into vegetative cells upon outgrowth. However, the mechanisms at the basis of the molecular machinery that triggers the spore germination and outgrowth processes are still largely unclear. To gain further insights into these processes, the transcriptome and proteome changes occurring during the conversion of spores to vegetative cells were analyzed in the present study. For each time point sampled, the changes in the spore proteome were quantitatively monitored relative to the proteome of metabolically 15N-labeled vegetative cells. Of the quantified proteins, 60% are shared by vegetative cells and spores, indicating that the spores have a minimal protein set, sufficient to resume metabolism upon completion of germination. These shared proteins thus represent the most basic "survival kit" for spore-based life. We observed no significant change in the proteome or the transcriptome until the been identified. In addition, in this analysis based on monitoring of protein levels in germinating and outgrowing spores, the transition from (ribo)nucleotide and amino acid biosynthesis to the restoration of all metabolic pathways can be clearly seen. The integrative multi-omics approach applied in this study thus has helped us to achieve a comprehensive overview of the molecular mechanisms at the basis of spore germination and outgrowth as well as to identify important knowledge gaps in need of further study.Dengue is the most prevalent arthropod-borne viral disease affecting humans, with severe dengue typified by potentially fatal microvascular leakage and hypovolemic shock. Blood vessels of the microvasculature are composed of a tubular structure of endothelial cells ensheathed by perivascular cells (pericytes). Pericytes support endothelial cell barrier formation and maintenance through paracrine and contact-mediated signaling and are critical to microvascular integrity. Pericyte dysfunction has been linked to vascular leakage in noncommunicable pathologies such as diabetic retinopathy but has never been linked to infection-related vascular leakage. Dengue vascular leakage has been shown to result in part from the direct action of the secreted dengue virus (DENV) nonstructural protein NS1 on endothelial cells. Using primary human vascular cells, we show here that NS1 also causes pericyte dysfunction and that NS1-induced endothelial hyperpermeability is more pronounced in the presence of pericytes. Notably, NS1culatory shock. We show here that perivascular cells (pericytes) amplify the vascular leakage-inducing effects of the dengue viral protein NS1 through contact-independent signaling to endothelial cells. While pericytes are known to contribute to noncommunicable vascular leakage, this is the first time these cells have been implicated in the vascular effects of an infectious disease. Our findings could pave the way for new therapies and diagnostics to combat dengue and potentially other infectious vascular leakage syndromes.With the rapid expansion of the application of genomics and sequencing in plant breeding, there is a constant drive for better reference genomes. In potato (Solanum tuberosum), the third largest food crop in the world, the related species S. phureja, designated "DM", has been used as the most popular reference genome for the last 10 years. Here, we introduce the de novo sequenced genome of Solyntus as the next standard reference in potato genome studies. A true Solanum tuberosum made up of 116 contigs that is also highly homozygous, diploid, vigorous and self-compatible, Solyntus provides a more direct and contiguous reference then ever before available. It was constructed by sequencing with state-of-the-art long and short read technology and assembled with Canu. The 116 contigs were assembled into scaffolds to form each pseudochromosome, with three contigs to 17 contigs per chromosome. This assembly contains 93.7% of the single-copy gene orthologs from the Solanaceae set and has an N50 of 63.7 Mbp. The genome and related files can be found at https//www.plantbreeding.wur.nl/Solyntus/ With the release of this research line and its draft genome we anticipate many exciting developments in (diploid) potato research.Identification of co-expressed sets of genes (gene modules) is used widely for grouping functionally related genes during transcriptomic data analysis. An organism-wide atlas of high-quality gene modules would provide a powerful tool for unbiased detection of biological signals from gene expression data. Here, using a method based on independent component analysis we call DEXICA, we have defined and optimized 209 modules that broadly represent transcriptional wiring of the key experimental organism C. elegans These modules represent responses to changes in the environment (e.g., starvation, exposure to xenobiotics), genes regulated by transcriptions factors (e.g., ATFS-1, DAF-16), genes specific to tissues (e.g., neurons, muscle), genes that change during development, and other complex transcriptional responses to genetic, environmental and temporal perturbations. Interrogation of these modules reveals processes that are activated in long-lived mutants in cases where traditional analyses of differentially expressed genes fail to do so. Additionally, we show that modules can inform the strength of the association between a gene and an annotation (e.g., GO term). Analysis of "module-weighted annotations" improves on several aspects of traditional annotation-enrichment tests and can aid in functional interpretation of poorly annotated genes. We provide an online interactive resource with tutorials at http//genemodules.org/, in which users can find detailed information on each module, check genes for module-weighted annotations, and use both of these to analyze their own gene expression data (generated using any platform) or gene sets of interest.A simultaneous arterial and venous approach has been widely described for the endovascular treatment of dural arteriovenous fistula (DAVFs) and recently for arteriovenous malformation (AVMs). Conventional venous approaches are performed by direct internal jugular puncture or by femoral access. Although complication rates are low, there are potential life-threatening complications that should be avoided. The advantages of radial artery access have been widely proven, nevertheless the use of upper limb veins in neurointervention are rarely reported. We present five cases of the simultaneous arteriovenous approach through the radial artery and superficial veins of the forearm for the treatment of intracranial neurovascular diseases.Atherosclerosis is responsible for a large percentage of all-cause mortality worldwide, but it is only now beginning to be understood as a complex disease process involving metabolic insult, chronic inflammation, and multiple immune mechanisms. Abs targeting apolipoprotein A-I (ApoA-I) have been found in patients with cardiovascular disease, autoimmune conditions, as well as those with no documented history of either. However, relatively little is known about how these Abs are generated and their relationship to diet and sex. In the current study, we modeled this aspect of autoimmunity using anti-ApoA-I immunization of male and female C57BL/6 mice. Unexpectedly, we found that autoantibodies directed against a single, previously unknown, epitope within the ApoA-I protein developed irrespective of immunization status or dyslipidemia in mice. When total IgG subclasses were analyzed over the course of time, we observed that rather than driving an increase in inflammatory IgG subclasses, consumption of Western diet suppressed age-dependent increases in IgG2b and IgG2c in male mice only.