Mechanisms Mediating Tart Cherry and Fish Oil Metabolic Effects in Diet-Induced (C57BL/6J) and Genetically (TALYHO/Jng) Obese Mice.

Background/objectives: Obesity is a major public health concern that increases the risk of chronic diseases. In obesity, adipose tissue undergoes remodeling, which is associated with chronic low-grade inflammation and disruption of its homeostatic mechanisms including endoplasmic reticulum (ER) function and autophagy. Fish oil (FO) and tart cherry (TC) have known anti-inflammatory properties.

Achieving theranostic probes targeting BRD3/BRD4 for imaging and therapy of tumor.

The BET family proteins play pleiotropic roles in the tumorigenesis and growth of various human malignancies that have aroused great interests as the cancer therapeutic targets. Therefore, it's significant to develop labeling toolkits for the dynamic monitoring of BET family proteins in living tumor cells and tissue slices. In particular, there are few small-molecule fluorescent probes based on BET family proteins developed for real-time imaging of these proteins in tumor cells and tissues and treatment of breast cancer.

Exploring CRISPR-Cas9 HNH-Domain-Catalyzed DNA Cleavage Using Accelerated Quantum Mechanical Molecular Mechanical Free Energy Simulation.

The target DNA (tDNA) cleavage catalyzed by the CRISPR Cas9 enzyme is a critical step in the Cas9-based genome editing technologies. Previously, the tDNA cleavage from an active SpyCas9 enzyme conformation was modeled by Palermo and co-workers (Nierzwicki et al., , 912) using ab initio quantum mechanical molecular mechanical (ai-QM/MM) free energy simulations, where the free energy barrier was found to be more favorable than that from a pseudoactive enzyme conformation.

The Impact of Sugar Conformation on the Single-Stranded DNA Selectivity of APOBEC3A and APOBEC3B Enzymes.

The APOBEC3 family of polynucleotide cytidine deaminases has diverse roles as viral restriction factors and oncogenic mutators. These enzymes convert cytidine to uridine in single-stranded (ss)DNA, inducing genomic mutations that promote drug resistance and tumor heterogeneity. Of the seven human APOBEC3 members, APOBEC3A (A3A) and APOBEC3B (A3B) are most implicated in driving pro-tumorigenic mutations.

Identification of an early subset of cerebellar nuclei neurons in mice.

Cerebellar nuclei (CN) neurons serve as the primary output of the cerebellum and originate from the cerebellar primordium at early stages of cerebellar development. These neurons are diverse, integrating information from the cerebellar cortex and relaying it to various brain regions. Employing various methodologies, we have characterized a specific subset of CN neurons that do not originate from the rhombic lip or ventricular zone of the cerebellar primordium.

Polysaccharide-Based Hydrogels for Advanced Biomedical Engineering Applications.

In recent years, numerous applications of hydrogels using polysaccharides have evolved, benefiting from their widespread availability, excellent biodegradability, biocompatibility, and nonpoisonous nature. These natural polymers are typically sourced from renewable materials or from manufacturing processes, contributing collaboratively to waste management and demonstrating the potential for enhanced and enduring sustainability. In the field of novel bioactive molecule carriers for biotherapeutics, natural polymers are attracting attention due to their inherent properties and adaptable chemical structures.

Long-term changes in soil biological activity and other properties of raised beds in Longan orchards.

Introduction: The Longan fruit tree of the Vietnam Mekong Delta is grown in raised beds to improve water drainage during the rainy season and can live as long as 100 years.

Objective: This research explores the extent to which the soil microorganisms as well as soil physical and chemical properties of these raised beds degrade over a period of 60 years under traditional management practices.

Materials And Methods: Raised bed topsoil samples at depths of 0-20 cm were obtained from four different Longan orchards raised bed age groups: group 1) 15-25 years (L1-L5); group 2) 26-37 years (L6-L10); group 3) 38-45 years (L11-L15); and group 4) 46-60 years.

Amino Acid Transfer Free Energies Reveal Thermodynamic Driving Forces in Biomolecular Condensate Formation.

