The Sec1/Munc18 protein Vps45 regulates cellular levels of its SNARE binding partners Tlg2 and Snc2 in Saccharomyces cerevisiae

Intracellular membrane trafficking pathways must be tightly regulated to ensure proper functioning of all eukaryotic cells. Central to membrane trafficking is the formation of specific SNARE (soluble N-ethylmeleimide-sensitive factor attachment protein receptor) complexes between proteins on opposing lipid bilayers. The Sec1/Munc18 (SM) family of proteins play an essential role in SNARE-mediated membrane fusion, and like the SNAREs are conserved through evolution from yeast to humans. The SM protein Vps45 is required for the formation of yeast endosomal SNARE complexes and is thus essential for traffic through the endosomal system. Here we report that, in addition to its role in regulating SNARE complex assembly, Vps45 regulates cellular levels of its SNARE binding partners: the syntaxin Tlg2 and the v-SNARE Snc2: Cells lacking Vps45 have reduced cellular levels of Tlg2 and Snc2; and elevation of Vps45 levels results in concomitant increases in the levels of both Tlg2 and Snc2. As well as regulating traffic through the endosomal system, the Snc v-SNAREs are also required for exocytosis. Unlike most vps mutants, cells lacking Vps45 display multiple growth phenotypes. Here we report that these can be reversed by selectively restoring Snc2 levels in vps45 mutant cells. Our data indicate that as well as functioning as part of the machinery that controls SNARE complex assembly, Vps45 also plays a key role in determining the levels of its cognate SNARE proteins; another key factor in regulation of membrane traffic

Lived Experience of Caregivers of Family-Centered Care in the Neonatal Intensive Care Unit: “Evocation of Being at Home

Background: In recent decades, family-centered care (FCC) has come to be known, accepted, and reported as the best care strategy for admitted children and their families. However, in spite of the increasing application of this approach, the experiences of the caregivers have not yet been studied. Objectives: The present study aimed at the description and interpretation of the FCC experience in two neonatal intensive care units (NICU) at Shiraz University of Medical Sciences. Methods: This study was conducted through the hermeneutic phenomenological approach. Semi-structured interviews were conducted with 17 professional and familial caregivers, and their interactions were observed in three work shifts. The interviews were audiotaped and transcribed verbatim. After observations, field notes were also written. Finally, the data were analyzed through van Manen’s methodology. Results: One of the essential themes that emerged in this study was the “evocation of being at home” among familial and even professional caregivers. This theme had three subthemes: i.e., “meta-family interaction,” “comprehensive support,” and “reconstruction of a normal family.” Accordingly, FCC eliminated borders between professional and non-professional caregivers and built close relationships among them in the NICU. It also provided for the needs of neonates, their families, and even professional caregivers through perceived and received support. Conclusions: Parents of the neonates admitted to the NICU experience hard moments. They not only play the role of primary caregivers, but they also receive the care. Focusing on the different meanings of this care from the caregivers’ points of view and having managers provide certain requirements can guarantee the establishment of comprehensive care for clients and proper support for the staff in this uni

Melting of polymer blends in single-screw extrusion : an experimental study

Melting is a major step in plasticating single screw extrusion, but most of the existing phenomenological know how was gathered by performing Maddock-type experiments with homopolymers. Given the current widespread industrial use of polymer blends, it is worth determining whether the same mechanisms and mathematical models apply, or whether different sequences develop. This work reports the results of Maddock-type experiments using a PA6/PP blend, both in its immiscible and compatibilized varieties. A melting mechanism combining the features of the classical Tadmor mechanism and of the dispersed melting mechanism, also previously reported in the literature, was observed.The authors are grateful to Portuguese Fundacao para a Ciencia e Tecnologia for supporting this work under grant SFRH/BD/19997/2004 and to DSM, the Netherlands, for supplying PA6

