Cortezgraham7256

Kauri dieback disease, caused by Phytophthora agathidicida currently threatens the kauri forest ecosystem. Results from this research highlight the need for further investigations into how changes to soil microbial diversity surrounding remnant kauri fragments impact tree health and disease expression. © FEMS 2020.Aromatase (P450arom, CYP19A1) is the terminal enzyme in the synthesis of the steroid hormone family of estrogens. Not surprisingly, this enzyme has structural similarities between the limited number of species studied thus far. This study examined the structure of aromatases from four diverse Australian species including a marsupial (tammar wallaby; Macropus eugenii), monotreme (platypus; Ornithorhynchus anatinus), ratite (emu; Dromaius novaehollandiae) and lizard (bearded dragon; Pogona vitticeps). We successfully built homology models for each species, using the only crystallographically determined structure available, human aromatase. The amino acid sequences showed high amino acid sequence identity to the human aromatase wallaby 81%, platypus 73%, emu 75% and bearded dragon at 74%. The overall structure was highly conserved among the five species, although there were non-secondary structures (loops and bends) that were variable and flexible that may result in some differences in catalytic activity. At the N-terminal regions there were deletions and variations that suggest functional distinctions may be found. We found that the active sites of all these proteins were identical, except for a slight variation in the emu. The electrostatic potential across the surfaces of these aromatases highlighted likely variations to the protein-protein interactions of these enzymes with both redox partner cytochrome P450 reductase and possibly homodimerization in the case of the platypus, which has been postulated for the human aromatase enzyme. Given the high natural selection pressures on reproductive strategies the relatively high degree of conservation of aromatase sequence and structure across species suggests that there is biochemically very little scope for changes to have evolved without the loss of enzyme activity. © The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction.The Glycosylphosphatidylinositol (GPI) anchor is a post-translational modification added to approximately 150 different proteins to facilitate proper membrane anchoring and trafficking to lipid rafts. Biosynthesis and remodeling of the GPI anchor requires the activity of over twenty distinct genes. Defects in the biosynthesis of GPI anchors in humans leads to Inherited Glycosylphosphatidylinositol Deficiency (IGD). IGD patients display a wide range of phenotypes though the central nervous system (CNS) appears to be the most commonly affected tissue. A full understanding of the etiology of these phenotypes has been hampered by the lack of animal models due to embryonic lethality of GPI biosynthesis gene null mutants. Here we model IGD by genetically ablating GPI production in the CNS with a conditional mouse allele of phosphatidylinositol glycan anchor biosynthesis, class A (Piga) and Nestin-Cre. We find that the mutants do not have structural brain defects but do not survive past weaning. The mutants show progressive decline with severe ataxia consistent with defects in cerebellar development. We show the mutants have reduced myelination and defective Purkinje cell development. Surprisingly we found Piga was expressed in a fairly restricted pattern in the early postnatal brain consistent with the defects we observed in our model. Thus, we have generated a novel mouse model of the neurological defects of IGD which demonstrates a critical role for GPI biosynthesis in cerebellar and white matter development. © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.The association between increased serum urate and hypertension has been a subject of intense controversy. Extracellular uric acid drives uric acid deposition in gout, kidney stones, and possibly vascular calcification. Mendelian randomization studies, however, indicate that serum urate is likely not the causal factor in hypertension although it does increase the risk for sudden cardiac death and diabetic vascular disease. Nevertheless, experimental evidence strongly suggests that an increase in intracellular urate is a key factor in the pathogenesis of primary hypertension. Pilot clinical trials show beneficial effect of lowering serum urate in hyperuricemic individuals who are young, hypertensive, and have preserved kidney function. Some evidence suggest that activation of the renin angiotensin system (RAS) occurs in hyperuricemia and blocking the RAS may mimic the effects of xanthine oxidase inhibitors. A reduction in intracellular urate may be achieved by lowering serum urate concentration or by suppressing intracellular urate production with dietary measures that include reducing sugar, fructose and salt intake. We suggest that these elements in the western diet may play a major role in the pathogenesis of primary hypertension. Studies are necessary to better define the interrelation between uric acid concentrations inside and outside the cell. In addition, large-scale clinical trials are needed to determine if extracellular and intracellular urate reduction can provide benefit hypertension and cardiometabolic disease. © American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email journals.permissions@oup.com.In plant cells, environmental stressors promote changes in connectivity between the cortical ER and the PM. Although this process is tightly regulated in space and