The self-assembly of intrinsically disordered proteins into biomolecular condensates shows a dependence on the primary sequence of the protein, leading to sequence-dependent phase separation. Methods to investigate this sequence-dependent phase separation rely on effective residue-level interaction potentials that quantify the propensity for the residues to remain in the dilute phase versus the dense phase. The most direct measure of these effective potentials are the distribution coefficients of the different amino acids between the two phases, but due to the lack of availability of these coefficients, proxies, most notably hydropathy, have been used.

The SWIB domain-containing DNA topoisomerase I of mediates DNA relaxation.

The obligate intracellular bacterial pathogen, (Ct), has a distinct DNA topoisomerase I (TopA) with a C-terminal domain (CTD) homologous to eukaryotic SWIB domains. Despite the lack of sequence similarity at the CTDs between TopA (CtTopA) and TopA (EcTopA), full-length CtTopA removed negative DNA supercoils and complemented the growth defect of an mutant. We demonstrated that CtTopA is less processive in DNA relaxation than EcTopA in dose-response and time course studies.

Considerations Regarding High Oil Density Bioreactor-Scale Fermentations of Yarrowia lipolytica Using CFD Modeling and Experimental Validation.

Hydrophobic feedstocks such as waste cooking oil have recently been considered for microbial biotransformation due to their abundance, low cost, and unique advantage for lipid-derived fermentation products. Most fermentations with hydrophobic substrates are conducted at the tube or flask scale (less than 1 L total volume) or with the hydrophobic substrate comprising a small fraction of the media. Low substrate concentrations require additional feeding.

Application of fluorescence i-motif DNA silver nanocluster sensor to visualize endogenous reactive oxygen species in plant cells.

A novel fluorescent i-motif DNA silver nanoclusters system has been developed for visualization of reactive oxygen species in plants, enabling the detection of intracellular signaling in plant cells. Reactive oxygen species (ROS) are crucial in plant growth, defense, and stress responses, making them vital for improving crop resilience. Various ROS sensing methods for plants have been developed to detect ROS in vitro and in vivo.

Characterization of SARS-CoV-2 nucleocapsid protein oligomers.

Oligomers of the SARS-CoV-2 nucleocapsid (N) protein are characterized by pronounced instability resulting in fast degradation. This property likely relates to two contrasting behaviors of the N protein: genome stabilization through a compact nucleocapsid during cell evasion and genome release by nucleocapsid disassembling during infection. In vivo, the N protein forms rounded complexes of high molecular mass from its interaction with the viral genome.

Hepatic Steatosis and Fibrosis, Cardiorespiratory Fitness, and Metabolic Mediators in the Community.

Background And Aims: Individuals with steatotic liver disease (SLD) are at high cardiovascular disease (CVD) risk, but approaches to characterise and mitigate this risk are limited. By investigating relations, and shared metabolic pathways, of hepatic steatosis/fibrosis and cardiorespiratory fitness (CRF), we sought to identify new avenues for CVD risk reduction in SLD.

Methods: In Framingham Heart Study (FHS) participants (N = 2722, age 54 ± 9 years, 53% women), vibration-controlled transient elastography (VCTE) was performed between 2016-2019 to assess hepatic steatosis (continuous attenuation parameter [CAP]) and fibrosis (liver fibrosis measure [LSM]).

Proline variants in the BRCA1 coiled-coil domain disrupt folding and binding to PALB2.

Inherited mutations in the genes coding for the tumor suppressor proteins BRCA1 and PALB2 can lead to increased risk of breast and ovarian cancer. Upon DNA damage, these two proteins form a complex to promote double-stranded break repair via homologous recombination. Missense mutations in either BRCA1 or PALB2 that disrupt this important interaction result in loss of effective DNA damage repair and are associated with breast tumorigenesis.

DPAM-AI: a domain parser for AlphaFold models powered by artificial intelligence.

