The presynaptic ribbon maintains vesicle populations at the hair cell afferent fiber synapse

The ribbon is the structural hallmark of cochlear inner hair cell (IHC) afferent synapses, yet its role in information transfer to spiral ganglion neurons (SGNs) remains unclear. We investigated the ribbon’s contribution to IHC synapse formation and function using KO mice lacking RIBEYE. Despite loss of the entire ribbon structure, synapses retained their spatiotemporal development and KO mice had a mild hearing deficit. IHCs of KO had fewer synaptic vesicles and reduced exocytosis in response to brief depolarization; a high stimulus level rescued exocytosis in KO. SGNs exhibited a lack of sustained excitatory postsynaptic currents (EPSCs). We observed larger postsynaptic glutamate receptor plaques, potentially compensating for the reduced EPSC rate in KO. Surprisingly, large-amplitude EPSCs were maintained in KO, while a small population of low-amplitude slower EPSCs was increased in number. The ribbon facilitates signal transduction at physiological stimulus levels by retaining a larger residency pool of synaptic vesicles.</jats:p

Large-scale annotated dataset for cochlear hair cell detection and classification

Our sense of hearing is mediated by cochlear hair cells, of which there are two types organized in one row of inner hair cells and three rows of outer hair cells. Each cochlea contains 5-15 thousand terminally differentiated hair cells, and their survival is essential for hearing as they do not regenerate after insult. It is often desirable in hearing research to quantify the number of hair cells within cochlear samples, in both pathological conditions, and in response to treatment. Machine learning can be used to automate the quantification process but requires a vast and diverse dataset for effective training. In this study, we present a large collection of annotated cochlear hair-cell datasets, labeled with commonly used hair-cell markers and imaged using various fluorescence microscopy techniques. The collection includes samples from mouse, rat, guinea pig, pig, primate, and human cochlear tissue, from normal conditions and following in-vivo and in-vitro ototoxic drug application. The dataset includes over 107,000 hair cells which have been identified and annotated as either inner or outer hair cells. This dataset is the result of a collaborative effort from multiple laboratories and has been carefully curated to represent a variety of imaging techniques. With suggested usage parameters and a well-described annotation procedure, this collection can facilitate the development of generalizable cochlear hair-cell detection models or serve as a starting point for fine-tuning models for other analysis tasks. By providing this dataset, we aim to give other hearing research groups the opportunity to develop their own tools with which to analyze cochlear imaging data more fully, accurately, and with greater ease

Research cardiac magnetic resonance imaging in end stage renal disease - incidence, significance and implications of unexpected incidental findings

Objectives: Left ventricular mass (LVM) at cardiac magnetic resonance imaging (CMR) is a frequent end point in clinical trials in nephrology. Trial participants with end stage renal disease (ESRD) may have a greater frequency of incidental findings (IF). We retrospectively investigated prevalence of IF in previous research CMR and reviewed their subsequent impact on participants. Methods: Between 2002 and 2006, 161 ESRD patients underwent CMR in a transplant assessment study. Images were used to assess LV mass and function. In the current study a radiologist reviewed the scans for IF. Review of patient records determined the subsequent clinical significance of IF. Results: There were 150 IF in 95 study participants. Eighty-four (56 %) were new diagnoses. One hundred and two were non-cardiac. Fifteen were suspicious of malignancy. There was a clinically significant IF for 14.9 % of the participants. In six cases earlier identification of an IF may have improved quality of life or survival. Conclusions: Without radiology support clinically important IF may be missed on CMR. Patients undergoing CMR in trials should be counselled about the frequency and implications of IF. Patients with ESRD have a higher prevalence of IF than reported in other populations. Nephrology studies require mechanisms for radiologist reporting and strategies for dealing with IF

The long-lasting impacts of the COVID-19 pandemic on population-based cancer survival: what are the implications for data analysis?

publishedVersio

Lake Michigan’s suitability for bigheaded carp: The importance of diet flexibility and subsurface habitat

