The anaerobic spirochete causes intestinal spirochetosis, characterized by the intimate attachment of bacterial cells to the colonic mucosa, potentially leading to symptoms such as diarrhea, abdominal pain, and weight loss. Despite the clinical significance of infections, the mechanism of the interaction between and the colon epithelium is not known. We characterized the molecular mechanism of the -epithelium interaction and its impact on the epithelial barrier during infection.
View Article and Find Full Text PDFNo study has evaluated the effects of dry needling on Paralympic athletes. Therefore, in this study, we will evaluate the effect of dry needling on lower limb spasticity and motor performance, as well as the range of motion of Paralympic athletes. The study will be a triple-blinded, randomised controlled trial.
View Article and Find Full Text PDFThe MUC2 mucin polymer is the main building unit of the intestinal mucus layers separating intestinal microbiota from the host epithelium. The MUC2 mucin is a large glycoprotein with a C-terminal domain similar to the MUC5AC and MUC5B mucins and the von Willebrand factor (VWF). A structural model of the C-terminal part of MUC2, MUC2-C, was generated by combining Cryo-electron microscopy, AlphaFold prediction, information of its glycosylation, and small angle X-ray scattering information.
View Article and Find Full Text PDFBackground: Stroke is the leading cause of disability in adults worldwide, with spasticity after stroke being one of the more common complications. Dry needling (DN) has been demonstrated to decrease spasticity in stroke patients, although its effects on improving function remain unclear. The purpose of this study protocol is to compare the short-term effects of DN versus acupoint DN on wrist flexor spasticity and upper extremity function in patients with stroke.
View Article and Find Full Text PDFASNA1 plays an essential role in cisplatin chemotherapy response, type 2 diabetes, and heart disease. It is also an important biomarker in the treatment response of many diseases. Biochemically, ASNA1 has two mutually exclusive redox-modulated roles: a tail-anchored protein (TAP) targeting function in the reduced state and a holdase/chaperone function in the oxidized state.
View Article and Find Full Text PDFMucus forms an important protective barrier that minimizes bacterial contact with the colonic epithelium. Intestinal mucus is organized in a complex network with several specific proteins, including the mucin-2 (MUC2) and the abundant IgGFc-binding protein, FCGBP. FCGBP is expressed in all intestinal goblet cells and is secreted into the mucus.
View Article and Find Full Text PDFAntioxidants (Basel)
November 2019
In this study, six different sofrito formulations were compared with the raw recipe for total phenolic content (TPC), antioxidant activity tested by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric-reducing antioxidant power (FRAP) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) methods. The volatile profile was also obtained by the headspace solid-phase microextraction-gas chromatography mass spectrometry (HS-SPME-GC-MS) procedure. The cooking process and the addition of herbs, and garlic improved the final content of antioxidant compounds compared to the basic recipe and the raw ingredients.
View Article and Find Full Text PDFMetallocarboxypeptidases (MCPs) of the M14 family are Zn-dependent exoproteases present in almost every tissue or fluid in mammals. These enzymes perform a large variety of physiological functions and are involved in several pathologies, such as pancreatic diseases, inflammation, fibrinolysis, and cancer. Here, we describe the synthesis and functional/structural characterization of a series of reversible tight-binding phosphinic pseudopeptide inhibitors that show high specificity and potency toward these proteases.
View Article and Find Full Text PDFMetallocarboxypeptidases (MCPs) are involved in many biological processes such as fibrinolysis or inflammation, development, Alzheimer's disease, and various types of cancer. We describe the synthesis and kinetic characterization of a focused library of 22 thiirane- and oxirane-based potential mechanism-based inhibitors, which led to discovery of an inhibitor for the human pro-carboxypeptidase A1. Our structural analyses show that the thiirane-based small-molecule inhibitor penetrates the barrier of the pro-domain to bind within the active site.
View Article and Find Full Text PDFTransthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses.
View Article and Find Full Text PDFMitotic spindle assembly requires the regulated activities of protein kinases such as Nek7 and Nek9. Nek7 is autoinhibited by the protrusion of Tyr97 into the active site and activated by the Nek9 non-catalytic C-terminal domain (CTD). CTD binding apparently releases autoinhibition because mutation of Tyr97 to phenylalanine increases Nek7 activity independently of Nek9.
View Article and Find Full Text PDFThe NIMA family protein kinases Nek9/Nercc1, Nek6, and Nek7 constitute a signaling module activated in early mitosis involved in the control of spindle organization. DYNLL/LC8 (dynein light chain 8) was originally described as a component of the dynein complex, but the recent discovery of multiple interaction partners for LC8 has suggested that it has a general role as a dimerization hub that organizes different protein partners. Recent experiments suggested that LC8 binding to Nek9 was regulated by Nek9 autophosphorylation on Ser(944), a residue immediately located N-terminal to the LC8 conserved (K/R)xTQT binding motif, and that this was crucial for the control of signal transduction through the Nek/Nek6/7 module.
View Article and Find Full Text PDFThe metabolism of arginine towards ATP synthesis has been considered a major source of energy for microorganisms such as Mycoplasma penetrans in anaerobic conditions. Additionally, this pathway has also been implicated in pathogenic and virulence mechanism of certain microorganisms, i.e.
View Article and Find Full Text PDF