Histone-binding protein RBBP4 is necessary to promote neurogenesis in the developing mouse neocortical progenitors.

Chromatin regulation plays a crucial role in neocortical neurogenesis, and mutations in chromatin modifiers are linked to neurodevelopmental disorders. RBBP4 is a core subunit of several chromatin-modifying complexes; however, its functional role and genome-wide occupancy profile in the neocortical primordium are unknown. To address this, we performed RBBP4 knockdown using CRISPR/Cas9 on neocortical progenitors derived from mice of both sexes at embryonic age 12.

Glutamylation imbalance impairs the molecular architecture of the photoreceptor cilium.

Microtubules, composed of conserved α/β-tubulin dimers, undergo complex post-translational modifications (PTMs) that fine-tune their properties and interactions with other proteins. Cilia exhibit several tubulin PTMs, such as polyglutamylation, polyglycylation, detyrosination, and acetylation, with functions that are not fully understood. Mutations in AGBL5, which encodes the deglutamylating enzyme CCP5, have been linked to retinitis pigmentosa, suggesting that altered polyglutamylation may cause photoreceptor cell degeneration, though the underlying mechanisms are unclear.

A cytoplasmic form of EHMT1N methylates viral proteins to enable inclusion body maturation and efficient viral replication.

Protein lysine methyltransferases (PKMTs) methylate histone and non-histone proteins to regulate biological outcomes such as development and disease including viral infection. While PKMTs have been extensively studied for modulating the antiviral responses via host gene regulation, their role in methylation of proteins encoded by viruses and its impact on host-pathogen interactions remain poorly understood. In this study, we discovered distinct nucleo-cytoplasmic form of euchromatic histone methyltransferase 1 (EHMT1N/C), a PKMT, that phase separates into viral inclusion bodies (IBs) upon cytoplasmic RNA-virus infection (Sendai Virus).

Biochemical curiosities : Piquing students' interest in biochemistry by exploring evolution's pursuit of the improbable.

A teaching course based on seemingly improbable curiosities could attract students’ interest in the magic of biochemical pathways and their evolution. [Image: see text]

SARS-CoV-2 infections before, during, and after the Omicron wave: a 2-year Indian community cohort study.

Background: We measured the incidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and re-infections in an adult community-based cohort in southern India.

Methods: We conducted a 2-year follow-up on 1229 participants enrolled between May and October 2021. Participants provided vaccination histories, weekly saliva samples, and blood samples at 0, 6, 12, and 24 months.

Senescent cells inhibit mouse myoblast differentiation via the SASP-lipid 15d-PGJ mediated modification and control of HRas.

Senescent cells are characterized by multiple features such as increased expression of senescence-associated β-galactosidase activity (SA β-gal) and cell cycle inhibitors such as p21 or p16. They accumulate with tissue damage and dysregulate tissue homeostasis. In the context of skeletal muscle, it is known that agents used for chemotherapy such as Doxorubicin (Doxo) cause buildup of senescent cells, leading to the inhibition of tissue regeneration.

Neuroepithelial bodies and terminal bronchioles are niches for distinctive club cells that repair the airways following acute notch inhibition.

Lower airway club cells (CCs) serve the dual roles of a secretory cell and a stem cell. Here, we probe how the CC fate is regulated. We find that, in response to acute perturbation of Notch signaling, CCs adopt distinct fates.

An economic demand-based framework for prioritization strategies in response to transient amino acid limitations.

Cells contain disparate amounts of distinct amino acids, each of which has different metabolic and chemical origins, but the supply cost vs demand requirements of each is unclear. Here, using yeast we quantify the restoration-responses after disrupting amino acid supply, and uncover a hierarchically prioritized restoration strategy for distinct amino acids. We comprehensively calculate individual amino acid biosynthetic supply costs, quantify total demand for an amino acid, and estimate cumulative supply/demand requirements for each amino acid.

Mitigating candidiasis with acarbose by targeting Candida albicans α-glucosidase: in-silico, in-vitro and transcriptomic approaches.

