Advancing nuclear transfer cloning in zebrafish (Danio rerio) into a translational pathway using interdisciplinary tools.

The Zebrafish International Resource Center (ZIRC) is an NIH-funded national stock center and germplasm repository that maintains and distributes genetically modified and wild-type zebrafish (Danio rerio) lines to the biomedical research community. The ZIRC and its community would benefit from incorporating somatic cell nuclear transfer (SCNT) cloning which would allow the preservation of diploid genomes. The goal of this study was to advance a zebrafish SCNT cloning protocol into a reproducible community-level pathway by use of process mapping and simulation modeling approaches to address training requirements, process constraints, and quality management gaps.

Inhibition of the H1 voltage-gated proton channel compromises the viability of human polarized macrophages in a polarization- and ceramide-dependent manner.

The human voltage-gated proton channel (H1) provides an efficient proton extrusion pathway from the cytoplasm contributing to the intracellular pH regulation and the oxidative burst. Although its pharmacological inhibition was previously shown to induce cell death in various cell types, no such effects have been examined in polarized macrophages albeit H1 was suggested to play important roles in these cells. This study highlights that 5-chloro-2-guanidinobenzimidazole (ClGBI), the most widely applied H1 inhibitor, reduces the viability of human THP-1-derived polarized macrophages at biologically relevant doses with M1 macrophages being the most, and M2 cells the least sensitive to this compound.

Modeling the Mutation and Competition of Certain Nutrient-Producing Protocells by Means of Specific Turing Machines.

It is very important to model the behavior of protocells as basic lifelike artificial organisms more and more accurately from the level of genomes to the level of populations. A better understanding of basic protocell communities may help us in describing more complex ecological systems accurately. In this article, we propose a new comprehensive, bilevel mathematical model of a community of three protocell species (one generalist and two specialists).

Potentiation of NMDA Receptors by AT1 Angiotensin Receptor Activation in Layer V Pyramidal Neurons of the Rat Prefrontal Cortex.

NMDA receptors in the prefrontal cortex (PFC) play a crucial role in cognitive functions. Previous research has indicated that angiotensin II (Ang II) affects learning and memory. This study aimed to examine how Ang II impacts NMDA receptor activity in layer V pyramidal cells of the rat PFC.

Survival cost sharing among altruistic full siblings in Mendelian population.

Background: We focus on Haldane's familial selection in monogamous families in a diploid population, where the survival probability of each sibling is determined by altruistic food sharing with its siblings during starvation. An autosomal recessive-dominant or intermediate allele pair uniquely determines the altruistic or selfish behavior, which are coded by homozygotes. We focus on the case when additive cost and benefit functions determine the survival probability of each full sibling.

CardiLect: A combined cross-species lectin histochemistry protocol for the automated analysis of cardiac remodelling.

Background: Cardiac remodelling, a crucial aspect of heart failure, is commonly investigated in preclinical models by quantifying cardiomyocyte cross-sectional area (CSA) and microvascular density (MVD) via histological methods, such as immunohistochemistry. To achieve this, optimized protocols are needed, and the species specificity is dependent on the antibody used. Lectin histochemistry offers several advantages compared to antibody-based immunohistochemistry, including as cost-effectiveness and cross-species applicability.

Surface-enhanced infrared spectroscopic study of extracellular vesicles using plasmonic gold nanoparticles.

Extracellular vesicles (EVs), sub-micrometer lipid-bound particles released by most cells, are considered a novel area in both biology and medicine. Among characterization methods, infrared (IR) spectroscopy, especially attenuated total reflection (ATR), is a rapidly emerging label-free tool for molecular characterization of EVs. The relatively low number of vesicles in biological fluids (∼10 particle/mL), however, and the complex content of the EVs' milieu (protein aggregates, lipoproteins, buffer molecules) might result in poor signal-to-noise ratio in the IR analysis of EVs.

Effects of sex and obesity on immune checkpoint inhibition-related cardiac systolic dysfunction in aged mice.

Despite accumulating data on underlying mechanisms, the influence of sex and prevalent cardio-metabolic co-morbidities on the manifestation and severity of immune checkpoint inhibitor (ICI)-induced cardiotoxicity has not been well defined. To elucidate whether sex and prevalent cardio-metabolic co-morbidities affect ICI-induced cardiotoxicity, we randomized 17-month-old male and female mice to receive control diet (CON) or high-fat diet (HFD) + L-NAME-a well-established mouse model of cardio-metabolic co-morbidities-for 17 weeks (n = 5-7), and evaluated markers of T-cell function in the spleen. As expected, HFD + L-NAME significantly increased body- and heart weight, and serum cholesterol levels, and caused no systolic dysfunction, however, led to diastolic dysfunction, cardiomyocyte hypertrophy, and increased fibrosis only in males compared to corresponding CON.

Pharmacokinetics and cardioprotective efficacy of intravenous miR-125b* microRNA mimic in a mouse model of acute myocardial infarction.

Background And Purpose: MicroRNA (miRNA) therapy is a promising approach to induce cardioprotection. We have previously identified cardiac microRNA-125b* (microRNA-125b-2-3p; miR-125b*) as a potential cardioprotective miRNA, termed ProtectomiR. We aimed to characterize the pharmacokinetics and pharmacodynamics, and the effect of miR-125b* mimic on infarct size using an in vivo mouse model.

