Agmatine suppresses glycolysis via the PI3K/Akt/mTOR/HIF-1α signaling pathway and improves mitochondrial function in microglia exposed to lipopolysaccharide.

Modulating metabolic pathways in activated microglia can alter their phenotype, which is relevant in uncontrolled neuroinflammation as a component of various neurodegenerative diseases. Here, we investigated how pretreatment with agmatine, an endogenous polyamine, affects metabolic changes in an in vitro model of neuroinflammation, a murine microglial BV-2 cell line exposed to lipopolysaccharide (LPS). Hence, we analyzed gene expression using qPCR and protein levels using Western blot and ELISA.

California annual grass phenology and allometry influence ecosystem dynamics and fire regime in a vegetation demography model.

Grass-dominated ecosystems cover wide areas of the land surface yet have received far less attention from the Earth System Model (ESM) community. This limits model projections of ecosystem dynamics in response to global change and coupled vegetation-climate dynamics. We used the Functionally Assembled Terrestrial Ecosystem Simulator (FATES), a dynamic vegetation demography model, to determine ecosystem sensitivity to alternate, observed grass allometries and biophysical traits, and evaluated model performance in capturing California C annual grasslands structure and fire regimes.

Blocking the mineralocorticoid receptor prevents cardiac and mitochondrial dysfunction through the activation of NOX-4 in female hormone deprivation rats.

Aim: Young women exhibit lower rates of cardiovascular disease (CVD) than age-matched men, a protective effect often attributed to estrogen's influence on cardiac and mitochondrial function. The risk of CVD increases in post-menopausal women, likely due to estrogen deficiency and aldosterone's negative effects, including those on mitochondria and other cellular targets. This study aimed to explore the link between estrogen deficiency and mitochondrial dysfunction in cardiac health.

Computational and experimental mapping of the allosteric network of two manganese ABC transporters.

Transition metals (e.g., Fe, Zn, Mn) are essential enzymatic cofactors in all organisms.

Beyond the mono-nucleosome.

Nucleosomes, the building block of chromatin, are responsible for regulating access to the DNA sequence. This control is critical for essential cellular processes, including transcription and DNA replication and repair. Studying chromatin can be challenging both in vitro and in vivo, leading many to use a mono-nucleosome system to answer fundamental questions relating to chromatin regulators and binding partners.

Electrical homeostasis of the inner mitochondrial membrane potential.

The electric potential across the inner mitochondrial membrane must be maintained within certain bounds for the proper functioning of the cell. A feedback control mechanism for the homeostasis of this membrane potential is proposed whereby an increase in the electric field decreases the rate-limiting steps of the electron transport chain (ETC). An increase in trans-membrane electric field limits the rate of proton pumping to the inter-membrane gap by slowing the ETC reactions and by intrinsically induced electroporation that depolarizes the inner membrane.

Scientific and Technological Prospecting on Polymeric Particles Containing Extracellular Matrix Peptides for the Treatment of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy is a neuromuscular disease with an overall incidence of between 1 in 5,000 newborn males. Carriers may manifest progressive muscle weakness, resulting from the progressive degeneration of skeletal muscles, generating cardiac and respiratory disorders. Considering the lack of effective treatments, different therapeutic approaches have been developed, such as protein synthesis and extracellular matrix derivatives that can be used to improve muscle regeneration, maintenance, or repair.

1,3,4-oxadiazole derivatives: synthesis, characterization, antifungal activity, DNA binding investigations, TD-DFT calculations, and molecular modelling.

1,3,4-Oxadiazole-based heterocyclic analogs (3a-3m) were synthesized cyclization of Schiff bases with substituted aldehydes in the presence of bromine and acetic acid. The structural clarification of synthesized molecules was carried out with various spectroscopic techniques such as FT-IR,H and C-NMR, UV-visible spectroscopy, and mass spectrometry. antifungal activity was performed against , and and analogs 3g, 3i, and 3m showed potent MIC at 200 µg/ml and excellent ZOI measurements of 17-21 nm.

