Quantitative Measurement of Molecular Permeability to a Synthetic Bacterial Microcompartment Shell System.

Naturally evolved and synthetically designed forms of compartmentalization benefit encapsulated function by increasing local concentrations of substrates and protecting cargo from destabilizing environments and inhibitors. Crucial to understanding the fundamental principles of compartmentalization are experimental systems enabling the measurement of the permeability rates of small molecules. Here, we report the experimental measurement of the small-molecule permeability of a 40 nm icosahedral bacterial microcompartment shell.

Are Department Heads Ready for Change? Leveraging a Leadership Action Team to Advance Teaching Evaluation Practices.

Teaching evaluation at many institutions is insufficient to support, recognize, and reward effective teaching. We developed a long-term intervention to support science, technology, engineering, and mathematics (STEM) department heads in advancing teaching evaluation practices. We describe the intervention and systematically investigate its impact on departmental practices within a research-intensive university.

MircoRNAs predict and modulate responses to chemotherapy in leukemic patients.

Leukemia covers a broad category of cancer malignancies that specifically affect bone marrow and blood cells. While different kinds of leukemia have been identified, effective treatments are still lacking for most forms, and even those treatments considered effective can lead to relapses. MicroRNAs, or miRNAs, are short endogenous non-coding single-stranded RNAs that help control the epigenetics of gene expression.

Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity.

Half the world's population is at risk of developing a malaria infection, which is caused by parasites of the genus . Currently, resistance has been identified to all clinically available antimalarials, highlighting an urgent need to develop novel compounds and better understand common mechanisms of resistance. We previously identified a novel tetrahydro-β-carboline compound, PRC1590, which potently kills the malaria parasite.

Evaluating the Association Between Methylenetetrahydrofolate Reductase (Rs1801131 and Rs1801133) Gene Polymorphisms and Severity of Coronary Lesions in Patients With STEMI and NSTEMI: A Retrospective Cross-Sectional Study.

Background And Aims: Mounting evidence have implicated that rs1801131 and rs1801133, located in the Methylenetetrahydrofolate reductase (MTHFR) gene, may emerge as novel biomarkers for coronary artery disease (CAD). The Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score is also an appropriate predictor for revascularization strategy in patients with complex CAD. The aim of this study is to investigate the correlation between rs1801131 and rs1801133 with the severity of coronary lesions in patients with ST‑Elevation Myocardial Infarction (STEMI) and Non‑ST‑Elevation Myocardial Infarction (NSTEMI) based on the SYNTAX score.

Discovering genetic modulators of the protein homeostasis system through multilevel analysis.

Every protein progresses through a natural lifecycle from birth to maturation to death; this process is coordinated by the protein homeostasis system. Environmental or physiological conditions trigger pathways that maintain the homeostasis of the proteome. An open question is how these pathways are modulated to respond to the many stresses that an organism encounters during its lifetime.

DNMT3A loss drives a HIF-1-dependent synthetic lethality to HDAC6 inhibition in non-small cell lung cancer.

encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed -defective NSCLC cells.

Integrated analysis of non‑coding RNAs (HOTAIR and miR‑130a) and their cross‑talk with TGF‑β1, SIRT1 and E‑cadherin as potential biomarkers in colorectal cancer.

Molecular changes have a substantial impact on the onset of colorectal cancer (CRC). Complexes of HOTAIR and miRNAs disrupt several cellular functions during carcinogenesis, primarily by disrupting several carcinogenic signaling pathways. In the present study, the relationships between the serum levels of transforming growth factor-β1 (TGF-β1), sirtuin-1 (SIRT1) and E-cadherin and those of HOX transcript antisense intergenic RNA (HOTAIR) and microRNA-130a (miR-130a) in individuals with CRC were analyzed, including their correlations and diagnostic potential.

Viroporins: discovery, methods of study, and mechanisms of host-membrane permeabilization.

The 'Viroporin' family comprises a number of mostly small-sized, integral membrane proteins encoded by animal and plant viruses. Despite their sequence and structural diversity, viroporins share a common functional trend: their capacity to assemble transmembrane channels during the replication cycle of the virus. Their selectivity spectrum ranges from low-pH-activated, unidirectional proton transporters, to size-limited permeating pores allowing passive diffusion of metabolites.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Structural insights into binding-site access and ligand recognition by human ABCB1.

ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.

ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.

Despite ongoing antibiotic development, evolution of resistance may render candidate antibiotics ineffective. Here we studied in vitro emergence of resistance to 13 antibiotics introduced after 2017 or currently in development, compared with in-use antibiotics. Laboratory evolution showed that clinically relevant resistance arises within 60 days of antibiotic exposure in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, priority Gram-negative ESKAPE pathogens.

Regulation of stress granule maturation and dynamics by poly(ADP-ribose) interaction with PARP13.

Non-covalent interactions of poly(ADP-ribose) (PAR) facilitate condensate formation, yet the impact of these interactions on condensate properties remains unclear. Here, we demonstrate that PAR-mediated interactions through PARP13, specifically the PARP13.2 isoform, are essential for modulating the dynamics of stress granules-a class of cytoplasmic condensates that form upon stress, including types frequently observed in cancers.

Involvement of p38 MAPK and MAPKAPK2 in promoting cell death and the inflammatory response to ischemic stress associated with necrotic glioblastoma.

The association of necrosis in tumors with poor prognosis implies a potential tumor-promoting role. However, the mechanisms underlying cell death in this context and how damaged tissue contributes to tumor progression remain unclear. Here, we identified p38 mitogen-activated protein kinases (p38 MAPK, a.

Effect of cardiomyocyte-specific lipid phosphate phosphatase 3 overexpression on high-fat diet-induced cardiometabolic dysfunction in mice.

