Interaction and cleavage of cell and plasma proteins by the platelet-aggregating serine protease PA-BJ of Bothrops jararaca venom.

PA-BJ is a serine protease present in Bothrops jararaca venom that triggers platelet aggregation and granule secretion by activating the protease-activated receptors PAR-1 and PAR-4, without clotting fibrinogen. These receptors also have a relevant role in endothelial cells, however, the interaction of PA-BJ with other membrane-bound or soluble targets is not known. Here we explored the activity of PA-BJ on endothelial cell receptor, cytoskeleton, and coagulation proteins in vitro, and show the degradation of fibrinogen and protein C, and the limited proteolysis of actin, EPCR, PAR-1, and thrombomodulin.

Jararaca GPIb-binding protein causes thrombocytopenia during Bothrops jararaca envenomation.

Inoculation of Bothrops jararaca snake venom (BjV) induces thrombocytopenia in humans and various animal species. Although several BjV toxins acting on hemostasis have been well characterized in vitro, it is not known which one is responsible for inducing thrombocytopenia in vivo. In previous studies, we showed that BjV incubated with metalloproteinase or serine proteinase inhibitors and/or anti-botrocetin antibodies still induced thrombocytopenia in rats and mice.

Venom proteomics and Duvernoy's venom gland histology of Pseudoboa neuwiedii (Neuwied's false boa; Dipsadidae, Pseudoboini).

The venom of Colombian specimens of the rear-fanged snake Pseudoboa neuwiedii contains proteolytic and phospholipase A (PLA) activities, but is devoid of esterases. Mass spectrometric analysis of electrophoretic bands indicated that this venom contains C-type lectins (CTL), cysteine-rich secretory proteins (CRiSP), PLA, snake venom metalloproteinases (SVMP), and snake venom matrix metalloproteinases (svMMP). In this investigation, we extended our characterization of P.

Optimizing rare disorder trials: a phase 1a/1b randomized study of KL1333 in adults with mitochondrial disease.

Over the past two decades there has been increased interest in orphan drug development for rare diseases. However, hurdles to clinical trial design for these disorders remain. This phase 1a/1b study addressed several challenges, while evaluating the safety and tolerability of the novel oral molecule KL1333 in healthy volunteers and subjects with primary mitochondrial disease.

Association of Cytotoxic T-Lymphocyte Antigen-4 () Genetic Variants with Risk and Outcome of Cutaneous Melanoma.

This study aimed to verify whether germline single nucleotide variants (SNV) in gene, c.-1765C>T, c.-1661A>G, c.

Protein kinase D1 mitigation against etoposide induced DNA damage in prostate cancer is associated with increased α-Catenin.

Background: The E-cadherin, α- and β-Catenin interaction at the cell adherens junction plays a key role in cell adhesion; alteration in the expression and function of these genes are associated with disease progression in several solid tumors including prostate cancer. The membranous β-Catenin is dynamically linked to the cellular cytoskeleton through interaction with α-Catenin at amino acid positions threonine 120 (T120) to 151 of β-Catenin. Nuclear presence of α-Catenin modulates the sensitivity of cells to DNA damage.

Beyond Harmful: Exploring Biofilm Formation by Enterococci Isolated from Portuguese Traditional Cheeses.

This study investigated the biofilm-forming capabilities of isolates from Portuguese traditional cheeses with protected designation of origin (PDO) status, specifically and . Given the absence of added starter cultures in the cheesemaking process, the characteristics of these cheeses are intrinsically linked to the autochthonous microbiota present in the raw materials and the production environment. Our findings demonstrate that all isolates possess biofilm production abilities, which are crucial for their colonization and persistence within cheese factories, thereby maintaining factory-specific microbial heritage.

Evaluating Procedure-Linked Risk Determinants in spp. Inspection under a Quality Management System in Southern Spain.

Trichinellosis is a major foodborne zoonotic disease responsible for 41 human cases, according to the European Union One Health Zoonoses Report. In southern Spain, a quality management system (QMS) was applied to satellite laboratories (SLs) that conduct meat inspections of spp. ensuring excellence practices.

Engaging Diverse African American/Black and Latine Youth and Emerging Adults Living with HIV into Research: Description of Recruitment Strategies and Lessons Learned.

Improving engagement along the HIV care continuum and reducing racial/ethnic disparities are necessary to end the HIV epidemic. Research on African American/Black and Latine (AABL) younger people living with HIV (LWH) is essential to this goal. However, a number of key subgroups are challenging to locate and engage, and are therefore under-represented in research.

Oropouche Fever, Cuba, May 2024.

Phylogenetic analyses showed that the virus responsible for a May 2024 Oropouche fever outbreak in Cuba was closely related to viruses from Brazil in 2023. Pools of Ceratopogonidae spp. biting midges and Culex quinquefasciatus mosquitoes were positive for Oropouche viral RNA.

