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51.
Sambasivan Venkatasubramanian Rohan Dhiman Padmaja Paidipally Satyanarayana S. Cheekatla Deepak Tripathi Elwyn Welch Amy R. Tvinnereim Brenda Jones Dan Theodorescu Peter F. Barnes Ramakrishna Vankayalapati 《PLoS pathogens》2015,11(2)
In this study, we found that a subpopulation of CD4+CD25+ (85% Foxp3+) cells from persons with latent tuberculosis infection (LTBI) inhibits growth of M. tuberculosis (M. tb) in human monocyte-derived macrophages (MDMs). A soluble factor, Rho GDP dissociation inhibitor (D4GDI), produced by apoptotic CD4+CD25+ (85% Foxp3+) cells is responsible for this inhibition of M. tb growth in human macrophages and in mice. M. tb-expanded CD4+CD25+Foxp3+D4GDI+ cells do not produce IL-10, TGF-β and IFN-γ. D4GDI inhibited growth of M. tb in MDMs by enhancing production of IL-1β, TNF-α and ROS, and by increasing apoptosis of M. tb-infected MDMs. D4GDI was concentrated at the site of disease in tuberculosis patients, with higher levels detected in pleural fluid than in serum. However, in response to M. tb, PBMC from tuberculosis patients produced less D4GDI than PBMC from persons with LTBI. M. tb-expanded CD4+CD25+ (85% Foxp3+) cells and D4GDI induced intracellular M. tb to express the dormancy survival regulator DosR and DosR-dependent genes, suggesting that D4GDI induces a non-replicating state in the pathogen. Our study provides the first evidence that a subpopulation of CD4+CD25+ (85% Foxp3+) cells enhances immunity to M. tb, and that production of D4GDI by this subpopulation inhibits M. tb growth. 相似文献
52.
Inna G. Ovsyannikova Neelam Dhiman Iana H. Haralambieva Robert A. Vierkant Megan M. O’Byrne Robert M. Jacobson Gregory A. Poland 《Human genetics》2010,127(2):207-221
Toll-like, vitamin A and D receptors and other innate proteins participate in various immune functions. We determined whether
innate gene-sequence variations are associated with rubella vaccine-induced cytokine immune responses. We genotyped 714 healthy
children (11–19 years of age) after two doses of rubella-containing vaccine for 148 candidate SNP markers. Rubella virus-induced
cytokines were measured by ELISA. Twenty-two significant associations (range of P values 0.002–0.048) were found between SNPs in the vitamin A receptor family (RARA, RARB, TOP2B and RARG), vitamin D receptor
and downstream mediator of vitamin D signaling (RXRA) genes and rubella virus-specific (IFN-γ, IL-2, IL-10, TNF-α, and GM-CSF)
cytokine immune responses. A TLR3 gene promoter region SNP (rs5743305, −8441A > T) was associated with rubella-specific GM-CSF
secretion. Importantly, SNPs in the TRIM5 gene coding regions, rs3740996 (His43Tyr) and rs10838525 (Gln136Arg), were associated
with an allele dose-related secretion of rubella virus-specific TNF-α and IL-2/GM-CSF, respectively, and have been previously
shown to have functional consequences regarding the antiviral activity and susceptibility to HIV-1 infection. We identified
associations between individual SNPs and haplotypes in, or involving, the RIG-I (DDX58) gene and rubella-specific TNF-α secretion.
This is the first paper to present evidence that polymorphisms in the TLR, vitamin A, vitamin D receptor, and innate immunity
genes can influence adaptive cytokine responses to rubella vaccination. 相似文献
53.
Jain RK; Piskorz CF; Huang BG; Locke RD; Han HL; Koenig A; Varki A; Matta KL 《Glycobiology》1998,8(7):707-717
The selectins interact in important normal and pathological situations with
certain sialylated, fucosylated glycoconjugate ligands containing sialyl
Lewisx(Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcN Ac). Much effort has gone
into the synthesis of sialylated and sulfated Lewisxanalogs as competitive
ligands for the selectins. Since the natural selectin ligands GlyCAM-1 and
PSGL-1 carry sialyl Lewisxas part of a branched Core 2 O-linked structure,
we recently synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(SE-3Galbeta1++
+-3)GalNAc1alphaOMe and found it to be a moderately superior ligand for L
and P-selectin (Koenig et al. , Glycobiology 7, 79-93, 1997). Other studies
have shown that sulfate esters can replace sialic acid in some selectin
ligands (Yeun et al. , Biochemistry, 31, 9126-9131, 1992; Imai et al. ,
Nature, 361, 555, 1993). Based upon these observations, we hypothesized
that Neu5Acalpha2-3Galbeta1-3GalNAc might have the capability of
interacting with L- and P-selectin. To examine this hypothesis, we
synthesized Galbeta1-4(Fucalpha1-3)GlcNAcbeta1-6(Neu5Acalpha2++
+-3Galbeta1-3)- GalNAc alpha1-OB, which was found to be 2- to 3-fold better
than sialyl Lexfor P and L selectin, respectively. We also report the
synthesis of an unusual structure GalNAcbeta1-4(Fucalpha1-
3)GlcNAcbeta1-OMe (GalNAc- Lewisx-O-methyl glycoside), which also proved to
be a better inhibitor of L- and P-selectin than sialyl Lewisx-OMe.
