Dynamic Cellular Proteome Remodeling during SARS-CoV-2 Infection. Identification of Plasma Protein Readouts.

The outbreak of COVID-19, led to an ongoing pandemic with devastating consequences for the global economy and human health. With the global spread of SARS-CoV-2, multidisciplinary initiatives were launched to explore new diagnostic, therapeutic, and vaccination strategies. From this perspective, proteomics could help to understand the mechanisms associated with SARS-CoV-2 infection and to identify new therapeutic options.

How Much Force is Needed to Kill a Single Bacterium?

The interaction between bacteria and nanomaterials, particularly from a physical or mechanical perspective, has emerged as a topic of significant interest in both science and medicine. Mechanobactericidal nanomaterials, which exert antimicrobial effects through purely physical mechanisms, hold promise as alternative strategies to combat bacterial resistance to traditional antibiotics. High-aspect-ratio nanoparticles and surface topographies are being engineered to enhance their mechanobactericidal properties.

Nanoscale distribution of potentially toxic elements in seaweeds revealed by synchrotron X-ray fluorescence.

Assessing the impact of potentially toxic elements (PTEs) on coastal waters requires understanding their interaction with seaweeds, as they are foundational organisms in nearshore ecosystems. While seaweeds are known to accumulate PTEs, information on the mechanisms and locations of this accumulation is very limited. We employed synchrotron-based X-ray fluorescence (S-XRF) to map the distribution of various chemical elements at nanometric resolution in Fucus vesiculosus, a brown alga dominant in intertidal zones.

Development of a + Cardiac Mouse Progenitor Immortalized Model to Unravel the Relationship with Its Protective Vascular Endothelial Niche.

The adult mammalian heart has been demonstrated to be endowed with low but real turnover capacity, especially for cardiomyocytes, the key functional cell type. The source, however, of that turnover capacity remains controversial. In this regard, we have defined and characterized a resident multipotent cardiac mouse progenitor population, +DR (for + Damage-Responsive cells).

WatFinder: a ProDy tool for protein-water interactions.

Summary: We introduce WatFinder, a tool designed to identify and visualize protein-water interactions (water bridges, water-mediated associations, or water channels, fluxes, and clusters) relevant to protein stability, dynamics, and function. WatFinder is integrated into ProDy, a Python API broadly used for structure-based prediction of protein dynamics. WatFinder provides a suite of functions for generating raw data as well as outputs from statistical analyses.

Global epistasis and the emergence of function in microbial consortia.

The many functions of microbial communities emerge from a complex web of interactions between organisms and their environment. This poses a significant obstacle to engineering microbial consortia, hindering our ability to harness the potential of microorganisms for biotechnological applications. In this study, we demonstrate that the collective effect of ecological interactions between microbes in a community can be captured by simple statistical models that predict how adding a new species to a community will affect its function.

CoMentG: comprehensive retrieval of generic relationships between biomedical concepts from the scientific literature.

The CoMentG resource contains millions of relationships between terms of biomedical interest obtained from the scientific literature. At the core of the system is a methodology for detecting significant co-mentions of concepts in the entire PubMed corpus. That method was applied to nine sets of terms covering the most important classes of biomedical concepts: diseases, symptoms/clinical signs, molecular functions, biological processes, cellular compartments, anatomic parts, cell types, bacteria and chemical compounds.

Single-Cell Bacterial Imaging Provides Mechanistic Insight into the Photodynamic Action of Photosensitizer-Loaded Hydrogels.

Hydrogels, three-dimensional hydrophilic polymeric networks with high water retaining capacity, have gained prominence in wound management and drug delivery due to their tunability, softness, permeability, and biocompatibility. Electron-beam polymerized poly(ethylene glycol) diacrylate (PEGDA) hydrogels are particularly useful for phototherapies such as antimicrobial photodynamic therapy (aPDT) due to their excellent optical properties. This work takes advantage of the transparency of PEGDA hydrogels to investigate bacterial responses to aPDT at the single-cell level, in real-time and .

