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71.
Pathogenic complement activation in collagen antibody-induced arthritis in mice requires amplification by the alternative pathway 总被引:1,自引:0,他引:1
Banda NK Takahashi K Wood AK Holers VM Arend WP 《Journal of immunology (Baltimore, Md. : 1950)》2007,179(6):4101-4109
Immune complex-induced inflammation can be mediated by the classical pathway of complement. However, using mice genetically deficient in factor B or C4, we have shown that the collagen Ab-induced model of arthritis requires the alternative pathway of complement and is not dependent on the classical pathway. We now demonstrate that collagen Ab-induced arthritis is not altered in mice genetically deficient in either C1q or mannose-binding lectins A and C, or in both C1q and mannose-binding lectins. These in vivo results prove the ability of the alternative pathway to carry out pathologic complement activation in the combined absence of intact classical and lectin pathways. C3 activation was also examined in vitro by adherent collagen-anti-collagen immune complexes using sera from normal or complement-deficient mice. These results confirm the ability of the alternative pathway to mediate immune complex-induced C3 activation when C4 or C1q, or both C1q and mannose-binding lectins, are absent. However, when all three activation pathways of complement are intact, initiation by immune complexes occurs primarily by the classical pathway. These results indicate that the alternative pathway amplification loop, with its ability to greatly enhance C3 activation, is necessary to mediate inflammatory arthritis induced by adherent immune complexes. 相似文献
72.
73.
Alexandru A. Hennrich Bevan Sawatsky Rosalía Santos-Mandujano Dominic H. Banda Martina Oberhuber Anika Schopf Verena Pfaffinger Kevin Wittwer Christiane Riedel Christian K. Pfaller Karl-Klaus Conzelmann 《PLoS pathogens》2021,17(4)
Vaccines of outstanding efficiency, safety, and public acceptance are needed to halt the current SARS-CoV-2 pandemic. Concerns include potential side effects caused by the antigen itself and safety of viral DNA and RNA delivery vectors. The large SARS-CoV-2 spike (S) protein is the main target of current COVID-19 vaccine candidates but can induce non-neutralizing antibodies, which might cause vaccination-induced complications or enhancement of COVID-19 disease. Besides, encoding of a functional S in replication-competent virus vector vaccines may result in the emergence of viruses with altered or expanded tropism. Here, we have developed a safe single round rhabdovirus replicon vaccine platform for enhanced presentation of the S receptor-binding domain (RBD). Structure-guided design was employed to build a chimeric minispike comprising the globular RBD linked to a transmembrane stem-anchor sequence derived from rabies virus (RABV) glycoprotein (G). Vesicular stomatitis virus (VSV) and RABV replicons encoding the minispike not only allowed expression of the antigen at the cell surface but also incorporation into the envelope of secreted non-infectious particles, thus combining classic vector-driven antigen expression and particulate virus-like particle (VLP) presentation. A single dose of a prototype replicon vaccine complemented with VSV G, VSVΔG-minispike-eGFP (G), stimulated high titers of SARS-CoV-2 neutralizing antibodies in mice, equivalent to those found in COVID-19 patients, and protected transgenic K18-hACE2 mice from COVID-19-like disease. Homologous boost immunization further enhanced virus neutralizing activity. The results demonstrate that non-spreading rhabdovirus RNA replicons expressing minispike proteins represent effective and safe alternatives to vaccination approaches using replication-competent viruses and/or the entire S antigen. 相似文献
74.
Input Subsidies to Improve Smallholder Maize Productivity in Malawi: Toward an African Green Revolution 总被引:1,自引:0,他引:1
75.
Introns and reading frames: correlation between splicing sites and their codon positions 总被引:4,自引:1,他引:3
Computer analyses of the entire GenBank database were conducted to examine
correlation between splicing sites and codon positions in reading frames.
Intron insertion patterns (i.e., splicing site locations with respect to
codon positions) have been analyzed for all of the 74 codons of all the
eukaryote taxonomic groups: primates, rodents mammals, vertebrates,
invertebrates, and plants. We found that reading frames are interrupted by
an intron at a codon boundary (as opposed to the middle of a codon)
significantly more often than expected. This observation is consistent with
the exon shuffling hypothesis, because exons that end at codon boundaries
can be concatenated without causing a frame shift and thus are
evolutionarily advantageous. On the other hand, when introns interrupt at
the middles of codons, they exist in between the first and second bases
much more frequently than between the second and third bases, despite the
fact that boundaries between the first and second bases of codons are
generally far more important than those between the second and third bases.
The reason for this is not clear and yet to be explained. We also show that
the length of an exon is a multiple of 3 more frequently than expected.
Furthermore, the total length of two consecutive exons is also more
frequently a multiple of 3. All the observations above are consistent with
results recently published by Long, Rosenberg, and Gilbert (1995).
相似文献
76.
