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IntroductionThe effects of healthcare-related inequalities are most evident in low-resource settings. Such settings are often not explicitly defined, and umbrella terms which are easier to operationalise, such as ‘low-to-middle-income countries’ or ‘developing countries’, are often used. Without a deeper understanding of context, such proxies are pregnant with assumptions, insinuate homogeneity that is unsupported and hamper knowledge translation between settings.MethodsA systematic scoping review was undertaken to start unravelling the term ‘low-resource setting’. PubMed, Africa-Wide, Web of Science and Scopus were searched (24 June 2019), dating back ≤5 years, using terms related to ‘low-resource setting’ and ‘rehabilitation’. Rehabilitation was chosen as a methodological vehicle due to its holistic nature (eg, multidisciplinary, relevance across burden of disease, and throughout continuum of care) and expertise within the research team. Qualitative content analysis through an inductive approach was used.ResultsA total of 410 codes were derived from 48 unique articles within the field of rehabilitation, grouped into 63 content categories, and identified nine major themes relating to the term ‘low-resource setting’. Themes that emerged relate to (1) financial pressure, (2) suboptimal healthcare service delivery, (3) underdeveloped infrastructure, (4) paucity of knowledge, (5) research challenges and considerations, (6) restricted social resources, (7) geographical and environmental factors, (8) human resource limitations and (9) the influence of beliefs and practices.ConclusionThe emerging themes may assist with (1) the groundwork needed to unravel ‘low-resource settings’ in health-related research, (2) moving away from assumptive umbrella terms like ‘low-to-middle-income countries’ or ‘low/middle-income countries’ and (3) promoting effective knowledge transfer between settings.

Background Gene expression and alternative splicing are strictly regulated processes that shape brain development and determine the cellular identity of differentiated neural cell populations. Despite the availability of multiple valuable datasets, many functional implications, especially those related to alternative splicing, remain poorly understood. Moreover, neuroscientists working primarily experimentally often lack the bioinformatics expertise required to process alternative splicing data and produce meaningful and interpretable results. Notably, re-analyzing publicly available datasets and integrating them with in-house data can provide substantial novel insights. However, such analyses necessitate developing harmonized data handling and processing pipelines which in turn require considerable computational resources and in-depth bioinformatics expertise. Results Here, we present Cortexa—a comprehensive web portal that incorporates RNA-sequencing datasets from the mouse cerebral cortex (longitudinal or cell-specific) and the hippocampus. Cortexa facilitates understandable visualization of the expression and alternative splicing patterns of individual genes. Our platform provides SplicePCA—a tool that allows users to integrate their alternative splicing dataset and compare it to cell-specific or developmental neocortical splicing patterns. All standardized gene expression and alternative splicing datasets can be downloaded for further in-depth downstream analysis without the need for extensive preprocessing. Conclusions Cortexa provides a robust and readily available resource for unraveling the complexity of gene expression and alternative splicing regulatory processes in the mouse brain. The data portal is available at https://cortexa-rna.com/

Most synapses in the mature CNS are wrapped by a dense extracellular matrix (ECM). The authors show that removing the ECM increased the lateral diffusion of AMPA receptors and affected short-term synaptic plasticity. This suggests that the ECM may modulate synaptic transmission by restricting receptor diffusion. Many synapses in the mature CNS are wrapped by a dense extracellular matrix (ECM). Using single-particle tracking and fluorescence recovery after photobleaching, we found that this net-like ECM formed surface compartments on rat primary neurons that acted as lateral diffusion barriers for AMPA-type glutamate receptors. Enzymatic removal of the ECM increased extrasynaptic receptor diffusion and the exchange of synaptic AMPA receptors. Whole-cell patch-clamp recording revealed an increased paired-pulse ratio as a functional consequence of ECM removal. These results suggest that the surface compartments formed by the ECM hinder lateral diffusion of AMPA receptors and may therefore modulate short-term synaptic plasticity.

AMPA glutamate receptors (AMPARs) mediate fast excitatory synaptic transmission. Upon fast consecutive synaptic stimulation, transmission can be depressed. Recuperation from fast synaptic depression has been attributed solely to recovery of transmitter release and/or AMPAR desensitization. We show that AMPAR lateral diffusion, observed in both intact hippocampi and cultured neurons, allows fast exchange of desensitized receptors with naïve functional ones within or near the postsynaptic density. Recovery from depression in the tens of millisecond time range can be explained in part by this fast receptor exchange. Preventing AMPAR surface movements through cross-linking, endogenous clustering, or calcium rise all slow recovery from depression. Physiological regulation of postsynaptic receptor mobility affects the fidelity of synaptic transmission by shaping the frequency dependence of synaptic responses.

Synapses are particularly prone to dynamic alterations and thus play a major role in neuronal plasticity. Dynamic excitatory synapses are located at the membranous neuronal protrusions called dendritic spines. The ability to change synaptic connections involves both alterations at the morphological level and changes in postsynaptic receptor composition. We report that endogenous matrix metalloproteinase (MMP) activity promotes the structural and functional plasticity of local synapses by its effect on glutamate receptor mobility and content. We used live imaging of cultured hippocampal neurons and quantitative morphological analysis to show that chemical long-term potentiation (cLTP) induces the permanent enlargement of a subset of small dendritic spines in an MMP-dependent manner. We also used a superresolution microscopy approach and found that spine expansion induced by cLTP was accompanied by MMP-dependent immobilization and synaptic accumulation as well as the clustering of GluA1-containing AMPA receptors. Altogether, our results reveal novel molecular and cellular mechanisms of synaptic plasticity.

