Keithwillard2313

The Salmonella enterica SseK1 protein is a type three secretion system effector that glycosylates host proteins during infection on specific arginine residues with N-acetyl glucosamine (GlcNAc). SseK1 also Arg-glycosylates endogenous bacterial proteins and we thus hypothesized that SseK1 activities might be integrated with regulating the intrabacterial abundance of UPD-GlcNAc, the sugar-nucleotide donor used by this effector. After searching for new SseK1 substrates, we found that SseK1 glycosylates arginine residues in the dual repressor-activator protein NagC, leading to increased DNA-binding affinity and enhanced expression of the NagC-regulated genes glmU and glmS. SseK1 also glycosylates arginine residues in GlmR, a protein that enhances GlmS activity. This Arg-glycosylation improves the ability of GlmR to enhance GlmS activity. We also discovered that NagC is a direct activator of glmR expression. Salmonella lacking SseK1 produce significantly reduced amounts of UDP-GlcNAc as compared with Salmonella expressing SseK1. Overall, we conclude that SseK1 up-regulates UDP-GlcNAc synthesis both by enhancing the DNA-binding activity of NagC and by increasing GlmS activity through GlmR glycosylation. Such regulatory activities may have evolved to maintain sufficient levels of UDP-GlcNAc for both bacterial cell wall precursors and for SseK1 to modify other bacterial and host targets in response to environmental changes and during infection.Interstitial lung disease associated with primary Sjögren's syndrome (SJS-ILD) has a variable clinical course. We aimed to investigate the role of blood biomarkers in predicting prognosis for SJS-ILD. Clinical data of 46 SJS-ILD patients were retrospectively reviewed. Plasma biomarker levels, including Krebs von den Lungen-6 (KL-6), CC chemokine ligand 18 (CCL18), chitinase-3-like-1 (YKL-40), interleukin-4 receptor alpha (IL-4Ra), and matrix metalloproteinase-7 (MMP-7) were measured using the multiplex Luminex assays (R&D Systems, Minneapolis, USA). The median follow-up period was 69.0 months. The mean age of the patients was 59.4 years; 17.4% were men. The KL-6 level was significantly higher in non-survivors (n = 12; 119.6 vs. 59.5 pg/mL, P = 0.037) than survivors (n = 34), while the levels of the other biomarkers did not differ. Receiver operating characteristic analysis indicated that KL-6 shows the best performance for predicting survival (area under the curve = 0.705, P = 0.037; best cut-off value = 53.5 pg/mL). Multivariable Cox analysis that was adjusted by age and diffusing capacity for carbon monoxide suggested a high KL-6 level (> 53.5 pg/mL) as an independent prognostic factor for survival (hazard ratio = 5.939, 95% confidence interval 1.312-26.881, P = 0.021). Our results suggest that blood KL-6 might be a useful in predicting the prognosis for patients with SJS-ILD.Meagre (Argyrosomus regius), is a benthopelagic species rapidly emerging in aquaculture, due to its low food to biomass conversion rate, good fillet yield and ease of production. Tracing a species genomic background along with describing the genetic basis of important traits can greatly influence both conservation strategies and production perspectives. In this study, we employed ddRAD sequencing of 266 fish from six F1 meagre families, to construct a high-density genetic map comprising 4529 polymorphic SNP markers. The QTL mapping analysis provided a genomic appreciation for the weight trait identifying a statistically significant QTL on linkage group 15 (LG15). The comparative genomics analysis with six teleost species revealed an evolutionarily conserved karyotype structure. The synteny observed, verified the already well-known fusion events of the three-spine stickleback genome, reinforced the evidence of reduced evolutionary distance of Sciaenids with the Sparidae family, reflected the evolutionary proximity with Dicentrarchus labrax, traced several putative chromosomal rearrangements and a prominent putative fusion event in meagre's LG17. This study presents novel elements concerning the genome evolutionary history of a non-model teleost species recently adopted in aquaculture, starts to unravel the genetic basis of the species growth-related traits, and provides a high-density genetic map as a tool that can help to further establish meagre as a valuable resource for research and production.A mother's postpartum ingestion of raw or processed placental tissue-referred to as human maternal placentophagy-is an emerging health trend observed in industrialized nations. Placenta is commonly consumed as small pieces of raw tissue, or as raw or steamed dehydrated pulverized and encapsulated tissue. To investigate the potential neonatal health risks of this behavior, the present study focused on microbial colonization of processed placenta preparations with potentially pathogenic bacteria Streptococcus agalactiae (Group-B-Streptococci; GBS) and Escherichia coli (E. coli). In the clinical approach placentas from 24 mothers were analyzed. Two placentas, from 13 mothers with confirmed positive maternal GBS status, showed GBS-growth on their surface (2/13; 15.4%) independent from delivery mode or antibiotic treatment. All processed samples (n = 24) were free from GBS. In the experimental approach, a standardized inoculation protocol was introduced to resemble ascending vaginal and hematogenous colonization. Six placentas from elective term C-sections of GBS negative mothers were collected and artificially inoculated with highly concentrated suspensions of GBS and E. coli. Heat processing significantly reduced the number of colony forming units (CFU) for GBS and E. coli. Our results suggest placentophagy of processed tissue is an unlikely source of clinical infection.A perceptual bias towards negative emotions is a consistent finding in mood disorders and a major target of therapeutic interventions. Placebo responses in antidepressant treatment are substantial, but it is unclear whether and how underlying expectancy effects can modulate response biases to emotional inputs. In a first attempt to approach