Combining this with our knowledge of Core 2 branched structures, we have
synthesized a molecule that is 5- to 6-fold better at inhibiting L- and
P-selectin than sialyl Lewisx-OMe, By contrast to unbranched structures,
substitution of a sulfate ester group for a sialic acid residue in such a
molecule resulted in a considerable loss of inhibition ability. Thus, the
combination of a sialic acid residue on the primary (beta1-3) arm, and a
modified Lexunit on the branched (beta1-6) arm on an O-linked Core 2
structure generated a monovalent synthetic oliogosaccharide inhibitor
superior to SLexfor both L- and P-selectin.
相似文献
54.
Peptide mapping by limited proteolysis of a highly protective 71-kDa cell wall-associated protein of Mycobacterium tuberculosis H37Ra was carried out in order to identify key protective determinants within the native protein. The 71-kDa protein, which had an isoelectric point of 4.25, was digested into eight major bands at 48 h using trypsin and pepsin at equal enzyme to protein ratios (pH 5.5). The in vitro lymphocyte reactivity of individual peptides suggested P1, P2 and P5 to be significantly immunoreactive in mice immunized with native 71-kDa-polylactide-coglyeolide (PLG); however, the reactivity was significantly lower than that of the native 71-kDa protein. Immunization of mice with a pooled fraction (upper fraction-71 kDa) of more immunoreactive peptides (consisting of P1 and P2) did not further boost their immunoreactivity. However, P1 and P2 exhibited comparable or even higher lymphocyte proliferation in human tuberculous and control subjects. These data suggest distinct antigenic specificities in humans and mice and further substantiate the use of the 71-kDa protein or its peptides P1 and P2 as potential vaccine candidates for tuberculosis. 相似文献
55.
TM?Matthews RK?Duncan M?Zidanic TH?Michael PA?FuchsEmail author 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2005,191(6):491-503
In the inner ear of birds, as in mammals, reptiles and amphibians, acetylcholine released from efferent neurons inhibits hair cells via activation of an apamin-sensitive, calcium-dependent potassium current. The particular potassium channel involved in avian hair cell inhibition is unknown. In this study, we cloned a small-conductance, calcium-sensitive potassium channel (gSK2) from a chicken cochlear library. Using RT-PCR, we demonstrated the presence of gSK2 mRNA in cochlear hair cells. Electrophysiological studies on transfected HEK293 cells showed that gSK2 channels have a conductance of approximately 16 pS and a half-maximal calcium activation concentration of 0.74±0.17 M. The expressed channels were blocked by apamin (IC50=73.3±5.0 pM) and d-tubocurarine (IC50=7.6±1.0 M), but were insensitive to charybdotoxin. These characteristics are consistent with those reported for acetylcholine-induced potassium currents of isolated chicken hair cells, suggesting that gSK2 is involved in efferent inhibition of chicken inner ear. These findings imply that the molecular mechanisms of inhibition are conserved in hair cells of all vertebrates. 相似文献
56.
Shubhashree Uppangala Shilly Dhiman Sujit Raj Salian Vikram Jeet Singh Guruprasad Kalthur Satish Kumar Adiga 《PloS one》2015,10(3)
Background
Concerns regarding the safety of ICSI have been intensified recently due to increased risk of birth defects in ICSI born children. Although fertilization rate is significantly higher in ICSI cycles, studies have failed to demonstrate the benefits of ICSI in improving the pregnancy rate. Poor technical skill, and suboptimal in vitro conditions may account for the ICSI results however, there is no report on the effects of oocyte manipulations on the ICSI outcome.Objective
The present study elucidates the influence of mock ICSI on the functional and genetic integrity of the mouse oocytes.Methods
Reactive Oxygen Species (ROS) level, mitochondrial status, and phosphorylation of H2AX were assessed in the in vivo matured and IVM oocytes subjected to mock ICSI.Results
A significant increase in ROS level was observed in both in vivo matured and IVM oocytes subjected to mock ICSI (P<0.05-0.001) whereas unique mitochondrial distribution pattern was found only in IVM oocytes (P<0.01-0.001). Importantly, differential H2AX phosphorylation was observed in both in vivo matured and IVM oocytes subjected to mock ICSI (P <0.001).Conclusion
The data from this study suggests that mock ICSI can alter genetic and functional integrity in oocytes and IVM oocytes are more vulnerable to mock ICSI induced changes. 相似文献57.