Background Utilisation of Antenatal care (ANC) in Ethiopia has shown a steady increase in the last two decades, from 27% in 2000 to 74% in 2019. While it is encouraging to see more women attending and receiving ANC, attention to ensuring the quality of the ANC services provided to the visiting women is important. Therefore, this study aimed to assess the provision of recommended ANC services and to identify client related factors associated with the provision of the services. Methods The study was conducted using the 2019 Ethiopian Demographic and Health Survey (EDHS) data. Provision of recommended ANC services was assessed for the EDHS sub-set of 1573 women who had a live birth in the two years preceding the survey and at least one ANC visit. Four components of ANC (i.e. blood pressure measurement, blood and urine test, and counselling on signs of pregnancy complications) were used to measure the provision of recommended ANC services. Bivariable and multivariable analysis was performed to identify client related factors associated with the provision of recommended ANC services. An adjustment was made to account for the complex survey design throughout the analysis (weight, stratification, and clustering). Results About one in two women (49.7%; 95% CI: 44.6–55.0) reported receiving the four components of ANC during their pregnancy. Having a higher educational level (adjusted Odds Ratio [aOR] = 2.84; 95%CI: 1.15–6.97), being in the middle (aOR = 1.87;95% CI: 1.14–3.06), richer (aOR = 2.56; 95% CI: 1.46–4.49), and richest (aOR = 4.21;95% CI: 1.93–9.21) wealth quintiles, and having two to three (aOR = 5.40;95% CI: 2.00-14.60) and four or more (aOR = 13.45; 95% CI: 4.81–37.58) ANC visits were client related factors associated with the provision of recommended ANC services. Conclusion Despite the high ANC1 coverage, only one in two women reported receiving the four recommended services. To produce the desired health outcome from ANC utilisation, expanding the coverage should be accompanied by a strong focus on the contents and quality of care. Moreover, regardless of their educational and economic status, all women should receive all components of care as per the recommendations.

The NR2 subunit composition of NMDA receptors (NMDARs) varies during development, and this change is important in NMDARdependent signaling. In particular, synaptic NMDAR switch from containing mostly NR2B subunit to a mixture of NR2B and NR2A subunits. The pathways by which neurons differentially traffic NR2A- and NR2B-containing NMDARs are poorly understood. Using single-particle and -molecule approaches and specific antibodies directed against NR2A and NR2B extracellular epitopes, we investigated the surface mobility of native NR2A and NR2B subunits at the surface of cultured neurons. The surface mobility of NMDARs depends on the NR2 subunit subtype, with NR2A-containing NMDARs being more stable than NR2B-containing ones, and NR2A subunit overexpression stabilizes surface NR2B-containing NMDARs. The developmental change in the synaptic surface content of NR2A and NR2B subunits was correlated with a developmental change in the time spent by the subunits within synapses. This suggests that the switch in synaptic NMDAR subtypes depends on the regulation of the receptor surface trafficking.

A combination of cell culture and animal studies has recently shown that adhesion between neurexins and neuroligins played important roles in synapse initiation, maturation, and function. Binding of neurexin-1β to neuroligin-1 triggers the postsynaptic clustering of the scaffold postsynaptic density protein 95, but the composition and timing of accumulation of glutamate receptors at those nascent contacts remain unclear. Using glutamate iontophoresis and patch-clamp recordings, we identified functional AMPA receptors (AMPARs) and NMDA receptors at postsynaptic density protein 95 clusters induced by neurexin-1β coated microspheres on primary hippocampal neurons. The recruitment of AMPARs occurred as early as 2 h after initial contact, and was not blocked by TTX/2-amino-5-phosphovaleric acid (APV) treatment. The differential recruitment of recombinant subunits GluR1 and GluR2, as well as the absence of rectification in voltage/current curves, further indicate that neurexin/neuroligin contacts primarily recruit GluR2-containing AMPARs. Finally, by using glutamate un-caging and calcium imaging, we show that AMPARs participate in calcium entry at neurexin-1β induced post-synapses, most likely through the activation of voltage-gated calcium channels. Such rapid and activity-independent accumulation of functional AMPARs at neurexin-1β-induced postsynapses points to a new role of AMPARs in synaptogenesis.

At many vertebrate synapses, presynaptic functions are tuned by expression of different Ca v 2 channels. Most invertebrate genomes contain only one Ca v 2 gene. The Drosophila Ca v 2 homolog, cacophony (cac), induces synaptic vesicle release at presynaptic active zones (AZs). We hypothesize that Drosophila cac functional diversity is enhanced by two mutually exclusive exon pairs that are not conserved in vertebrates, one in the voltage sensor and one in the loop binding Ca β and G βγ subunits. We find that alternative splicing in the voltage sensor affects channel activation voltage. Only the isoform with the higher activation voltage localizes to AZs at the glutamatergic Drosophila larval neuromuscular junction and is imperative for normal synapse function. By contrast, alternative splicing at the other alternative exon pair tunes multiple aspects of presynaptic function. While expression of one exon yields normal transmission, expression of the other reduces channel number in the AZ and thus release probability. This also abolishes presynaptic homeostatic plasticity. Moreover, reduced channel number affects short-term plasticity, which is rescued by increasing the external calcium concentration to match release probability to control. In sum, in Drosophila alternative splicing provides a mechanism to regulate different aspects of presynaptic functions with only one Ca v 2 gene.