Astrocyte regulation of critical period plasticity across neural circuits.

Critical periods are brief windows of heightened neural circuit plasticity that allow circuits to permanently reset their structure and function to facilitate robust organismal behavior. Understanding the cellular and molecular mechanisms that instruct critical period timing is of broad clinical interest, as altered developmental plasticity is linked to multiple neurodevelopmental disorders. While intrinsic, neuronal mechanisms shape both neural circuit remodeling and critical period timing, recent data indicate that signaling from astrocytes and surrounding glia can both promote and limit critical period plasticity.

The N-degron pathway mediates the autophagic degradation of cytosolic mitochondrial DNA during sterile innate immune responses.

The human body reacts to tissue damage by generating damage-associated molecular patterns (DAMPs) that activate sterile immune responses. To date, little is known about how DAMPs are removed to avoid excessive immune responses. Here, we show that proteasomal dysfunction induces the release of mitochondrial DNA (mtDNA) as a DAMP that activates the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) pathway and is subsequently degraded through the N-degron pathway.

Increased nuclear factor I-mediated chromatin access drives transition to androgen receptor splice variant dependence in prostate cancer.

Androgen receptor (AR) splice variants, of which ARv7 is the most common, are increased in castration-resistant prostate cancer, but the extent to which they drive AR activity is unclear. We generated a subline of VCaP cells (VCaP16) that is resistant to the AR inhibitor enzalutamide (ENZ). AR activity in VCaP16 is driven by ARv7, independently of full-length AR (ARfl), and its cistrome and transcriptome mirror those of ARfl in VCaP cells.

Interrogation of RNA-bound proteome with XRNAX illuminates molecular alterations in the mouse brain affected with dysmyelination.

RNA-protein interactions orchestrate hundreds of pathways in homeostatic and stressed cells. We applied an RNA-protein interactome capture method called protein cross-linked RNA extraction (XRNAX) to shed light on the RNA-bound proteome in dysmyelination. We found sets of canonical RNA-binding proteins (RBPs) regulating alternative splicing and engaged in the cytoplasmic granules to be perturbed at the level of their RNA interactome.

Symmetry breaking and mismatch in the torsional mechanism of ATP synthesis by FF-ATP synthase: mathematical number theory proof and its chemical and biological implications.

Can mathematical proofs be employed for the solution of fundamental molecular-level problems in biology? Recently, I mathematically tackled complex mechanistic problems arising during the synthesis of the universal biological currency, adenosine triphosphate (ATP) by the FF-ATP synthase, nature's smallest rotary molecular motor, using graph-theoretical and combinatorial approaches for the membrane-bound F and water-soluble F domains of this fascinating molecule (see Nath in Theory Biosci 141:249‒260, 2022 and Theory Biosci 143:217‒227, 2024). In the third part of this trilogy, I investigate another critical aspect of the molecular mechanism-that of coupling between the F and F domains of the ATP synthase mediated by the central γ-subunit of nanometer diameter. According to Nath's torsional mechanism of energy transduction and ATP synthesis the γ-subunit twists during ATP synthesis and the release of stored torsional energy in the central γ-stalk causes conformational changes in the catalytic sites that lead to ATP synthesis, with 1 ATP molecule synthesized per discrete 120° rotation.

Faecal metaproteomics analysis reveals a high cardiovascular risk profile across healthy individuals and heart failure patients.

The gut microbiota is a crucial link between diet and cardiovascular disease (CVD). Using fecal metaproteomics, a method that concurrently captures human gut and microbiome proteins, we determined the crosstalk between gut microbiome, diet, gut health, and CVD. Traditional CVD risk factors (age, BMI, sex, blood pressure) explained < 10% of the proteome variance.

CSF1-R inhibition attenuates posttraumatic osteoarthritis and quadriceps atrophy following ligament injury.