Who is dominant? Occupational Health and Safety management in Chinese shipping

This paper investigates the implementation of the International Safety Management (ISM) Code in the Chinese chemical shipping industry. In particular, it examines the tension between management focus on speedy production and seafarers’ participation in safety related decision making and analyses how this tension is managed. It shows that while on paper companies have policies stating safety commitment in compliance with the ISM Code, in practice shore management tends to prioritise efficient production. When Occupational Health and Safety (OHS) and ship’s sailing schedules are in conflict, managers implicitly request shipmasters to prioritise the ‘core interest’ of the company. Although the ISM Code endows shipmasters with overriding authorities in relation to shipboard safety management, they tend to read between the lines and tacitly follow managers’ intentions. The study suggests that if the ISM implementation makes a difference, it is the practice that managers become more subtle in giving orders to exert their dominance. The study further reveals that the management’s practice is not only irresponsive to seafarers’ safety concerns but also makes rather limited contributions to promote OHS Management

Seasonality and the effects of weather on Campylobacter infections

Background Campylobacteriosis is a major public health concern. The weather factors that influence spatial and seasonal distributions are not fully understood. Methods To investigate the impacts of temperature and rainfall on Campylobacter infections in England and Wales, cases of Campylobacter were linked to local temperature and rainfall at laboratory postcodes in the 30 days before the specimen date. Methods for investigation included a comparative conditional incidence, wavelet, clustering, and time series analyses. Results The increase of Campylobacter infections in the late spring was significantly linked to temperature two weeks before, with an increase in conditional incidence of 0.175 cases per 100,000 per week for weeks 17 to 24; the relationship to temperature was not linear. Generalized structural time series model revealed that changes in temperature accounted for 33.3% of the expected cases of Campylobacteriosis, with an indication of the direction and relevant temperature range. Wavelet analysis showed a strong annual cycle with additional harmonics at four and six months. Cluster analysis showed three clusters of seasonality with geographic similarities representing metropolitan, rural, and other areas. Conclusions The association of Campylobacteriosis with temperature is likely to be indirect. High-resolution spatial temporal linkage of weather parameters and cases is important in improving weather associations with infectious diseases. The primary driver of Campylobacter incidence remains to be determined; other avenues, such as insect contamination of chicken flocks through poor biosecurity should be explored

Neuronal circuitry for pain processing in the dorsal horn

Neurons in the spinal dorsal horn process sensory information, which is then transmitted to several brain regions, including those responsible for pain perception. The dorsal horn provides numerous potential targets for the development of novel analgesics and is thought to undergo changes that contribute to the exaggerated pain felt after nerve injury and inflammation. Despite its obvious importance, we still know little about the neuronal circuits that process sensory information, mainly because of the heterogeneity of the various neuronal components that make up these circuits. Recent studies have begun to shed light on the neuronal organization and circuitry of this complex region

Bottom up ethics - neuroenhancement in education and employment

Neuroenhancement involves the use of neurotechnologies to improve cognitive, affective or behavioural functioning, where these are not judged to be clinically impaired. Questions about enhancement have become one of the key topics of neuroethics over the past decade. The current study draws on in-depth public engagement activities in ten European countries giving a bottom-up perspective on the ethics and desirability of enhancement. This informed the design of an online contrastive vignette experiment that was administered to representative samples of 1000 respondents in the ten countries and the United States. The experiment investigated how the gender of the protagonist, his or her level of performance, the efficacy of the enhancer and the mode of enhancement affected support for neuroenhancement in both educational and employment contexts. Of these, higher efficacy and lower performance were found to increase willingness to support enhancement. A series of commonly articulated claims about the individual and societal dimensions of neuroenhancement were derived from the public engagement activities. Underlying these claims, multivariate analysis identified two social values. The Societal/Protective highlights counter normative consequences and opposes the use enhancers. The Individual/Proactionary highlights opportunities and supports use. For most respondents these values are not mutually exclusive. This suggests that for many neuroenhancement is viewed simultaneously as a source of both promise and concern

Impairment of Auditory-Motor Timing and Compensatory Reorganization after Ventral Premotor Cortex Stimulation

