Morphological development and cytochrome c oxidase activity in Streptomyces lividans are dependent on the action of a copper bound Sco protein

Copper has an important role in the life cycle of many streptomycetes, stimulating the developmental switch between vegetative mycelium and aerial hyphae concomitant with the production of antibiotics. In streptomycetes, a gene encoding for a putative Sco-like protein has been identified and is part of an operon that contains two other genes predicted to handle cellular copper. We report on the Sco-like protein from Streptomyces lividans (Sco Sl ) and present a series of experiments that firmly establish a role for Sco Sl as a copper metallochaperone as opposed to a role as a thiol-disulphide reductase that has been assigned to other bacterial Sco proteins. Under low copper concentrations, a Δ sco mutant in S. lividans displays two phenotypes; the development switch between vegetative mycelium and aerial hyphae stalls and cytochrome c oxidase (CcO) activity is significantly decreased. At elevated copper levels, the development and CcO activity in the Δ sco mutant are restored to wild-type levels and are thus independent of Sco Sl . A CcO knockout reveals that morphological development is independent of CcO activity leading us to suggest that Sco Sl has at least two targets in S. lividans . We establish that one Sco Sl target is the dinuclear Cu A domain of CcO and it is the cupric form of Sco Sl that is functionally active. The mechanism of cupric ion capture by Sco Sl has been investigated, and an important role for a conserved His residue is identified. </jats:p

Assessment of adjustment to electrical threshold (T) level and electrical stimulation rate on intensity discrimination and amplitude modulation detection at soft presentation level in adult CI users

© 2019 Proceedings of the International Congress on Acoustics. All rights reserved. A pilot study was conducted to evaluate the influence of electrical stimulation rate and the setting of electrical threshold (T) level on intensity difference limens (IDLs) and amplitude modulation (AM) perception. Participants were ten adult experienced Advanced Bionics cochlear implant (CI) users. The frequency of acoustic sinusoidal stimuli was set at 1076Hz with the intention of stimulating intra-cochlear electrode 7 of the 16 electrode array. Nine experimental maps were created with T levels set at: the threshold of audibility; a level perceived as 'very soft' and 10% of the level judged to produce 'most comfortable loudness'. Rates of electrical stimulation were 905, 1811 and 2750 pulses-per-second (pps). Adaptive 2I-2AFC IDL and AM perception tasks were presented via headphones at soft presentation levels (approximately 50dBSPL). The influence of T Level and stimulation rate adjustments on IDL and AM perception have been explored with the intention of understanding the impact of altering individual parameter settings to optimise detection of acoustic cues at low presentation levels

Antibiotic resistance profiles and relatedness of enteric bacterial pathogens isolated from HIV/AIDS patients with and without diarrhoea and their household drinking water in rural communities in Limpopo Province South Africa

Antibiotic resistance profiles and the correlation of enteric bacterial pathogens from HIV positive individuals with and without diarrhoea and their household drinking water were determined using the KirbyBauer disk diffusion and polymerase chain reaction methods respectively. The sef gene of Salmonella enteritidis was amplified with the primer pair sefA-1 and sefA-2. The fliC gene of Salmonella typhimurium was amplified with the primer pair flicA-1 and flicA-2. Heat-labile toxin (LT) primers (Lta and LTb) were used to amplify Escherichia coli isolates and VirA1 and VirA2 for the Vir A gene of Shigella dysenteriae. Results of antibiotic resistance profiles of enteric bacterial pathogens isolated from stool samples of HIV positive and negative individuals with and without diarrhea and their household drinking water showed very similar drug resistance patterns. Over 90% of all the organisms isolated from the various study cohorts showed resistance to penicillin, cloxacillin and amoxicillin. Conversely, almost all the organisms were sensitive to ciprofloxacin, gentamycin, meropenem and imipenem. About 50% of E. coli isolated from the various study cohorts showed multiple antibiotic resistance to penicillin, amoxicillin, ampicillin, erythromycin, tetracycline, doxycycline and cotri-moxazole ( PR, AR, APR, ER, TR, DXTR, and TSR ) whereas less than 10% resistance was consistently reported for ofloxacin, gentamycin, meropenem cefotaxime, cefuroxime and imipenem ( OFXS, GMS, MEMS, CTXS, CXMS and IMIS ). The majority of Salmonella and Shigella isolates from all the groups were sensitive to ciprofloxacin, gentamicin, amikacin, meropenem, imipenem, nalidixic acid, kanamycin, piperacillin-tazo bactam, cefuroxime, doxycyclin, cefepime and ceftazidime (CIPS, GMS, AKS, MEMS, IMIS, NAS, KNS, DXTS, CXMS, CPMS, CAZS and PTZS). For Campylobacter, over 30% of the isolates were resistant to erythromycin, ampicillin, tetracycline,cotrimoxazole and ceftazidime (ER, APR TSR and CAZR) whereas over 85% were susceptible to ciprofloxacin, ofloxacin, gentamycin, amikacin, mero-penem, and nalidixic acid (CIPS, OFXS, GMS, AKS,MEMS and NAS). In addition to penicillin, amoxicillin, ampicillin and erythromycin, Aeromonas and Plesiomonas spp were more resistant to chloramphenicol, but were susceptible to ciprofloxacin, gentamycin, amikacin, meropenem, imipenem and nalidixic acid (CIPS, GMS, AKS, MEMS, IMIS and NAS). Polymerase Chain Reaction (PCR) experiments using targeted species genes of S. enteritidis, S. typhimurium, E. coli, Sh. dysenteriae showed that isolates from stool samples of HIV positive and HIV negative individuals with and without diarrhoea were also present in the household drinking water of the same study cohorts, suggesting that drinking water may have been the sources of the organisms in stool sample. Furthermore, by showing that the primers were able to amplify the genes in both clinical and environmental isolates, the link between the virulence of the pathogens was established