Abraham Patchornik: The Contemporary Relevance of His Work for Chemistry and Biology.

Abraham Patchornik was born in 1926 in Ness Ziona, a town in Palestine founded by his great-grandfather Reuben Lehrer in 1883. He started to study chemistry as an undergraduate at the Hebrew University. However, this was interrupted by the war, and he completed his studies in various locations in West Jerusalem.

Phenotypic consequences of logarithmic signaling in MAPK stress response.

How cells respond to dynamic environmental changes is crucial for understanding fundamental biological processes and cell physiology. In this study, we developed an experimental and quantitative analytical framework to explore how dynamic stress gradients that change over time regulate cellular volume, signaling activation, and growth phenotypes. Our findings reveal that gradual stress conditions substantially enhance cell growth compared to conventional acute stress.

Oligodendrocyte precursor cells facilitate neuronal lysosome release.

Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes.

Cell adhesion and spreading on fluid membranes through microtubules-dependent mechanotransduction.

Integrin clusters facilitate mechanical force transmission (mechanotransduction) and regulate biochemical signaling during cell adhesion. However, most studies have focused on rigid substrates. On fluid substrates like supported lipid bilayers (SLBs), integrin ligands are mobile, and adhesive complexes are traditionally thought unable to anchor for cell spreading.

Structural insights into polyisoprenyl-binding glycosyltransferases.

Glycosyltransferases (GTs) catalyze the addition of sugars to diverse substrates facilitating complex glycoconjugate biosynthesis across all domains of life. When embedded in or associated with the membrane, these enzymes often depend on polyisoprenyl-phosphate or -pyrophosphate (PP) lipid carriers, including undecaprenyl phosphate in bacteria and dolichol phosphate in eukaryotes, to transfer glycan moieties. GTs that bind PP substrates (PP-GTs) are functionally diverse but share some common structural features within their family or subfamily, particularly with respect to how they interact with their cognate PP ligands.

Conformational dynamics of a multienzyme complex in anaerobic carbon fixation.

In the ancient microbial Wood-Ljungdahl pathway, carbon dioxide (CO) is fixed in a multistep process that ends with acetyl-coenzyme A (acetyl-CoA) synthesis at the bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS). In this work, we present structural snapshots of the CODH/ACS from the gas-converting acetogen , characterizing the molecular choreography of the overall reaction, including electron transfer to the CODH for CO reduction, methyl transfer from the corrinoid iron-sulfur protein (CoFeSP) partner to the ACS active site, and acetyl-CoA production. Unlike CODH, the multidomain ACS undergoes large conformational changes to form an internal connection to the CODH active site, accommodate the CoFeSP for methyl transfer, and protect the reaction intermediates.

Tumor cells upregulate neurotransmitter GABA in the choroid plexus through STAT6-Bestrophin1 signaling, promoting leptomeningeal dissemination.

Background: Leptomeningeal dissemination (LMD) occurs when tumor cells interact with choroid plexus epithelium (CPE) to gain access to cerebrospinal fluid (CSF) in the brain's meninges and ventricular system. This disease is particularly devastating for patients due to our limited understanding and few therapeutic options. The leptomeningeal CSF is a nutritionally deprived microenvironment for tumor cells.

Cryo-EM structure of AAV2 Rep68 bound to integration site AAVS1: insights into the mechanism of DNA melting.

The Rep68 protein from Adeno-Associated Virus (AAV) is a multifunctional SF3 helicase that performs most of the DNA transactions necessary for the viral life cycle. During AAV DNA replication, Rep68 assembles at the origin of replication, catalyzing the DNA melting and nicking reactions during the hairpin rolling replication process to complete the second-strand synthesis of the AAV genome. We report the cryo-electron microscopy structures of Rep68 bound to the adeno-associated virus integration site 1 in different nucleotide-bound states.

