Inhibitors Based on Arylated Quinoline Carboxylic Acid Backbones with Anti- Gyrase Activity.

New antitubercular agents with either a novel mode of action or novel mode of inhibition are urgently needed to overcome the threat of drug-resistant tuberculosis (TB). The present study profiles new arylated quinoline carboxylic acids (QCAs) having activity against replicating and non-replicating (), the causative agent of TB. Thus, the synthesis, characterization, and in vitro screening (MABA and LORA) of 48 QCAs modified with alkyl, aryl, alkoxy, halogens, and nitro groups in the quinoline ring led to the discovery of two QCA derivatives, and adorned with C-2 2-(naphthalen-2-yl)/C-6 1-butyl and C-2 22-(phenanthren-3-yl)/C-6 isopropyl, respectively, as the best inhibitors.

The prevailing infection of and other zoonotic parasites in bubaline reservoir hosts in the ricefield of lake ecosystem: the case of Lake Mainit, Philippines.

Bovines are important reservoir hosts of schistosomiasis, placing humans and animals in rice fields areas at risk of infection. This study reported the prevailing infection of zoonotic parasites from bovine feces in the rice fields adjacent to Lake Mainit, Philippines. Formalin Ethyl Acetate Sedimentation was performed on 124 bovine fecal samples from rice fields and documented eggs and cysts from seven parasites: sp.

Quantum Descriptors for Predicting and Understanding the Structure-Activity Relationships of Michael Acceptor Warheads.

Predictive modeling and understanding of chemical warhead reactivities have the potential to accelerate targeted covalent drug discovery. Recently, the carbanion formation free energies as well as other ground-state electronic properties from density functional theory (DFT) calculations have been proposed as predictors of glutathione reactivities of Michael acceptors; however, no clear consensus exists. By profiling the thiol-Michael reactions of a diverse set of singly- and doubly-activated olefins, including several model warheads related to afatinib, here we reexamined the question of whether low-cost electronic properties can be used as predictors of reaction barriers.

Balance Assessment Using a Smartwatch Inertial Measurement Unit with Principal Component Analysis for Anatomical Calibration.

Balance assessment, or posturography, tracks and prevents health complications for a variety of groups with balance impairment, including the elderly population and patients with traumatic brain injury. Wearables can revolutionize state-of-the-art posturography methods, which have recently shifted focus to clinical validation of strictly positioned inertial measurement units (IMUs) as replacements for force-plate systems. Yet, modern anatomical calibration (i.

Gene regulatory network inference in soybean upon infection by Phytophthora sojae.

Phytophthora sojae is a soil-borne oomycete and the causal agent of Phytophthora root and stem rot (PRR) in soybean (Glycine max [L.] Merrill). Yield losses attributed to P.

Black sexual and gender diverse scholars' contributions to psychology.

Psychology has a long history of perpetuating scientific racism and pathologizing gender and sexually diverse individuals. The field has been criticized for the reproduction of racism, sexism, cissexism, and other social inequities. This intersectional epistemological exclusion has led to a lack of appreciation for the work of Black sexual and gender diverse (SGD) scholars within the field of psychology.

Fibroblasts at the curtain call: from ensemble to principal dancers in immunometabolism and inflammaging.

Inflammation is a necessary step in response to injuries, being vital in restoring homeostasis and facilitating tissue healing. Among the cells that play a crucial role in inflammatory responses, stromal cells, including fibroblasts, have an undeniable significance in fine-tuning the magnitude of mediators that directly affect hyper-inflammatory responses and tissue destruction. Fibroblasts, the dominant cells in the gingival connective tissue, are a very heterogeneous population of cells, and more recently they have been receiving well deserved attention as central players and often the 'principal dancers' of many pathological processes ranging from inflammation and fibrosis to altered immunity and cancer.

Time-Dependent Demineralization of Tilapia ( Bones Using Hydrochloric Acid for Extracellular Matrix Extraction.

Tilapia ) is a widely cultivated fish in tropical and subtropical regions such as the Philippines, generating substantial waste during processing, including bones that are a valuable source of extracellular matrix (ECM). However, the extraction of ECM from fish bones requires an essential step of demineralization. This study aimed to assess the efficiency of tilapia bone demineralization using 0.

A prognostic matrix code defines functional glioblastoma phenotypes and niches.