Failure modes in high strength and stiffness to weight scaffolds produced by Selective Laser Melting

The production of porous scaffold structures using additive manufacturing is becoming widespread, however a detailed understanding of the scaffold failure mechanisms is lacking. In this research, Selective Laser Melting (SLM) is used to produce Ti–6Al–4V scaffold structures consisting of a regular array of unit cells previously designed using topology optimisation. Interrupted compression testing and subsequent X-Ray Micro Tomography (XMT) characterisation is used to study the deformation and failure of the scaffolds for a range of solid fractions. Further, the XMT data of the unloaded scaffolds is used to generate meshes for finite element analysis which allowed direct comparison of desired and as built behaviour. Likely failure sites predicted from the finite element analysis compare favourably with the experimentally observed ones. Failure is initiated in areas that exhibit the greatest tensile stress, while the onset of the commonly observed layered failure occurs afterwards. The XMT of the unloaded scaffolds also highlights the inaccuracies in the SLM build process, which contributes to stress concentrations in the horizontal arms within the scaffolds. The results indicate that although the strength of the topology optimised structures is very high, further refinement in both the unit cell design and build quality would further increase the strength

Effects of exercise intensity and nutrition advice on myocardial function in obese children and adolescents: a multicentre randomised controlled trial study protocol.

INTRODUCTION: The prevalence of paediatric obesity is increasing, and with it, lifestyle-related diseases in children and adolescents. High-intensity interval training (HIIT) has recently been explored as an alternate to traditional moderate-intensity continuous training (MICT) in adults with chronic disease and has been shown to induce a rapid reversal of subclinical disease markers in obese children and adolescents. The primary aim of this study is to compare the effects of HIIT with MICT on myocardial function in obese children and adolescents. METHODS AND ANALYSIS: Multicentre randomised controlled trial of 100 obese children and adolescents in the cities of Trondheim (Norway) and Brisbane (Australia). The trial will examine the efficacy of HIIT to improve cardiometabolic outcomes in obese children and adolescents. Participants will be randomised to (1) HIIT and nutrition advice, (2) MICT and nutrition advice or (3) nutrition advice. Participants will partake in supervised exercise training and/or nutrition sessions for 3 months. Measurements for study end points will occur at baseline, 3 months (postintervention) and 12 months (follow-up). The primary end point is myocardial function (peak systolic tissue velocity). Secondary end points include vascular function (flow-mediated dilation assessment), quantity of visceral and subcutaneous adipose tissue, myocardial structure and function, body composition, cardiorespiratory fitness, autonomic function, blood biochemistry, physical activity and nutrition. Lean, healthy children and adolescents will complete measurements for all study end points at one time point for comparative cross-sectional analyses. ETHICS AND DISSEMINATION: This randomised controlled trial will generate substantial information regarding the effects of exercise intensity on paediatric obesity, specifically the cardiometabolic health of this at-risk population. It is expected that communication of results will allow for the development of more effective evidence-based exercise prescription guidelines in this population while investigating the benefits of HIIT on subclinical markers of disease. TRIAL REGISTRATION NUMBER: NCT01991106

Development of complex executive function over childhood: Longitudinal growth curve modeling of performance on the Groton Maze Learning Task

Supporting Information is available online at https://srcd.onlinelibrary.wiley.com/doi/10.1111/cdev.13888#support-information-section .Copyright © 2023 The Authors. This longitudinal study modeled children's complex executive function (EF) development using the Groton Maze Learning Task (GMLT). Using a cohort-sequential design, 147 children (61 males, 5.5–11 years) were recruited from six multicultural primary schools in Melbourne and Perth, Australia. Race/ethnicity data were not available. Children were assessed on the GMLT at 6-month intervals over 2-years between 2010 and 2012. Growth curve models describe age-related change from 5.5 to 12.5 years old. Results showed a quadratic growth trajectory on each measure of error—that is, those that reflect visuospatial memory, executive control (or the ability to apply rules for action), and complex EF. The ability to apply rules for action, while a rate-limiting factor in complex EF, develops rapidly over early-to-mid childhood.Australian Research Council. Grant Number: DP1094535; Open access publishing facilitated by Australian Catholic University, as part of the Wiley - Australian Catholic University agreement via the Council of Australian University Librarians

A Surprising Prevention Success: Why Did the HIV Epidemic Decline in Zimbabwe?

Daniel Halperin and colleagues examine reasons for the remarkable decline in HIV in Zimbabwe, in the context of severe social, political, and economic disruption

Notch signaling during human T cell development

Notch signaling is critical during multiple stages of T cell development in both mouse and human. Evidence has emerged in recent years that this pathway might regulate T-lineage differentiation differently between both species. Here, we review our current understanding of how Notch signaling is activated and used during human T cell development. First, we set the stage by describing the developmental steps that make up human T cell development before describing the expression profiles of Notch receptors, ligands, and target genes during this process. To delineate stage-specific roles for Notch signaling during human T cell development, we subsequently try to interpret the functional Notch studies that have been performed in light of these expression profiles and compare this to its suggested role in the mouse