Mutation of the GABRA1 gene is associated with neurodevelopmental defects and epilepsy. GABRA1 encodes for the α1 subunit of the γ-aminobutyric acid type A receptor (GABAR), which regulates the fast inhibitory impulses of the nervous system. Multiple model systems have been developed to understand the function of GABRA1, but these models have produced complex and, at times, incongruent data.
View Article and Find Full Text PDFCerebral cavernous malformations (CCMs) are a neurological disorder characterized by enlarged intracranial capillaries in the brain, increasing the susceptibility to hemorrhagic strokes, a major cause of death and disability worldwide. The limited treatment options for CCMs underscore the importance of prognostic biomarkers to predict the likelihood of hemorrhagic events, aiding in treatment decisions and identifying potential pharmacological targets. This study aimed to identify blood biomarkers capable of diagnosing and predicting the risk of hemorrhage in CCM1 patients, establishing an initial set of circulating biomarker signatures.
View Article and Find Full Text PDFTrypanosomatids are a diverse group of uniflagellate protozoan parasites that include globally relevant pathogens such as Trypanosoma cruzi, the causative agent of Chagas disease. Trypanosomes lack the fatty acid synthase system typically used for de novo fatty acid (FA) synthesis in other eukaryotes. Instead, these microbes have evolved a modular FA elongase (ELO) system comprised of individual ELO enzymes (ELO1-4) that can operate processively to generate long chain- and very long chain-FAs.
View Article and Find Full Text PDFMutations in the HCFC1 transcriptional co-factor protein are the cause of cblX syndrome and X-linked intellectual disability (XLID). cblX is the more severe disorder associated with intractable epilepsy, abnormal cobalamin metabolism, facial dysmorphia, cortical gyral malformations, and intellectual disability. In vitro, murine Hcfc1 regulates neural precursor (NPCs) proliferation and number, which has been validated in zebrafish.
View Article and Find Full Text PDFMutation of the gene is associated with neurodevelopmental defects and epilepsy. encodes for the α1 subunit of the gamma-aminobutyric acid type A receptor (GABAR), which regulates the fast inhibitory impulses of the nervous system. Multiple model systems have previously been developed to understand the function of during development, but these models have produced complex and at times incongruent data.
View Article and Find Full Text PDF, a protozoan parasite, is a major cause of waterborne infection, worldwide. While the trophozoite form of this parasite induces pathological symptoms in the gut, the cyst form transmits the infection. Since is a noninvasive parasite, the actual mechanism by which it causes disease remains elusive.
View Article and Find Full Text PDFChagas disease (CD) is caused by the parasite and affects 6-7 million people worldwide. The diagnosis is still challenging, due to extensive parasite diversity encompassing seven genotypes (TcI-VI and Tcbat) with diverse ecoepidemiological, biological, and pathological traits. Chemotherapeutic intervention is usually effective but associated with severe adverse events.
View Article and Find Full Text PDFBackground: Breast cancer, the most diagnosed cancer, remains the second leading cause of cancer death in the United States, and excessive Progesterone (PRG) or Mifepristone (MIF) exposure may be at an increased risk for developing breast cancer. PRG exerts its cellular responses through signaling cascades involving classic, non-classic, or combined responses by binding to either classic nuclear PRG receptors (nPRs) or non-classic membrane PRG receptors (mPRs). Currently, the intricate balance and switch mechanisms between these two signaling cascades remain elusive.
View Article and Find Full Text PDFThrough the applications of recycling sewage sludge to soils as nutrients, bisphenol A (BPA) and titanium dioxide nanoparticles (TiO-NPs) are commonly found in the agricultural environment. Previous studies have reported that BPA and nanoparticles are harmful to the environment. However, the combined toxicity of both compounds is not yet understood.
View Article and Find Full Text PDFIn this study, we investigated the influence of fungal extracellular vesicles (EVs) during biofilm formation and morphogenesis in Candida albicans. Using crystal violet staining and scanning electron microscopy (SEM), we demonstrated that C. albicans EVs inhibited biofilm formation .