Clifford DL Folmes D Kent Arrell Jelena Zlatkovic-Lindor Almudena Martinez-Fernandez Carmen Perez-Terzic Timothy J Nelson Andre Terzic 《Cell cycle (Georgetown, Tex.)》2013,12(15):2355-2365
Nuclear reprogramming resets differentiated tissue to generate induced pluripotent stem (iPS) cells. While genomic attributes underlying reacquisition of the embryonic-like state have been delineated, less is known regarding the metabolic dynamics underscoring induction of pluripotency. Metabolomic profiling of fibroblasts vs. iPS cells demonstrated nuclear reprogramming-associated induction of glycolysis, realized through augmented utilization of glucose and accumulation of lactate. Real-time assessment unmasked downregulated mitochondrial reserve capacity and ATP turnover correlating with pluripotent induction. Reduction in oxygen consumption and acceleration of extracellular acidification rates represent high-throughput markers of the transition from oxidative to glycolytic metabolism, characterizing stemness acquisition. The bioenergetic transition was supported by proteome remodeling, whereby 441 proteins were altered between fibroblasts and derived iPS cells. Systems analysis revealed overrepresented canonical pathways and interactome-associated biological processes predicting differential metabolic behavior in response to reprogramming stimuli, including upregulation of glycolysis, purine, arginine, proline, ribonucleoside and ribonucleotide metabolism, and biopolymer and macromolecular catabolism, with concomitant downregulation of oxidative phosphorylation, phosphate metabolism regulation, and precursor biosynthesis processes, prioritizing the impact of energy metabolism within the hierarchy of nuclear reprogramming. Thus, metabolome and metaboproteome remodeling is integral for induction of pluripotency, expanding on the genetic and epigenetic requirements for cell fate manipulation. 相似文献
77.
Hannock Tweya Caryl Feldacker Sam Phiri Anne Ben-Smith Lukas Fenner Andreas Jahn Mike Kalulu Ralf Weigel Chancy Kamba Rabecca Banda Matthias Egger Olivia Keiser 《PloS one》2013,8(2)
Background
Smear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients demonstrated conflicting results, reducing understanding of important issues.Methods
All adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawi’s largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression.Results
Of 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment), 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV-negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.14–1.94). Of 1,275 HIV-infected pulmonary TB patients, 492 (38%) received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio : 1.83; 95% CI: 1.29–2.60).Conclusion
HIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients. 相似文献78.
Yamikani Mastala Phempo Nyangulu Rodrick V. Banda Bongani Mhemedi Sarah A. White Theresa J. Allain 《PloS one》2013,8(3)
Objectives
To determine the prevalence of vitamin D deficiency (VDD) in adult medical, non-tuberculous (non-TB) patients. To investigate associations with VDD. To compare the results with a similar study in TB patients at the same hospital.Design
Cross-sectional sample.Setting
Central hospital in Malawi.Participants
Adult non-TB patients (n = 157), inpatients and outpatients.Outcome Measures
The primary outcome was the prevalence of VDD. Potentially causal associations sought included nutritional status, in/outpatient status, HIV status, anti-retroviral therapy (ART) and, by comparison with a previous study, a diagnosis of tuberculosis (TB).Results
Hypovitaminosis D (≤75 nmol/L) occurred in 47.8% (75/157) of patients, 16.6% (26/157) of whom had VDD (≤50 nmol/L). None had severe VDD (≤25 nmol/L). VDD was found in 22.8% (23/101) of in-patients and 5.4% (3/56) of out-patients. In univariable analysis in-patient status, ART use and low dietary vitamin D were significant predictors of VDD. VDD was less prevalent than in previously studied TB patients in the same hospital (68/161 = 42%). In multivariate analysis of the combined data set from both studies, having TB (OR 3.61, 95%CI 2.02–6.43) and being an in-patient (OR 2.70, 95%CI 1.46–5.01) were significant independent predictors of VDD.Conclusions
About half of adult medical patients without TB have suboptimal vitamin D status, which is more common in in-patients. VDD is much more common in TB patients than non-TB patients, even when other variables are controlled for, suggesting that vitamin D deficiency is associated with TB. 相似文献79.
Silvana Tapia-Paniagua Carmen Lobo Xabier Moreno-Ventas Inés García de la Banda Miguel A. Moriñigo M. Carmen Balebona 《Marine biotechnology (New York, N.Y.)》2014,16(6):716-728
Ingestion of bacteria at early stages results in establishment of a primary intestinal microbiota which likely undergoes several stages along fish life. The role of this intestinal microbiota regulating body functions is crucial for larval development. Probiotics have been proved to modulate this microbiota and exert antagonistic effects against fish pathogens. In the present study, we aimed to determine bacterial diversity along different developmental stages of farmed Senegalese sole (Solea senegalensis) after feeding probiotic (Shewanella putrefaciens Pdp11) supplemented diet for a short period (10–30 days after hatching, DAH). Intestinal lumen contents of sole larvae fed control and probiotic diets were collected at 23, 56, 87, and 119 DAH and DNA was amplified using 16S rDNA bacterial domain-specific primers. Amplicons obtained were separated by denaturing gradient gel electrophoresis (DGGE), cloned, and resulting sequences compared to sequences in GenBank. Results suggest that Shewanella putrefaciens Pdp11 induces a modulation of the dominant bacterial taxa of the intestinal microbiota from 23 DAH. DGGE patterns of larvae fed the probiotic diet showed a core of bands related to Lactobacillus helveticus, Pseudomonas acephalitica, Vibrio parahaemolyticus, and Shewanella genus, together with increased Vibrio genus presence. In addition, decreased number of clones related to Photobacterium damselae subsp piscicida at 23 and 56 DAH was observed in probiotic-fed larvae. A band corresponding to Shewanella putrefaciens Pdp11 was sequenced as predominant from 23 to 119 DAH samples, confirming the colonization by the probiotics. Microbiota modulation obtained via probiotics addition emerges as an effective tool to improve Solea senegalensis larviculture. 相似文献
80.
Joseph Mumba Zulu Mpala Mwanza Lisulo Ellen Besa Patrick Kaonga Caroline C. Chisenga Mumba Chomba Michelo Simuyandi Rosemary Banda Paul Kelly 《PloS one》2014,9(9)