Integrating auditory and motor information often requires precise timing as in speech and music. In humans, the position of the ventral premotor cortex (PMv) in the dorsal auditory stream renders this area a node for auditory-motor integration. Yet, it remains unknown whether the PMv is critical for auditory-motor timing and which activity increases help to preserve task performance following its disruption. 16 healthy volunteers participated in two sessions with fMRI measured at baseline and following rTMS (rTMS) of either the left PMv or a control region. Subjects synchronized left or right finger tapping to sub-second beat rates of auditory rhythms in the experimental task, and produced self-paced tapping during spectrally matched auditory stimuli in the control task. Left PMv rTMS impaired auditory-motor synchronization accuracy in the first sub-block following stimulation (p<0.01, Bonferroni corrected), but spared motor timing and attention to task. Task-related activity increased in the homologue right PMv, but did not predict the behavioral effect of rTMS. In contrast, anterior midline cerebellum revealed most pronounced activity increase in less impaired subjects. The present findings suggest a critical role of the left PMv in feed-forward computations enabling accurate auditory-motor timing, which can be compensated by activity modulations in the cerebellum, but not in the homologue region contralateral to stimulation

Lithium and GSK3-β promoter gene variants influence white matter microstructure in bipolar disorder

Lithium is the mainstay for the treatment of bipolar disorder (BD) and inhibits glycogen synthase kinase 3-β (GSK3-β). The less active GSK3-β promoter gene variants have been associated with less detrimental clinical features of BD. GSK3-β gene variants and lithium can influence brain gray matter structure in psychiatric conditions. Diffusion tensor imaging (DTI) measures of white matter (WM) integrity showed widespred disruption of WM structure in BD. In a sample of 70 patients affected by a major depressive episode in course of BD, we investigated the effect of ongoing long-term lithium treatment and GSK3-β promoter rs334558 polymorphism on WM microstructure, using DTI and tract-based spatial statistics with threshold-free cluster enhancement. We report that the less active GSK3-β rs334558*C gene-promoter variants, and the long-term administration of the GSK3-β inhibitor lithium, were associated with increases of DTI measures of axial diffusivity (AD) in several WM fiber tracts, including corpus callosum, forceps major, anterior and posterior cingulum bundle (bilaterally including its hippocampal part), left superior and inferior longitudinal fasciculus, left inferior fronto-occipital fasciculus, left posterior thalamic radiation, bilateral superior and posterior corona radiata, and bilateral corticospinal tract. AD reflects the integrity of axons and myelin sheaths. We suggest that GSK3-β inhibition and lithium could counteract the detrimental influences of BD on WM structure, with specific benefits resulting from effects on specific WM tracts contributing to the functional integrity of the brain and involving interhemispheric, limbic, and large frontal, parietal, and fronto-occipital connections

The role of modelling and analytics in South African COVID-19 planning and budgeting

Background The South African COVID-19 Modelling Consortium (SACMC) was established in late March 2020 to support planning and budgeting for COVID-19 related healthcare in South Africa. We developed several tools in response to the needs of decision makers in the different stages of the epidemic, allowing the South African government to plan several months ahead. Methods Our tools included epidemic projection models, several cost and budget impact models, and online dashboards to help government and the public visualise our projections, track case development and forecast hospital admissions. Information on new variants, including Delta and Omicron, were incorporated in real time to allow the shifting of scarce resources when necessary. Results Given the rapidly changing nature of the outbreak globally and in South Africa, the model projections were updated regularly. The updates reflected 1) the changing policy priorities over the course of the epidemic; 2) the availability of new data from South African data systems; and 3) the evolving response to COVID-19 in South Africa, such as changes in lockdown levels and ensuing mobility and contact rates, testing and contact tracing strategies and hospitalisation criteria. Insights into population behaviour required updates by incorporating notions of behavioural heterogeneity and behavioural responses to observed changes in mortality. We incorporated these aspects into developing scenarios for the third wave and developed additional methodology that allowed us to forecast required inpatient capacity. Finally, real-time analyses of the most important characteristics of the Omicron variant first identified in South Africa in November 2021 allowed us to advise policymakers early in the fourth wave that a relatively lower admission rate was likely. Conclusion The SACMC’s models, developed rapidly in an emergency setting and regularly updated with local data, supported national and provincial government to plan several months ahead, expand hospital capacity when needed, allocate budgets and procure additional resources where possible. Across four waves of COVID-19 cases, the SACMC continued to serve the planning needs of the government, tracking waves and supporting the national vaccine rollout