Environmental modulation of global epistasis in a drug resistance fitness landscape.

Interactions between mutations (epistasis) can add substantial complexity to genotype-phenotype maps, hampering our ability to predict evolution. Yet, recent studies have shown that the fitness effect of a mutation can often be predicted from the fitness of its genetic background using simple, linear relationships. This phenomenon, termed global epistasis, has been leveraged to reconstruct fitness landscapes and infer adaptive trajectories in a wide variety of contexts.

Metabolic similarity and the predictability of microbial community assembly.

When microbial communities form, their composition is shaped by selective pressures imposed by the environment. Can we predict which communities will assemble under different environmental conditions? Here, we hypothesize that quantitative similarities in metabolic traits across metabolically similar environments lead to predictable similarities in community composition. To that end, we measured the growth rate and by-product profile of a library of proteobacterial strains in a large number of single nutrient environments.

Recommendations for the classification of germline variants in the exonuclease domain of POLE and POLD1.

Background: Germline variants affecting the proofreading activity of polymerases epsilon and delta cause a hereditary cancer and adenomatous polyposis syndrome characterized by tumors with a high mutational burden and a specific mutational spectrum. In addition to the implementation of multiple pieces of evidence for the classification of gene variants, POLE and POLD1 variant classification is particularly challenging given that non-disruptive variants affecting the proofreading activity of the corresponding polymerase are the ones associated with cancer. In response to an evident need in the field, we have developed gene-specific variant classification recommendations, based on the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology) criteria, for the assessment of non-disruptive variants located in the sequence coding for the exonuclease domain of the polymerases.

Statistically learning the functional landscape of microbial communities.

Microbial consortia exhibit complex functional properties in contexts ranging from soils to bioreactors to human hosts. Understanding how community composition determines function is a major goal of microbial ecology. Here we address this challenge using the concept of community-function landscapes-analogues to fitness landscapes-that capture how changes in community composition alter collective function.

SARS-CoV-2 ORF8 accessory protein is a virulence factor.

The relevance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ORF8 in the pathogenesis of COVID-19 is unclear. Virus natural isolates with deletions in ORF8 were associated with wild milder disease, suggesting that ORF8 might contribute to SARS-CoV-2 virulence. This manuscript shows that ORF8 is involved in inflammation and in the activation of macrophages in two experimental systems: humanized K18-hACE2 transgenic mice and organoid-derived human airway cells.

Synthesizing microbial biodiversity.

The diversity of microbial ecosystems is linked to crucial ecological processes and functions. Despite its significance, the ecological mechanisms responsible for the initiation and maintenance of microbiome diversity are still not fully understood. The primary challenge lies in the difficulty of isolating, monitoring, and manipulating the complex and interrelated ecological processes that modulate the diversity of microbial communities in their natural habitats.

MBROLE3: improved functional enrichment of chemical compounds for metabolomics data analysis.

MBROLE (Metabolites Biological Role) facilitates the biological interpretation of metabolomics experiments. It performs enrichment analysis of a set of chemical compounds through statistical analysis of annotations from several databases. The original MBROLE server was released in 2011 and, since then, different groups worldwide have used it to analyze metabolomics experiments from a variety of organisms.

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children.

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of , , or in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L).

Affinity of cefotiam for the alternative penicillin binding protein PBP3SAL used by Salmonella inside host eukaryotic cells.

Background: Following the invasion of eukaryotic cells, Salmonella enterica serovar Typhimurium replaces PBP2/PBP3, main targets of β-lactam antibiotics, with PBP2SAL/PBP3SAL, two homologue peptidoglycan synthases absent in Escherichia coli. PBP3SAL promotes pathogen cell division in acidic environments independently of PBP3 and shows low affinity for β-lactams that bind to PBP3 such as aztreonam, cefepime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime and cefalotin.