Entangling gates on degenerate spin qubits dressed by a global field.

Semiconductor spin qubits represent a promising platform for future large-scale quantum computers owing to their excellent qubit performance, as well as the ability to leverage the mature semiconductor manufacturing industry for scaling up. Individual qubit control, however, commonly relies on spectral selectivity, where individual microwave signals of distinct frequencies are used to address each qubit. As quantum processors scale up, this approach will suffer from frequency crowding, control signal interference and unfeasible bandwidth requirements.

Understanding the role of B cells in CAR T-cell therapy in leukemia through a mathematical model.

Chimeric antigen receptor T (CAR T) cell therapy has been proven to be successful against a variety of leukemias and lymphomas. This paper undertakes an analytical and numerical study of a mathematical model describing the competition of CAR T, leukemia, tumor, and B cells. Considering its significance in sustaining anti-CD19 CAR T-cell stimulation, a B-cell source term is integrated into the model.

Non-endothelial expression of endomucin in the mouse and human choroid.

Endomucin (EMCN) is a 261 amino acid transmembrane glycoprotein that is highly expressed by venous and capillary endothelial cells where it plays a role in VEGF-mediated angiogenesis and regulation of immune cell recruitment. However, it is better known as a histological marker, where it has become widespread due to the commercial availability of high-quality antibodies that work under a wide range of conditions and in many tissues. The specificity of EMCN staining has been well-validated in retinal vessels, but while it has been used extensively as a marker in other tissues of the eye, including the choroid, the pattern of expression has not been described in detail.

Influence of footshock number and intensity on the behavioral and endocrine response to fear conditioning and cognitive fear generalization in male rats.

Foot-shock paradigms have provided valuable insights into the neurobiology of stress and fear conditioning. An extensive body of literature indicates that shock exposure can elicit both conditioned and unconditioned effects, although delineating between the two is a challenging task. This distinction holds crucial implications not only for the theoretical interpretation of fear conditioning, but also for properly evaluating putative preclinical models of post-traumatic stress disorder (PTSD) involving shock exposure.

Clinical History Method versus Corneal Tomographers in Estimating Corneal Power after Photorefractive Surgery.

Aims: To investigate the concordance between the corneal power determined by various approaches with two tomographers (MS-39® and Galilei G6®) and the clinical history method (CHM) in patients undergoing photorefractive surgery with excimer laser for myopic errors.

Material And Methods: Prospective cohort study. Patients undergoing keratorefractive surgery, and having pre- and postoperative keratometries, and tomographies, were included.

Bridging the vitamin A and deworming coverage gap among underserved populations in India through government and civil society organization partnerships.

Background: Vitamin A deficiency (VAD) is a major public health problem in India, where approximately 62% of children under five have low retinol levels (< 70 µmol/L). This study aims to (1) evaluate vitamin A supplementation (VAS) and deworming (VAS + D) coverage in Nagaland state through government and civil society organization (CSO) partnerships, (2) examine socio-demographic barriers and facilitators to VAS + D coverage, (3) examine associations between socio-demographic characteristics and source of VAS coverage (i.e.

Bounds to electron spin qubit variability for scalable CMOS architectures.

Spins of electrons in silicon MOS quantum dots combine exquisite quantum properties and scalable fabrication. In the age of quantum technology, however, the metrics that crowned Si/SiO as the microelectronics standard need to be reassessed with respect to their impact upon qubit performance. We chart spin qubit variability due to the unavoidable atomic-scale roughness of the Si/SiO interface, compiling experiments across 12 devices, and develop theoretical tools to analyse these results.

A multicenter study of the efficacy and safety of treatments (endovascular or conservative) in small intracranial aneurysms in Colombia.

Background: The registry of cerebral aneurysms <5 mm, known for their low risk of rupture, is significant, given their high incidence globally. Our study aimed to identify, in small aneurysms (<5 mm), the potential morphological characteristics, risk factors that can predict the risk of rupture, and the risk or benefit of treating them with endovascular or conservative treatment in ruptured and unruptured intracranial aneurysms.

Methods: The medical records of patients with cerebral aneurysms <5 mm were retrospectively reviewed between January 2014 and December 2022 at two neurovascular centers in Colombia.

Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.

Non-endothelial expression of Endomucin in the mouse and human choroid.

Endomucin (EMCN) is a 261 AA transmembrane glycoprotein that is highly expressed by venous and capillary endothelial cells where it plays a role in VEGF-mediated angiogenesis and regulation of immune cell recruitment. However, it is better known as a histological marker, where it has become widespread due to the commercial availability of high-quality antibodies that work under a wide range of conditions and in many tissues. The specificity of EMCN staining has been well-validated in retinal vessels, but while it has been used extensively as a marker in other tissues of the eye, including the choroid, the pattern of expression has not been described in detail.