Spatial Transcriptomics Reveals the Temporal Architecture of the Seminiferous Epithelial Cycle and Precise Sertoli-Germ Synchronization.

Spermatogenesis is characterized by the seminiferous epithelial cycle, a periodic pattern of germ cell differentiation with a wave-like progression along the length of seminiferous tubules. While key signaling and metabolic components of the cycle are known, the transcriptional changes across the cycle and the correlations between germ cell and somatic lineages remain undefined. Here, we use spatial transcriptomics via RNA SeqFISH+ to profile 2,638 genes in 216,090 cells in mouse testis and identify a periodic transcriptional pattern across tubules that precisely recapitulates the seminiferous epithelial cycle, enabling us to map cells to specific timepoints along the developmental cycle.

On delivering polar solvation free energy of proteins from energy minimized structures using a regularized super-Gaussian Poisson-Boltzmann model.

The biomolecules interact with their partners in an aqueous media; thus, their solvation energy is an important thermodynamics quantity. In previous works (J. Chem.

Anti-Inflammatory Potential of Costus speciosus rhizome Bioactive Phytochemicals: A Combined GC-MS and Computational Approach Targeting TLR-4 Signaling.

Background: Plants represent a rich reservoir of bioactive compounds with established therapeutic value in diverse diseases. Notably, the Toll-like receptor-4 (TLR-4) signaling pathway plays a pivotal role in inflammation. Upon engagement with pro-inflammatory ligands like lipopolysaccharide, TLR-4 triggers downstream cascades involving nuclear factor ĸappa B and mitogen- activated protein kinases.

Small molecule FICD inhibitors suppress endogenous and pathologic FICD-mediated protein AMPylation.

The AMP transferase, FICD, is an emerging drug target finetuning stress signaling in the endoplasmic reticulum (ER). FICD is a bi-functional enzyme, catalyzing both AMP addition (AMPylation) and removal (deAMPylation) from the ER resident chaperone BiP/GRP78. Despite increasing evidence linking excessive BiP/GRP78 AMPylation to human diseases, small molecules to inhibit pathogenic FICD variants are lacking.

Exploring the Limits of the Generalized CHARMM and AMBER Force Fields through Predictions of Hydration Free Energy of Small Molecules.

Accurate force field parameters, potential energy functions, and receptor-ligand models are essential for modeling the solvation and binding of drug-like molecules to a receptor. A large and ever-growing chemical space of medicinally relevant scaffolds has also required these factors, especially force field parameters, to be highly transferable. Generalized force fields such as the CHARMM General Force Field (CGenFF) and the generalized AMBER force field (GAFF) have accomplished this feat along with other contemporaneous ones like OPLS.

Drosophila melanogaster Neuromuscular Junction as a Model to Study Synaptopathies and Neuronal Autophagy.

Neuronal synapse dysfunction is a key characteristic of several neurodegenerative disorders, such as Alzheimer's disease, spinocerebellar ataxias, and Huntington's disease. Modeling these disorders to study synaptic dysfunction requires a robust and reproducible method for assaying the subtle changes associated with synaptopathies in terms of structure and function of the synapses. Drosophila melanogaster neuromuscular junctions (NMJs) serve as good models to study such alterations.

Electronic Cigarette (E-Cig) Use in the Chronic Pain Population.

Background: Since electronic cigarettes (E-Cigs) were introduced to the United States (US) in 2007 its use has increased. Like other tobacco products, E-Cigs too pose health risks. Studies have shown a correlation between pain and tobacco use, with the association being bidirectional.

Novel predictors of response to therapy with terlipressin and albumin in hepatorenal syndrome-acute kidney injury.

Background: A combination of terlipressin and albumin is the first-line pharmacologic treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI). We assessed the response rates to terlipressin-albumin therapy in patients with HRS-AKI and determined early predictors of treatment response and survival.

Methods: A total of 84 patients with HRS-AKI (International Club of Ascites definition 2015) treated with terlipressin-albumin were included.

