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The role of prokaryotic CRISPR/Cas system proteins as a defensive shield against invasive nucleic acids has been studied extensively. Non-canonical roles in pathogenesis involving intracellular targeting of certain virulence-associated endogenous mRNA have also been reported for some Type I and Type II CRISPR/Cas proteins, but no such roles have yet been established for Type III system proteins. Here, we demonstrate that M. tuberculosis (Type III-A system) CRISPR/Cas proteins Csm1, Csm3, Csm5, Csm6, and Cas6 are secreted and induce host immune responses. Using cell and animal experiments, we show that Cas6, in particular, provokes IFN-γ release from PBMCs from active tuberculosis (TB) patients, and its deletion markedly attenuates virulence in a murine M. tuberculosis challenge model. Recombinant MTBCas6 induces apoptosis of macrophages and lung fibroblasts, and interacts with the surface of cells in a caspase and TLR-2 independent manner. Transcriptomic and signal pathway studies using THP-1 macrophages stimulated with MTBCas6 indicated that MTBCas6 upregulates expression of genes associated with the NF-κB pathway leading to higher levels of IL-6, IL-1β, and TNF-α release, cytokines known to activate immune system cells in response to M. tuberculosis infection. Our findings suggest that, in addition to their intracellular shielding role, M. tuberculosis CRISPR/Cas proteins have non-canonical extracellular roles, functioning like a virulent sword, and activating host immune responses.

Objective to develop specific genes associated with the formation of these severe tuberculosis lesions by comparing gene expression changes of macrophages between the lesions and normal lung tissue around it Material and methods select lesions tissue and surrounding normal lung tissue specimens from three tuberculosis patients, magnetic bead separation method was applied to filter out the macrophages within the organization, extracted RNA and detected with gene chip to contrast the difference of gene expression patterns. between the lesions and surrounding normal lung tissue Results there were 332 genes up regulation and 102 genes down regulation to 2 fold in normal lung tissues. making the selecting criteria rising to 4 fold, the number of up regulation and down regulation genes would decrease to 19 and 2. The two down regulation genes were FER1L4 and PPIL5. During the up regulation group. the AREG gene was very special because the up regulation fold of this gene in our three groups were more than 11 times respectively. Moreover, the expression level of four genes which were related with TNF were obviously up regulationd in normal lung tissues Conclusion PPIL5, AREG and TNF may be associated with the formation of pulmonary tuberculosis lesions.

Daugiavožtuvio įsiurbimo kanalo technologija dabar yra placiai taikoma, taciau sudėtinga įsiurbimo kanalo geometrija apsunkina trimatį tiesioginį modeliavimą. Programos UG ir „Matlab“ buvo isrinktos kaip projektavimo platforma analizuojant tangentine kanalo orientavimo sekcijos konstrukciją ir spiralinio tekėjimo segmento charakteristikas. Rysio lygtys, sudarytos taikant analizinės geometrijos metodą, panaudotos tekėjimo charakteristikoms įsiurbimo kanale ir cilindre tirti. CFD imitavimo rezultatai parodė, kad, modifikuojant eksploatacinius parametrus, tokius kaip perėjimo kampą α , spiralės polinkio kampą β ir dugno polinkį ξ, fizinis modelis su akivaizdžiais charakteristikų skirtumais gali būti sukurtas ir, maksimaliai patobulinus vožtuvą, tekėjimo koeficientas keistųsi nuo 0,563 iki 0,736. Maksimali paklaida tarp apskaiciuoto ir eksperimentinio dydžio yra mažesnė, nei 6%. Sis pažangus projektavimo metodas, naudojantis matematinius modelius, pritaikytas daugiavožtuviam įsiurbimo kanalui, padės sudaryti sudėtingos konstrukcijos CAD modelį ir leis optimizuoti charakteristikas. http://dx.doi.org/10.5755/j01.mech.17.6.1008

Infection with non-tuberculous mycobacteria (NTM) is relatively rare in areas that are high-endemic for tuberculosis. We identified 126 strains of NTM in respiratory specimens collected by the Chinese Nationwide Survey in 2000, the Beijing Tuberculosis and Thoracic Tumour Institution, and the Guangzhou Thoracic Hospital. Species diagnosis was attained by sequencing of 16S-rDNA complemented by phenotypic characterization when necessary. Mycobacterium avium-intracellulare-complex - well known as a potential pulmonary pathogen - was diagnosed in all 3 surveys. Potentially pathogenic rapid growing strains of M. abscessus, M. chelonae and M. fortuitum were also detected. Moreover, species non-pathogenic in the airways such as M. nonchromogenicum, M. terrae and M. gordonae were encountered. Also, single strains of rare NTM species were isolated. Thus, several potentially pathogenic species of NTM were isolated from pulmonary specimens in China, and molecular techniques made possible exact species diagnosis.

The wound-inducible expression of proteinase inhibitors (PIs) genes in tomato provides a powerful model system to elucidate the signal transduction pathway of systemic defense response. An increasing body of evidence indicates that systemin and jasmonic acid (JA)_work in the same signaling pathway to activate the expression of PIs and other defense-related genes. However, little is known about how systemin and JA interact to regulate cell to cell communication over long distances. Genetic analysis of the systemin/JA signaling pathway in tomato plants provides a unique opportunity to dissect the mechanism by which peptide and oxylipin signals interact to coordinate systemic expression of defense-related genes. Previously, it has been proposed that systemin is the long-distance mobile signal for systemic expression of defense related genes. However, recent genetic approach provided new evidence that jasmonic acid, rather than systemin, functions as the systemic wound signal, and that the peptide systemin works to regulate the biosynthesis of JA.