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781.
Ian M. Carroll Tamar Ringel-Kulka Laurent Ferrier Michael C. Wu Jennica P. Siddle Lionel Bueno Yehuda Ringel 《PloS one》2013,8(10)
Objective
Intestinal proteases carry out a variety of functions in the gastrointestinal (GI) tract. Studies have reported that elevated enteric proteases in patients with GI disease can alter intestinal physiology, however the origin (human vs. microbial) of elevated proteases in patients with GI disease is unclear.Aim
The aim of this study was to investigate the association between protease activity and the microbiota in human fecal samples.Design
In order to capture a wide range of fecal protease (FP) activity stool samples were collected from 30 IBS patients and 24 healthy controls. The intestinal microbiota was characterized using 454 high throughput pyro-sequencing of the 16S rRNA gene. The composition and diversity of microbial communities were determined and compared using the Quantitative Insights Into Microbial Ecology (QIIME) pipeline. FP activity levels were determined using an ELISA-based method. FP activity was ranked and top and bottom quartiles (n=13 per quartile) were identified as having high and low FP activity, respectively.Results
The overall diversity of the intestinal microbiota displayed significant clustering separation (p = 0.001) between samples with high vs. low FP activity. The Lactobacillales, Lachnospiraceae, and Streptococcaceae groups were positively associated with FP activity across the entire study population, whilst the Ruminococcaceae family and an unclassified Coriobacteriales family were negatively associated with FP activity.Conclusions
These data demonstrate significant associations between specific intestinal bacterial groups and fecal protease activity and provide a basis for further causative studies investigating the role of enteric microbes and GI diseases. 相似文献782.
Patrick J. Cummings Ray Ahmed Jeffrey A. Durocher Adam Jessen Tamar Vardi Kristina M. Obom 《Journal of visualized experiments : JoVE》2013,(78)
Pyrosequencing is a versatile technique that facilitates microbial genome sequencing that can be used to identify bacterial species, discriminate bacterial strains and detect genetic mutations that confer resistance to anti-microbial agents. The advantages of pyrosequencing for microbiology applications include rapid and reliable high-throughput screening and accurate identification of microbes and microbial genome mutations. Pyrosequencing involves sequencing of DNA by synthesizing the complementary strand a single base at a time, while determining the specific nucleotide being incorporated during the synthesis reaction. The reaction occurs on immobilized single stranded template DNA where the four deoxyribonucleotides (dNTP) are added sequentially and the unincorporated dNTPs are enzymatically degraded before addition of the next dNTP to the synthesis reaction. Detection of the specific base incorporated into the template is monitored by generation of chemiluminescent signals. The order of dNTPs that produce the chemiluminescent signals determines the DNA sequence of the template. The real-time sequencing capability of pyrosequencing technology enables rapid microbial identification in a single assay. In addition, the pyrosequencing instrument, can analyze the full genetic diversity of anti-microbial drug resistance, including typing of SNPs, point mutations, insertions, and deletions, as well as quantification of multiple gene copies that may occur in some anti-microbial resistance patterns. 相似文献
783.
784.
785.
Type 1 Usher syndrome (USH1) is a recessively inherited condition, characterized by profound prelingual deafness, vestibular
areflexia, and prepubertal onset of retinitis pigmentosa (RP). While the auditory component of USH1 can be treated by cochlear
implants, to date there is no effective treatment for RP. USH1 can be caused by mutations in each of at least six genes. While
truncating mutations of these genes cause USH1, some missense mutations of the same genes cause nonsyndromic deafness. These
observations suggest that partial or low level activity of the encoded proteins may be sufficient for normal retinal function,
although not for normal hearing. In individuals with USH1 due to nonsense mutations, interventions enabling partial translation
of a full-length functional protein may delay the onset and/or progression of RP. One such possible therapeutic approach is
suppression of nonsense mutations by small molecules such as aminoglycosides. We decided to test this approach as a potential
therapy for RP in USH1 patients due to nonsense mutations. We initially focused on nonsense mutations of the PCDH15 gene, underlying USH1F. Here, we show suppression of several PCDH15 nonsense mutations, both in vitro and ex vivo. Suppression was achieved both by commercial aminoglycosides and by NB30, a
new aminoglycoside-derivative developed by us. NB30 has reduced cytotoxicity in comparison to commercial aminoglycosides,
and thus may be more efficiently used for therapeutic purposes. The research described here has important implications for
the development of targeted interventions that are effective for patients with USH1 caused by various nonsense mutations.