Quantitative Biodistribution of OMVs Using SPECT/CT Imaging with HYNIC-Duramycin Radiolabeling.

Bacterial outer membrane vesicles (OMVs) are emerging as important players in the host-microbiome interaction, while also proving to be a promising platform for vaccine development and targeted drug delivery. The available methods for measuring their biodistribution, however, are limited. We aimed to establish a high-efficiency radiolabeling method for the treatment of OMVs.

Reduced circulating CD63 extracellular vesicle levels associate with atherosclerosis in hypercholesterolaemic mice and humans.

Aims: The association and co-isolation of low-density lipoproteins (LDL) and extracellular vesicles (EVs) have been shown in blood plasma. Here we explore this relationship to better understand the role of EVs in atherogenesis.

Methods And Results: Wild type (WT), PCSK9, and LDLR C57BL/6 mice were used in this study.

Advancing Zebrafish Husbandry: Takeaways From the 2024 Husbandry Workshop and Husbandry Summit.

The 2024 Zebrafish Husbandry Workshop and Summit held during the World Aquaculture Society Meeting in San Antonio focused on key areas for improving zebrafish husbandry research. Discussions highlighted the need for comprehensive literature on husbandry, better communication and collaboration between researchers and facility staff, and the adoption of a standardized reference diet. Current literature lacks comprehensive data and often overlooks crucial factors such as housing density and space requirements for fish development.

Correction: Kovács et al. ABT-333 (Dasabuvir) Increases Action Potential Duration and Provokes Early Afterdepolarizations in Canine Left Ventricular Cells via Inhibition of I. 2023, , 488.

Text Correction [...

Acute pulmonary embolism pretest probability estimation by d-dimer test, our modified, new ECG score and clinical prediction rules.

Objectives: We investigated whether a sufficiently sensitive D-dimer test could exclude acute pulmonary embolism (acPE) as a stand-alone diagnostic test and compared our previously published, modified ECG score with the Wells and Geneva scores in the estimation of acPE pretest probability.

Methods: We retrospectively evaluated 345 patients who underwent chest CT angiography (CTA) for the suspicion of acPE. The pretest probability of acPE was assessed in 120 D-dimer negative [DD (-)] and 225 D-dimer positive [DD (+)] patients.

Theoretical Study of Metal-Ligand Interactions in Lead Complexes with Radiopharmaceutical Interest.

The Pb and Pb lead radioisotopes are attracting growing interest as they can aid in the development of personalized, targeted radionuclide treatment for advanced and currently untreatable cancers. In the present study, the bonding interactions of Pb with twelve macrocyclic ligands, having an octa and nona coordination, were assessed using Density Functional Theory (DFT) calculations. The molecular structures in an aqueous solution were computed utilizing the polarized continuum model.

Size and fluorescence calibrated imaging flow cytometry: From arbitrary to standard units.

Imaging flow cytometry (IFCM) is a technique that can detect, size, and phenotype extracellular vesicles (EVs) at high throughput (thousands/minute) in complex biofluids without prior EV isolation. However, the generated signals are expressed in arbitrary units, which hinders data interpretation and comparison of measurement results between instruments and institutes. While fluorescence calibration can be readily achieved, calibration of side scatter (SSC) signals presents an ongoing challenge for IFCM.

Semiochemical-baited traps as a new method supplementing light traps for faunistic and ecological studies of Macroheterocera (Lepidoptera).

Attractivity and selectivity of two types of traps with synthetic, long-lasting, bisexual generic attractants were compared to conventional light traps to promote their wider use, as an easy-to-use standardised method for entomology. The targeted herbivorous Macroheterocera species playing important role in ecosystems as food source for higher trophic levels (e.g.

Endocannabinoid and neuroplasticity-related changes as susceptibility factors in a rat model of posttraumatic stress disorder.

Traumatic experiences result in the development of posttraumatic stress disorder (PTSD) in 10-25% of exposed individuals. While human clinical studies suggest that susceptibility is potentially linked to endocannabinoid (eCB) signaling, neurobiological PTSD susceptibility factors are poorly understood. Employing a rat model of contextual conditioned fear, we characterized distinct resilient and susceptible subpopulations based on lasting generalized fear, a core symptom of PTSD.

Fitting of Coupled Potential Energy Surfaces via Discovery of Companion Matrices by Machine Intelligence.

Fitting coupled potential energy surfaces is a critical step in simulating electronically nonadiabatic chemical reactions and energy transfer processes. Analytic representation of coupled potential energy surfaces enables one to perform detailed dynamics calculations. Traditionally, fitting is performed in a diabatic representation to avoid fitting the cuspidal ridges of coupled adiabatic potential energy surfaces at conical intersection seams.

Novel insights into the modulation of the voltage-gated potassium channel K1.3 activation gating by membrane ceramides.

Membrane lipids extensively modulate the activation gating of voltage-gated potassium channels (K), however, much less is known about the mechanisms of ceramide and glucosylceramide actions including which structural element is the main intramolecular target and whether there is any contribution of indirect, membrane biophysics-related mechanisms to their actions. We used two-electrode voltage-clamp fluorometry capable of recording currents and fluorescence signals to simultaneously monitor movements of the pore domain (PD) and the voltage sensor domain (VSD) of the K1.3 ion channel after attaching an MTS-TAMRA fluorophore to a cysteine introduced into the extracellular S3-S4 loop of the VSD.