Prokaryotic clustered regularly interspaced short palindromic repeat (CRISPR)/Cas (CRISPR-associated sequences) systems provide adaptive immunity against viruses when a spacer sequence of small CRISPR RNA (crRNA) matches a protospacer sequence in the viral genome. Viruses that escape CRISPR/Cas resistance carry point mutations in protospacers, though not all protospacer mutations lead to escape. Here, we show that in the case of Escherichia coli subtype CRISPR/Cas system, the requirements for crRNA matching are strict only for a seven-nucleotide seed region of a protospacer immediately following the essential protospacer-adjacent motif.
View Article and Find Full Text PDFTo date, the mechanisms responsible for radical change of chromatin structure in male germ cells during fertilization are unclear. Evidence suggesting the existence of proteolytic nuclear enzymes in mature human spermatozoids are presented in this work. The possible role of these previously unknown proteases in decondensation of chromatin of spermatozoids in a fertilized ovum is discussed.
View Article and Find Full Text PDFCapistruin, a ribosomally synthesized, post-translationally modified peptide produced by Burkholderia thailandensis E264, efficiently inhibits growth of Burkholderia and closely related Pseudomonas strains. The functional target of capistruin is not known. Capistruin is a threaded-lasso peptide (lariat peptide) consisting of an N-terminal ring of nine amino acids and a C-terminal tail of 10 amino acids threaded through the ring.
View Article and Find Full Text PDFOxidative (respiratory) burst is an important manifestation of inflammation. Precise quantitative assessment of this reaction by flow cytometry made it possible to record and evaluate the severity of the inflammatory processes in a wide spectrum of diseases including diphtheria, hepatitis, pneumonia, bronchial asthma, arthritis, vasculitis, postoperative complications, tuberculosis, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and myocardial infarction. This approach can be employed as a highly sensitive method of detection of inflammatory reactions and monitoring of their course in various pathological processes.
View Article and Find Full Text PDFBackground: Diurnal behavior in humans is governed by the period length of a circadian clock in the suprachiasmatic nuclei of the brain hypothalamus. Nevertheless, the cell-intrinsic mechanism of this clock is present in most cells of the body. We have shown previously that for individuals of extreme chronotype ("larks" and "owls"), clock properties measured in human fibroblasts correlated with extreme diurnal behavior.
View Article and Find Full Text PDFNetherton syndrome (NS) is a debilitating congenital skin disorder caused by mutations in the SPINK5 gene encoding the lymphoepithelial Kazal-type-related inhibitor (LEKTI). It is characterized by defective keratinization, recurrent infections, and hypernatraemic dehydration with a mortality rate of about 10% in the first year of life. Currently, there are no curative treatments for NS.
View Article and Find Full Text PDFThe heptapeptide-nucleotide microcin C (McC) is a potent inhibitor of enteric bacteria growth. Inside a sensitive cell, McC is processed by aminopeptidases, which release a nonhydrolyzable aspartyl-adenylate, a strong inhibitor of aspartyl-tRNA synthetase. The mccABCDE operon is sufficient for McC production and resistance of the producing cell to McC.
View Article and Find Full Text PDFCRISPR/Cas, bacterial and archaeal systems of interference with foreign genetic elements such as viruses or plasmids, consist of DNA loci called CRISPR cassettes (a set of variable spacers regularly separated by palindromic repeats) and associated cas genes. When a CRISPR spacer sequence exactly matches a sequence in a viral genome, the cell can become resistant to the virus. The CRISPR/Cas systems function through small RNAs originating from longer CRISPR cassette transcripts.
View Article and Find Full Text PDFCardiomyopathy and neuropathy are the two commonly observed complications in diphtheria patients and in, some instances, individuals vaccinated against diphtheria. The nature of these complications remains not well understood. It was suggested that autoimmunity may play a role in the development of these afflictions.
View Article and Find Full Text PDFOphthalmic Surg Lasers Imaging
March 2010
Fundus autofluorescence imaging (FAF) in a case of diffuse uveal melanocytic proliferation is described in this study. It is a rare chorioretinopathy associated with systemic cancer, for which the exact pathological mechanisms are poorly understood. FAF-imaging revealed a diffuse background of hyper-autofluorescence associated with diffuse orange pigment deposition and islands of persistent hypo-fluorescence corresponding to loss of retinal pigment epithelium (RPE).
View Article and Find Full Text PDFThe heptapeptide-nucleotide microcin C (McC) is a potent inhibitor of enteric bacteria growth. McC is excreted from producing cells by the MccC transporter. The residual McC that remains in the producing cell can be processed by cellular aminopeptidases with the release of a non-hydrolyzable aspartyl-adenylate, a strong inhibitor of aspartyl-tRNA synthetase.
View Article and Find Full Text PDFThirty-eight patients (16 males and 22 females) with recurrent and residual choroidal melanomas who had undergone brachytherapy were followed up. The indication for transpupillary thermotherapy (TTT) was an active residual tumor (36 patients) and recurrent melanoma (2 patients). The follow-up interval between brachytherapy and TTT was 10 to 127 months.