Interactions among tumor, immune and vascular niches play major roles in driving glioblastoma (GBM) malignancy and treatment responses. The composition, heterogeneity, and localization of extracellular core matrix proteins (CMPs) that mediate such interactions, however, are not well understood. Here, we characterize functional and clinical relevance of genes encoding CMPs in GBM at bulk, single cell, and spatial anatomical resolution.

Revolving ATPase motors as asymmetrical hexamers in translocating lengthy dsDNA via conformational changes and electrostatic interactions in phi29, T7, herpesvirus, mimivirus, , and .

Investigations of the parallel architectures of biomotors in both prokaryotic and eukaryotic systems suggest a similar revolving mechanism in the use of ATP to drive translocation of the lengthy double-stranded (ds)DNA genomes. This mechanism is exemplified by the dsDNA packaging motor of bacteriophage phi29 that operates through revolving but not rotating dsDNA to "Push through a one-way valve". This unique and novel revolving mechanism discovered in phi29 DNA packaging motor was recently reported in other systems including the dsDNA packaging motor of herpesvirus, the dsDNA ejecting motor of bacteriophage T7, the plasmid conjugation machine TraB in , the dsDNA translocase FtsK of gram-negative bacteria, and the genome-packaging motor in mimivirus.

Applications of Electrical Impedance Tomography in Neurology.

Introduction: Electrical impedance tomography (EIT) is a non-invasive technique utilized in various medical applications, including brain imaging and other neurological diseases. Recognizing the physiological and anatomical characteristics of organs based on their electrical properties is one of the main applications of EIT, as each variety of tissue structure has its own electrical characteristics. The high potential of brain EIT is established in real-time supervision and early recognition of cerebral brain infarction, hemorrhage, and other diseases.

Aquatic toxicity of hydroquinone and catechol following metal oxide treatment to Ceriodaphnia dubia and Pimephales promelas.

Metal oxides comprise a large group of chemicals used in water treatment to adsorb organic pollutants. The ability of titanium dioxide (TiO) and iron (III) oxide (FeO) to reduce the chronic toxicity of (phenolic) CH(OH) isomers, namely hydroquinone (HQ) and catechol (CAT) to Ceriodaphnia dubia and Pimephales promelas (less than 24 h-old) were investigated. The toxic endpoints following metal oxide treatment were compared to endpoints of untreated CAT and HQ.

Juneteenth in STEMM and the barriers to equitable science.

We are 52 Black scientists. Here, we establish the context of Juneteenth in STEMM and discuss the barriers Black scientists face, the struggles they endure, and the lack of recognition they receive. We review racism's history in science and provide institutional-level solutions to reduce the burdens on Black scientists.

Catalytic Mechanism of Human T-Cell Leukemia Virus Type 1 Protease Investigated by Combined QM/MM Molecular Dynamics Simulations.

Combined quantum mechanical and molecular mechanical (QM/MM) molecular dynamics simulations were performed to investigate the catalytic mechanism of human T-cell leukemia virus type 1 (HTLV-1) protease, a retroviral aspartic protease that is a potential therapeutic target for curing HTLV-1-associated diseases. To elucidate the proteolytic cleavage mechanism, we determined the two-dimensional free energy surfaces of the HTLV-1 protease-catalyzed reactions through various possible pathways. The free energy simulations suggest that the catalytic reactions of the HTLV-1 protease occur in the following sequential steps: (1) a proton is transferred from the lytic water to Asp32', followed by the nucleophilic addition of the resulting hydroxyl to the carbonyl carbon of the scissile bond, forming a tetrahedral oxyanion intermediate, and (2) a proton is transferred from Asp32 to the peptide nitrogen of the scissile bond, leading to the spontaneous breakage of the scissile bond.

Impact of early pericardial fluid chymase activation after cardiac surgery.

Introduction: Chymase is a highly destructive serine protease rapidly neutralized in the circulation by protease inhibitors. Here we test whether pericardial fluid (PCF) chymase activation and other inflammatory biomarkers determine intensive care unit length of stay, and explore mechanisms of chymase delivery by extracellular vesicles to the heart.

Methods: PCF was collected from adult patients (17 on-pump; 13 off-pump) 4 h after cardiac surgery.

Anti-Toxoplasma gondii activity of Trametes versicolor (Turkey tail) mushroom extract.

