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Stress granules (SGs) are mRNA-protein aggregates induced during stress, which accumulate in many neurodegenerative diseases. Previously, the autophagy-lysosome pathway and valosin-containing protein (VCP), key players of the protein quality control (PQC), were shown to regulate SG degradation. This is consistent with the idea that PQC may survey and/or assist SG dynamics. However, despite these observations, it is currently unknown whether the PQC actively participates in SG assembly. Here, we describe that inhibition of autophagy, lysosomes and VCP causes defective SG formation after induction. Silencing the VCP co-factors UFD1L and PLAA, which degrade defective ribosomal products (DRIPs) and 60S ribosomes, also impaired SG assembly. Intriguingly, DRIPs and 60S, which are released from disassembling polysomes and are normally excluded from SGs, were significantly retained within SGs in cells with impaired autophagy, lysosome or VCP function. Our results suggest that deregulated autophagy, lysosomal or VCP activities, which occur in several neurodegenerative (VCP-associated) diseases, may alter SG morphology and composition.

Climate and land use are rapidly changing environmental conditions. Behavioral responses to such global perturbations can be used to incorporate interspecific interactions into predictive models of population responses to global change. Flight initiation distance (FID) reflects antipredator behaviour defined as the distance at which an individual takes flight when approached by a human, under standardized conditions. This behavioural trait results from a balance between disturbance, predation risk, food availability and physiological needs, and it is related to geographical range and population trends in European birds. Using 32,145 records of flight initiation distances for 229 bird species during 2006–2019 in 24 European localities, we show that FIDs decreased with increasing temperature and precipitation, as expected if foraging success decreased under warm and humid conditions. Trends were further altered by latitude, urbanisation and body mass, as expected if climate effects on FIDs were mediated by food abundance and need, differing according to position in food webs, supporting foraging models. This provides evidence for a role of behavioural responses within food webs on how bird populations and communities are affected by global change.

Several shreds of evidence indicate that visual deprivation does not alter numerical competence neither in adults nor in children. However, studies reporting non-impaired numerical abilities in the visually impaired population present some limitations: (a) they mainly assessed the ability to process numbers (e.g. mathematical competence) rather than represent numbers (e.g. mental number line); (b) they principally focused on positive rather than negative number estimates; (c) they investigated numerical abilities in adult individuals except one focusing on children (Crollen et al. in Cognition 210:104586, 2021). Overall, this could limit a comprehensive explanation of the role exerted by vision on numerical processing when vision is compromised. Here we investigated how congenital visual deprivation affects the ability to represent positive and negative numbers in horizontal and sagittal planes in visually impaired children (thirteen children with low vision, eight children with complete blindness, age range 6–15 years old). We adapted the number-to-position paradigm adopted by Crollen et al. (Cognition 210:104586, 2021), asking children to indicate the spatial position of positive and negative numbers on a graduated rule positioned horizontally or sagittally in the frontal plane. Results suggest that long-term visual deprivation alters the ability to identify the spatial position of numbers independently of the spatial plane and the number polarity. Moreover, results indicate that relying on poor visual acuity is detrimental for low vision children when asked to localize both positive and negative numbers in space, suggesting that visual experience might have a differential role in numerical processing depending on number polarity. Such findings add knowledge related to the impact of visual experience on numerical processing. Since both positive and negative numbers are fundamental aspects of learning mathematical principles, the outcomes of the present study inform about the need to implement early rehabilitation strategies to prevent the risk of numerical difficulties in visually impaired children.

BAG3 is a multi-domain hub that connects two classes of chaperones, small heat shock proteins (sHSPs) via two isoleucine-proline-valine (IPV) motifs and Hsp70 via a BAG domain. Mutations in either the IPV or BAG domain of BAG3 cause a dominant form of myopathy, characterized by protein aggregation in both skeletal and cardiac muscle tissues. Surprisingly, for both disease mutants, impaired chaperone binding is not sufficient to explain disease phenotypes. Recombinant mutants are correctly folded, show unaffected Hsp70 binding but are impaired in stimulating Hsp70-dependent client processing. As a consequence, the mutant BAG3 proteins become the node for a dominant gain of function causing aggregation of itself, Hsp70, Hsp70 clients and tiered interactors within the BAG3 interactome. Importantly, genetic and pharmaceutical interference with Hsp70 binding completely reverses stress-induced protein aggregation for both BAG3 mutations. Thus, the gain of function effects of BAG3 mutants act as Achilles heel of the HSP70 machinery. BAG3 is a Hsp70 co-chaperone that is highly expressed in muscles. Here the authors show that several myofibrillar myopathy causing BAG3 mutations are not impaired in Hsp70 binding, but rather impair the ADP-ATP exchange step of the Hsp70 cycle, causing the aggregation of BAG3, Hsp70 and Hsp70 clients and leading to a collapse of protein homeostasis.

A soy protein isolate was hydrolyzed with Alcalase®, Flavourzyme® and their combination, and the resulting hydrolysates (A, F and A + F) were ultrafiltered and analyzed through SDS-PAGE. Fractions with MW < 1 kDa were investigated for their ACE-inhibitory activity, and the most active one (A < 1 kDa) was purified by semi-preparative RP-HPLC, affording three further subfractions. NMR analysis and Edman degradation of the most active subfraction (A1) enabled the identification of four putative sequences (ALKPDNR, VVPD, NDRP and NDTP), which were prepared by solid-phase synthesis. The comparison of their ACE-inhibitory activities suggested that the novel peptide NDRP might be the main agent responsible for A1 fraction ACE inhibition (ACE inhibition = 87.75 ± 0.61%; IC50 = 148.28 ± 9.83 μg mL−1). NDRP acts as a non-competitive inhibitor and is stable towards gastrointestinal simulated digestion. The Multiple Reaction Monitoring (MRM) analysis confirmed the presence of NDRP in A < 1 kDa.