The Cytotoxic Assessment of Antibacterial-Enhanced Mineral Trioxide Aggregate Compared to Commercially Available Bioceramic Cements by Using Methyl-Thiazoldiphenyl-Tetrazolium (MTT) Assay on Human Dental Pulp Stem Cells: An In Vitro Study.

Background and objective Preserving the vitality of the tooth is of prime significance during therapies such as direct pulp capping and pulpotomy that promote tertiary dentine formation and healing of pulp stumps. Procedures like apexogenesis and apexification also stimulate dentin and bone formation for root growth and closure. Conventional mineral trioxide aggregate (MTA) has good biocompatible and physical properties like longer setting time, presence of a cytotoxic component, i.

A case-cohort study of left ventricular diastolic dysfunction in patients with cirrhosis: the liver-heart axis.

Background: Left ventricular diastolic dysfunction (LVDD) is an early manifestation of cirrhotic cardiomyopathy. Few studies have addressed its clinical significance in cirrhosis. We assessed the association of LVDD with the factors affecting cirrhosis patients' severity, complications, and survival.

Association of TGF-β1 Polymorphism and TGF-β1 Levels With Chronic Hepatitis C and Cirrhosis: A Systematic Review and Meta-Analysis.

Despite the extensive research conducted on the relationship between transforming growth factor-beta 1 (TGF-β1) polymorphisms and levels and the onset and development of liver disease, there are still certain gaps that need to be addressed. To address these gaps and provide a comprehensive overview of the current knowledge, this review aimed to identify relevant published research on TGF-β1/TGF-β1 polymorphism, TGF-β1/TGF-β1 levels, and their associations with cirrhosis and hepatitis C. The synthesis of available data was performed to further enhance our understanding in this area.

A rise-to-threshold process for a relative-value decision.

Whereas progress has been made in the identification of neural signals related to rapid, cued decisions, less is known about how brains guide and terminate more ethologically relevant decisions in which an animal's own behaviour governs the options experienced over minutes. Drosophila search for many seconds to minutes for egg-laying sites with high relative value and have neurons, called oviDNs, whose activity fulfills necessity and sufficiency criteria for initiating the egg-deposition motor programme. Here we show that oviDNs express a calcium signal that (1) dips when an egg is internally prepared (ovulated), (2) drifts up and down over seconds to minutes-in a manner influenced by the relative value of substrates-as a fly determines whether to lay an egg and (3) reaches a consistent peak level just before the abdomen bend for egg deposition.

Investigating the thermal stability of ultra-small Ag, Au and AuAg alloy nanoparticles embedded in a silica matrix.

Thermal growth kinetics of embedded bimetallic (AuAg/SiO) nanoparticles are explored and compared with their monometallic (Au/SiO and Ag/SiO) counterparts, as their practical applicability demands stability and uniformity. The plasmonic properties of these nanoparticles (NPs) significantly improve when their size falls in the ultra-small region (diameter < 10 nm), owing to their large active surface area. Interestingly, the bimetallic NPs exhibit better optical properties and structural stability as compared to their monometallic counterparts.

pyCHARMM: Embedding CHARMM Functionality in a Python Framework.

CHARMM is rich in methodology and functionality as one of the first programs addressing problems of molecular dynamics and modeling of biological macromolecules and their partners, e.g., small molecule ligands.

Nanoparticle-Reinforced Tough Hydrogel as a Versatile Platform for Pharmaceutical Drug Delivery: Preparation and Characterization.

Natural polymer-based hydrogels are excellent for encapsulating hydrophilic drugs, but they are mechanically weak and degrade easily. In this communication, we exploit the electrostatic interaction between nanosilicates (nSi) and gelatin methacrylate (GelMA) to form a mechanically tough nanocomposite hydrogel for pharmaceutical drug delivery. These hydrogels, prepared at subzero temperatures to form cryogels, displayed macroporous structures, which favors cell infiltration.

An internal expectation guides egg-laying decisions.

To better understand how animals make ethologically relevant decisions, we studied egg-laying substrate choice in . We found that flies dynamically increase or decrease their egg-laying rates while exploring substrates so as to target eggs to the best, recently visited option. Visiting the best option typically yielded inhibition of egg laying on other substrates for many minutes.

