Motivation: The rapid expansion of Bioinformatics research has led to a proliferation of computational tools for scientific analysis pipelines. However, constructing these pipelines is a demanding task, requiring extensive domain knowledge and careful consideration. As the Bioinformatics landscape evolves, researchers, both novice and expert, may feel overwhelmed in unfamiliar fields, potentially leading to the selection of unsuitable tools during workflow development.
View Article and Find Full Text PDFPer- and polyfluoroalkyl substances (PFAS), nicknamed "forever chemicals" due to the strength of their carbon-fluorine bonds, are a class of potent micropollutants that cause deleterious health effects in mammals. The current state-of-the-art detection method requires the collection and transport of water samples to a centralized facility where chromatography and mass spectrometry are performed for the separation, identification, and quantification of PFAS. However, for efficient remediation efforts to be properly informed, a more rapid in-field testing method is required.
View Article and Find Full Text PDFEmergent Coronaviridae viruses, such as SARS-CoV-1 in 2003, MERS-CoV in 2012, and SARS-CoV-2 (CoV-2) in 2019, have caused millions of deaths. These viruses have added to the existing respiratory infection burden along with respiratory syncytial virus (RSV) and influenza. There are limited therapies for respiratory viruses, with broad-spectrum treatment remaining an unmet need.
View Article and Find Full Text PDFTreatment of late-stage lung cancers remains challenging with a five-year survival rate of 8%. Immune checkpoint blockers (ICBs) revolutionized the treatment of non-small cell lung cancer (NSCLC) by reactivating anti-tumor immunity. Despite achieving durable responses, ICBs are effective in only 20% of patients due to immune resistance.
View Article and Find Full Text PDFEpidermal Growth Factor Receptor (EGFR) signaling and EGFR mutations play key roles in cancer pathogenesis, particularly in the development of drug resistance. For the ∼20% of all non-small cell lung cancer (NSCLC) patients that harbor an activating mutation, EGFR tyrosine kinase inhibitors (TKIs) provide initial clinical responses. However, long-term efficacy is not possible due to acquired drug resistance.
View Article and Find Full Text PDFThere is currently a growing interest in the use of cannabidiol (CBD) to alleviate the symptoms caused by cancer, including pain, sleep disruption, and anxiety. CBD is often self-administered as an over-the-counter supplement, and patients have reported benefits from its use. However, despite the progress made, the mechanisms underlying CBD's anti-cancer activity remain divergent and unclear.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
December 2022
The coronavirus disease 2019 (COVID-19) pandemic has caused over 600,000,000 infections globally thus far. Up to 30% of individuals with mild to severe disease develop long COVID, exhibiting diverse neurologic symptoms including dementias. However, there is a paucity of knowledge of molecular brain markers and whether these can precipitate the onset of Alzheimer's disease (AD).
View Article and Find Full Text PDFUltraviolet (UV) irradiation-based methods used for viral inactivation have provided an important avenue targeting severe acute respiratory-syndrome coronavirus-2 (SARS-CoV-2) virus. A major problem with state-of-the-art UV inactivation technology is that it is based on UV lamps, which have limited efficiency, require high power, large doses, and long irradiation times. These drawbacks limit the use of UV lamps in air filtering systems and other applications.
View Article and Find Full Text PDFOrientia tsutsugamushi is a genetically intractable obligate intracellular bacterium, causes scrub typhus, and has one of the largest known armamentariums of ankyrin repeat-containing effectors (Anks). Most have a C-terminal F-box presumed to interact with the SCF ubiquitin ligase complex primarily based on their ability to bind overexpressed Skp1. Whether all F-box-containing Anks bind endogenous SCF components and the F-box residues essential for such interactions has gone unexplored.
View Article and Find Full Text PDFA novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), arose late in 2019, with disease pathology ranging from asymptomatic to severe respiratory distress with multi-organ failure requiring mechanical ventilator support. It has been found that SARS-CoV-2 infection drives intracellular complement activation in lung cells that tracks with disease severity. However, the cellular and molecular mechanisms responsible remain unclear.