Annie Rebibo-Sabbah and Igor Nudelman contributed equally to this work. 相似文献
786.
With the rapid rate of COVID-19 infections and deaths, treatments and cures besides hand washing, social distancing, masks, isolation, and quarantines are urgently needed. The treatments and vaccines rely on the basic biophysics of the complex viral apparatus. Although proteins are serving as main drug and vaccine targets, therapeutic approaches targeting the 30,000 nucleotide RNA viral genome form important complementary approaches. Indeed, the high conservation of the viral genome, its close evolutionary relationship to other viruses, and the rise of gene editing and RNA-based vaccines all argue for a focus on the RNA agent itself. One of the key steps in the viral replication cycle inside host cells is the ribosomal frameshifting required for translation of overlapping open reading frames. The RNA frameshifting element (FSE), one of three highly conserved regions of coronaviruses, is believed to include a pseudoknot considered essential for this ribosomal switching. In this work, we apply our graph-theory-based framework for representing RNA secondary structures, “RAG (or RNA-As-Graphs),” to alter key structural features of the FSE of the SARS-CoV-2 virus. Specifically, using RAG machinery of genetic algorithms for inverse folding adapted for RNA structures with pseudoknots, we computationally predict minimal mutations that destroy a structurally important stem and/or the pseudoknot of the FSE, potentially dismantling the virus against translation of the polyproteins. Our microsecond molecular dynamics simulations of mutant structures indicate relatively stable secondary structures. These findings not only advance our computational design of RNAs containing pseudoknots, they pinpoint key residues of the SARS-CoV-2 virus as targets for antiviral drugs and gene editing approaches. 相似文献
787.
Merav Vonshak Tamar Dayan Armin Ionescu-Hirsh Amnon Freidberg Abraham Hefetz 《Biological invasions》2010,12(6):1825-1837
The little fire ant, Wasmannia auropunctata, probably arrived in Israel in ca. 1998 and was identified in 2005; this is the first record of this species from open areas outside the tropics and subtropics. It survives harsher conditions than in its native habitats, with minimal annual temperatures as low as 6°C, and 5–12 consecutive rainless months (under 15 mm rainfall per month). It is now known from 26 localities in Israel, mostly in irrigated gardens. As in other regions where they have invaded, these ants pose a serious threat to local biodiversity. At high densities they displaced almost all the local ant species sampled, affecting population abundances, species richness, and community structure. W. auropunctata seems to have a detrimental effect also on other ground arthropods, judging from the observed decline in spider and beetle abundances. We show here that this tropical species can pose a critical threat to local arthropods at a wider range of climatic conditions than was previously known. 相似文献
788.
Klipper E Levy N Gilboa T Muller L Meidan R 《Experimental biology and medicine (Maywood, N.J.)》2006,231(6):723-728
Endothelin-converting enzyme (ECE)-1 cleaves big endothelins, as well as bradykinin and beta-amyloid peptide. Several isoforms of ECE-1 (ECE-1a, 1b, 1c, and 1d) have been identified to date, they differ only in their amino terminus and share the catalytic domain located in the C-terminal end. In addition to full-length ECE-1 forms, we identified novel, alternatively spliced messenger RNAs (mRNAs) of ECE-1b, 1c, and 1d. These splice variants (SVs) lack exon 3', which codes for the transmembrane (TM) region and is present in full-length forms. SV mRNAs were highly expressed in endothelial cells (EC) derived from macrovascular and microvascular beds. Analyses of ECE-1d and its SV forms in stably transfected human embryonic kidney (HEK)-293 cells revealed that both proteins were recognized by antibodies to C-terminal ECE-1, but an antibody to the N-terminal only bound ECE-1d. The novel protein, designated ECE-1sv, has an apparent molecular weight of 75 kDa. ECE-1sv lacks the TM sequence (or signal peptide) and, therefore, is expected to remain cytosolic. Presence of ECE-1sv in different cellular compartments than the full-length forms of the ECE-1 may suggest a distinct physiologic role for these proteins. 相似文献
789.
Chappell S Daly L Morgan K Baranes TG Roca J Rabinovich R Millar A Donnelly SC Keatings V MacNee W Stolk J Hiemstra PS Miniati M Monti S O'Connor CM Kalsheker N 《American journal of human genetics》2006,79(1):184-6; author reply 186-7
790.
Increased CUG triplet repeat-binding protein-1 predisposes to impaired adipogenesis with aging 总被引:2,自引:0,他引:2