Targeting protein-ligand neosurfaces with a generalizable deep learning tool.

Molecular recognition events between proteins drive biological processes in living systems. However, higher levels of mechanistic regulation have emerged, in which protein-protein interactions are conditioned to small molecules. Despite recent advances, computational tools for the design of new chemically induced protein interactions have remained a challenging task for the field.

Image-Based Shrimp Aquaculture Monitoring.

Shrimp farming is a growing industry, and automating certain processes within aquaculture tanks is becoming increasingly important to improve efficiency. This paper proposes an image-based system designed to address four key tasks in an aquaculture tank with : estimating shrimp length and weight, counting shrimps, and evaluating feed pellet food attractiveness. A setup was designed, including a camera connected to a Raspberry Pi computer, to capture high-quality images around a feeding plate during feeding moments.

Wild-Mouse-Derived Gut Microbiome Transplantation in Laboratory Mice Partly Alleviates House-Dust-Mite-Induced Allergic Airway Inflammation.

Laboratory mice are instrumental for preclinical research but there are serious concerns that the use of a clean standardized environment for specific-pathogen-free (SPF) mice results in poor bench-to-bedside translation due to their immature immune system. The aim of the present study was to test the importance of the gut microbiota in wild vs. SPF mice for evaluating host immune responses in a house-dust-mite-induced allergic airway inflammation model without the influence of pathogens.

The physiological landscape and specificity of antibody repertoires are consolidated by multiple immunizations.

Diverse antibody repertoires spanning multiple lymphoid organs (i.e., bone marrow, spleen, lymph nodes) form the foundation of protective humoral immunity.

BindCraft: one-shot design of functional protein binders.

Protein-protein interactions (PPIs) are at the core of all key biological processes. However, the complexity of the structural features that determine PPIs makes their design challenging. We present BindCraft, an open-source and automated pipeline for protein binder design with experimental success rates of 10-100%.

An Investigation of the Sodium Nitroprusside Effects on Serum Lipids in an Animal Model of Schizophrenia by the Magnetic Resonance Study.

Schizophrenia (SCZ) is a multifactorial mental illness with limited knowledge concerning pathogenesis, contributing to the lack of effective therapies. More recently, the use of a nitric oxide donor named sodium nitroprusside (sNP) was suggested as a potential therapeutic drug for the treatment of SCZ. Despite the mixed results regarding the effectiveness of the sNP in reducing SCZ symptoms, successful trials on sNP in treatment-resistant SCZ were published.

A modular toolbox for the optogenetic deactivation of transcription.

Light-controlled transcriptional activation is a commonly used optogenetic strategy that allows researchers to regulate gene expression with high spatiotemporal precision. The vast majority of existing tools are, however, limited to light-triggered induction of gene expression. Here, we inverted this mode of action and created optogenetic systems capable of efficiently terminating transcriptional activation in response to blue light.

Epitope-focused immunogens targeting the hepatitis C virus glycoproteins induce broadly neutralizing antibodies.

Hepatitis C virus (HCV) infection causes ~290,000 annual human deaths despite the highly effective antiviral treatment available. Several viral immune evasion mechanisms have hampered the development of an effective vaccine against HCV, among them the remarkable conformational flexibility within neutralization epitopes in the HCV antigens. Here, we report the design of epitope-focused immunogens displaying two distinct HCV cross-neutralization epitopes.

A deep mutational scanning platform to characterize the fitness landscape of anti-CRISPR proteins.

Deep mutational scanning is a powerful method for exploring the mutational fitness landscape of proteins. Its adaptation to anti-CRISPR proteins, which are natural CRISPR-Cas inhibitors and key players in the co-evolution of microbes and phages, facilitates their characterization and optimization. Here, we developed a robust anti-CRISPR deep mutational scanning pipeline in Escherichia coli that combines synthetic gene circuits based on CRISPR interference with flow cytometry coupled sequencing and mathematical modeling.

Myositis-Associated Interstitial Lung Disease: The Experience of a Tertiary Center.

: Interstitial lung disease (ILD) is a common extra-muscular manifestation of idiopathic inflammatory myopathies (IIMs), often associated with a poorer prognosis and increased mortality risk. : This retrospective study aimed to characterize lung involvement and treatment response in an IIM cohort at a Portuguese tertiary center, followed between June 2016 and March 2024. We analyzed data from high-resolution computed tomography (HRCT) scans and pulmonary function tests (PFTs) to assess associations with autoantibody profiles and treatment regimens.

Dual ON/OFF-switch chimeric antigen receptor controlled by two clinically approved drugs.

The ability to remotely control the activity of chimeric antigen receptors (CARs) with small molecules can improve the safety and efficacy of gene-modified T cells. Split ON- or OFF-switch CARs involve the dissociation of tumor-antigen binding from T cell activation (i.e.

Structures of the Foamy virus fusion protein reveal an unexpected link with the F protein of paramyxo- and pneumoviruses.

Foamy viruses (FVs) constitute a subfamily of retroviruses. Their envelope (Env) glycoprotein drives the merger of viral and cellular membranes during entry into cells. The only available structures of retroviral Envs are those from human and simian immunodeficiency viruses from the subfamily of orthoretroviruses, which are only distantly related to the FVs.