View Article and Find Full Text PDFAim: To define an association of bone marrow microvessel density (MVD) with histological properties (the magnitude of fibrosis and quantification of megakaryocytes (MGKC)) in patients with Ph-negative chronic myeloproliferative diseases (CMPD).
Subjects And Methods: MVD was analyzed in 93 patients with different forms of CMPD, by estimating histological parameters. True polycythemia (TP) was present in 28 patients; 20 patients had essential thrombocythemia (ET), 36 had subleukemic myelosis, out them 6 were in a prefibrotic stage, and 9 with diagnosed post-TP (ET) myelofibrosis.
The article demonstrates objective difficulties and subjective mistakes in assessment of a clinical picture in a patient with subleukemic myelosis and thrombosis of the portal system. A careful examination of such patients is necessary to reveal latent disorders (in this case--a complete selective IgA deficiency) influencing treatment policy.
View Article and Find Full Text PDFAim: To analyse clinical implications of chromosome 8 trisomy in Ph-negative cells of the bone marrow in patients with chronic myeloid leukemia (CML) treated with inhibitors of tyrosinkinases (ITK).
Material And Methods: A total of 386 patients with CML (chronic phase--288, acceleration phase--77) received imatinib (400-800 mg/day). Because of resistance and/or intolerance some patients were switched to ITK II (nilotinib, dasatinib, bozutinib).
Microcin C (McC) is a potent antibacterial agent produced by some strains of Escherichia coli. McC consists of a ribosomally synthesized heptapeptide with a modified AMP attached through a phosphoramidate linkage to the alpha-carboxyl group of the terminal aspartate. McC is a Trojan horse inhibitor: it is actively taken inside sensitive cells and processed there, and the product of processing, a nonhydrolyzable aspartyl-adenylate, inhibits translation by preventing aminoacylation of tRNA(Asp) by aspartyl-tRNA synthetase (AspRS).
View Article and Find Full Text PDFPurpose: To determine the reliability and role of conjunctival exfoliative cytologic and histopathologic diagnosis of biopsied tissue in ocular surface squamous neoplasia.
Design: Retrospective review of an interventional case series of patients biopsied and treated for squamous conjunctival and corneal neoplasia.
Methods: Forty-nine patients who underwent conjunctival cytologic analysis (n = 36), conjunctival biopsy (n = 35), or both were evaluated.
Fifty-two patients that had ParkinsonTs disease with autosomal dominant type of inheritance were analyzed for the presence of duplications and triplications in exons 4--6 of alpha-synuclein gene using real-time PCR with Taq-Man probes. No mutations involving the examined exons dosage were revealed in alpha-synuclein gene. Thus, mutations modifying copy number of alpha-synuclein gene do not significantly affect the pathogenesis of the autosomal dominant form of ParkinsonTs disease in patients from Russia.
View Article and Find Full Text PDFClustered regularly interspaced short palindromic repeat (CRISPR) is a bacterial immunity system that requires a perfect sequence match between the CRISPR cassette spacer and a protospacer in invading DNA for exclusion of foreign genetic elements. CRISPR cassettes are hypervariable, possibly reflecting different exposure of strains of the same species to foreign genetic elements. Here, we determined CRISPR cassette sequences of two Xanthomonas oryzae strains and found that one of the strains remains sensitive to phage Xop411 despite carrying a cassette that has a spacer exactly matching a fragment of the Xop411 genome.
View Article and Find Full Text PDFUsing far-field optical lithography, a single quantum dot is positioned within a pillar microcavity with a 50 nm accuracy. The lithography is performed in situ at 10 K while measuring the quantum dot emission. Deterministic spectral and spatial matching of the cavity-dot system is achieved in a single step process and evidenced by the observation of strong Purcell effect.
View Article and Find Full Text PDFBiochemistry (Mosc)
February 2009
The interaction of human cytoplasmic phenylalanyl-tRNA synthetase (an enzyme with yet unknown 3D-structure) with homologous tRNA(Phe) under functional conditions was studied by footprinting based on iodine cleavage of thiophosphate-substituted tRNA transcripts. Most tRNA(Phe) nucleotides recognized by the enzyme in the anticodon (G34), anticodon stem (G30-C40, A31-U39), and D-loop (G20) have effectively or moderately protected phosphates. Other important specificity elements (A35 and A36) were found to form weak nonspecific contacts.
View Article and Find Full Text PDFWe present an ultrahigh resolution Raman study of the lifetime of 1 THz acoustic phonons confined in nanocavities. We demonstrate that the cavity Q factor can be controlled by design. Anharmonicity contributes only marginally to limit the cavity phonon lifetime, even at room temperature, while thickness fluctuations in the scale of 1/10 of a unit cell are the main limitation for the performance of THz phonon cavities.
View Article and Find Full Text PDFMicrocin C (McC), an inhibitor of the growth of enteric bacteria, consists of a heptapeptide with a modified AMP residue attached to the backbone of the C-terminal aspartate through an N-acyl phosphamidate bond. Here we identify maturation intermediates produced by cells lacking individual mcc McC biosynthesis genes. We show that the products of the mccD and mccE genes are required for attachment of a 3-aminopropyl group to the phosphate of McC and that this group increases the potency of inhibition of the McC target, aspartyl-tRNA synthetase.
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