Motivation: Due to the breakthrough in protein structure prediction by AlphaFold, the scientific community has access to 200 million predicted protein structures with near-atomic accuracy from the AlphaFold protein structure DataBase (AFDB), covering nearly the entire protein universe. Segmenting these models into domains and classifying them into an evolutionary hierarchy hold tremendous potential for unraveling essential insights into protein function.

Results: We introduce DPAM-AI, a Domain Parser for AlphaFold Models based on Artificial Intelligence.

Nascent matrix deposition supports alveolar organoid formation from aggregates in synthetic hydrogels.

Human induced pluripotent stem cell (iPSC)-derived alveolar organoids have emerged as a system to model the alveolar epithelium in homeostasis and disease. However, alveolar organoids are typically grown in Matrigel, a mouse sarcoma-derived basement membrane matrix that offers poor control over matrix properties, prompting the development of synthetic hydrogels as a Matrigel alternative. Here, we develop a two-step culture method that involves pre-aggregation of organoids in hydrogel-based microwells followed by embedding in a synthetic hydrogel that supports alveolar organoid growth, while also offering considerable control over organoid and hydrogel properties.

Sulfur-functionalized sawdust biochar for enhanced cadmium adsorption and environmental remediation: A multidisciplinary approach and density functional theory insights.

Pristine biochar typically exhibits limited capacity for heavy metal adsorption due to its inadequate pore development and insufficient surface functionality. This study introduces an innovative chemical strategy to enhance the surface of sawdust biochar with sulfur-based functional groups (C=S, C-S, S-S, S, S-H, -SO, -SO) to significantly improve cadmium (Cd) adsorption. Sulfur-doping using HSO, NaS, and NaSO markedly increased the sulfur content from 0.

Exploring the uptake, accumulation, and distribution of nitrate in Swiss chard and spinach and their impact on food safety and human health.

Greenhouse vegetable production is often associated with the excessive use of nitrogen fertilizers and a high rate of nitrate accumulation. We evaluated the uptake, translocation, and accumulation of nitrate in chard and spinach under greenhouse conditions with optimal fertilization. The results revealed low levels of nitrate in the leachates and substrates (chard ˃ spinach).

Screening of a kinase inhibitor library identified novel targetable kinase pathways in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly invasive breast cancer subtype that is challenging to treat due to inherent heterogeneity and absence of estrogen, progesterone, and human epidermal growth factor 2 receptors. Kinase signaling networks drive cancer growth and development, and kinase inhibitors are promising anti-cancer strategies in diverse cancer subtypes. Kinase inhibitor screens are an efficient, valuable means of identifying compounds that suppress cancer cell growth in vitro , facilitating the identification of kinase vulnerabilities to target therapeutically.

Insertion and Anchoring of the HIV-1 Fusion Peptide into a Complex Membrane Mimicking the Human T-Cell.

A fundamental understanding of how the HIV-1 envelope (Env) protein facilitates fusion is still lacking. The HIV-1 fusion peptide, consisting of 15 to 22 residues, is the N-terminus of the gp41 subunit of the Env protein. Further, this peptide, a promising vaccine candidate, initiates viral entry into target cells by inserting and anchoring into human immune cells.

Observation of the distribution of macro-, micro-, and toxic element contents of almond kernels burned with different digestion methods.

In this study, the elemental contents of almonds burned with four different methods to capture the elemental amount of almond kernels in the best way, to increase the release of obtainable elements by decomposing plant tissues, and to make them more atomized were measured and compared with ICP-AES. Depending on the digestion types, the K and Ca contents of almond varieties were determined as 10,167.35 (microwave) and 13,004.

Insurmountable antagonism of human mu opioid receptors by buprenorphine is due to hemi-equilibrium.

Buprenorphine is an FDA approved drug for the treatment of opioid use disorder and is a long-lasting, low efficacy (partial) agonist of the μ opioid receptor. As a partial agonist, buprenorphine can act as either an agonist or an antagonist depending on the efficiency of the cellular signaling system. Here we investigated the antagonist properties of buprenorphine using a genetically-encoded biosensor to monitor cAMP levels in real time in HEK293 cells expressing a relatively low density of the human μ receptor.