Pathogenicity Island 1 (SPI1) encodes a type three secretion system (T3SS) essential for invasion of intestinal epithelial cells. Many environmental and regulatory signals control SPI1 gene expression, but in most cases, the molecular mechanisms remain unclear. Many of these regulatory signals control SPI1 at a post-transcriptional level and we have identified a number of small RNAs (sRNAs) that control the SPI1 regulatory circuit.
View Article and Find Full Text PDFThe introduction of early diagnostic methods for keratoconus into clinical practice has become the basis for the development of surgical treatment techniques for this pathology, such as corneal collagen crosslinking and interlamellar keratoplasty with implantation of intrastromal segments. The article analyzes the results of research by Russian and foreign specialists in these areas and presents the data on the combination of SMILE surgery and corneal crosslinking, the Rome protocol of corneal crosslinking, modifications of interlamellar keratoplasty, the use of femtosecond laser technologies, and some pilot studies. Modern requirements for ophthalmological care require a personalized approach to each patient, and therefore the surgeon should have a wide range of surgical methods of treatment applicable to different patient cohorts.
View Article and Find Full Text PDFThe impact of isomerism of pyrimidine-based ligands and their rhodium(III) complexes with regard to their structures and properties was investigated. Two isomeric ligands, 4-(3,5-dimethyl-1-pyrazol-1-yl)-2,5-diphenylpyrimidine (HL2,5) and 4-(3,5-dimethyl-1-pyrazol-1-yl)-2,6-diphenylpyrimidine (HL2,6), were synthesized. The ligands differ by the degree of steric bulk: the molecular structure of HL2,5 is more distorted due to presence of pyrazolyl and phenyl groups in the neighbouring positions 4 and 5 of the pyrimidine ring.
View Article and Find Full Text PDFBy reacting a series of 2,6-diacetylpyridine bis-hydrazones containing pyrimidine (H2L1), benzimidazole (H2L2) and phthalazine (H2L3) heterocyclic fragments with copper(II) chloride and bromide, a variety of pentacoordinated complexes of the composition , and , where X = Cl, Br, are formed. The properties and structure of the compounds were studied by means of NMR, IR, UV-vis, ESR, and X-ray absorption spectroscopy, cyclic voltammetry and X-Ray single crystal diffraction methods. It was shown that complexes of the cationic type have an asymmetric structure with a distorted square-pyramidal geometry of the coordination unit.
View Article and Find Full Text PDFsurvive and replicate in macrophages, which normally kill bacteria by exposing them to a variety of harsh conditions and antimicrobial effectors, many of which target the bacterial cell envelope. The PhoPQ two-component system responds to the phagosome environment and induces factors that protect the outer membrane, allowing adaptation and growth in the macrophage. We show that PhoPQ induces the transcription of the operon both and in macrophages.
View Article and Find Full Text PDFUnlabelled: FGFR3 and PIK3CA are among the most frequently mutated genes in bladder tumors. We hypothesized that recurrent mutations in these genes might be caused by common carcinogenic exposures such as smoking and other factors. We analyzed 2,816 bladder tumors with available data on FGFR3 and/or PIK3CA mutations, focusing on the most recurrent mutations detected in ≥10% of tumors.
View Article and Find Full Text PDFA small percentage of bladder cancers in the general population have been found to harbor DNA viruses. In contrast, up to 25% of tumors of solid organ transplant recipients, who are at an increased risk of developing bladder cancer and have an overall poorer outcomes, harbor BK polyomavirus (BKPyV). To better understand the biology of the tumors and the mechanisms of carcinogenesis from potential oncoviruses, we performed whole genome and transcriptome sequencing on bladder cancer specimens from 43 transplant patients.
View Article and Find Full Text PDFIn this study, the mechanochemical synthesis of substituted hydroxyapatite (HA) containing zinc and silicon ions having a chemical formula of CaZn(PO)(SiO)(OH), where x = 0.2, 0.6, 1.
View Article and Find Full Text PDFPolyamines are organic cations that are important in all domains of life. Here, we show that in Salmonella, polyamine levels and Mg levels are coordinately regulated and that this regulation is critical for viability under both low and high concentrations of polyamines. Upon Mg starvation, polyamine synthesis is induced, as is the production of the high-affinity Mg transporters MgtA and MgtB.
View Article and Find Full Text PDFSalmonella enterica serovar Typhimurium invades the intestinal epithelium and induces inflammatory diarrhea using the Salmonella pathogenicity island 1 (SPI1) type III secretion system (T3SS). Expression of the SPI1 T3SS is controlled by three AraC-like regulators, HilD, HilC, and RtsA, which form a feed-forward regulatory loop that leads to activation of , encoding the main transcriptional regulator of the T3SS structural genes. This complex system is affected by numerous regulatory proteins and environmental signals, many of which act at the level of mRNA translation or HilD protein function.