time, the molecular signals and structural components mediating these changes in inter-organelle communication are only starting to be characterized. In this report, we confirm the presence of a putative tethering complex containing the synaptotagmins 1 and 5 (SYT1 and SYT5) and the Ca2+ and lipid binding protein 1 (CLB1/SYT7). This complex is enriched at ER-PM contact sites (EPCS), have slow responses to changes in extracellular Ca2+, and display severe cytoskeleton-dependent rearrangements in response to the trivalent lanthanum (La3+) and gadolinium (Gd3+) rare earth elements (REEs). Although REEs are generally used as non-selective cation channel blockers at the PM, here we show that the slow internalization of REEs into the cytosol underlies the activation of the Ca2+/Calmodulin intracellular signaling, the accumulation of phosphatidylinositol-4-phosphate (PI4P) at the PM, and the cytoskeleton-dependent rearrangement of the SYT1/SYT5 EPCS complexes. We propose that the observed EPCS rearrangements act as a slow adaptive response to sustained stress conditions, and that this process involves the accumulation of stress-specific phosphoinositides species at the PM. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Experimental Biology.Human noroviruses are the most common viral agents of acute gastroenteritis. Recently, human intestinal enteroids were shown to be permissive for norovirus infection. We tested their suitability as a system to study norovirus neutralization. Hyperimmune sera raised against virus-like particles (VLPs) representing different genotypes showed highly-specific neutralization activity against GII.4 and GII.6 noroviruses. Carbohydrate blocking assays and neutralization exhibited similar patterns in antibody responses. Notably, sera produced against chimeric VLPs that presented swapped structural domains, shell and protruding (P), from different genotypes showed that neutralization is primarily mediated by antibodies mapping to the P domain of the norovirus capsid protein. This study provides empirical information on the antigenic differences among genotypes as measured by neutralization, which could guide vaccine design. Published by Oxford University Press for the Infectious Diseases Society of America 2020. This work is written by (a) US Government employee(s) and is in the public domain in the US.CONTEXT Clinicians, researchers, and global health advocates often include pubertal development in outcomes. However, assessments of pubertal stage can be challenging due to the sensitive nature and feasibility of clinical examinations, especially in larger settings. OBJECTIVE To determine the accuracy of self-assessed Tanner Staging when compared to physically-assessed Tanner Stages by a clinician. DATA SOURCES MEDLINE, Pubmed, Embase, Web of Science, Scopus, the Cochrane Library, CINHAL. STUDY SELECTION Studies were included if they reported 5x5 tables of self-assessment compared to clinician-assessment for the five-stage Tanner scale. DATA EXTRACTION We extracted data to generate complete 5x5 tables for each study, including any sub-group eligible for the analysis, such as overweight/obese youth. DATA SYNTHESIS After screening, 22 studies representing 21,801 participants met our inclusion criteria for the meta-analysis. Overall agreement was moderate or substantial between the two assessments, with breast stage 1, female pubic hair 1, male pubic hair 1 and male pubic hair 5 having the highest agreement. When stages were collapsed into pre- (Tanner stage1), in- (stages 2,3) and completing- (stages 4,5) puberty, levels of agreement improved, especially for pre- and completing- pubertal development. Most included studies were comprised of Caucasian youth. More studies from broader geographic and socioeconomic settings and including a broader range of racial/ethnic groups are needed. CONCLUSIONS Self-assessment of puberty is most accurate when identifying Tanner stage 1 and Tanner stage 5 and when development is categorized into pre-puberty, in- and completing-puberty phases. Use of self-assessment data should be structured accordingly. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Corona Virus Disease 2019 (COVID-19) originated in Wuhan, China has caused many healthcare workers (HCWs) infected. selleck chemicals Seventy-two HCWs manifested with acute respiratory illness were retrospectively enrolled to analyze the risk factors. The high-risk department, longer duty hours, and suboptimal hand hygiene after contacting with patients were linked to COVID-19. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.BACKGROUND Blastomyces is a dimorphic fungus that infects persons with or without underlying immunocompromise. To date, no study has compared the clinical features and outcomes of blastomycosis between immunocompromised and immunocompetent persons. METHODS A retrospective study of adult patients with proven blastomycosis from 2004 - 2016 was conducted at the University of Wisconsin. Epidemiology, clinical features, and outcomes were analyzed among solid organ transplantation (SOT) recipients, persons with non-SOT immunocompromise (non-SOT IC), and persons with no immunocompromise (NIC). RESULTS A total of 106 cases met inclusion criteria including 74 NIC, 19 SOT, and 13 non-SOT IC (malignancy, HIV/AIDS, idiopathic CD4+ lymphopenia). The majority of patients (61.3%) had at least 1 epidemiologic risk factor for acquisition of Blastomyces. Pneumonia was the most common manifestation in all groups; however, immunocompromised patients had higher rates of acute pulmonary disease (p = 0.03), more severe infection (p = 0.