Hodemant0682

ainst neuropathic pain. Chronic EGF or PDGF administration induces mechanical sensitization, a prominent component of neuropathic pain, and renders animals 'pre-tolerant' to subsequent analgesic doses of morphine. Taken together, these results suggest a direct mechanistic link between opioid tolerance and neuropathic pain. EGFR antagonism could eventually play an important role in the treatment of opioid tolerance and severe neuropathic pain that requires ever increasing doses of opioids. Copyright © 2020 Puig et al.Plasma DNA fragmentomics is an emerging area of research covering plasma DNA sizes, end-points, and nucleosome footprints. In the present study, we found a significant increase in the diversity of plasma DNA end motifs in patients with hepatocellular carcinoma (HCC). Compared with patients without HCC, patients with HCC showed a preferential pattern of 4-mer end motifs. In particular, the abundance of plasma DNA motif CCCA was much lower in patients with HCC than that in subjects without HCC. The aberrant end motifs were also observed in patients with other cancer types, including colorectal cancer, lung cancer, nasopharyngeal carcinoma, and head and neck squamous cell carcinoma. We further observed that the profile of plasma DNA end motifs originating from the same organ, such as the liver, placenta, and hematopoietic cells, generally clustered together. The profile of end motifs may therefore serve as a class of biomarkers for liquid biopsy. Copyright ©2020, American Association for Cancer Research.The anti-HER2-drug conjugate trastuzumab deruxtecan (T-DXd) was effective in HER2-low breast cancer. ©2020 American Association for Cancer Research.The structure of CD20 with the antibody drug rituximab showed the binding mode and 22 stoichiometry. ©2020 American Association for Cancer Research.Group 2 innate lymphoid cells (ILC2) exerted antitumor effects in pancreatic adenocarcinomas. ©2020 American Association for Cancer Research.PD-1 depletion or nivolumab treatment dampened morphine antinociception in mice and rhesus macaques. selleck chemicals llc ©2020 American Association for Cancer Research.The 'First Thousand Days' refers to the period from conception to the child's second birthday. It is increasingly gaining traction as a concept to guide public health policy. It is seen as a crucial window of opportunity for interventions that improve child and population health. This review outlines the origin and growth of the First Thousand Days concept, and the evidence behind it, particularly in the areas of brain development and cognition; mental and emotional health; nutrition and obesity; programming and economic benefits. The review then describes UK experience of use of the concept to inform policy, and a recent government inquiry that mandates more widespread implementation. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.OBJECTIVE To evaluate the use of cerebrospinal fluid (CSF) ferritin levels in the diagnosis of purulent meningitis (PM). METHOD We studied 81 children between 28 days and 12 years of age who presented with clinical suspicion of meningitis to the emergency department. CSF ferritin levels were measured and compared between diagnostic groups (PM, aseptic meningitis (AM) and no meningitis). RESULTS The median age was 24 (IQR 8-69) months. There were 32 patients with AM (39%), 23 with PM (28%) and 26 with no meningitis (32%). Median CSF ferritin was 4.2 ng/mL (IQR 3.0-6.5), 52.9 ng/mL (IQR 30.7-103 ng/mL) and 2.4 ng/mL (IQR 2-4), respectively. CSF ferritin was higher in children with PM compared with AM (p less then 0.001) or no meningitis (p less then 0.001). There was no difference between AM and no meningitis. CONCLUSION CSF ferritin may be a useful biomarker to discriminate PM in children with clinical symptoms of this disease. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.Lactococcus lactis encounters various environmental challenges, especially acid stress, during its growth. Cell wall can maintain the integrity and shape of the cell under the environmental stress, and D-amino acids play an important role in the cell wall synthesis. Here, by analyzing the effects of 19 diverse D-amino acids on the physiology of L. lactis F44, we found that the exogenously supplied D-methionine and D-phenylalanine could increase the nisin yield by 93.22 % and 101.29 % respectively as well as significantly increasing the acid-resistant ability in L. lactis F44. The composition of the cell wall in L. lactis F44 with exogenously supplied D-Met or D-Phe was further investigated via vancomycin fluorescence experiment and liquid chromatography-mass spectrometry assay, demonstrating that D-Met could be incorporated into the fifth position of peptidoglycan (PG) muropeptides and D-Phe could be added to the fourth and fifth position. Moreover, the overexpression of PG synthesis gene murF further enhanced the levels of D-Met and D-Phe involved in PG and increased the survival rate under acid stress and the nisin yield of the strain. This study reveals that the exogenous supply of D-Met or D-Phe can change the composition of the cell wall and influence acid tolerance as well as nisin yield in L. lactis ImportanceAs D-amino acids play an important role in cell wall synthesis, we analyzed the effects of 19 diverse D-amino acids on L. lactis F44, demonstrating that D-Met and D-Phe could participate in the peptidoglycan (PG) synthesis, and improve the acid resistance and nisin yield of the strain. murF overexpression could further increase the levels of D-Met and D-Phe incorporated into PG and contributed