Remodeling of ER Membrane Contact Sites During Cell Division.

Membrane contact sites (MCS) provide specialized conduits for inter-organelle communications to maintain cellular homeostasis. Most organelles are interconnected, which supports their coordination and function. M-phase (mitosis or meiosis) is associated with dramatic cellular remodeling to support cell division, including the equal distribution of organelles to the two daughter cells.

Case Report: Targeted treatment by fluoxetine/norfluoxetine of a variant causing developmental and epileptic encephalopathy.

The Kv3.2 subfamily of voltage activated potassium channels encoded by the gene is abundantly expressed in neurons that fire trains of fast action potentials that are a major source of cortical inhibition. Gain-of-function (GOF) pathogenic variants in and , encoding Kv3.

Outside-in engineering of cadherin endocytosis using a conformation strengthening antibody.

P-cadherin, a crucial cell-cell adhesion protein which is overexpressed in numerous malignant cancers, is a popular target for drug delivery antibodies. However, molecular guidelines for engineering antibodies that can be internalized upon binding to P-cadherin are unknown. Here, we use a combination of biophysical, biochemical, and cell biological methods to demonstrate that trapping the P-cadherin extracellular region in an X-dimer adhesive conformation triggers cadherin endocytosis via an outside-in signaling mechanism.

Distinct bacteria display genus and species-specific associations with mycobionts in paramo lichens in Colombia.

Lichens are complex symbiotic systems where fungi interact with an extracellular arrangement of one or more photosynthetic partners and an indeterminate number of other microbes. Recently, specific lichen-microbial community associations have been proposed. In this study, we aimed to characterize the differences in bacteria associated with closely related lichens, under a defined set of environmental conditions in Colombian paramos.

Endothelial Growth Media Components Alters SARS-CoV-2 Spike-Directed Growth Kinetics.

Direct SARS-CoV-2 infection of endothelial cells is challenging to study in vitro. To examine whether endothelial cell culture conditions impact the ability of SARS-CoV-2 to infect cells, we evaluated the effects of commercial cell culture media composition on SARS-CoV-2 Spike-directed viral infection. In African Green Monkey kidney epithelial cells (VeroE6), we found that commercial cell culture media (EGM2) produced inhibitory effects on recombinant vesicular stomatitis virus (rVSV-SARS-CoV-2) growth that is not seen in Dulbecco's Modified Eagle Medium (DMEM).

Association between ACE (I/D) polymorphism and physical performance in Brazilian handballers.

This study investigated the association between the ACE (I/D) polymorphism and strength phenotypes in Brazilian male handball players, considering their playing position. A total of 105 male junior handball players and 92 controls were evaluated. The ACE I/D polymorphism was genotyped by conventional PCR followed by electrophoresis in agarose gel.

Ultrasound-assisted enhancement of bioactive compounds in hawthorn vinegar: A functional approach to anticancer and antidiabetic effects.

In this study, the effects of ultrasound treatment on bioactive components and functional properties of hawthorn vinegar (Crataegus tanacetifolia) were investigated. Parameters such as total phenolic compound (TPC), total flavonoid content (TFC), ascorbic acid (AA), DPPH radical scavenging activity and CUPRAC reducing capacity were optimised by surface response method (RSM) and 14 min duration and 61.40 % amplitude were determined as the most suitable treatment conditions.

The multifunctionality of the brainstem breathing control circuit.

Subconscious breathing is generated by a network of brainstem nodes with varying purposes, like pacing breathing or patterning a certain breath phase. Decades of anatomy, pharmacology, and physiology studies have identified and characterized the system's fundamental properties that produce robust breathing, and we now have well-conceived computational models of breathing that are based on the detailed descriptions of neuronal connectivity, biophysical properties, and functions in breathing. In total, we have a considerable understanding of the brainstem breathing control circuit.