Lipid phosphate phosphatase 3 (LPP3) is a membrane-bound enzyme that hydrolyzes lipid phosphates including the bioactive lipid, lysophosphatidic acid (LPA). Elevated circulating LPA production and cellular LPA signaling are implicated in obesity-induced metabolic and cardiac dysfunction. Deletion of LPP3 in the cardiomyocyte increases circulating LPA levels and causes heart failure and mitochondrial dysfunction in mice.

Constitutive deletion of the obscurin-Ig58/59 domains induces atrial remodeling and Ca2+-based arrhythmogenesis.

Obscurin is a giant protein that coordinates diverse aspects of striated muscle physiology. Obscurin immunoglobulin domains 58/59 (Ig58/59) associate with essential sarcomeric and Ca2+ cycling proteins. To explore the pathophysiological significance of Ig58/59, we generated the Obscn-ΔIg58/59 mouse model, expressing obscurin constitutively lacking Ig58/59.

Robust single-nucleus RNA sequencing reveals depot-specific cell population dynamics in adipose tissue remodeling during obesity.

Single-nucleus RNA sequencing (snRNA-seq), an alternative to single-cell RNA sequencing (scRNA-seq), encounters technical challenges in obtaining high-quality nuclei and RNA, persistently hindering its applications. Here, we present a robust technique for isolating nuclei across various tissue types, remarkably enhancing snRNA-seq data quality. Employing this approach, we comprehensively characterize the depot-dependent cellular dynamics of various cell types underlying mouse adipose tissue remodeling during obesity.

Association of circulating Treg and plasma microRNA-21 with rheumatoid arthritis progression.

The etiology of rheumatoid arthritis (RA) is multifaceted. One of the hypothesized pathways that results in the progression of RA is regulatory T cell (Treg) dysfunction. The pro-osteoclastogenic and immunogenic characteristics of microribonucleic acid (microRNA)-21 (miR-21) suggest its role in RA progression.

Microcephaly protein ANKLE2 promotes Zika virus replication.

Orthoflaviviruses are positive-sense single-stranded RNA viruses that hijack host proteins to promote their own replication. Zika virus (ZIKV) is infamous among orthoflaviviruses for its association with severe congenital birth defects, notably microcephaly. We previously mapped ZIKV-host protein interactions and identified the interaction between ZIKV non-structural protein 4A (NS4A) and host microcephaly protein ankyrin repeat and LEM domain-containing 2 (ANKLE2).

Assembly and Quantification of Co-Cultures Combining Heterotrophic Yeast with Phototrophic Sugar-Secreting Cyanobacteria.

With the increasing demand for sustainable biotechnologies, mixed consortia containing a phototrophic microbe and heterotrophic partner species are being explored as a method for solar-driven bioproduction. One approach involves the use of CO2-fixing cyanobacteria that secrete organic carbon to support the metabolism of a co-cultivated heterotroph, which in turn transforms the carbon into higher-value goods or services. In this protocol, a technical description to assist the experimentalist in the establishment of a co-culture combining a sucrose-secreting cyanobacterial strain with a fungal partner(s), as represented by model yeast species, is provided.

Cardiac-targeted delivery of a novel Drp1 inhibitor for acute cardioprotection.

Dynamin-related protein 1 (Drp1) is a mitochondrial fission protein and a viable target for cardioprotection against myocardial ischaemia-reperfusion injury. Here, we reported a novel Drp1 inhibitor (DRP1i1), delivered using a cardiac-targeted nanoparticle drug delivery system, as a more effective approach for achieving acute cardioprotection. DRP1i1 was encapsulated in cubosome nanoparticles with conjugated cardiac-homing peptides (NanoDRP1i1) and the encapsulation efficiency was 99.

Nutritional, Antibacterial and Thrombolytic Prospects of Freshwater Protein Hydrolysate and Its Anti-Inflammatory Potential in LPS-Induced RAW 264.7 Macrophage Cells.

Chronic inflammation and heme-iron overload can result from bacterial hemolysis. Along with the synthetic drugs, numerous traditional and functional food approaches are equally trialed to eradicate the problem. As a prospective new source of dietary protein hydrolysates, freshwater mollusks () have recently drawn huge interest from researchers.

Yogurt Supplementation Can Ameliorate Fatty Liver Diseases and Metabolic Syndrome in High Fat-Induced Conditions in Mice.

Hepatic steatosis/non-alcoholic fatty liver disease is a major public health delinquent caused by the excess deposition of lipid into lipid droplets (LDs) as well as metabolic dysregulation. Hepatic cells buildup with more fat molecules when a person takes high fat diet that is excessive than the body can handle. At present, millions of people in the world are affected by this problem.

Molecular Characterization and Potential Inhibitors Prediction of Protein Arginine Methyltransferase-2 in Carcinoma: An Insight from Molecular Docking, ADMET Profiling and Molecular Dynamics Simulation Studies.

Objectives: To predict and characterize the three-dimensional (3D) structure of protein arginine methyltransferase 2 (PRMT2) using homology modeling, besides, the identification of potent inhibitors for enhanced comprehension of the biological function of this protein arginine methyltransferase (PRMT) family protein in carcinogenesis.

Materials And Methods: An method was employed to predict and characterize the three-dimensional structure. The bulk of PRMTs in the PDB shares just a structurally conserved catalytic core domain.

Molecular dynamics simulation of wild and mutant proteasome subunit beta type 8 (PSMB8) protein: Implications for restoration of inflammation in experimental autoimmune encephalomyelitis pathogenesis.

Multiple Sclerosis (MS) is an autoimmune and chronic disease in the brain and spinal cord. MS has inflammatory progression characterized by its hallmark inflammatory plaques. The histological and clinical characteristics of MS are shared by Experimental Autoimmune Encephalomyelitis (EAE).