Evolutionary Relationships of Unclassified Coronaviruses in Canadian Bat Species.

Bats are recognized as natural reservoirs for an array of diverse viruses, particularly coronaviruses, which have been linked to major human diseases like SARS-CoV and MERS-CoV. These viruses are believed to have originated in bats, highlighting their role in virus ecology and evolution. Our study focuses on the molecular characterization of bat-derived coronaviruses (CoVs) in Canada.

New Benzofuran-Pyrazole-Based Compounds as Promising Antimicrobial Agents: Design, Synthesis, DNA Gyrase B Inhibition, and In Silico Studies.

Background/objectives: The alarming rise in antibiotic resistance necessitates the discovery of novel antimicrobial agents. This study aims to design, synthesize, and evaluate new benzofuran-pyrazole-based compounds for their antimicrobial, antioxidant, and anti-inflammatory properties.

Methods: New benzofuran-pyrazole hybrid molecules were synthesized using the Vilsmeier-Haach reaction and other chemical processes.

Identification of Protein Networks and Biological Pathways Driving the Progression of Atherosclerosis in Human Carotid Arteries Through Mass Spectrometry-Based Proteomics.

Vulnerable atherosclerotic plaques, especially hemorrhaged lesions, are the major cause of mortalities related to vascular pathologies. The early identification of vulnerable plaques helps to stratify patients at risk of developing acute vascular events. In this study, proteomics analyses of human carotid artery samples collected from patients with atheromatous plaques and complicated lesions, respectively, as well as from healthy controls were performed.

Modeling Viral Capsid Assembly: A Review of Computational Strategies and Applications.

Viral capsid assembly is a complex and critical process, essential for understanding viral behavior, evolution, and the development of antiviral treatments, vaccines, and nanotechnology. Significant progress in studying viral capsid assembly has been achieved through various computational approaches, including molecular dynamics (MD) simulations, stochastic dynamics simulations, coarse-grained (CG) models, electrostatic analyses, lattice models, hybrid techniques, machine learning methods, and kinetic models. Each of these techniques offers unique advantages, and by integrating these diverse computational strategies, researchers can more accurately model the dynamic behaviors and structural features of viral capsids, deepening our understanding of the assembly process.

Small Molecule with Big Impact: Metarrestin Targets the Perinucleolar Compartment in Cancer Metastasis.

Metarrestin (ML246) is a first-in-class pyrrole-pyrimidine-derived small molecule that selectively targets the perinucleolar compartment (PNC). PNC is a distinct subnuclear structure predominantly found in solid tumor cells. The occurrence of PNC demonstrates a positive correlation with malignancy, serving as an indicator of tumor aggressiveness, progression, and metastasis.

Neuroprotective Effects of Functionalized Hydrophilic Carbon Clusters: Targeted Therapy of Traumatic Brain Injury in an Open Blast Rat Model.

Unlabelled: Traumatic brain injury (TBI) causes multiple cerebrovascular disruptions and oxidative stress. These pathological mechanisms are often accompanied by serious impairment of cerebral blood flow autoregulation and neuronal and glial degeneration.

Background/objectives: Multiple biochemical cascades are triggered by brain damage, resulting in reactive oxygen species production alongside blood loss and hypoxia.

Installation of an Indole on the BRCA1 Disordered Domain Using Triazine Chemistry.

The functionalization of protein sidechains with highly water-soluble chlorotriazines (or derivatives thereof) using nucleophilic aromatic substitution reactions has been commonly employed to install various functional groups, including poly(ethylene glycol) tags or fluorogenic labels. Here, a poorly soluble dichlorotriazine with an appended indole is shown to react with a construct containing the disordered domain of BRCA1. Subsequently, this construct can undergo proteolytic cleavage to remove the SUMO-tag: the -terminal poly(His) tag is still effective for purification.

Structures of ATP-binding cassette transporter ABCC1 reveal the molecular basis of cyclic dinucleotide cGAMP export.

Cyclic nucleotide GMP-AMP (cGAMP) plays a critical role in mediating the innate immune response through the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. Recent studies showed that ATP-binding cassette subfamily C member 1 (ABCC1) is a cGAMP exporter. The exported cGAMP can be imported into uninfected cells to stimulate a STING-mediated innate immune response.

Setdb1 and Atf7IP form a hetero-trimeric complex that blocks Setdb1 nuclear export.

Histone H3K9 methylation (H3K9me) by Setdb1 silences retrotransposons (rTE) by sequestering them in constitutive heterochromatin. Atf7IP is a constitutive binding partner of Setdb1 and is responsible for Setdb1 nuclear localization, activation and chromatin recruitment. However, structural details of the Setdb1/Atf7IP interaction have not been evaluated.

Nucleosome Spacing Can Fine-Tune Higher Order Chromatin Assembly.

Cellular chromatin displays heterogeneous structure and dynamics, properties that control diverse nuclear processes. Models invoke phase separation of conformational ensembles of chromatin fibers as a mechanism regulating chromatin organization . Here we combine biochemistry and molecular dynamics simulations to examine, at single base-pair resolution, how nucleosome spacing controls chromatin phase separation.

Cellular Function of a Biomolecular Condensate Is Determined by Its Ultrastructure.

Biomolecular condensates play key roles in the spatiotemporal regulation of cellular processes. Yet, the relationship between atomic features and condensate function remains poorly understood. We studied this relationship using the polar organizing protein Z (PopZ) as a model system, revealing how its material properties and cellular function depend on its ultrastructure.

Whole genome sequence-based association analysis of African American individuals with bipolar disorder and schizophrenia.