View Article and Find Full Text PDFSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) extensively glycosylates its spike proteins, which are necessary for host cell invasion and the target of both vaccines and immunotherapies. These glycans are predicted to modulate spike binding to the host receptor by stabilizing its open conformation and host immunity evasion. Here, we investigated the essentiality of both the host -glycosylation pathway and SARS-CoV-2 glycans for infection.
View Article and Find Full Text PDFChagas disease (CD) can be accurately diagnosed by detecting in patients' blood using polymerase chain reaction (PCR). However, parasite-derived biomarkers are of great interest for the serological diagnosis and early evaluation of chemotherapeutic efficacy when PCR may fail, owing to a blood parasite load below the method's limit of detection. Previously, we focused on the detection of specific anti-α-galactopyranosyl (α-Gal) antibodies in chronic CD (CCD) patients elicited by α-Gal glycotopes copiously expressed on insect-derived and mammal-dwelling infective parasite stages.
View Article and Find Full Text PDFChagas disease is emerging in countries to which it is not endemic. Biomarkers for earlier therapeutic response assessment in patients with chronic Chagas disease are needed. We profiled plasma-derived extracellular vesicles from a heart transplant patient with chronic Chagas disease and showed the potential of this approach for discovering such biomarkers.
View Article and Find Full Text PDFExtracellular vesicles (EVs) shed by trypomastigote forms of have the ability to interact with host tissues, increase invasion, and modulate the host innate response. In this study, EVs shed from -infected macrophages were investigated as immunomodulatory agents during the initial steps of infection. Initially, by scanning electron microscopy and nanoparticle tracking analysis, we determined that -infected macrophages release higher numbers of EVs (50-300 nm) as compared to non-infected cells.
View Article and Find Full Text PDFBackground: The worldwide emergence of multi-drug resistant bacteria has become a health crisis, as fewer or sometimes no antimicrobial agents are effective against these bacteria. The Rio Grande River is the natural boundary between the United States (US) and Mexico. It spans a border region between Texas, New Mexico and Mexico.
View Article and Find Full Text PDF, a single-celled eukaryote, colonizes and thrives in the small intestine of humans. Because of its compact and reduced genome, has adapted a "minimalistic" life style, as it becomes dependent on available resources of the small intestine. Because expresses fewer sphingolipid (SL) genes-and glycosphingolipids are critical for encystation-we investigated the SL metabolic cycle in this parasite.
View Article and Find Full Text PDFBackground: Cardiovascular disease is the main cause of death in the United States, with smoking being the primary preventable cause of premature death, and thrombosis being the main mechanism of cardiovascular mortality in smokers. Due to the perception that electronic/e-cigarettes are "safer/less harmful" than conventional cigarettes, their usage-among a variety of ages-has increased tremendously during the past decade. Notably, there are limited studies regarding the negative effects of e-cigarettes on the cardiovascular system, which is also the subject of significant debate.
View Article and Find Full Text PDF, the aetiologic agent of Chagas disease, releases vesicles containing a wide range of surface molecules known to affect the host immunological responses and the cellular infectivity. Here, we compared the secretome of two distinct strains (Y and YuYu) of , which were previously shown to differentially modulate host innate and acquired immune responses. Tissue culture-derived trypomastigotes of both strains secreted extracellular vesicles (EVs), as demonstrated by electron scanning microscopy.
View Article and Find Full Text PDFA 34-amino acid long collagen-like peptide rich in proline, hydroxyproline, and glycine, and with four photoreactive N-acyl-7-nitroindoline units incorporated into the peptide backbone was synthesized by on-resin fragment condensation. Its circular dichroism supports a stable triple helix structure. The built-in photochemical function enables the decomposition of the peptide into small peptide fragments by illumination with UV light of 350 nm in aqueous solution.
View Article and Find Full Text PDF