Influence of gabapentin on the degree of sedation, physiological variables and propofol dosage in cats premedicated with acepromazine and methadone: a randomized, prospective, blinded, clinical study.

This study evaluated the influence of gabapentin on sedation, propofol dosage, and physiological variables in cats premedicated with acepromazine and methadone. Thirty-four cats were randomly assigned to receive 100 mg of oral gabapentin (Gabapentin group) or placebo (Control group) 100 min before intramuscular premedication with acepromazine (0.05 mg/kg) plus methadone (0.

Effect of Density and Lineage on Dorsal Surface Temperature, Performance, and Carcass Condemnation of Broiler Grillers.

The aims of this study were (i) to evaluate the effect of density, lineage, age, and time of day on dorsal surface temperature and (ii) to evaluate the effect of density and lineage on performance and carcass condemnations in broiler grillers. The evaluations were carried out in barns with the Dark House system, with two densities, 17 and 19 chickens/m and two lineages, Cobb and Ross. The dorsal surface temperature of the chickens was measured by infrared thermography at 7, 14, 21, 23, 25 and 27 days of age, four times a day.

Changes in the urinary metabolome accompanied alterations in body mass and composition in women with overweight - impact of high versus low protein breakfast.

Introduction: Understanding why subjects with overweight and with obesity vary in their response to dietary interventions is of major interest for developing personalized strategies for body mass regulation.

Objectives: The aim of this study was to investigate the relationship between changes in the urine metabolome and body mass during a breakfast meal intervention. Furthermore, we aimed to elucidate if the baseline urine metabolome could predict the response to the two types of breakfast meals (high versus low protein) during the intervention.

An evolved artificial radical cyclase enables the construction of bicyclic terpenoid scaffolds via an H-atom transfer pathway.

While natural terpenoid cyclases generate complex terpenoid structures via cationic mechanisms, alternative radical cyclization pathways are underexplored. The metal-catalysed H-atom transfer reaction (M-HAT) offers an attractive means for hydrofunctionalizing olefins, providing access to terpenoid-like structures. Artificial metalloenzymes offer a promising strategy for introducing M-HAT reactivity into a protein scaffold.

Computational design of soluble and functional membrane protein analogues.

De novo design of complex protein folds using solely computational means remains a substantial challenge. Here we use a robust deep learning pipeline to design complex folds and soluble analogues of integral membrane proteins. Unique membrane topologies, such as those from G-protein-coupled receptors, are not found in the soluble proteome, and we demonstrate that their structural features can be recapitulated in solution.

Antibody-peptide conjugates deliver covalent inhibitors blocking oncogenic cathepsins.

Cysteine cathepsins are a family of proteases that are relevant therapeutic targets for the treatment of different cancers and other diseases. However, no clinically approved drugs for these proteins exist, as their systemic inhibition can induce deleterious side effects. To address this problem, we developed a modular antibody-based platform for targeted drug delivery by conjugating non-natural peptide inhibitors (NNPIs) to antibodies.

Joint host-pathogen genomic analysis identifies hepatitis B virus mutations associated with human NTCP and HLA class I variation.

Evolutionary changes in the hepatitis B virus (HBV) genome could reflect its adaptation to host-induced selective pressure. Leveraging paired human exome and ultra-deep HBV genome-sequencing data from 567 affected individuals with chronic hepatitis B, we comprehensively searched for the signatures of this evolutionary process by conducting "genome-to-genome" association tests between all human genetic variants and viral mutations. We identified significant associations between an East Asian-specific missense variant in the gene encoding the HBV entry receptor NTCP (rs2296651, NTCP S267F) and mutations within the receptor-binding region of HBV preS1.

Influence of intravenous fentanyl or dexmedetomidine infusions, combined with lidocaine and ketamine, on cardiovascular response, sevoflurane requirement and postoperative pain in dogs anesthetized for unilateral mastectomy.

Objective: To compare the effects of constant rate infusions (CRI) of fentanyl or dexmedetomidine, combined with lidocaine and ketamine, on cardiovascular response during surgery, sevoflurane requirement and postoperative pain in dogs undergoing mastectomy.

Study Design: Prospective, randomized, blinded, clinical trial.

Animals: A total of 29 female dogs with mammary tumors.

Opportunities and challenges in design and optimization of protein function.

The field of protein design has made remarkable progress over the past decade. Historically, the low reliability of purely structure-based design methods limited their application, but recent strategies that combine structure-based and sequence-based calculations, as well as machine learning tools, have dramatically improved protein engineering and design. In this Review, we discuss how these methods have enabled the design of increasingly complex structures and therapeutically relevant activities.

The Cardiometabolic Impact of Rebaudioside A Exposure during the Reproductive Stage.

The consumption of non-sugar sweeteners (NSS) has increased during pregnancy. The European Food Safety Agency suggested that steviol glycosides, such as Rebaudioside A (RebA), the major sweetener component of stevia, are safe for humans up to a dose of 4 mg/kg body weight/day. However, the World Health Organization recommended in 2023 the restraint of using NSS, including stevia, at any life stage, highlighting the need to study NSS safety in early periods of development.