Dairy Cattle and the Iconic Autochthonous Cattle in Northern Portugal Are Reservoirs of Multidrug-Resistant .

Animals destined for human consumption play a key role in potentially transmitting bacteria carrying antibiotic resistance genes. However, there is limited knowledge about the carriage of antibiotic-resistant bacteria in native breeds. We aimed to characterize the phenotypic profiles and antibiotic resistance genes in isolated from bovines, including three native Portuguese bovine breeds.

Approaches and Challenges in Characterizing the Molecular Content of Extracellular Vesicles for Biomarker Discovery.

Extracellular vesicles (EVs) are lipid bilayer nanoparticles released from all known cells and are involved in cell-to-cell communication via their molecular content. EVs have been found in all tissues and body fluids, carrying a variety of biomolecules, including DNA, RNA, proteins, metabolites, and lipids, offering insights into cellular and pathophysiological conditions. Despite the emergence of EVs and their molecular contents as important biological indicators, it remains difficult to explore EV-mediated biological processes due to their small size and heterogeneity and the technical challenges in characterizing their molecular content.

Insights into the Molecular Mechanisms of Purine Compounds Synergistically Inducing Larval Settlement in Using Multi-Group Comparative Transcriptomic Analysis.

Most benthic marine invertebrates exhibit a characteristic biphasic life cycle, consisting of a planktonic larval stage followed by a benthic adult stage [...

Biology: The Open Road to a Theory of Life.

The journal was launched in 2012 [...

Phylogenetic characterization of Bifidobacterium kimbladii sp. nov., a novel species from the honey stomach of the honeybee Apis mellifera.

Six novel Bifidobacterium strains H1HS16N, Bin2N, Hma3N, H6bp22N, H1HS10N, and H6bp9N, were isolated from the honey stomach of Apis mellifera. Cells are Gram-positive, non-motile, non-sporulating, facultatively anaerobic, and fructose 6-phosphate phosphoketolase-positive. Optimal growth conditions occur at 37 °C in anaerobiosis in MRS medium added with 2 % fructose and 0.

Protocol for evaluating the activity of R2 retrotransposons in mammalian cells.

R2 retrotransposons can be harnessed to insert genes at targeted sites by all-RNA delivery, presenting a new technology for next-generation biotherapeutics. Here, we report a protocol for evaluating the gene integration activity of R2 retrotransposons in mammalian cells. We describe the construction of vectors separately expressing R2 protein and donor, the process of liposome transfection, and flow cytometry.

Integrated View of Baseline Protein Expression in Human Tissues Using Public Data Independent Acquisition Data Sets.

The PRIDE database is the largest public data repository of mass spectrometry-based proteomics data and currently stores more than 40,000 data sets covering a wide range of organisms, experimental techniques, and biological conditions. During the past few years, PRIDE has seen a significant increase in the amount of submitted data-independent acquisition (DIA) proteomics data sets. This provides an excellent opportunity for large-scale data reanalysis and reuse.

WhiA transcription factor provides feedback loop between translation and energy production in a genome-reduced bacterium.

Introduction: WhiA is a conserved protein found in numerous bacteria. It consists of an HTH DNA-binding domain linked with a homing endonuclease (HEN) domain. WhiA is one of the most conserved transcription factors in reduced bacteria of the class Mollicutes.

The IBEX Imaging Knowledge-Base: A Community Resource Enabling Adoption and Development of Immunofluoresence Imaging Methods.

The iterative bleaching extends multiplexity (IBEX) Knowledge-Base is a central portal for researchers adopting IBEX and related 2D and 3D immunofluorescence imaging methods. The design of the Knowledge-Base is modeled after efforts in the open-source software community and includes three facets: a development platform (GitHub), static website, and service for data archiving. The Knowledge-Base facilitates the practice of open science throughout the research life cycle by providing validation data for recommended and non-recommended reagents, e.

Comparative genomics of the sexually transmitted parasite reveals relaxed and convergent evolution and genes involved in spillover from birds to humans.

is the causative agent of the venereal disease trichomoniasis which infects men and women globally and is associated with serious outcomes during pregnancy and cancers of the human reproductive tract. Trichomonads parasitize a range of hosts in addition to humans including birds, livestock, and domesticated animals. Recent genetic analysis of trichomonads recovered from columbid birds has provided evidence that these parasite species undergo frequent host-switching, and that a current epoch spillover event from columbids likely gave rise to in humans.

Asynchronous Transitions from Hepatoblastoma to Carcinoma in High-Risk Pediatric Tumors.

Most malignant hepatocellular tumors in children are classified as either hepatoblastoma (HB) or hepatocellular carcinoma (HCC), but some tumors demonstrate features of both HB and HCC. These tumors have been recognized under a provisional diagnostic category by the World Health Organization and are distinguished from HB and HCC by a combination of histological, immunohistochemical, and molecular features. Their outcomes and cellular composition remain an open question.

An Expanded Registry of Candidate cis-Regulatory Elements for Studying Transcriptional Regulation.

Mammalian genomes contain millions of regulatory elements that control the complex patterns of gene expression. Previously, The ENCODE consortium mapped biochemical signals across many cell types and tissues and integrated these data to develop a Registry of 0.9 million human and 300 thousand mouse candidate cis-Regulatory Elements (cCREs) annotated with potential functions.

PSGL-1 excludes HIV Env from virion surface through spatial hindrance involving structural folding of the decameric repeats (DR).

P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like surface glycoprotein, is primarily expressed on lymphoid and myeloid cells. PSGL-1 has recently been identified as an HIV restriction factor, blocking HIV infectivity mainly through virion incorporation that sterically hinders virion attachment to target cells. PSGL-1 also inhibits HIV Env incorporation into virions.