Biofilm-associated candidiasis poses a significant challenge in clinical settings due to the limited effectiveness of existing antifungal treatments. The challenges include increased pathogen virulence, multi-drug resistance, and inadequate penetration of antimicrobials into biofilm structures. One potential solution to this problem involves the development of novel drugs that can modulate fungal virulence and biofilm formation, which is essential for pathogenesis.

Cold-shock proteome of myoblasts reveals role of RBM3 in promotion of mitochondrial metabolism and myoblast differentiation.

Adaptation to hypothermia is important for skeletal muscle cells under physiological stress and is used for therapeutic hypothermia (mild hypothermia at 32  °C). We show that hypothermic preconditioning at 32  °C for 72 hours improves the differentiation of skeletal muscle myoblasts using both C2C12 and primary myoblasts isolated from 3 month and 18-month-old mice. We analyzed the cold-shock proteome of myoblasts exposed to hypothermia (32  °C for 6 and 48 h) and identified significant changes in pathways related to RNA processing and central carbon, fatty acid, and redox metabolism.

TANGO1 inhibitors reduce collagen secretion and limit tissue scarring.

Uncontrolled secretion of ECM proteins, such as collagen, can lead to excessive scarring and fibrosis and compromise tissue function. Despite the widespread occurrence of fibrotic diseases and scarring, effective therapies are lacking. A promising approach would be to limit the amount of collagen released from hyperactive fibroblasts.

Altered neuroepithelial morphogenesis and migration defects in iPSC-derived cerebral organoids and 2D neural stem cells in familial bipolar disorder.

Bipolar disorder (BD) is a severe mental illness that can result from neurodevelopmental aberrations, particularly in familial BD, which may include causative genetic variants. In the present study, we derived cortical organoids from BD patients and healthy (control) individuals from a clinically dense family in the Indian population. Our data reveal that the patient organoids show neurodevelopmental anomalies, including organisational, proliferation and migration defects.

phytochemicals regulate fibroblast cell migration via modulation of focal adhesions.

The plant contains phytochemicals that have been used extensively in traditional medicine to treat various diseases. More recently it has been shown to accelerate wound healing, though its mechanism of action is largely unknown. Here we investigated the cellular pathways activated by a methanol extract of in human dermal fibroblasts, which play many critical roles in the wound healing program.

LSD1 Regulates Neurogenesis in Human Neural Stem Cells Through the Repression of Human-Enriched Extracellular Matrix and Cell Adhesion Genes.

Neurogenesis begins with neural stem cells undergoing symmetric proliferative divisions to expand and then switching to asymmetric differentiative divisions to generate neurons in the developing brain. Chromatin regulation plays a critical role in this switch. Histone lysine-specific demethylase LSD1 demethylates H3K4me1/2 and H3K9me1/2 but the mechanisms of its global regulatory functions in human neuronal development remain unclear.

Demonstrating the immunostimulatory and cytokine-augmentation effects of bacterial ghosts on natural killer cells and Caenorhabditis Elegans.

The potential of bacteria-based immunotherapy lies in its ability to inherently enhance immune responses. However, the "liveness" of bacteria poses risks of bacterial escape, nonspecific immuno-stimulation, and ethical concerns, limiting their acceptability in immunotherapy. In this scenario, nonliving empty bacterial-cell envelopes, named bacterial ghosts (BGs), have emerged as immuno-stimulants with the potential to side-step the limitations of live bacterial therapies.

Photostimulated Extended Nitric Oxide (NO) Release from Water-Soluble Block Copolymer to Enhance Antibacterial Activity.

-Nitrosamines are well established motifs to release nitric oxide (NO) under photoirradiation. Herein, a series of amphiphilic -nitrosamine-based block copolymers () are developed to attain controlled NO release under photoirradiation (365 nm, 3.71 mW/cm).

Niacinamide enhances cathelicidin mediated SARS-CoV-2 membrane disruption.

