Exploring the Potential Interaction between the Functional Prion Protein CPEB3 and the Amyloidogenic Pathogenic Protein Tau.

Abnormal aggregation of tau protein is pathologically linked to Alzheimer's disease, while the aggregation of the prion-like RNA-binding protein (RBP) CPEB3 is functional and is associated with long-term memory. However, the interaction between these two memory-related proteins has not yet been explored. Our residue-specific NMR relaxation study revealed that the first prion domain of CPEB3 (PRD1) interacts with the VQIVYKPVDLSKV segment of tau and prevents the aggregation of tau-K18.

Improving Patient Handoffs and Transitions in Care Among Residents: A Chief Resident-Led Initiative.

Introduction: Effective handoff between pediatric residents is crucial to ensure continuity of care and patient safety. Omissions in information and communication breakdowns can be associated with uncertainty in clinical decision-making and adverse patient events. In our role as chief residents, we were notified of an increase in patient safety alerts due to communication failures and gaps during handoff.

A bleomycin-mimicking manganese-porphyrin-conjugated mitochondria-targeting peptoid for cancer therapy.

Bleomycin (BLM) is a natural product with established anticancer activity, attributed to its ability to cleave intracellular DNA. BLM complexes with iron (BLM-Fe) exhibit peroxidase-like activity, generate reactive oxygen species (ROS), and cause DNA cleavage. Inspired by the mechanism of BLM, we synthesized a novel conjugate of manganese tetraphenylporphyrin (MnTPP) with a biomimetic peptoid (i.

Identifying potential inhibitors against galectin-3-binding protein (LGALS3BP) for therapeutic targeting of glioma.

Glioblastoma is one of the most lethal types of Gliomas, and its treatment greatly depends on the stage of its detection. Galactin-3-binding protein (LGALS3BP) serves as a novel circulatory biomarker for detecting glioma at an early stage. This protein is also responsible for metastasis, proliferative signaling, angiogenesis, and immune system evasion in the case of brain tumors.

Profiling of MicroRNAs for the Identification of Unique and Common MicroRNAs in Preeclamptic Patients of South India Using Next-Generation Sequencing.

Introduction: Preeclampsia (PE) is a serious pregnancy complication with an unclear cause. Recent studies suggest that microRNAs (miRNAs), particularly miR-1, may play a role in controlling the genes associated with this condition. This study aimed to compare the expression of miRNAs in the blood and placental tissues of women with PE to those with normal pregnancies.

Mechanisms of gait speed changes in middle-aged adults: Simultaneous analysis of magnitude and temporal effects.

Background: Middle-aged adults represent the transition between younger and older adults, where some of the characteristic gait differences due to aging begins to surface. However, the gait characteristics of middle-aged adults across the whole gait cycle remains an understudied topic. As speed is a sensitive indicator of health, characterizing the effects of speed on the gait of middle-aged adults and differentiating it from the response of young adults will provide insights into the effects of aging on gait speed modulation mechanisms.

Multiprong CD38 targeting to enhance anti-PD1 immune checkpoint blockade efficacy.

CD38, a multifunctional enzyme involved in NAD+ catabolism, is hypothesized to act as a metabolic checkpoint for antitumor CD8 T cells. A recent study discovered that, apart from its direct metabolic mechanisms, CD38-mediated RyR2-AKT-TCF1 signaling regulates responsiveness to anti-PD1 cancer therapy at the molecular level. These findings advocate multiprong CD38 targeting to overcome resistance to immune checkpoint blockade therapy.

A Review of Regulatory Frameworks for Biobanking in Southeast Asia.

Southeast Asian countries are at the forefront of public health pressures due to a confluence of factors such as population growth, urbanization, environmental pollution, and infectious diseases (re)emergence. Therefore, the ability to be able to conduct research addressing local and regional needs is of paramount importance. As such, biobanking activities, the standardized collection of biological samples, and associated data, developed over the past few decades supporting ongoing biomedical and clinical research, as well as surveillance are of critical importance.

Cardiac troponin I directly binds and inhibits mitochondrial ATP synthase with a noncanonical role in the post-ischemic heart.

Cardiac troponin I (cTnI) is a key regulator of cardiomyocyte contraction. However, its role in mitochondria is unknown. Here we show that cTnI localized to mitochondria in the heart, inhibited mitochondrial functions when stably expressed in noncardiac cells and increased the opening of the mitochondrial permeability transition pore under oxidative stress.

Evaluation of Penetration Depth and Caries Progression using Resin Infiltrant in Natural White Spot Lesions of Primary Molars.

Background: Management of white spot lesions (WSLs) using resin infiltrants, like ICON®, is a novel technique that emphasizes the concept of minimally invasive dentistry.

Aim: Evaluate penetration depth and its effect on caries progression of ICON® in natural WSLs of primary molars.

Design: A total of 30 human primary molars with natural WSLs were selected.

3D printing assisted surface patterning process on acrylated hydrogels for contact guidance of fibroblasts.

Generating stable and customizable topography on hydrogel surfaces with contact guidance potential is critical as it can direct/influence cell growth. This necessitates the development of new techniques for surface patterning of the hydrogels. We report on the design of a square grid template for surface patterning hydrogels.

Homophobic beliefs and attitudes among mid-adolescent boys: exploring the ideas of hybrid masculinities.

Introduction: Homophobia is well-documented as key to social regulation of masculine behavior and practices in Western settings. Yet, empirical data from a number of Western settings has shown a decline in overt homophobic attitudes in the past decade, leading some to suggest that the nature of masculinities is also changing. However, theorizing on the changing nature of masculinities among adolescents has received limited quantitative attention.