As bighead (Hypophthalmichthys nobilis) and silver carp (Hypophthalmichthys molitrix)—collectively bigheaded carp (BHC)—arrive at Lake Michigan’s doorstep, questions remain as to whether there is sufficient food to support these invasive filter‐feeding fishes in the upper Laurentian Great Lakes. Previous studies suggest that suitable BHC habitat is limited to a few productive, nearshore areas. However, those studies did not consider the influence of BHC’s diet plasticity or the presence of spatially‐discrete subsurface prey resources. This study aimed to characterise Lake Michigan’s suitability for BHC and evaluate the importance of these considerations in habitat suitability assessments.We used simulated outputs of prey biomass (phytoplankton, zooplankton, and detritus) and water temperature from a three‐dimensional biophysical model of Lake Michigan to evaluate growth rate potential (GRP, quantitative index of habitat suitability) of adult BHC throughout the entire volume of the lake. Our GRP model applied a foraging model and a bioenergetics model to translate prey concentrations and water temperatures into habitat quality indexed by individual fish growth rate. We defined suitable habitat as habitats that can support GRP ≥ 0 g g−1 day−1. We developed six feeding scenarios to evaluate the impact of diet flexibility and subsurface prey resources on suitable habitat quantity. Scenarios were defined by the number of prey types the fish could consume and the depths at which they could feed (surface or whole water column).Consistent with previous studies, we found that habitats with the highest quality were concentrated near river mouths and in eutrophic areas of Green Bay. However, in contrast to previous studies, we found suitable offshore habitat for bighead carp owing to our added considerations of diet plasticity and subsurface prey resources. For silver carp, these considerations extended suitable habitat within Green Bay and in some tributary‐influenced nearshore areas, but offshore areas remained predominantly unsuitable in all feeding scenarios. Differences in simulated habitat suitability between these two species probably reflect differences in energy density and mass of the specific fishes we used in our model. However, reports of these two species in environments where they coexist indicate that bighead carp grow at faster rates than silver carp, as our model simulated.Our vertical analysis at Muskegon, MI, U.S.A. indicates that subsurface temperature and prey biomass are not only sufficient to support bighead carp growth but provide maximum habitat quality during late summer stratification.Overall, our study demonstrates that BHC are capable of surviving and growing in much larger areas of Lake Michigan than predicted by previous studies, and thus suggests that the risk of establishment is not sufficiently reduced by low plankton concentrations. Maps generated by our model identified the potential for cross‐lake migration corridors that may facilitate and accelerate lake‐wide movements. We believe these maps could be used to prioritise surveillance protocols by identifying areas to which BHC might spread upon entering the lake. More broadly, this research demonstrates how the physiology and trophic ecology of BHC contributes to their high invasive capacity and can permit their survival in novel environments.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151968/1/fwb13382_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151968/2/fwb13382.pd

Reshaping Regional Institutions: APEC and the IMF in East Asia

One of the most striking aspects of attempts to manage the crisis in East Asia has been the very differing roles played by APEC and the IMF. Although both organisations have similar market-centred reform agendas, APEC has been conspicuous by its absence in the wake of the crisis. This paper considers the actions of both organisations, and their very dfferent approaches to institutional reform. It is suggested that the crisis in general and the actions of these two organisations in particular provides a timely opportunity to review the more influential varieties of institutional theory to see whether they provide either useful tools for understanding the roles and activities of APEC and the IMF, or plausible models of reform for policy makers

Integrated community case management in a peri-urban setting: a qualitative evaluation in Wakiso District, Uganda.

Integrated community case management (iCCM) strategies aim to reach poor communities by providing timely access to treatment for malaria, pneumonia and diarrhoea for children under 5 years of age. Community health workers, known as Village Health Teams (VHTs) in Uganda, have been shown to be effective in hard-to-reach, underserved areas, but there is little evidence to support iCCM as an appropriate strategy in non-rural contexts. This study aimed to inform future iCCM implementation by exploring caregiver and VHT member perceptions of the value and effectiveness of iCCM in peri-urban settings in Uganda.A qualitative evaluation was conducted in seven villages in Wakiso district, a rapidly urbanising area in central Uganda. Villages were purposively selected, spanning a range of peri-urban settlements experiencing rapid population change. In each village, rapid appraisal activities were undertaken separately with purposively selected caregivers (n = 85) and all iCCM-trained VHT members (n = 14), providing platforms for group discussions. Fifteen key informant interviews were also conducted with community leaders and VHT members. Thematic analysis was based on the 'Health Access Livelihoods Framework'.iCCM was perceived to facilitate timely treatment access and improve child health in peri-urban settings, often supplanting private clinics and traditional healers as first point of care. Relative to other health service providers, caregivers valued VHTs' free, proximal services, caring attitudes, perceived treatment quality, perceived competency and protocol use, and follow-up and referral services. VHT effectiveness was perceived to be restricted by inadequate diagnostics, limited newborn care, drug stockouts and VHT member absence - factors which drove utilisation of alternative providers. Low community engagement in VHT selection, lack of referral transport and poor availability of referral services also diminished perceived effectiveness. The iCCM strategy was widely perceived to result in economic savings and other livelihood benefits.In peri-urban areas, iCCM was perceived as an effective, well-utilised strategy, reflecting both VHT attributes and gaps in existing health services. Depending on health system resources and organisation, iCCM may be a useful transitional service delivery approach. Implementation in peri-urban areas should consider tailored community engagement strategies, adapted selection criteria, and assessment of population density to ensure sufficient coverage

PomBase 2015: updates to the fission yeast database.