this question, we investigated how placebo induced expectation can shape the perception of specific emotional stimuli in healthy individuals. In a controlled cross-over design, positive treatment expectations were induced by verbal instructions and a hidden training manipulation combined with an alleged oxytocin nasal spray before participants performed an emotion classification task on happy and fearful facial expressions with varying intensity. Analyses of response criterion and discrimination ability as derived from emotion-specific psychometric functions demonstrate that expectation specifically lowered participants' threshold for identifying happy emotions in general, while they became less sensitive to subtle differences in emotional expressions. These indications of a positivity bias were directly correlated with participants' treatment expectations as well as subjective experiences of treatment effects and went along with a significant mood enhancement. Our findings show that expectations can induce a perceptual positivity effect in healthy individuals which is probably modulated by top-down emotion regulation and which may be able to improve mood state. click here Clinical implications of these promising results now need to be explored in studies of expectation manipulation in patients with mood disorders.The acute effects of anesthesia and their underlying mechanisms are still not fully understood. Thus, comprehensive analysis and efficient generalization require their description in various brain regions. Here we describe a large-scale, annotated collection of 2-photon calcium imaging data and multi-electrode, extracellular electrophysiological recordings in CA1 of the murine hippocampus under three distinct anesthetics (Isoflurane, Ketamine/Xylazine and Medetomidine/Midazolam/Fentanyl), during natural sleep, and wakefulness. We cover several aspects of data quality standardization and provide a set of tools for autonomous validation, along with analysis workflows for reuse and data exploration. The datasets described here capture various aspects of neural activity in hundreds of pyramidal cells at single cell resolution. In addition to relevance for basic biological research, the dataset may find utility in computational neuroscience as a benchmark for models of anesthesia and sleep.Electrical impedance methods, including electrical impedance myography, are increasingly being used as biomarkers of muscle health since they measure passive electrical properties of muscle that alter in disease. One disorder, Pompe Disease (Glycogen storage disease type II (GSDII)), remains relatively unstudied. This disease is marked by dramatic accumulation of intracellular myofiber glycogen. Here we assessed the electrical properties of skeletal muscle in a model of GSDII, the Pompe6neo/6neo (Pompe) mouse. Ex vivo impedance measurements of gastrocnemius (GA) were obtained using a dielectric measuring cell in 30-week-old female Pompe (N = 10) and WT (N = 10) mice. Longitudinal and transverse conductivity, σ, and the relative permittivity, εr, and Cole-Cole complex resistivity parameters at 0 Hz and infinite frequency, ρo and ρ∞, respectively, and the intracellular resistivity, ρintracellular were determined from the impedance data. Glycogen content (GC) was visualized histologically and quantified biochemically. At frequencies > 1 MHz, Pompe mice demonstrated significantly decreased longitudinal and transverse conductivity, increased Cole-Cole parameters, ρo and ρo-ρ∞, and decreased ρintracellular. Changes in longitudinal conductivity and ρintracellular correlated with increased GC in Pompe animals. Ex vivo high frequency impedance measures are sensitive to alterations in intracellular myofiber features considered characteristic of GSDII, making them potentially useful measures of disease status.An estimated one billion people globally live with hypovitaminosis D. Studies have indicated that vitamin D deficiency is a risk factor for active tuberculosis (TB) disease. The aim of this study was to determine the association between vitamin D deficiency and TB status among patients with active TB, latent TB infection (LTBI) and those without TB infection. In a cross-sectional study of active TB patients, LTBI, QuantiFERON GOLD testpositive and (QFN+TST+) household contact and controls QuantiFERON GOLD testnegative (QFN-TST-) samples vitamin D levels were compared. Vitamin D status was determined by measurement of total vitamin D levels with 56 samples of active TB patients, 17 with LTBI, and 22 without TB infection using electrochemiluminescence. The median interquartile range (IQR) age of the study participants was 28 (20-35) years, and the majority (63%) were females. The median (IQR) vitamin D levels were 18 ng/ml (14-24). All groups had vitamin D hypovitaminosis with significantly lower levels among active TB patients (17 ng/ml, 13, 2) than among LTBI individuals (23 ng/ml 16-29) and those without TB infection (22 ng/ml, 17-28).The Yucatán Peninsula, Mexico is a carbonate platform well-known for extensive karst networks of densely stratified aquifer ecosystems. This aquifer supports diverse anchialine fauna, including species of the globally distributed anchialine shrimp genus Typhlatya (Atyidae). Four species (T. campecheae, T. pearsei, T. dzilamensis and T. mitchelli) are endemic to the Peninsula, of which three are federally listed in Mexico. This first integrative evaluation (i.e., molecular, morphological, broad geographic and type locality sampling, and environmental data) of Yucatán Typhlatya reveals considerable species identity conflict in prior phylogenetic assessments, broad species ranges, syntopy within cave systems and five genetic lineages (of which two are new to science). Despite sampling from the type locality of endangered T. campecheae, specimens (and molecular data) were indistinguishable from vulnerable T. pearsei. Ancestral/divergence reconstructions support convergent evolution of a low-salinity ancestor for a post-Paleogene arc Yucatán + Cuba Typhlatya clade within the anchialine Atyidae clade.