Ezrin defines TSC complex activation at endosomal compartments through EGFR-AKT signaling.

Endosomes have emerged as major signaling hubs where different internalized ligand-receptor complexes are integrated and the outcome of signaling pathways are organized to regulate the strength and specificity of signal transduction events. Ezrin, a major membrane-actin linker that assembles and coordinates macromolecular signaling complexes at membranes, has emerged recently as an important regulator of lysosomal function. Here, we report that endosomal-localized EGFR/Ezrin complex interacts with and triggers the inhibition of the Tuberous Sclerosis Complex (TSC complex) in response to EGF stimuli.

Population bottlenecks and sexual recombination shape diatom microevolution.

Diatoms are single-celled organisms that contribute approximately 20% of the global primary production and play a crucial role in biogeochemical cycles and trophic chains. Despite their ecological importance, our knowledge of microevolution is limited. We developed a model using the SLiM evolutionary framework to address this knowledge gap.

Plant growth promoting rhizobacteria (PGPR) application for coping with salinity and drought: a bibliometric network multi-analysis.

Rhizobacteria play a crucial role in plant growth and yield, stimulating primary production and improving stress resistance. Climate change has several consequences worldwide that affect arable land and agriculture. Studies on plant-soil-microorganism interactions to enhance plant productivity and/or resistance to abiotic stress may open new perspectives.

Drug Repurposing and Lysosomal Storage Disorders: A Trick to Treat.

Rare diseases, or orphan diseases, are defined as diseases affecting a small number of people compared to the general population. Among these, we find lysosomal storage disorders (LSDs), a cluster of rare metabolic diseases characterized by enzyme mutations causing abnormal glycolipid storage. Drug repositioning involves repurposing existing approved drugs for new therapeutic applications, offering advantages in cost, time savings, and a lower risk of failure.

Exploring ligand interactions with human phosphomannomutases using recombinant bacterial thermal shift assay and biochemical validation.

PMM2-CDG, a disease caused by mutations in phosphomannomutase-2, is the most common congenital disorder of glycosylation. Yet, it still lacks a cure. Targeting phosphomannomutase-2 with pharmacological chaperones or inhibiting the phosphatase activity of phosphomannomutase-1 to enhance intracellular glucose-1,6-bisphosphate have been proposed as therapeutical approaches.

A maternal-effect variant causes nuclear and cytoplasmic abnormalities in oocytes, as well as failure of epigenetic reprogramming and zygotic genome activation in embryos.

Maternal inactivation of genes encoding components of the subcortical maternal complex (SCMC) and its associated member, PADI6, generally results in early embryo lethality. In humans, SCMC gene variants were found in the healthy mothers of children affected by multilocus imprinting disturbances (MLID). However, how the SCMC controls the DNA methylation required to regulate imprinting remains poorly defined.

Female Sex Determination Factors in : Molecular and Structural Basis of TRA and TRA2 Recognition.

In the model system for genetics, , sexual differentiation and male courtship behavior are controlled by sex-specific splicing of () and (). In vitro and in vivo studies showed that female-specific Transformer (TRA) and the non-sex-specific Transformer 2 (TRA2) splicing factors interact, forming a complex promoting and female-specific splicing. TRA/TRA2 complex binds to 13 nt long sequence repeats in their pre-mRNAs.

Oxidoreductases and metal cofactors in the functioning of the earth.

Life sustains itself using energy generated by thermodynamic disequilibria, commonly existing as redox disequilibria. Metals are significant players in controlling redox reactions, as they are essential components of the engine that life uses to tap into the thermodynamic disequilibria necessary for metabolism. The number of proteins that evolved to catalyze redox reactions is extraordinary, as is the diversification level of metal cofactors and catalytic domain structures involved.

Characterization of Linezolid-Analogue L3-Resistance Mutation in .

In a previous study, a linezolid analogue, called 10f, was synthesized. The 10f molecule has an antimicrobial activity comparable to that of the parental compound. In this study, we isolated a () strain resistant to 10f.

Computational modeling of cambium activity provides a regulatory framework for simulating radial plant growth.

Precise organization of growing structures is a fundamental process in developmental biology. In plants, radial growth is mediated by the cambium, a stem cell niche continuously producing wood (xylem) and bast (phloem) in a strictly bidirectional manner. While this process contributes large parts to terrestrial biomass, cambium dynamics eludes direct experimental access due to obstacles in live-cell imaging.

Curcumin Has Beneficial Effects on Lysosomal Alpha-Galactosidase: Potential Implications for the Cure of Fabry Disease.

Fabry disease is a lysosomal storage disease caused by mutations in the gene that encodes alpha-galactosidase (AGAL). The disease causes abnormal globotriaosylceramide (Gb3) storage in the lysosomes. Variants responsible for the genotypic spectrum of Fabry disease include mutations that abolish enzymatic activity and those that cause protein instability.

The mismatch-repair proteins MSH2 and MSH6 interact with the imprinting control regions through the ZFP57-KAP1 complex.