Pradeep K. Singh Dhiman Ghosh Debanjan Tewari Ganesh M. Mohite Edmund Carvalho Narendra Nath Jha Reeba S. Jacob Shruti Sahay Rinti Banerjee Amal K. Bera Samir K. Maji 《PloS one》2015,10(3)
Conversion of amyloid fibrils by many peptides/proteins involves cytotoxic helix-rich oligomers. However, their toxicity and biophysical studies remain largely unknown due to their highly dynamic nature. To address this, we chose two helical peptides (melittin, Mel and pancreatic polypeptide, PP) and studied their aggregation and toxicity. Mel converted its random coil structure to oligomeric helical structure upon binding to heparin; however, PP remained as helix after oligomerization. Interestingly, similar to Parkinson’s associated α-synuclein (AS) oligomers, Mel and PP also showed tinctorial properties, higher hydrophobic surface exposure, cellular toxicity and membrane pore formation after oligomerization in the presence of heparin. We suggest that helix-rich oligomers with exposed hydrophobic surface are highly cytotoxic to cells irrespective of their disease association. Moreover as Mel and PP (in the presence of heparin) instantly self-assemble into stable helix-rich amyloidogenic oligomers; they could be represented as models for understanding the biophysical and cytotoxic properties of helix-rich intermediates in detail. 相似文献
58.
Macrophage activation of NAD(P)H oxidase (NOX2) and reactive oxygen species (ROS) is suggested to kill Trypanosoma cruzi that causes Chagas disease. However, the role of NOX2 in generation of protective immunity and whether these mechanisms are deregulated in the event of NOX2 deficiency are not known, and examined in this study. Our data showed that C57BL/6 p47phox−/− mice (lack NOX2 activity), as compared to wild-type (WT) mice, succumbed within 30 days post-infection (pi) to low doses of T. cruzi and exhibited inability to control tissue parasites. P47phox−/− bone-marrow and splenic monocytes were not compromised in maturation, phagocytosis and parasite uptake capacity. The deficiency of NOX2 mediated ROS was compensated by higher level of inducible nitric oxide synthase (iNOS) expression, and nitric oxide and inflammatory cytokine (TNF-α, IFN-γ, IL-1β) release by p47phox−/− macrophages as compared to that noted in WT controls infected by T. cruzi. Splenic activation of Th1 CD4+T cells and tissue infiltration of immune cells in T. cruzi infected p47phox−/− mice were comparable to that noted in infected control mice. However, generation and activation of type 1 CD8+T cells was severely compromised in p47phox−/− mice. In comparison, WT mice exhibited a robust T. cruzi-specific CD8+T cell response with type 1 (IFN-γ+TNF-α>IL-4+IL-10), cytolytic effector (CD8+CD107a+IFN-γ+) phenotype. We conclude that NOX2/ROS activity in macrophages signals the development of antigen-specific CD8+T cell response. In the event of NOX2 deficiency, a compromised CD8+T cell response is generated, leading to increased parasite burden, tissue pathogenesis and mortality in chagasic mice. 相似文献
59.
Tonyia Eaves-Pyles Jignesh Patel Emma Arigi Yingzi Cong Anthony Cao Nisha Garg Monisha Dhiman Richard B Pyles Bernard Arulanandam Aaron L Miller Vsevolod L Popov Lynn Soong Eric D Carlsen Ciro Coletta Csaba Szabo Igor C. Almeida 《Molecular medicine (Cambridge, Mass.)》2013,19(1):263-275
Cystatin 9 (CST9) is a member of the type 2 cysteine protease inhibitor family, which has been shown to have immunomodulatory effects that restrain inflammation, but its functions against bacterial infections are unknown. Here, we report that purified human recombinant (r)CST9 protects against the deadly bacterium Francisella tularensis (Ft) in vitro and in vivo. Macrophages infected with the Ft human pathogen Schu 4 (S4), then given 50 pg of rCST9 exhibited significantly decreased intracellular bacterial replication and increased killing via preventing the escape of S4 from the phagosome. Further, rCST9 induced autophagy in macrophages via the regulation of the mammalian target of rapamycin (mTOR) signaling pathways. rCST9 promoted the upregulation of macrophage proteins involved in antiinflammation and antiapoptosis, while restraining proinflammatory-associated proteins. Interestingly, the viability and virulence of S4 also was decreased directly by rCST9. In a mouse model of Ft inhalation, rCST9 significantly decreased organ bacterial burden and improved survival, which was not accompanied by excessive cytokine secretion or subsequent immune cell migration. The current report is the first to show the immunomodulatory and antimicrobial functions of rCST9 against Ft. We hypothesize that the attenuation of inflammation by rCST9 may be exploited for therapeutic purposes during infection. 相似文献
60.
Characterization of statistically produced xylanase for enrichment of fruit juice clarification process 总被引:1,自引:0,他引:1
Critical factors for xylanase production of Bacillus stearothermophilus under batch fermentation and for clarification of citrus fruit juice using this xylanase were optimized through central composite design of response surface methodology. Statistical approach resulted in an increase of 1.19-fold in xylanase yield over conventional method. Model equation for juice clarification included independent variables viz. temperature, incubation time and enzyme dose to study the dependent variables such as yield, acidic neutrality and filterability etc. Coefficient of determination, R(2) for enzyme production model and for different juice properties were in accordance with the linearity of the model. On the basis of the contour plots the optimum enzyme dose was 12.5 IU/g of xylanase. Enzymatic treatment has resulted in the improvement of twofold in the release of reducing sugars and 52.97% in juice yield, whereas 35.34% reduction in turbidity was observed. 相似文献