COVID-19: An Accelerator for Global Plastic Consumption and Its Implications.

Plastic has been ingrained in our society. Repercussions on the usage of nonbiodegradable plastics and their problems have been recently realized. Despite its detrimental environmental impact, the COVID-19 epidemic has compelled worldwide citizens to increase their plastic use due to affordability and availability.

Free Gangliosides Can Alter Amyloid-β Aggregation.

A recently proposed lipid-chaperone hypothesis suggests that free lipid molecules, not bound to membranes, affect the aggregation of amyloidogenic peptides such as amyloid-β (Aβ) peptides, whose aggregates are the hallmarks of Alzheimer's disease. Here, we combine experiments with all-atom molecular dynamics simulations in explicit solvent to explore the effects of neuronal ganglioside GM1, abundant in mammalian brains, on the aggregation of two principal isoforms of Aβ, Aβ40 and Aβ42. Our simulations show that free GM1 forms stable, highly water-soluble complexes with both isoforms, and nuclear magnetic resonance experiments support the formation of well-ordered, structurally compact GM1+Aβ complexes.

A Combinatorial Study Investigating the Growth of Ultrasmall Embedded Silver Nanoparticles upon Thermal Annealing.

Ultrasmall nanoparticles (NPs) with a high active surface area are essential for optoelectronic and photovoltaic applications. However, the structural stability and sustainability of these ultrasmall NPs at higher temperatures remain a critical problem. Here, we have synthesized the nanocomposites (NCs) of Ag NPs inside the silica matrix using the atom beam co-sputtering technique.

Total free energy analysis of fully hydrated proteins.

The total free energy of a hydrated biomolecule and its corresponding decomposition of energy and entropy provides detailed information about regions of thermodynamic stability or instability. The free energies of four hydrated globular proteins with different net charges are calculated from a molecular dynamics simulation, with the energy coming from the system Hamiltonian and entropy using multiscale cell correlation. Water is found to be most stable around anionic residues, intermediate around cationic and polar residues, and least stable near hydrophobic residues, especially when more buried, with stability displaying moderate entropy-enthalpy compensation.

Glutamatergic Synapse Dysfunction in Neuromuscular Junctions Can Be Rescued by Proteostasis Modulation.

Glutamate is the major excitatory neurotransmitter in the nervous system, and the glutamatergic neuromuscular junctions (NMJs) offer a tractable platform to understand excitatory synapse biology both in health and disease. Synaptopathies are neurodegenerative diseases that are associated with synaptic dysfunction and often display compromised proteostasis. One such rare, progressive neurodegenerative condition, Spinocerebellar Ataxia Type 3 (SCA3) or Machado-Joseph Disease (MJD), is characterized by cerebellar ataxia, Parkinsonism, and degeneration of motor neuron synapses.

Surgical anatomy of the lateral femoral cutaneous nerve for meralgia paraesthetica: A simple technical guide for surgeons and trainees alike.

Meralgia paraesthetica is an entrapment neuropathy of the lateral femoral cutaneous nerve, usually due to compression at the inguinal ligament as the nerve passes from the pelvis into the thigh. Surgical decompression of the lateral femoral cutaneous nerve is a simple and effective treatment option, but the surgical anatomy of the area is not always familiar to neurosurgeons and neurosurgical trainees alike. This paper is a simple review of the relevant surgical anatomy and the surgical steps of lateral femoral cutaneous nerve decompression, with the aim of providing the busy surgeon and trainee a quick and easy reference guide to the procedure.

The Epstein-Barr Virus Oncogene EBNA1 Suppresses Natural Killer Cell Responses and Apoptosis Early after Infection of Peripheral B Cells.

The innate immune system serves as frontline defense against pathogens, such as bacteria and viruses. Natural killer (NK) cells are a part of innate immunity and can both secrete cytokines and directly target cells for lysis. NK cells express several cell surface receptors, including NKG2D, which bind multiple ligands.