Knee osteoarthritis contributes substantially to worldwide disability. Post-traumatic osteoarthritis (PTOA) develops secondary to joint injury, such as ligament rupture, and there is increasing evidence suggesting a key role for inflammation in the aetiology of PTOA and associated functional deficits. Colony stimulating factor 1 receptor (CSF1-R) has been implicated in the pathogenesis of musculoskeletal degeneration following anterior cruciate ligament (ACL) injury.

Recent advances in the structure, function and regulation of the volume-regulated anion channels and their role in immunity.

Volume-regulated anion channels (VRACs) are heteromeric complexes formed by proteins of the leucine-rich repeat-containing 8 (LRRC8) family. LRRC8A (also known as SWELL1) is the core subunit required for VRAC function, and it must combine with one or more of the other paralogues (i.e.

Diet therapy abates mutant APC and KRas effects by reshaping plasma membrane cholesterol nanodomains.

Cholesterol-enriched plasma membrane domains are known to serve as signaling platforms in a diverse array of cellular processes. However, the link between cholesterol homeostasis and mutant APC-KRas-associated colorectal tumorigenesis remains to be established. Thus, we investigated the impact of Apc-Kras on (i) colonocyte plasma membrane cholesterol homeostasis, order, and receptor nanoclustering, (ii) colonocyte cell proliferation, and (iii) whether these effects are modulated by select membrane active dietaries (MADs).

RNA modifications in plant adaptation to abiotic stresses.

Epitranscriptomic chemical modifications of RNAs have emerged as potent regulatory mechanisms in the plant stress adaptation process. Currently, over 170 distinct chemical modifications have been identified in mRNAs, tRNAs, rRNAs, microRNAs (miRNAs), and long-noncoding RNAs (lncRNAs). The genetic and molecular studies have identified the genes responsible for adding and removing chemical modifications on RNA molecules, known as "writers" and "erasers," respectively.

Topical Ivermectin-metronidazole gel therapy improves Meibomian gland Function in blepharitis caused by demodex spp.

Purpose: To evaluate the efficacy and safety of topical Ivermectin- Metronidazol in the management of demodex infestation and their effect in Meibomian gland dysfunction (MGD) METHODS: Fifty-four patients (108 eyes) with demodex diagnosis and Meibomian gland dysfunction received Ivermectin 0.3 %+Metronidazole 0.5 % gel in the night for 5 weeks.

Low-molecular-weight polyphenol promotes cell sensitivity to cisplatin and alleviates cancer-related muscle atrophy via NF-κB suppression in oral squamous cell carcinoma.

Objective: Drug resistance and subsequent adverse effects, such as cancer cachexia, limit the clinical use of cisplatin. Oligonol® (Olg), a low-molecular-weight polyphenol, exhibits NF-κB inhibitory properties. NF-κB activation has been implicated in cisplatin resistance of cancer cells and skeletal muscle wasting.

Single-cell RNA seq-derived signatures define response patterns to atezolizumab + bevacizumab in advanced hepatocellular carcinoma.

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

Kinetic studies of bifurcating flavoproteins.

Since their original proposal in 2008, a number of broadly distributed flavoprotein systems catalyzing electron bifurcation have been identified that play key roles in the bioenergetics of anaerobic bacteria and archaea. While the overall thermodynamics of flavin-based electron bifurcation are now quite well-understood, the same cannot be said of their kinetic behavior. The present account represents a summary of results obtained with several electron-electron bifurcating systems, shamelessly focusing on work done in the authors' laboratory.

Exosomal Signaling in Cancer Metastasis: Molecular Insights and Therapeutic Opportunities.

Exosomes are membrane-bound extracellular vesicles that play a role in exchanging biological products across membranes and serve as intermediaries in intercellular communication to maintain normal homeostasis. Numerous molecules, including lipids, proteins, and nucleic acids are enclosed in exosomes. Exosomes are constantly released into the extracellular environment and exhibit distinct characteristics based on the secreted cells that produce them.