View Article and Find Full Text PDFThe axis of Programmed cell death-1 receptor (PD-1) with its ligand (PD-L1) plays a critical role in colorectal cancer (CRC) in escaping immune surveillance, and blocking this axis has been found to be effective in a subset of patients. Although blocking PD-L1 has been shown to be effective in 5-10% of patients, the majority of the cohorts show resistance to this checkpoint blockade (CB) therapy. Multiple factors assist in the growth of resistance to CB, among which T cell exhaustion and immunosuppressive effects of immune cells in the tumor microenvironment (TME) play a critical role along with other tumor intrinsic factors.
View Article and Find Full Text PDFThe emergence of a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019 led to a worldwide pandemic with over 170 million confirmed infections and over 3.5 million deaths (as of May 2021). Early studies have shown higher mortality rates from SARS-CoV-2 infection in cancer patients than individuals without cancer.
View Article and Find Full Text PDFSevere Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel coronavirus that emerged from Wuhan, China in late 2019 causing coronavirus disease-19 (COVID-19). SARS-CoV-2 infection begins by attaching to angiotensin-converting enzyme 2 receptor (ACE2) via the spike glycoprotein, followed by cleavage by TMPRSS2, revealing the viral fusion domain. Other presumptive receptors for SARS-CoV-2 attachment include CD147, neuropilin-1 (NRP1), and Myeloid C-lectin like receptor (CLR), each of which might play a role in the systemic viral spread.
View Article and Find Full Text PDFis an obligate intracellular bacterium that invades monocytes to cause the emerging and potentially severe disease, monocytic ehrlichiosis. Ehrlichial invasion of host cells, a process that is essential for the bacterium's survival and pathogenesis, is incompletely understood. In this study, we identified ECH_0377, henceforth designated as EplA ( PDI ligand A) as an adhesin that interacts with host cell protein disulfide isomerase (PDI) to mediate bacterial entry into host cells.
View Article and Find Full Text PDFTumor-associated macrophages (TAMs) can exist in pro- and anti-inflammatory states. Anti-inflammatory TAMs (also referred to as M2-polarized) generally suppress antitumor immune responses and enhance the metastatic progression of cancer. To explore the mechanisms behind this phenomenon, we isolated macrophages from mice and humans, polarized them ex vivo, and examined their functional interaction with breast cancer cells in culture and in mice.
View Article and Find Full Text PDFJ Pediatr Neuropsychol
September 2019
Although diminished proficiency on tasks that require visual-motor integration (VMI) has been reported in individuals with autism spectrum disorder (ASD), very few studies have examined the association between VMI performance and neuroanatomical regions of interest (ROI) involved in motor and perceptual functioning. To address these issues, the current study included an all-male sample of 41 ASD (ages 3-23 years) and 27 typically developing (TD) participants (ages 5-26 years) who completed the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) as part of a comprehensive neuropsychological battery. All participants underwent 3.
View Article and Find Full Text PDFThe tumor microenvironment plays a critical role in tumor initiation, progression, metastasis, and drug resistance. However, models recapitulating the complex 3D structure, heterogeneous cell environment, and cell-cell interactions found in vivo are lacking. Herein, we report on a gravitational microfluidic platform (GMP) retrofitted with MEMS sensors, which is integrated with 3D nanofiber scaffold-aided tumoroid culture.
View Article and Find Full Text PDFcauses granulocytic anaplasmosis, a debilitating infection that can be fatal in the immunocompromised. It also afflicts animals, including dogs, horses, and sheep. No granulocytic anaplasmosis vaccine exists.
View Article and Find Full Text PDFEpidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) provide clinical benefits over chemotherapy for lung cancer patients with EGFR activating mutations. Despite initial clinical responses, long-term efficacy is not possible because of acquired resistance to these therapies. We have developed EGFR TKI drug-tolerant (DT) human lung cancer cell lines as a model for de novo resistance.
View Article and Find Full Text PDFDiverse intracellular pathogens rely on eukaryotic cell surface disulfide reductases to invade host cells. Pharmacologic inhibition of these enzymes is cytotoxic, making it impractical for treatment. Identifying and mechanistically dissecting microbial proteins that co-opt surface reductases could reveal novel targets for disrupting this common infection strategy.
View Article and Find Full Text PDFThe failure of lung cancer treatments has been attributed mostly to the development of drug resistance, however the underlying cellular and molecular mechanisms are poorly understood. Cancer initiating stem cells (CSCs), present in tumors in a small percentage, play critical roles in the development of drug resistance, metastasis, and cancer relapse. Hence, novel treatments targeting both bulk cancer cells and CSCs are under intense investigation.
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