to the acid resistance of the strain. These findings suggest that D-Met and D-Phe can be incorporated into PG to improve the acid resistance and nisin yield of L. lactis, and this study provides new ideas for the enhancement of the strain production. Copyright © 2020 American Society for Microbiology.Metallothionein (MT) genes are valuable genetic materials for developing metal bioremediation tools. Currently, a limited number of prokaryotic MTs have been experimentally identified, which necessitates the expansion of bacterial MTs diversity. In this study, we conducted a metagenomics-guided analysis for the discovery of potential bacterial MT genes from the soil microbiome. More specifically, we combined resistance gene enrichment through diversity loss, metagenomic mining with a dedicated MTs database, evolutionary trace analysis, DNA chemical synthesis and functional genomic validation to identify novel MTs. Results showed that Cu stress induced a compositional change in the soil microbiome, with an enrichment of metal resistant bacteria in soils with higher Cu concentrations. Shotgun metagenomic sequencing was done to obtain the gene pool of environmental DNA (eDNA), which was subjected to a Local BLAST search against an MT database for detecting putative MT genes. Evolutional trace analysis led to the identification of 27 potential MTs with conserved cysteine/histidine motifs different from those of known prokaryotic MTs. Following chemical synthesis of these 27 potential MT genes and heterologous expression in Escherichia coli, six of them were found to improve the hosts' growth substantially and enhanced the hosts' sorption of Cu, Cd, and Zn, among which MT5 led to a 13.7-fold increase in Cd accumulation. Further, four of them restored Cu and/or Cd resistance in two metal-sensitive E. coli strains.IMPORTANCEThe metagenomics-guided procedure developed here bypasses the difficulties encountered in classic PCR-based approaches and led to the discovery of novel MT genes, which may be useful in developing bio-remediation tools. The procedure used here expands our knowledge on the diversity of bacterial MTs in the environment, and may also be applicable to identify other functional genes from eDNA. Copyright © 2020 American Society for Microbiology.Changing nutritional conditions challenge microbes and shape their evolutionary optimization. Here we investigated the role of glycogen in dynamic physiological adaptation of Escherichia coli to fluctuating nutrients following carbon starvation using real-time metabolomics. We found significant metabolic activity remaining after the depletion of environmental glucose that was linked to a rapid utilization of intracellular glycogen. Glycogen was depleted by 80% within minutes of glucose starvation and similarly replenished within minutes of glucose availability. link2 These fast timescales of glycogen utilization correspond to the short-term benefits that glycogen provided to cells undergoing various physiological transitions. Cells capable of utilizing glycogen exhibited shorter lag times than glycogen mutants when starved between different carbon sources. The ability to utilize glycogen was also important for the transition between planktonic and biofilm lifestyles and enabled increased glucose uptake during pulsetarved between different carbon sources. While wild- type and mutant strains exhibited comparable growth rates in steady environments, mutants deficient in glycogen utilization grew more poorly in environments that fluctuated on minute- scales between carbon availability and starvation. These results highlight an underappreciated role of glycogen to rapidly provide carbon and energy in changing environments, thereby increasing survival and competition capabilities in fluctuating and nutrient poor conditions. Copyright © 2020 American Society for Microbiology.Campylobacter has been recognized as a major foodborne pathogen worldwide. An increasing frequency of antibiotic-resistant pathogens including Campylobacter is identified to transmit from food products to humans and causes severe threats to public health. To better mitigate antibiotic resistance crisis, rapid detection methods are required to provide timely antimicrobial resistance surveillance data for the agri-food systems. Herein, we developed a polymer-based microfluidic device for the identification and antimicrobial susceptibility testing (AST) of Campylobacter An array of bacterial incubation chambers was created in the microfluidic device, where chromogenic medium and antibiotics were loaded. The growth of Campylobacter was visualized by color change due to the chromogenic reaction. This platform achieved 100% specificity of Campylobacter identification. Sensitive detection of multiple Campylobacter species (i.e., C. jejuni, C. coli, and C. lari) was obtained in artificially contaminated milk and poulluidic device. Our developed method not only reduced total analysis time, but also simplified food sample preparation and chip operation for end users. Due to the miniaturized size of lab-on-a-chip platform, the detection was achieved by using up to 1000-time less reagents than standard reference methods, making it a competitive approach for rapid screening and surveillance study in food industries. In addition, multiple clinically important Campylobacter species (C. link3 jejuni, C. coli, C. lari) could be tested by our device. This device has potential for wide application in food safety management and clinical diagnostics especially in the resource-limited regions. Copyright © 2020 American Society for Microbiology.