Secret Weapon of Insects: The Oral Secretion Cocktail and Its Modulation of Host Immunity.

Plants and insects have co-existed for almost 400 million years and their interactions can be beneficial or harmful, thus reflecting their intricate co-evolutionary dynamics. Many herbivorous arthropods cause tremendous crop loss, impacting the agro-economy worldwide. Plants possess an arsenal of chemical defenses that comprise diverse secondary metabolites that help protect against harmful herbivorous arthropods.

A plasma-3D print combined platform with implications for reliable materiobiological screening.

Materiobiology is an emerging field focused on the physiochemical properties of biomaterials concerning biological outcomes which includes but is not limited to the biological responses and bioactivity of surface-modified biomaterials. Herein, we report a novel characterization platform for characterizing nanoparticle surface-modified 3D printed PLA scaffolds. We have introduced innovative design parameters that were practical for ubiquitous assays like those utilizing 96 and 24-well plates.

ε-Poly-l-lysine: A Naturally Occurring Biodegradable Polypeptide for Selective Detection of 5-Nitroimidazole Antibiotics in Animal Products and Living Cells via Fluorescence.

The 5-nitroimidazole (5-NI) class of antibiotics, such as metronidazole, ornidazole, secnidazole, and tinidazole, are widely used to prevent bacterial infection in humans and livestock industries. However, their overuse contaminates the farmed animal products and water bodies. Hence, a selective, sensitive, and cost-effective method to detect 5-NI antibiotics is the need of the hour.

Distinct metabolic responses to heme in inflammatory human and mouse macrophages - Role of nitric oxide.

Activation of inflammation is tightly associated with metabolic reprogramming in macrophages. The iron-containing tetrapyrrole heme can induce pro-oxidant and pro-inflammatory effects in murine macrophages, but has been associated with polarization towards an anti-inflammatory phenotype in human macrophages. In the current study, we compared the regulatory responses to heme and the prototypical Toll-like receptor (TLR)4 ligand lipopolysaccharide (LPS) in human and mouse macrophages with a particular focus on alterations of cellular bioenergetics.

Extracellular release of damaged mitochondria induced by prehematopoietic stem cell transplant conditioning exacerbates GVHD.

Despite therapeutic advancements, graft-versus-host disease (GVHD) is a major complication of hematopoietic stem cell transplantation (HSCT). In current models of GVHD, tissue injury induced by cytotoxic conditioning regimens, along with translocation of microbes expressing pathogen-associated molecular patterns, result in activation of host antigen-presenting cells (APCs) to stimulate alloreactive donor T lymphocytes. Recent studies have demonstrated that in many pathologic states, tissue injury results in the release of mitochondria from the cytoplasm to the extracellular space.

The FAM13A Long Isoform Regulates Cilia Movement and Coordination in Airway Mucociliary Transport.

Single nucelotide polymorphisms (SNPs) at the locus are among the most commonly reported risk alleles associated with chronic obstructive pulmonary disease (COPD) and other respiratory diseases; however, the physiological role of FAM13A is unclear. In humans, two major protein isoforms are expressed at the locus: "long" and "short," but their functions remain unknown, partly because of a lack of isoform conservation in mice. We performed in-depth characterization of organotypic primary human airway epithelial cell subsets and show that multiciliated cells predominantly express the FAM13A long isoform containing a putative N-terminal Rho GTPase-activating protein (RhoGAP) domain.

Role of G326 in Determining the Aggregation Propensity of R3 Tau Repeat: Insights from Studies on R1R3 Tau Construct.

The Microtubule-binding repeat region (MTBR) of Tau has been studied extensively due to its pathological implications in neurodegenerative diseases like Alzheimer's disease. The pathological property of MTBR is mainly due to the R3 repeat's high propensity for self-aggregation, highlighting the critical molecular grammar of the repeat. Utilizing the R1R3 construct (WT) and its G326E mutant (EE), we determine the distinct characteristics of various peptide segments that modulate the aggregation propensity of the R3 repeat using NMR spectroscopy.

Enhancing cancer immunotherapy with photodynamic therapy and nanoparticle: making tumor microenvironment hotter to make immunotherapeutic work better.

Cancer immunotherapy has made tremendous advancements in treating various malignancies. The biggest hurdle to successful immunotherapy would be the immunosuppressive tumor microenvironment (TME) and low immunogenicity of cancer cells. To make immunotherapy successful, the 'cold' TME must be converted to 'hot' immunostimulatory status to activate residual host immune responses.

A Novel Method to Enhance the Mechanical Properties of Polyacrylonitrile Nanofiber Mats: An Experimental and Numerical Investigation.

This study addresses the challenge of enhancing the transverse mechanical properties of oriented polyacrylonitrile (PAN) nanofibers, which are known for their excellent longitudinal tensile strength, without significantly compromising their inherent porosity, which is essential for effective filtration. This study explores the effects of doping PAN nanofiber composites with varying concentrations of polyvinyl alcohol (PVA) (0.5%, 1%, and 2%), introduced into the PAN matrix via a dip-coating method.

Precision proteoform design for 4R tau isoform selective templated aggregation.

Prion-like spread of disease-specific tau conformers is a hallmark of all tauopathies. A 19-residue probe peptide containing a P301L mutation and spanning the R2/R3 splice junction of tau folds and stacks into seeding-competent fibrils and induces aggregation of 4R, but not 3R tau. These tau peptide fibrils propagate aggregated intracellular tau over multiple generations, have a high β-sheet content, a colocalized lipid signal, and adopt a well-defined U-shaped fold found in 4R tauopathy brain-derived fibrils.