PomBase (http://www.pombase.org) is the model organism database for the fission yeast Schizosaccharomyces pombe. PomBase provides a central hub for the fission yeast community, supporting both exploratory and hypothesis-driven research. It provides users easy access to data ranging from the sequence level, to molecular and phenotypic annotations, through to the display of genome-wide high-throughput studies. Recent improvements to the site extend annotation specificity, improve usability and allow for monthly data updates. Both in-house curators and community researchers provide manually curated data to PomBase. The genome browser provides access to published high-throughput data sets and the genomes of three additional Schizosaccharomyces species (Schizosaccharomyces cryophilus, Schizosaccharomyces japonicus and Schizosaccharomyces octosporus)

A Randomized Controlled Trial of the Effect of Allopurinol on Left Ventricular Mass Index in Hemodialysis Patients

Introduction: Increased left ventricular mass index (LVMI) is associated with mortality in end-stage renal disease. LVMI regression may improve outcomes. Allopurinol has reduced LVMI in randomized controlled trials in chronic kidney disease, diabetes, and ischemic heart disease. This study investigated whether allopurinol would regress LVMI in hemodialysis patients. Methods: This was a randomized placebo-controlled double-blind multicenter trial. A total of 80 patients undergoing regular maintenance hemodialysis were recruited from NHS Tayside, NHS Greater Glasgow and Clyde and NHS Ayrshire and Arran in Scotland, UK. Participants were randomly assigned on a 1:1 ratio to 12 months of therapy with allopurinol 300 mg or placebo after each dialysis session. The primary outcome was change in LVMI, as assessed by cardiac magnetic resonance imaging (MRI) at baseline and 12 months. Secondary outcomes were change in BP, flow-mediated dilation (FMD), augmentation indices (AIx), and pulse wave velocity (PWV). Results: A total of 53 patients, with a mean age of 58 years, completed the study and had MRI follow-up data for analysis. Allopurinol did not regress LVMI (change in LVMI: placebo +3.6 ± 10.4 g/m2; allopurinol: +1.6 ± 11 g/m2; P = 0.49). Allopurinol had no demonstrable effect on BP, FMD, AIx, or PWV. Conclusion: Compared with placebo, treatment with allopurinol did not regress LVMI in this trial

Sequencing and functional annotation of avian pathogenic Escherichia coli serogroup O78 strains reveals the evolution of E. coli lineages pathogenic for poultry via distinct mechanisms

Avian pathogenic Escherichia coli (APEC) causes respiratory and systemic disease in poultry. Sequencing of a multilocus sequence type 95 (ST95) serogroup O1 strain previously indicated that APEC resembles E. coli causing extraintestinal human diseases. We sequenced the genomes of two strains of another dominant APEC lineage (ST23 serogroup O78 strains χ7122 and IMT2125) and compared them to each other and to the reannotated APEC O1 sequence. For comparison, we also sequenced a human enterotoxigenic E. coli (ETEC) strain of the same ST23 serogroup O78 lineage. Phylogenetic analysis indicated that the APEC O78 strains were more closely related to human ST23 ETEC than to APEC O1, indicating that separation of pathotypes on the basis of their extraintestinal or diarrheagenic nature is not supported by their phylogeny. The accessory genome of APEC ST23 strains exhibited limited conservation of APEC O1 genomic islands and a distinct repertoire of virulence-associated loci. In light of this diversity, we surveyed the phenotype of 2,185 signature-tagged transposon mutants of χ7122 following intra-air sac inoculation of turkeys. This procedure identified novel APEC ST23 genes that play strain- and tissue-specific roles during infection. For example, genes mediating group 4 capsule synthesis were required for the virulence of χ7122 and were conserved in IMT2125 but absent from APEC O1. Our data reveal the genetic diversity of E. coli strains adapted to cause the same avian disease and indicate that the core genome of the ST23 lineage serves as a chassis for the evolution of E. coli strains adapted to cause avian or human disease via acquisition of distinct virulence genes