Evaluation of Mesoporous Silica Nanoparticles as Carriers of Triarylmethyl Radical Spin Probes for EPR Oximetry.

measurement and mapping of oxygen levels within the tissues are crucial in understanding the physiopathological processes of numerous diseases, such as cancer, diabetes, or peripheral vascular diseases. Electron paramagnetic resonance (EPR) associated with biocompatible exogenous spin probes, such as Ox071 triarylmethyl (TAM) radical, is becoming the new gold standard for oxygen mapping in preclinical settings. However, these probes do not show tissue selectivity when injected systemically, and they are not cell permeable, reporting oxygen from the extracellular compartment only.

Plasmids encode and can mobilize onion pathogenicity in Pantoea agglomerans.

Pantoea agglomerans is one of four Pantoea species reported in the USA to cause bacterial rot of onion bulbs. However, not all P. agglomerans strains are pathogenic to onion.

Polystyrene Nanoplastics Hitch-Hike the Gut-Brain Axis to Exacerbate Parkinson's Pathology.

The neurological implications of micro- and nanoplastic exposure have recently come under scrutiny due to the environmental prevalence of these synthetic materials. Parkinson's disease (PD) is a major neurological disorder clinically characterized by intracellular Lewy-body inclusions and dopaminergic neuronal death. These pathological hallmarks of PD, according to Braak's hypothesis, are mediated by the afferent propagation of α synuclein (αS) via the enteric nervous system, or the so-called gut-brain axis.

Coagulation abnormalities following brown recluse spider (Loxosceles reclusa) envenomation: A description of 2 cases and review of the literature.

Objective: Hemostatic abnormalities, including disseminated intravascular coagulation (DIC), are often cited as a common finding in patients following Loxosceles spider envenomation (ie, loxoscelism). The prevalence and severity of coagulopathy, however, particularly following L reclusa (ie, brown recluse) envenomation, is not well described. This study aimed to characterize coagulation laboratory parameters and coagulopathy in patients following L reclusa envenomation.

Exome sequencing reveals a sparse genomic landscape in Kaposi sarcoma.

Kaposi Sarcoma (KS) is a frequently aggressive malignancy caused by Kaposi sarcoma herpesvirus (KSHV/HHV-8). People with immunodeficiencies, including HIV, are at increased risk for developing KS, but our understanding of the contributions of the cellular genome to KS pathogenesis remains limited. To determine if there are cellular genetic alterations in KS that might provide biological or therapeutic insights, we performed whole exome sequencing on 78 KS tumors and matched normal control skin from 59 adults with KS (46 with HIV-associated KS and 13 with HIV-negative KS) receiving treatment at the Uganda Cancer Institute in Kampala, Uganda.

Synthetically Relevant Post-Transition State Bifurcation Leading to Diradical and Zwitterionic Intermediates: Controlling Nonstatistical Kinetic Selectivity through Solvent Effects.

A post-transition state surface intersection (PTSSI) between radical and zwitterionic states that causes a bifurcation in the reaction pathway was discovered through density functional theory calculations on potential energy surfaces and ab initio molecular dynamics simulations of cycloadditions between a bicyclobutane and a triazolinedione (BCB-TAD). It was predicted that changes to the solvent polarity would enable control over the dynamic selectivity in this system; indeed, experimental evidence supported this prediction. This work not only provides new insights into an unusual type of post-transition state bifurcation, but also demonstrates how the nonstatistical dynamic effects that control selectivity for such reactions can be manipulated rationally to increase the yields of synthetically useful reactions.

Dedenser: A Python Package for Clustering and Downsampling Chemical Libraries.

The screening of chemical libraries is an essential starting point in the drug discovery process. While some researchers desire a more thorough screening of drug targets against a narrower scope of molecules, it is not uncommon for diverse screening sets to be favored during the early stages of drug discovery. However, a cost burden is associated with the screening of molecules, with potential drawbacks if particular areas of chemical space are needlessly overrepresented.

Beyond Surfactants: Janus Particles for Functional Interfaces and Coatings.

Janus particles (JPs), initially introduced as soft matter, have evolved into a distinctive class of materials that set them apart from traditional surfactants, dispersants, and block copolymers. This mini-review examines the similarities and differences between JPs and their molecular counterparts to elucidate the unique properties of JPs. Key studies on the assembly behavior of JPs in bulk phases and at interfaces are reviewed, highlighting their unique ability to form diverse, complex structures.

G-quadruplex structures in 16S rRNA regions correlate with thermal adaptation in prokaryotes.

G-quadruplex (G4) structure is a nucleic acid secondary structure formed by guanine-rich sequences, playing essential roles in various biological processes such as gene regulation and environmental stress adaptation. Although prokaryotes growing at high temperatures have higher GC contents, the pattern of G4 structure associated with GC content variation in thermal adaptation remains elusive. This study analyzed 681 bacterial genomes to explore the role of G4 structures in thermal adaptation.

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.

Early events in G-quadruplex folding captured by time-resolved small-angle X-ray scattering.

Time-resolved small-angle X-ray experiments are reported here that capture and quantify a previously unknown rapid collapse of the unfolded oligonucleotide as an early step in the folding of hybrid 1 and hybrid 2 telomeric G-quadruplex structures. The rapid collapse, initiated by a pH jump, is characterized by an exponential decrease in the radius of gyration from 24.3 to 12.