Background: Imprinting Control Regions (ICRs) are CpG-rich sequences acquiring differential methylation in the female and male germline and maintaining it in a parental origin-specific manner in somatic cells. Despite their expected high mutation rate due to spontaneous deamination of methylated cytosines, ICRs show conservation of CpG-richness and CpG-containing transcription factor binding sites in mammalian species. However, little is known about the mechanisms contributing to the maintenance of a high density of methyl CpGs at these loci.

Novel genetic variants of KHDC3L and other members of the subcortical maternal complex associated with Beckwith-Wiedemann syndrome or Pseudohypoparathyroidism 1B and multi-locus imprinting disturbances.

Background: Beckwith-Wiedemann syndrome (BWS) and Pseudohypoparathyroidism type 1B (PHP1B) are imprinting disorders (ID) caused by deregulation of the imprinted gene clusters located at 11p15.5 and 20q13.32, respectively.

Drug Repositioning for Fabry Disease: Acetylsalicylic Acid Potentiates the Stabilization of Lysosomal Alpha-Galactosidase by Pharmacological Chaperones.

Fabry disease is caused by a deficiency of lysosomal alpha galactosidase and has a very large genotypic and phenotypic spectrum. Some patients who carry hypomorphic mutations can benefit from oral therapy with a pharmacological chaperone. The drug requires a very precise regimen because it is a reversible inhibitor of alpha-galactosidase.

Protective Role of a Variant on Severe COVID-19 Outcome in Young Males and Elderly Women.

The protease encoded by the gene facilitates viral infections and has been implicated in the pathogenesis of SARS-CoV-2. We analyzed the sequence and correlated the protein variants with the clinical features of a cohort of 1177 patients affected by COVID-19 in Italy. Nine relatively common variants (allele frequency > 0.

Bioinformatics tools for marine biotechnology: a practical tutorial with a metagenomic approach.

Background: Bioinformatics has pervaded all fields of biology and has become an indispensable tool for almost all research projects. Although teaching bioinformatics has been incorporated in all traditional life science curricula, practical hands-on experiences in tight combination with wet-lab experiments are needed to motivate students.

Results: We present a tutorial that starts from a practical problem: finding novel enzymes from marine environments.

Ecological assessment of anthropogenic impact in marine ecosystems: The case of Bagnoli Bay.

Pollutants alter marine systems, interfering with provisioning of ecosystem services; understanding their interaction with ecological communities is therefore critical to inform environmental management. Here we propose a joint compositional- and interaction-based analysis for ecological status assessment and apply it on the benthic communities of the Bagnoli Bay. We found that contamination differentially affects the communities' composition in the bay, with prokaryotes influenced only by depth, and benthos not following the environmental gradient at all.

Rewiring and indirect effects underpin modularity reshuffling in a marine food web under environmental shifts.

Species are characterized by physiological and behavioral plasticity, which is part of their response to environmental shifts. Nonetheless, the collective response of ecological communities to environmental shifts cannot be predicted from the simple sum of individual species responses, since co-existing species are deeply entangled in interaction networks, such as food webs. For these reasons, the relation between environmental forcing and the structure of food webs is an open problem in ecology.

Suitability of Solanum lycopersicum L. 'Microtom' for growth in Bioregenerative Life Support Systems: exploring the effect of high-LET ionising radiation on photosynthesis, leaf structure and fruit traits.

The realisation of manned space exploration requires the development of Bioregenerative Life Support Systems (BLSS). In such self-sufficient closed habitats, higher plants have a fundamental role in air regeneration, water recovery, food production and waste recycling. In the space environment, ionising radiation represents one of the main constraints to plant growth.

Challenging popular tools for the annotation of genetic variations with a real case, pathogenic mutations of lysosomal alpha-galactosidase.

Background: Severity gradation of missense mutations is a big challenge for exome annotation. Predictors of deleteriousness that are most frequently used to filter variants found by next generation sequencing, produce qualitative predictions, but also numerical scores. It has never been tested if these scores correlate with disease severity.

The Analysis of Variants in the General Population Reveals That Is Extremely Tolerant to Missense Mutations and That Diagnosis of PMM2-CDG Can Benefit from the Identification of Modifiers.

Type I disorders of glycosylation (CDG), the most frequent of which is phosphomannomutase 2 (PMM2-CDG), are a group of diseases causing the incomplete -glycosylation of proteins. PMM2-CDG is an autosomal recessive disease with a large phenotypic spectrum, and is associated with mutations in the gene. The biochemical analysis of mutants does not allow a precise genotype⁻phenotype correlation for PMM2-CDG.

Drug repositioning can accelerate discovery of pharmacological chaperones.

A promising strategy for the treatment of genetic diseases, pharmacological chaperone therapy, has been proposed recently. It exploits small molecules which can be administered orally, reach difficult tissues such as the brain and have low cost. This strategy has a vast field of application.