View Article and Find Full Text PDFThe tumor microenvironment (TME), including immune cells, cancer-associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high-grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial-to-mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry.
View Article and Find Full Text PDFAccording to the World Health Organization, human life expectancy has increased significantly around the world over the past century, but this process is inevitably accompanied by aging. Therefore, persons who have reached the elderly and senile age often become infirm, especially physically. As a result, such people find it increasingly difficult to make movements related to self-service and movement when using standard clothing and shoes.
View Article and Find Full Text PDFZh Nevrol Psikhiatr Im S S Korsakova
November 2020
Objective: To study the features of the rehabilitation of patients with foot drop syndrome and to develop recommendations for the appointment of technical means of rehabilitation (TMR) for this pathology.
Material And Methods: Retrospective analysis of the survey data of 375 patients in need of lower limb orthosis was carried out. General clinical and biomechanical methods were used to study the disturbances of statodynamic function of the musculoskeletal system.
The evolutionary progression from primary to metastatic prostate cancer is largely uncharted, and the implications for liquid biopsy are unexplored. We infer detailed reconstructions of tumor phylogenies in ten prostate cancer patients with fatal disease, and investigate them in conjunction with histopathology and tumor DNA extracted from blood and cerebrospinal fluid. Substantial evolution occurs within the prostate, resulting in branching into multiple spatially intermixed lineages.
View Article and Find Full Text PDFHuman gammaherpesviruses are associated with malignancies in HIV infected individuals; in macaques used in non-human primate models of HIV infection, gammaherpesvirus infections also occur. Limited data on prevalence and tumorigenicity of macaque gammaherpesviruses, mostly cross-sectional analyses of small series, are available. We comprehensively examine all three-rhesus macaque gammaherpesviruses -Rhesus rhadinovirus (RRV), Rhesus Lymphocryptovirus (RLCV) and Retroperitoneal Fibromatosis Herpesvirus (RFHV) in macaques experimentally infected with Simian Immunodeficiency Virus or Simian Human Immunodeficiency Virus (SIV/SHIV) in studies spanning 15 years at the AIDS and Cancer Virus Program of the Frederick National Laboratory for Cancer Research.
View Article and Find Full Text PDFThe mouse model characterized by spontaneous lung metastasis from JygMC (A) cells closely resembles the human triple negative breast cancer (TNBC) subtype. The primary tumors morphologically present both epithelial and spindle-like cells, but metastases in lung parenchyma display only adenocarcinoma properties. In the study of molecular signatures, laser capture microdissection (LCM) on frozen tissue sections was used to separate the following regions of interest: the epithelial-mesenchymal transition (EMT), mesenchymal-epithelial transition (MET), carcinoma, lung metastases, normal mammary gland and normal lung parenchyma.
View Article and Find Full Text PDFLaser Capture Microdissection has earned a permanent place among modern techniques connecting histology and molecular biology. Laser Capture Microdissection has become an invaluable tool in medical research as a means for collection of specific cell populations isolated from their environment. Such genomic sample enrichment dramatically increases the sensitivity and precision of downstream molecular assays used for biomarker discovery, monitoring disease onset and progression, and in the development of personalized medicine.
View Article and Find Full Text PDFBiomarker discovery is a crucial part of the fast developing field of personalized medicine. Antibody-based techniques including immunostaining of tissue samples are widely used for biomarker evaluation in preclinical and clinical studies. When used in conjunction with robust image analysis methods, it provides a powerful means to assess biomarker modulation, toxicity, and patient response to targeted agents.
View Article and Find Full Text PDFLaser capture microdissection (LCM) of tissue is an established tool in medical research for collection of distinguished cell populations under direct microscopic visualization for molecular analysis. LCM samples have been successfully analyzed in a number of genomic and proteomic downstream molecular applications. However, LCM sample collection and preparation procedure has to be adapted to each downstream analysis platform.
View Article and Find Full Text PDFMethods Mol Biol
July 2014
The need for large-scale collection of rodent embryos and individual embryonic tissues for genomic and proteomic studies requires modification of traditional practices of embryo necropsy. The sample intended for transcriptome study should be rapidly dissected and stabilized to preserve its molecular integrity. The retrieval of high-quality RNA, DNA, and proteins from the target tissue is crucial for informative molecular analysis (e.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
August 2013
Increased serum levels of IL-15 are reported in type 1 diabetes (T1D). Here we report elevated serum soluble IL-15Rα levels in human T1D. To investigate the role of IL-15/IL-15Rα in the pathogenesis of T1D, we generated double transgenic mice with pancreatic β-cell expression of IL-15 and IL-15Rα.
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