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991.
J Guardia J Gomez C Martin J M Martinez-Vazquez R Bacardi J Tornos 《BMJ (Clinical research ed.)》1975,1(5954):370-371
Four women with fever, arthromyalgias, pericarditis, pleural effusion, high erythrocyte sedimentation rates, and lymphopenia had mitochondrial antibodies in the serum in the absence of antinuclear antibody. Their illness lasted 5-12 weeks and the antibody test results became negative on remission. Absence of specific bacteriological findings, normal antistreptolysin O titres, resistance to antibiotics, and good response to steroids suggested that these cases represented a milder and less persistent form of the syndrome resembling systemic lupus erythematosus described by German authors. 相似文献
992.
993.
Blood-perfused working isolated rat heart 总被引:5,自引:0,他引:5
994.
Dusanka Milenkovic Adrin Sanz-Moreno Julia Calzada-Wack Birgit Rathkolb Oana Veronica Amarie Raffaele Gerlini Antonio Aguilar-Pimentel Jelena Misic Marie-Lune Simard Eckhard Wolf Helmut Fuchs Valerie Gailus-Durner Martin Hrab de Angelis Nils-Gran Larsson 《PLoS genetics》2022,18(5)
Mitochondrial DNA (mtDNA) maintenance disorders are caused by mutations in ubiquitously expressed nuclear genes and lead to syndromes with variable disease severity and tissue-specific phenotypes. Loss of function mutations in the gene encoding the mitochondrial genome and maintenance exonuclease 1 (MGME1) result in deletions and depletion of mtDNA leading to adult-onset multisystem mitochondrial disease in humans. To better understand the in vivo function of MGME1 and the associated disease pathophysiology, we characterized a Mgme1 mouse knockout model by extensive phenotyping of ageing knockout animals. We show that loss of MGME1 leads to de novo formation of linear deleted mtDNA fragments that are constantly made and degraded. These findings contradict previous proposal that MGME1 is essential for degradation of linear mtDNA fragments and instead support a model where MGME1 has a critical role in completion of mtDNA replication. We report that Mgme1 knockout mice develop a dramatic phenotype as they age and display progressive weight loss, cataract and retinopathy. Surprisingly, aged animals also develop kidney inflammation, glomerular changes and severe chronic progressive nephropathy, consistent with nephrotic syndrome. These findings link the faulty mtDNA synthesis to severe inflammatory disease and thus show that defective mtDNA replication can trigger an immune response that causes age-associated progressive pathology in the kidney. 相似文献
995.
Wanzhen Liu David A. S. Smith Gayatri Raina Rowan Stanforth Ivy Ng'Iru Piera Ireri Dino J. Martins Ian J. Gordon Simon H. Martin 《Biology letters》2022,18(6)
Warning coloration provides a textbook example of natural selection, but the frequent observation of polymorphism in aposematic species presents an evolutionary puzzle. We investigated biogeography and polymorphism of warning patterns in the widespread butterfly Danaus chrysippus using records from citizen science (n = 5467), museums (n = 8864) and fieldwork (n = 2586). We find that polymorphism in three traits controlled by known mendelian loci is extensive. Broad allele frequency clines, hundreds of kilometres wide, suggest a balance between long-range dispersal and predation of unfamiliar morphs. Mismatched clines for the white hindwing and forewing tip in East Africa are consistent with a previous finding that the black wingtip allele has spread recently in the region through hitchhiking with a heritable endosymbiont. Light/dark background coloration shows more extensive polymorphism. The darker genotype is more common in cooler regions, possibly reflecting a trade-off between thermoregulation and predator warning. Overall, our findings show how studying local adaptation at the global scale provides a more complete picture of the evolutionary forces involved. 相似文献
996.
997.