The continual emergence of SARS-CoV-2 variants threatens to compromise the effectiveness of worldwide vaccination programs, and highlights the need for complementary strategies for a sustainable containment plan. An effective approach is to mobilize the body's own antimicrobial peptides (AMPs), to combat SARS-CoV-2 infection and propagation. We have found that human cathelicidin (LL37), an AMP found at epithelial barriers as well as in various bodily fluids, has the capacity to neutralise multiple strains of SARS-CoV-2.

Genomic profiling and characteristics of a C1 degrading heterotrophic fresh-water bacterium Paracoccus sp. strain DMF.

Paracoccus species are metabolically versatile gram-negative, aerobic facultative methylotrophic bacteria showing enormous promise for environmental and bioremediation studies. Here we report, the complete genome analysis of Paracoccus sp. strain DMF (P.

Methotrexate delivering microneedle patches for improved therapeutic efficacy in treatment of rheumatoid arthritis.

Arthritis is an inflammatory disorder that leads to degeneration and swelling in the joints thereby severely affecting mobility. Till date, a complete cure for this disorder remains elusive. Administration of disease modifying anti-rheumatic drugs has not proved effective owing to poor retention of drugs at the site of inflammation in the joints.

Hyaluronic Acid-Based Bioconjugate Systems, Scaffolds, and Their Therapeutic Potential.

In recent years, the development of hyaluronic acid or hyaluronan (HA) based scaffolds, medical devices, bioconjugate systems have expanded into a broad range of research and clinical applications. Research findings over the last two decades suggest that the abundance of HA in most mammalian tissues with distinctive biological roles and chemical simplicity for modifications have made it an attractive material with a rapidly growing global market. Besides its use as native forms, HA has received much interest on so-called "HA-bioconjugates" and "modified-HA systems".

Generation of OCIAD2 homozygous knockout (BJNhem20-OCIAD2-CRISPR-33) and heterozygous knockout (BJNhem20-OCIAD2-CRISPR-40) human embryonic stem cell lines using CRISPR-Cas9 mediated targeting.

Ovarian Carcinoma Immunoreactive Antigen domain containing 2 (OCIAD2) was knocked out by targeting its exon 4 through CRISPR-Cas9 paired nickase strategy to generate two OCIAD2 knockout human embryonic stem cell lines- one homozygous (BJNhem20-OCIAD2-CRISPR-33) and one heterozygous (BJNhem20-OCIAD2-CRISPR-40) for mutant ociad2. Both lines maintain pluripotency, normal karyotype, and trilineage differentiation potential.

Generation of an OCIAD2 overexpressing transgenic human embryonic stem cell line, BJNhem20-OCIAD2-OV.

Overexpression of Ovarian Carcinoma Immunoreactive Antigen Domain containing protein 2 (OCIAD2) was carried out in BJNhem20 human Embryonic Stem Cell line (hESC). A stable line was generated through nucleofection of the plasmid construct pCAG-OCIAD2.

Single step fabrication of hollow microneedles and an experimental package for controlled drug delivery.

Hollow microneedle arrays (HMNs) are an excellent choice for managing chronic diseases requiring the administration of multiple drug doses over a prolonged duration. However, HMNs have gained partial success due to limitations in their manufacturing capabilities, and cumbersome processes. In the present study, polymeric HMNs were fabricated using a novel single-step drop-casting process without needing cleanroom facilities, and sophisticated instrumentation.

Intermittent scavenging of storage lesion from stored red blood cells by electrospun nanofibrous sheets enhances their quality and shelf-life.

Transfusion of healthy red blood cells (RBCs) is a lifesaving process. However, upon storing RBCs, a wide range of damage-associate molecular patterns (DAMPs), such as cell-free DNA, nucleosomes, free-hemoglobin, and poly-unsaturated-fatty-acids are generated. DAMPs can further damage RBCs; thus, the quality of stored RBCs declines during the storage and limits their shelf-life.