A bacterial NLR-related protein recognizes multiple unrelated phage triggers to sense infection.

Immune systems must rapidly sense viral infections to initiate antiviral signaling and protect the host. Bacteria encode >100 distinct viral (phage) defense systems and each has evolved to sense crucial components or activities associated with the viral lifecycle. Here we used a high-throughput AlphaFold-multimer screen to discover that a bacterial NLR-related protein directly senses multiple phage proteins, thereby limiting immune evasion.

Polymers for mRNA Delivery.

mRNA delivery has emerged as a transformative approach in biotechnology and medicine, offering a versatile platform for the development of novel therapeutics. Unlike traditional small molecule drugs or protein-based biologics, mRNA therapeutics have the unique ability to direct cells to generate therapeutic proteins, allowing for precise modulation of biological processes. The delivery of mRNA into target cells is a critical step in realizing the therapeutic potential of this technology.

Endotoxin-Free Outer Membrane Vesicles for Safe and Modular Anticancer Immunotherapy.

Bacterial outer membrane vesicles (OMVs) have emerged as promising vehicles for anticancer drug delivery due to their inherent tumor tropism, immune-stimulatory properties, and potential for functionalization with therapeutic proteins. Despite their advantages, the high lipopolysaccharide (LPS) endotoxin content in the OMVs raises significant safety and regulatory challenges. In this work, we produce LPS-attenuated and LPS-free OMVs and systematically assess the effects of LPS modification on OMVs' physicochemical characteristics, membrane protein content, immune-stimulatory capacity, tolerability, and anticancer efficacy.

Aberrant splicing in Huntington's disease accompanies disrupted TDP-43 activity and altered m6A RNA modification.

Huntington's disease (HD) is caused by a CAG repeat expansion in the HTT gene, leading to altered gene expression. However, the mechanisms leading to disrupted RNA processing in HD remain unclear. Here we identify TDP-43 and the N6-methyladenosine (m6A) writer protein METTL3 to be upstream regulators of exon skipping in multiple HD systems.

A multiplex method for rapidly identifying viral protease inhibitors.

With current treatments addressing only a fraction of pathogens and new viral threats constantly evolving, there is a critical need to expand our existing therapeutic arsenal. To speed the rate of discovery and better prepare against future threats, we establish a high-throughput platform capable of screening compounds against 40 diverse viral proteases simultaneously. This multiplex approach is enabled by using cellular biosensors of viral protease activity combined with DNA-barcoding technology, as well as several design innovations that increase assay sensitivity and correct for plate-to-plate variation.

Algae- and bacteria-based biodegradation of phthalic acid esters towards the sustainable green solution.

Phthalic acid esters are widely used worldwide as plasticizers. The high consumption of phthalates in China makes it the world's largest plasticizer market. The lack of phthalic acid ester's chemical bonding with the polymer matrix facilitates their detachment from plastic products and subsequent release into the environment and causes serious threats to the health of living organisms.

Intellectual frameworks to understand complex biochemical systems at the origin of life.

Understanding the emergence of complex biochemical systems, such as protein translation, is a great challenge. Although synthetic approaches can provide insight into the potential early stages of life, they do not address the equally important question of why the complex systems of life would have evolved. In particular, the intricacies of the mechanisms governing the transfer of information from nucleic acid sequences to proteins make it difficult to imagine how coded protein synthesis could have emerged from a prebiotic soup.

Apoptotic priming in senescence predicts specific senolysis by quantitative analysis of mitochondrial dependencies.

Cellular senescence contributes to a variety of pathologies associated with aging and is implicated as a cellular state in which cancer cells can survive treatment. Reported senolytic drug treatments act through varying molecular mechanisms, but heterogeneous efficacy across the diverse contexts of cellular senescence indicates a need for predictive biomarkers of senolytic activity. Using multi-parametric analyses of commonly reported molecular features of the senescent phenotype, we assayed a variety of models, including malignant and nonmalignant cells, using several triggers of senescence induction and found little univariate predictive power of these traditional senescence markers to identify senolytic drug sensitivity.

Coherent manipulation of photochemical spin-triplet formation in quantum dot-molecule hybrids.

The interconversion between singlet and triplet spin states of photogenerated radical pairs is a genuine quantum process, which can be harnessed to coherently manipulate the recombination products through a magnetic field. This control is central to such diverse fields as molecular optoelectronics, quantum sensing, quantum biology and spin chemistry, but its effect is typically fairly weak in pure molecular systems. Here we introduce hybrid radical pairs constructed from semiconductor quantum dots and organic molecules.

Microplastics can alter structural configurations of human non-canonical G-quadruplex DNA.

Microplastics (MP) with a diameter of less than 150 μm can enter the lymph and bloodstream systems, induce cellular toxicity and damage DNA. G-quadruplexes (GQs) are tetraplex DNA secondary structures found in the human genomes that play important roles in replication, transcription and genomic integrity. Comprehending the biological and molecular processes underlying the activities of MPs could aid in estimating potential hazards to humans.

Leveraging cancer mutation data to inform the pathogenicity classification of germline missense variants.

Innovative and easy-to-implement strategies are needed to improve the pathogenicity assessment of rare germline missense variants. Somatic cancer driver mutations identified through large-scale tumor sequencing studies often impact genes that are also associated with rare Mendelian disorders. The use of cancer mutation data to aid in the interpretation of germline missense variants, regardless of whether the gene is associated with a hereditary cancer predisposition syndrome or a non-cancer-related developmental disorder, has not been systematically assessed.