Martin Gael Oyono Sebastien Kenmoe Ngu Njei Abanda Guy Roussel Takuissu Jean Thierry Ebogo-Belobo Raoul Kenfack-Momo Cyprien Kengne-Nde Donatien Serge Mbaga Serges Tchatchouang Josiane Kenfack-Zanguim Robertine Lontuo Fogang Elisabeth Zeukoo Menkem Juliette Laure Ndzie Ondigui Ginette Irma Kame-Ngasse Jeannette Nina Magoudjou-Pekam Arnol Bowo-Ngandji Seraphine Nkie Esemu Lucy Ndip 《PLoS neglected tropical diseases》2022,16(7)
Yellow fever (YF) has re-emerged in the last two decades causing several outbreaks in endemic countries and spreading to new receptive regions. This changing epidemiology of YF creates new challenges for global public health efforts. Yellow fever is caused by the yellow fever virus (YFV) that circulates between humans, the mosquito vector, and non-human primates (NHP). In this systematic review and meta-analysis, we review and analyse data on the case fatality rate (CFR) and prevalence of YFV in humans, and on the prevalence of YFV in arthropods, and NHP in sub-Saharan Africa (SSA). We performed a comprehensive literature search in PubMed, Web of Science, African Journal Online, and African Index Medicus databases. We included studies reporting data on the CFR and/or prevalence of YFV. Extracted data was verified and analysed using the random effect meta-analysis. We conducted subgroup, sensitivity analysis, and publication bias analyses using the random effect meta-analysis while I2 statistic was employed to determine heterogeneity. This review was registered with PROSPERO under the identification CRD42021242444. The final meta-analysis included 55 studies. The overall case fatality rate due to YFV was 31.1% (18.3–45.4) in humans and pooled prevalence of YFV infection was 9.4% (6.9–12.2) in humans. Only five studies in West and East Africa detected the YFV in mosquito species of the genus Aedes and in Anopheles funestus. In NHP, YFV antibodies were found only in members of the Cercopithecidae family. Our analysis provides evidence on the ongoing circulation of the YFV in humans, Aedes mosquitoes and NHP in SSA. These observations highlight the ongoing transmission of the YFV and its potential to cause large outbreaks in SSA. As such, strategies such as those proposed by the WHO’s Eliminate Yellow Fever Epidemics (EYE) initiative are urgently needed to control and prevent yellow fever outbreaks in SSA. 相似文献
998.
Alaa Droubi Connor Wallis Karen E. Anderson Saifur Rahman Aloka de Sa Taufiq Rahman Len R. Stephens Philip T. Hawkins Martin Lowe 《The Journal of cell biology》2022,221(9)
Upon antigen binding, the B cell receptor (BCR) undergoes clustering to form a signalosome that propagates downstream signaling required for normal B cell development and physiology. BCR clustering is dependent on remodeling of the cortical actin network, but the mechanisms that regulate actin remodeling in this context remain poorly defined. In this study, we identify the inositol 5-phosphatase INPP5B as a key regulator of actin remodeling, BCR clustering, and downstream signaling in antigen-stimulated B cells. INPP5B acts via dephosphorylation of the inositol lipid PI(4,5)P2 that in turn is necessary for actin disassembly, BCR mobilization, and cell spreading on immobilized surface antigen. These effects can be explained by increased actin severing by cofilin and loss of actin linking to the plasma membrane by ezrin, both of which are sensitive to INPP5B-dependent PI(4,5)P2 hydrolysis. INPP5B is therefore a new player in BCR signaling and may represent an attractive target for treatment of B cell malignancies caused by aberrant BCR signaling. 相似文献
999.
Radhika AiyappaMaudsley Lina Elsalem Ali I. M. Ibrahim Klaus Pors Stewart G. Martin 《Journal of cellular and molecular medicine》2022,26(16):4577
KP167 is a novel hypoxia‐activated prodrug (HAP), targeting cancer cells via DNA intercalating and alkylating properties. The single agent and radiosensitizing efficacy of KP167 and its parental comparator, AQ4N, were evaluated in 2D and 3D cultures of luminal and triple negative breast cancer (TNBC) cell lines and compared against DNA damage repair inhibitors. 2D normoxic treatment with the DNA repair inhibitors, Olaparib or KU‐55933 caused, as expected, substantial radiosensitization (sensitiser enhancement ratio, SER0.01 of 1.60–3.42). KP167 induced greater radiosensitization in TNBC (SER0.01 2.53 in MDAMB‐231, 2.28 in MDAMB‐468, 4.55 in MDAMB‐436) and luminal spheroids (SER0.01 1.46 in MCF‐7 and 1.76 in T47D cells) compared with AQ4N. Significant radiosensitization was also obtained using KP167 and AQ4N in 2D normoxia. Although hypoxia induced radioresistance, radiosensitization by KP167 was still greater under 2D hypoxia, yielding SER0.01 of 1.56–2.37 compared with AQ4N SER0.01 of 1.13–1.94. Such data show KP167 as a promising single agent and potent radiosensitiser of both normoxic and hypoxic breast cancer cells, with greater efficacy in TNBCs. 相似文献