Diagnostic Accuracy of Ambient Mass Spectrometry with Blood Plasma in a Murine Glioma Model Using Machine Learning.

Objective: Malignant glioma progresses rapidly and shows poor prognosis, but clinically applicable blood plasma-based biochemical tumor markers remain lacking. This study aimed to develop a diagnostic system using probe electrospray ionization mass spectrometry (PESI-MS) and a machine-learning logistic regression model to detect plasma changes at various time points in a murine glioma model.

Methods: We used a syngeneic intracranial orthotopic murine model with GL261 glioma cells.

Psychotropic Taxonomies: Constructing a Therapeutic Framework for Psychiatry.

Pharmacological interventions are a cornerstone of psychiatric practice. The taxonomies used to classify these interventions influence the treatment and interpretation of psychiatric symptoms. Disease-based classification systems (e.

Protective effects of Mycobacterium vaccae ATCC 15483 against "Western"-style diet-induced weight gain and visceral adiposity in adolescent male mice.

The prevalence of noncommunicable inflammatory disease is increasing in modern urban societies, posing significant challenges to public health. Novel prevention and therapeutic strategies are needed to effectively deal with this issue. One promising approach is leveraging microorganisms such as Mycobacterium vaccae ATCC 15483, known for its anti-inflammatory, immunoregulatory, and stress-resilience properties.

Chrysin modulates the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway: Acting in the improvement of cognitive flexibility and declarative, working and aversive memory deficits caused by hypothyroidism in C57BL/6 female mice.

Hypothyroidism is known to affect memory consolidation, and our prior research highlighted the potential of chrysin as a therapeutic agent to restore cognitive function. The present study aimed to investigate the action mechanism of chrysin on memory deficits in hypothyroid in C57BL/6 female mice. We assessed cognitive flexibility, declarative, working, and aversive memories while analyzing the BDNF/TrkB/AKT/Creb neuroplasticity signaling pathway and synaptic function in the hippocampus and prefrontal cortex.

Brain glucose metabolism: Role of nitric oxide.

One possible reason for failure in achieving optimal glycemic control in patients with type 2 diabetes (T2D) is that less attention has been paid to the brain, a fundamental player in glucose homeostasis, that consumes about 25% of total glucose utilization. In addition, animal and human studies indicate that nitric oxide (NO) is a critical player in glucose metabolism. NO synthesis from L-arginine is lower in patients with T2D, and endothelial NO synthase (eNOS)-derived NO bioavailability is lower in T2D.

Histone acetylation alteration by KAT6A inhibitor WM-1119 suppresses IgE-mediated mast cell activation and allergic inflammation via reduction in AP-1 signaling.

Activation of immunoglobulin E (IgE)-associated mast cells (MCs) triggers the onset of pro-inflammatory signals associated with type I allergic diseases. Although histone acetylation changes have been associated with inflammatory diseases, the impact of lysine-acetyltransferase (KAT) inhibitors on IgE-mediated MCs function is unclear. Potential anti-allergic effects of the KAT6A inhibitor WM-1119 on IgE-mediated MCs activation and allergic inflammation were examined in this study.

Whole-genome sequencing surveillance of Siberian tick-borne encephalitis virus (TBEV) identifies an additional lineage in Kyrgyzstan.

Tick-borne encephalitis virus (TBEV) is the most prevalent tick-borne viral disease in Europe and Asia. There are three main subtypes of the virus: European, Siberian, and Far Eastern, each of which having distinctive ecology, clinical presentation, and geographic distribution. In recent years, other TBEV subtypes have been described, namely the Himalayan and Baikalian subtypes.

Maternal separation stress increases alcohol preference regardless of DNA methylation and histone acetylation or methylation in the amygdala.

Alcohol use disorder (AUD) is a condition with multifactorial causes, including biopsychosocial factors. Childhood exposure to stress may increase susceptibility to AUD in adulthood. Despite its significance, the interaction between stress and AUD remains unclear.