High-Throughput Quantification and Characterization of Dual Payload mRNA/LNP Cargo via Deformulating Size Exclusion and Ion Pairing Reversed Phase Assays.

Therapeutic drugs and multivalent vaccines based on the delivery of mRNA via lipid nanoparticle (LNP) technologies are expected to dominate the biopharmaceutical industry landscape in the coming years. Many of these innovative therapies include several nucleic acid components (e.g.

Inactivation of CaV1 and CaV2 channels.

Voltage-gated Ca2+ channels (VGCCs) are highly expressed throughout numerous biological systems and play critical roles in synaptic transmission, cardiac excitation, and muscle contraction. To perform these various functions, VGCCs are highly regulated. Inactivation comprises a critical mechanism controlling the entry of Ca2+ through these channels and constitutes an important means to regulate cellular excitability, shape action potentials, control intracellular Ca2+ levels, and contribute to long-term potentiation and depression.

Sickle Cell Trait Does Not Cause "Sickle Cell Crisis" Leading to Exertion-Related Death: A Systematic Review.

Globally, an estimated 300 million individuals have sickle cell trait (SCT), the carrier state for sickle cell disease. While sickle cell disease (SCD) is associated with increased morbidity and shortened lifespan, SCT has a lifespan comparable to that of the general population. However, "sickle cell crisis" has been used as a cause of death for decedents with SCT in reports of exertion-related death in athletes, military personnel, and individuals in police custody.

Management of adhesive small bowel obstruction during pregnancy in the United States.

Background: Adhesive small bowel obstruction (ASBO) is a rare, nonobstetrical abdominal emergency. Optimal management of ASBO during pregnancy remains unknown. This study analyzes management trends and outcomes of pregnant patients with ASBO in the United States.

Dark-Field Absorbance Circular Dichroism of Oriented Chiral Thin Films.

Dark-field and confocal approaches to circular dichroism (CD) spectroscopy of uniaxial thin films examine the relationship between symmetry and incoherence in the nonreciprocal CD response, or the component that is antisymmetric about the light propagation direction. Modifying a conventional CD spectrometer for low-angle scattering detection isolates incoherent contributions to nonreciprocal CD of drop-cast thin films, boasting 5-to-10-fold enhancements in CD dissymmetry parameters. Conversely, confocal detection suppresses the nonreciprocal CD response.

Reversible Electrochemical Sensor for NDMA: Leveraging Molecularly Imprinted Polymers for Enhanced Sensitivity and Selectivity.

Herein, we present the development and evaluation of a molecularly imprinted polymer (MIP) sensor for the sensitive and selective detection of -nitrosodimethylamine (NDMA) in aqueous environments. MIP coatings over electrochemically active electrodes enable NDMA detection with a notably low detection limit of 1.16 ppb.

Myristoylated Neuronal Calcium Sensor-1 captures the ciliary vesicle at distal appendages.

The primary cilium is a microtubule-based organelle that cycles through assembly and disassembly. In many cell types, formation of the cilium is initiated by recruitment of ciliary vesicles to the distal appendage of the mother centriole. However, the distal appendage mechanism that directly captures ciliary vesicles is yet to be identified.

Synaptic enrichment and dynamic regulation of the two opposing dopamine receptors within the same neurons.

Dopamine can play opposing physiological roles depending on the receptor subtype. In the fruit fly , and encode the D- and D-like receptors, respectively, and are reported to oppositely regulate intracellular cAMP levels. Here, we profiled the expression and subcellular localization of endogenous Dop1R1 and Dop2R in specific cell types in the mushroom body circuit.

Cold induces brain region-selective cell activity-dependent lipid metabolism.

It has been well documented that cold is an enhancer of lipid metabolism in peripheral tissues, yet its effect on central nervous system lipid dynamics is underexplored. It is well recognized that cold acclimations enhance adipocyte functions, including white adipose tissue lipid lipolysis and beiging, and brown adipose tissue thermogenesis in mammals. However, it remains unclear whether and how lipid metabolism in the brain is also under the control of ambient temperature.

A hierarchical pathway for assembly of the distal appendages that organize primary cilia.

Distal appendages are nine-fold symmetric blade-like structures attached to the distal end of the mother centriole. These structures are critical for formation of the primary cilium, by regulating at least four critical steps: ciliary vesicle recruitment, recruitment and initiation of intraflagellar transport (IFT), and removal of CP110. While specific proteins that localize to the distal appendages have been identified, how exactly each protein functions to achieve the multiple roles of the distal appendages is poorly understood.

Discovery and Development of CFTR Modulators for the Treatment of Cystic Fibrosis.

Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which regulates ion and fluid transport across epithelial cells. Mutations lead to complications, with life-limiting lung disease being the most severe manifestation. Traditional treatments focused on managing symptoms, but advances in understanding CF's molecular basis led to small-molecule CFTR modulators.

Deriving the Landauer Principle From the Quantum Shannon Entropy.

We derive an expression to determine the equilibrium probability distribution of a quantum state in contact with a noisy thermal environment that formally separates contributions from quantum and classical forms of probabilistic uncertainty. A statistical mechanical interpretation of this probability distribution enables us to derive an expression for the minimum free energy costs for arbitrary (reversible or irreversible) quantum state changes. Based on this derivation, we demonstrate that─in contrast to classical systems─the free energy required to erase or reset a qubit depends sensitively on both the fidelity of the target state and on the physical properties of the environment, such as the number of quantum bath states, due primarily to the entropic effects of system-bath entanglement.