Objectives: To find compounds with high affinity for PBP3SAL to control Salmonella intracellular infections.

MicroRNA-4732-3p Is Dysregulated in Breast Cancer Patients with Cardiotoxicity, and Its Therapeutic Delivery Protects the Heart from Doxorubicin-Induced Oxidative Stress in Rats.

Anthracycline-induced cardiotoxicity is the most severe collateral effect of chemotherapy originated by an excess of oxidative stress in cardiomyocytes that leads to cardiac dysfunction. We assessed clinical data from patients with breast cancer receiving anthracyclines and searched for discriminating microRNAs between patients that developed cardiotoxicity (cases) and those that did not (controls), using RNA sequencing and regression analysis. Serum levels of 25 microRNAs were differentially expressed in cases versus controls within the first year after anthracycline treatment, as assessed by three different regression models (elastic net, Robinson and Smyth exact negative binomial test and random forest).

Lack of EGFR catalytic activity in hepatocytes improves liver regeneration following DDC-induced cholestatic injury by promoting a pro-restorative inflammatory response.

Despite the well-known hepatoprotective role of the epidermal growth factor receptor (EGFR) pathway upon acute damage, its specific actions during chronic liver disease, particularly cholestatic injury, remain ambiguous and unresolved. Here, we analyzed the consequences of inactivating EGFR signaling in the liver on the regenerative response following cholestatic injury. For that, transgenic mice overexpressing a dominant negative mutant human EGFR lacking tyrosine kinase activity (ΔEGFR) in albumin-positive cells were submitted to liver damage induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC), an experimental model resembling human primary sclerosing cholangitis.

Cryo-EM structure of a type IV secretion system.

Bacterial conjugation is the fundamental process of unidirectional transfer of DNAs, often plasmid DNAs, from a donor cell to a recipient cell. It is the primary means by which antibiotic resistance genes spread among bacterial populations. In Gram-negative bacteria, conjugation is mediated by a large transport apparatus-the conjugative type IV secretion system (T4SS)-produced by the donor cell and embedded in both its outer and inner membranes.

CoMent: Relationships Between Biomedical Concepts Inferred From the Scientific Literature.

The mining of the massive amounts of biomedical information is hindered by the still scarce representation of these data using formal vocabularies and ontologies, which is necessary for cross-linking conceptual entities between different resources and, in general, representing the information in a computer-tractable way. Basic things such as retrieving a comprehensive list of associations between complex diseases and their reported symptoms or underlying biological processes, given in terms of formal identifiers, are not trivial and, in many cases, these have to be generated by manual curation or inferred/predicted from indirect evidences. In this work, using a text-mining approach based on detecting significant co-mentions in the scientific literature, we generated a resource with millions of relationships between thousands of terms representing diseases, symptoms, biological processes, molecular functions and cellular compartments, all given in terms of formal identifiers of these terms in the main resources dealing with them.

The Vascular Niche for Adult Cardiac Progenitor Cells.

Research on cardiac progenitor cell populations has generated expectations about their potential for cardiac regeneration capacity after acute myocardial infarction and during physiological aging; however, the endogenous capacity of the adult mammalian heart is limited. The modest efficacy of exogenous cell-based treatments can guide the development of new approaches that, alone or in combination, can be applied to boost clinical efficacy. The identification and manipulation of the adult stem cell environment, termed niche, will be critical for providing new evidence on adult stem cell populations and improving stem-cell-based therapies.

Ferrous Iron Uptake Is Required for Salmonella to Persist within Vacuoles of Host Cells.

Iron is an essential oligoelement that incorporates into proteins as a biocatalyst or electron carrier. The intracellular pathogen Salmonella enterica serovar Typhimurium ( Typhimurium) takes iron as free reduced ferrous cation or as oxidized ferric cation complexed to siderophores or ferrichromes. Deficiencies in ferrous or ferric iron uptake attenuate Typhimurium virulence, but how the uptake systems are used in the intracellular environment remains poorly understood.