Toxoplasma gondii (T. gondii) infection continues to rise globally in humans and animals with high socioeconomic and public health challenges. Current medications used against T.

Cryptic Genetic Diversity in the Coastal Isopod from the Pacific Ocean.

The isopod sub-order Oniscidea includes over 3,700 species and is known to occur in all terrestrial environments, except those at extreme elevations and polar latitudes. Current estimates of the biodiversity of the Oniscidea may be underestimates, as recent molecular studies have uncovered high levels of cryptic diversity in several taxa in the sub-order. High levels of cryptic diversity have been found in coastal species, species from remote and isolated regions, and species with complex taxonomic histories.

Computational analysis of drug resistance of taxanes bound to human β-tubulin mutant (D26E).

The single-point mutation D26E in human β-tubulin is associated with drug resistance seen with two anti-mitotic taxanes (paclitaxel and docetaxel) when used to treat cancers. The molecular mechanism of this resistance remains elusive. However, docetaxel and a third-generation taxane, cabazitaxel, are thought to overcome this resistance.

Selective PPAR-Delta/PPAR-Gamma Activation Improves Cognition in a Model of Alzheimer's Disease.

The continuously increasing association of Alzheimer's disease (AD) with increased mortality rates indicates an unmet medical need and the critical need for establishing novel molecular targets for therapeutic potential. Agonists for peroxisomal proliferator activating receptors (PPAR) are known to regulate energy in the body and have shown positive effects against Alzheimer's disease. There are three members of this class (delta, gamma, and alpha), with PPAR-gamma being the most studied, as these pharmaceutical agonists offer promise for AD because they reduce amyloid beta and tau pathologies, display anti-inflammatory properties, and improve cognition.

Mood disturbance, but not overall diet quality, is associated with fecal microbiome diversity in free-living adults.

Objectives: To investigate the gut-brain axis, we explored the relationships among mood disturbance (MD), diet quality (DQ), and fecal microbiota in free-living adults.

Methods: A cross-sectional analysis was conducted with data from 75 healthy adults enrolled in two studies. Anthropometrics, 16s rRNA gene sequencing of fecal microbes, DQ as assessed by Healthy Eating Index-2015 (HEI), and MD determined by Profile of Mood States (POMS) were included.

Topological data analysis of antibody dynamics of severe and non-severe patients with COVID-19.

The COVID-19 pandemic is a significant public health threat with unanswered questions regarding the immune system's role in the disease's severity level. Here, based on antibody kinetic data of severe and non-severe COVID-19 patients, topological data analysis (TDA) highlights that severity is not binary. However, there are differences in the shape of antibody responses that further classify COVID-19 patients into non-severe, severe, and intermediate cases of severity.

Voluntary wheel running promotes resilience to the behavioral effects of unpredictable chronic mild stress in male and female mice.

Besides significant benefits to physical health, exercise promotes mental health, reduces symptoms of mental illness, and enhances psychological development. Exercise can offset the impact of chronic stress, which is a major precursor to the development of mental disorders. The effects of exercise on chronic stress-induced behaviors are contradictory in preclinical studies, primarily due to the lack of data and sex-specific investigations.

Biodegradation of polycyclic aromatic hydrocarbons (PAHs) by microbial consortium from paddy rice soil.

Polycyclic aromatic hydrocarbons (PAHs) are among the most widely spread pollutants in the environment including the agricultural soil. PAH degradation by indigenous bacteria is an effective and economical means to remove these pollutants from the environment. Here, we report a bacterial consortium (Pdy-1) isolated from paddy rice soil in northern Japan able to degrade polycyclic aromatic hydrocarbons (PAHs) at high rates.

Reduced O-GlcNAcylation diminishes cardiomyocyte Ca dependent facilitation and frequency dependent acceleration of relaxation.

Ca dependent facilitation (CDF) and frequency dependent acceleration of relaxation (FDAR) are regulatory mechanisms that potentiate cardiomyocyte Ca channel function and increase the rate of Ca sequestration following a Ca-release event, respectively, when depolarization frequency increases. CDF and FDAR likely evolved to maintain EC coupling at increased heart rates. Ca/calmodulin-dependent kinase II (CaMKII) was shown to be indispensable to both; however, the mechanisms remain to be completely elucidated.