Unwebbing the Presynaptic Web

AbstractThe release of neurotransmitter from nerve terminals occurs at a specialized region of the presynaptic plasma membrane called the active zone. A dense matrix of proteins associated with the active zone, called the presynaptic web, is thought to play a fundamental role in defining these neurotransmitter release sites. In this issue of Neuron, Phillips et al. have identified conditions for the biochemical purification of the presynaptic web and show that the web is comprised of proteins involved in the docking, fusion, and recycling of synaptic vesicles

Effect of L-Hyp supplementation on collagen muscle histology, gene expression, growth performance, body composition and fillet texture on big size European sea bass (Dicentrarchux labrax)

Hydroxyproline (L-Hyp) is amply present in fishmeal but limited in plant-protein sources. This study was conducted to evaluate the effects of supplementation with dietary L-Hyp on the distribution of collagen types in the muscle, and on the texture, survival rate, growth rate, feed utilization, body composition as well as the expression of the gene that encodes the pro-alpha2 chains of type I collagen (Col Iα2) of large European sea bass (initial body weight 609.21 ± 75.39 g) from high plant-protein diets. Four isoproteic (42 % crude protein) and isolipidic (20 % crude lipid) experimental diets were formulated adding 0.6 (HL diet), 1.2 (HM diet), and 2% (HH diet) L-Hyp, respectively. Three periods of feeding of 45, 99 and 143 days were studied. L-Hyp supplementation at 1.2 % and 2 % significantly improved specific growth rate (SGR) and feed conversion ratio (FCR). In the white muscle, type I, IV collagen and trichromic stain were significantly higher in HH feed than the control diet. In the red muscle, only type I collagen was higher. HH diet, also increases Col Iα2 mRNA levels in muscle significantly. It can be concluded that the addition of crystalline l-Hyp at 1.2 % or 2 % in high plant-protein diets indicates positive effects on growth performance of adult European sea bass and increase in muscle total collagen deposition.info:eu-repo/semantics/publishedVersio

Piccolo modulation of Synapsin1a dynamics regulates synaptic vesicle exocytosis

Active zones are specialized regions of the presynaptic plasma membrane designed for the efficient and repetitive release of neurotransmitter via synaptic vesicle (SV) exocytosis. Piccolo is a high molecular weight component of the active zone that is hypothesized to participate both in active zone formation and the scaffolding of key molecules involved in SV recycling. In this study, we use interference RNAs to eliminate Piccolo expression from cultured hippocampal neurons to assess its involvement in synapse formation and function. Our data show that Piccolo is not required for glutamatergic synapse formation but does influence presynaptic function by negatively regulating SV exocytosis. Mechanistically, this regulation appears to be calmodulin kinase II–dependent and mediated through the modulation of Synapsin1a dynamics. This function is not shared by the highly homologous protein Bassoon, which indicates that Piccolo has a unique role in coupling the mobilization of SVs in the reserve pool to events within the active zone

Towards a runtime verification framework for the Ada Programming Language

Runtime verification is an emerging discipline that investigates methods and tools to enable the verification of program properties during the execution of the application. The goal is to complement static analysis approaches, in particular when static verification leads to the explosion of states. Non-functional properties, such as the ones present in real-time systems are an ideal target for this kind of verification methodology, as are usually out of the range of the power and expressiveness of classic static analyses. In this paper, we present a framework that allows real-time programs written in Ada to be augmented with runtime verification capabilities. Our framework provides the infrastructures which is needed to instrument the code with runtime monitors. These monitors are responsible for observing the system and reaching verdicts about whether its behavior is compliant with its non-functional properties. We also sketch a contract language to extend the one currently provided by Ada, with the long term goal of having an elegant way in which runtime monitors can be automatically synthesized and instrumented into the target systems. The usefulness of the proposed approach is demonstrated by showing its use for an application scenario.This work was partially supported by Portuguese National Funds through FCT (Portuguese Founda- tion for Science and Technology) and by ERDF (European Regional Develop- ment Fund) through COMPETE (Operational Programme ’Thematic Factors of Competitiveness’), within projects FCOMP-01-0124-FEDER-037281 (CISTER), FCOMP-01-0124-FEDER-015006 (VIPCORE) and FCOMP-01-0124-FEDER- 020486 (AVIACC); and by FCT and EU ARTEMIS JU, within project ARTEMIS/0003/2012, JU grant nr. 333053 (CONCERTO)

Country-level gender inequality is associated with structural differences in the brains of women and men

男女間の不平等と脳の性差 --男女間の不平等は脳構造の性差と関連する--. 京都大学プレスリリース. 2023-05-10.Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7, 876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality

Microbial Hotspots in Lithic Macrohabitats Inferred from DNA Fractionation and Metagenomics in the Atacama Desert

The existence of microbial activity hotspots in temperate regions of Earth is driven by soil heterogeneities, especially the temporal and spatial availability of nutrients. Here we investigate whether microbial activity hotspots also exist in lithic microhabitats in one of the most arid regions of the world, the Atacama Desert in Chile. While previous studies evaluated the total DNA fraction to elucidate the microbial communities, we here for the first time use a DNA separation approach on lithic microhabitats, together with metagenomics and other analysis methods (i.e., ATP, PLFA, and metabolite analysis) to specifically gain insights on the living and potentially active microbial community. Our results show that hypolith colonized rocks are microbial hotspots in the desert environment. In contrast, our data do not support such a conclusion for gypsum crust and salt rockenvironments, because only limited microbial activity could be observed. The hypolith community is dominated by phototrophs, mostly Cyanobacteria and Chloroflexi, at both study sites. The gypsum crusts are dominated by methylotrophs and heterotrophic phototrophs, mostly Chloroflexi, and the salt rocks (halite nodules) by phototrophic and halotolerant endoliths, mostly Cyanobacteria and Archaea. The major environmental constraints in the organic-poor arid and hyperarid Atacama Desert are water availability and UV irradiation, allowing phototrophs and other extremophiles to play a key role in desert ecology

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

The Dynamics of SAP90/PSD-95 Recruitment to New Synaptic Junctions

SAP90/PSD-95 is thought to be a central organizer of the glutamatergic synapse postsynaptic reception apparatus. To assess its potential role during glutamatergic synapse formation, we used GFP-tagged SAP90/PSD-95, time lapse confocal microscopy, and cultured hippocampal neurons to determine its dynamic recruitment into new synaptic junctions. We report that new SAP90/PSD-95 clusters first appeared at new axodendritic contact sites within 20–60 min of contact establishment. SAP90/PSD-95 clustering was rapid, with kinetics that fit a single exponential with a mean time constant of ∼23 min. Most new SAP90/PSD-95 clusters were found juxtaposed to functional presynaptic boutons as determined by labeling with FM 4–64. No evidence was found for the existence of discrete transport particles similar to those previously reported to mediate presynaptic active zone cytoskeleton assembly. Instead, we found that SAP90/PSD-95 is recruited to nascent synapses from a diffuse dendritic cytoplasmic pool. Our findings show that SAP90/PSD-95 is recruited to nascent synaptic junctions early during the assembly process and indicate that its assimilation is fundamentally different from that of presynaptic active zone components