The primary aim of this review is to provide an overview of relevant and efficient methods in organic electrosynthesis, presented in a reader‐friendly format. The focus is on the electrochemical oxidation of primary alcohols to aldehydes and carboxylic acids, the oxidation of aldehydes to carboxylic acids, and the oxidation of secondary alcohols to ketones. Additionally, the corresponding electrochemical reductions, such as the reduction of carboxylic acids to aldehydes and primary alcohols, the reduction of aldehydes to primary alcohols, and the reduction of ketones to secondary alcohols, are also covered. For each type of reaction, an easy‐to‐follow table provides readers with essential information (e.g., substrates, working electrode, electrolyte, cell type, synthesis notes, and references), enabling a quick yet comprehensive overview of the electrosynthetic possibilities for a given functional group. The review also explores recent advancements in organic electrosynthesis, encompassing both direct and mediated techniques. As electrochemical alternatives to classical organic synthesis continue to garner increasing attention, it is hoped that this review will serve as a valuable resource for those interested in evaluating these synthetic approaches. This review aims to provide the reader with a useful tool to deal with electrochemical redox reactions involving alcohols and carbonyl compounds. The review is organized in an accessible format and divided into sections that focus on key parameters of wide‐ranging electrosynthetic methods.

Poly-γ-glutamate (γ-PGA) is an industrially interesting polymer secreted mainly by members of the class Bacilli which forms a shield able to protect bacteria from phagocytosis and phages. Few enzymes are known to degrade γ-PGA; among them is a phage-encoded γ-PGA hydrolase, PghP. The supposed role of PghP in phages is to ensure access to the surface of bacterial cells by dismantling the γ-PGA barrier. We identified four unannotated B. subtilis genes through similarity of their encoded products to PghP; in fact these genes reside in prophage elements of B. subtilis genome. The recombinant products of two of them demonstrate efficient polymer degradation, confirming that sequence similarity reflects functional homology. Genes encoding similar γ-PGA hydrolases were identified in phages specific for the order Bacillales and in numerous microbial genomes, not only belonging to that order. The distribution of the γ-PGA biosynthesis operon was also investigated with a bioinformatics approach; it was found that the list of organisms endowed with γ-PGA biosynthetic functions is larger than expected and includes several pathogenic species. Moreover in non-Bacillales bacteria the predicted γ-PGA hydrolase genes are preferentially found in species that do not have the genetic asset for polymer production. Our findings suggest that γ-PGA hydrolase genes might have spread across microbial genomes via horizontal exchanges rather than via phage infection. We hypothesize that, in natural habitats rich in γ-PGA supplied by producer organisms, the availability of hydrolases that release glutamate oligomers from γ-PGA might be a beneficial trait under positive selection.

One of the critical events that regulates muscle cell differentiation is the replacement of the lamin B receptor (LBR)-tether with the lamin A/C (LMNA)-tether to remodel transcription and induce differentiation-specific genes. Here, we report that localization and activity of the LBR-tether are crucially dependent on the muscle-specific chaperone HSPB3 and that depletion of HSPB3 prevents muscle cell differentiation. We further show that HSPB3 binds to LBR in the nucleoplasm and maintains it in a dynamic state, thus promoting the transcription of myogenic genes, including the genes to remodel the extracellular matrix. Remarkably, HSPB3 overexpression alone is sufficient to induce the differentiation of two human muscle cell lines, LHCNM2 cells, and rhabdomyosarcoma cells. We also show that mutant R116P-HSPB3 from a myopathy patient with chromatin alterations and muscle fiber disorganization, forms nuclear aggregates that immobilize LBR. We find that R116P-HSPB3 is unable to induce myoblast differentiation and instead activates the unfolded protein response. We propose that HSPB3 is a specialized chaperone engaged in muscle cell differentiation and that dysfunctional HSPB3 causes neuromuscular disease by deregulating LBR.

Fires are intrinsic disturbances in ecosystems functioning and structure in fire-prone biomes. In recent decades there has been an increase in the number of fire events in Brazilian biomes, especially due to misuse of fire in the land use and deforestation. The spatial and temporal pattern fire risk is a important way to understanding the seasonality and intensity of fire in different climate and fuel conditions. However, consistent long-term assessment at biome level is only possible with the support of remote sensing and modeling information. Thus, the objective of this work was to evaluate the fire risk patterns for the Brazilian biomes in the last years (2015–2018), using the new version of INPE’s fire risk (FR, v2). Regarding the temporal and spatial FR patterns by this new version from FR model, we evaluated that elevation and latitude correction factors, as well as the meteorological and land cover datasets with finer spatial scales can be contributed to adjust better the fire season vulnerability, notably in the less prone-biomes, such as Mata Atlantica, Pampa and Pantanal. However, there is still a need for adjustment to match the spatial active fire distribution, considering a biomass (fuel) map and the vegetation water status indicators. These improvements help to inform with more accuracy the most fire prone areas to define the strategies and decisions for fire combat and management.