In studies of individuals of primarily European genetic ancestry, common and low-frequency variants and rare coding variants have been found to be associated with the risk of bipolar disorder (BD) and schizophrenia (SZ). However, less is known for individuals of other genetic ancestries or the role of rare non-coding variants in BD and SZ risk. We performed whole genome sequencing of African American individuals: 1,598 with BD, 3,295 with SZ, and 2,651 unaffected controls (InPSYght study).

Control of Two Solid Electrolyte Interphases at the Negative Electrode of an Anode-Free All Solid-State Battery based on Argyrodite Electrolyte.

Anode-free all solid-state batteries (AF-ASSBs) employ "empty" current collector with three active interfaces that determine electrochemical stability; lithium metal - Solid electrolyte (SE) interphase (SEI-1), lithium - current collector interface, and collector - SE interphase (SEI-2). Argyrodite LiPSCl (LPSCl) solid electrolyte (SE) displays SEI-2 containing copper sulfides, formed even at open circuit. Bilayer of 140 nm magnesium/30 nm tungsten (Mg/W-Cu) controls the three interfaces and allows for state-of-the-art electrochemical performance in half-cells and fullcells.

Novel and potent MICA/B antibody is therapeutically effective in mutant lung cancer models.

Background: Concurrent (STK11, KL) mutant non-small cell lung cancers (NSCLC) do not respond well to current immune checkpoint blockade therapies, however targeting major histocompatibility complex class I-related chain A or B (MICA/B), could pose an alternative therapeutic strategy through activation of natural killer (NK) cells.

Methods: Expression of NK cell activating ligands in NSCLC cell line and patient data were analyzed. Cell surface expression of MICA/B in NSCLC cell lines was determined through flow cytometry while ligand shedding in both patient blood and cell lines was determined through ELISA.

Ion-Induced Phase Changes in 2D MoTe Films for Neuromorphic Synaptic Device Applications.

Two-dimensional molybdenum ditelluride (2D MoTe) is an interesting material for artificial synapses due to its unique electronic properties and phase tunability in different polymorphs 2H/1T'. However, the growth of stable and large-scale 2D MoTe on a CMOS-compatible Si/SiO substrate remains challenging because of the high growth temperature and impurity-involved transfer process. We developed a large-scale MoTe film on a Si/SiO wafer by simple sputtering followed by lithium-ion intercalation and applied it to artificial synaptic devices.

Thermally Activated Delayed Fluorescence in B,N-Substituted Tetracene Derivatives: A Theoretical Pathway to Enhanced OLED Materials.

Polycyclic aromatic hydrocarbons (PAHs) exhibit intriguing characteristics that position them as promising candidates for advancements in organic semiconductor technologies. Notably, tetracene finds substantial utility in Electronics due to its application in organic light-emitting diodes (OLEDs) and organic field-effect transistors (OFETs). The strategic introduction of an isoelectronic boron-nitrogen (B,N) pair to replace a carbon-carbon pair in acenes introduces changes in the electronic structure, allowing for the controlled modulation of diradical characteristics.

Visible-Light-Fueled Polymerizations for 3D Printing.

ConspectusLight-driven polymerizations and their application in 3D printing have revolutionized manufacturing across diverse sectors, from healthcare to fine arts. Despite the popularized notion that with 3D printing "imagination is the only limit", we and others in the scientific community have identified fundamental hurdles that restrict our capabilities in this space. Herein, we describe the group's efforts in developing photochemical systems that respond to nontraditional colors of light to elicit the rapid, spatiotemporally controlled formation of plastics.

Introductory Analysis and Validation of CUT&RUN Sequencing Data.

The CUT&RUN technique facilitates detection of protein-DNA interactions across the genome. Typical applications of CUT&RUN include profiling changes in histone tail modifications or mapping transcription factor chromatin occupancy. Widespread adoption of CUT&RUN is driven, in part, by technical advantages over conventional ChIP-seq that include lower cell input requirements, lower sequencing depth requirements, and increased sensitivity with reduced background signal due to a lack of cross-linking agents that otherwise mask antibody epitopes.

Surface interactions of gelatin-sourced carbon quantum dots with a model globular protein: insights into carbon-based nanomaterials and biological systems.

Carbon nanomaterials (CNMs), such as carbon nanotubes (CNTs), graphene quantum dots (GQDs), and carbon quantum dots (CQDs), are prevalent in biological systems and have been widely utilized in applications like environmental sensing and biomedical fields. While their presence in human matrices is projected to increase, the interfacial interactions between carbon-based nanoscopic platforms and biomolecular systems continue to remain underexplored. In this study, we investigated the effect of gelatin-sourced CQDs on the globular milk protein beta-lactoglobulin (BLG).

Fire Resistant Adhesive from Chitosan.

Chitosan is one of the most abundant biopolymers on earth. It is used as a nontoxic alternative in a wide range of medicines, packaging, adhesives, and flame retardants. Chitosan is poorly soluble in neutral or alkaline solutions, but it dissolves in solutions of weak acids, such as acetic acid or citric acid, both of which occur naturally.

Depletion of myeloid-derived suppressor cells sensitizes murine multiple myeloma to PD-1 checkpoint inhibitors.

Background: Cancer immunotherapy using immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, patients with multiple myeloma (MM) rarely respond to ICB. Accumulating evidence indicates that the complicated tumor microenvironment (TME) significantly impacts the efficacy of ICB therapy.

Autocorrelation and Multifractal Detrended Fluctuation Analyses Reveal Superdiffusive Mass Transport in Solvent-Filled Nanoporous Media.

Fluorescence fluctuation spectroscopy experiments were conducted to better understand the complex mass transport dynamics of organic molecules in liquid-filled nanoporous media. Anodic aluminum oxide (AAO) membranes incorporating 10 and 20 nm diameter cylindrical pores were employed as model materials. Nile red (NR) dye was used as a fluorescent tracer.