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131.
Bright Adu Daniel Dodoo Selorme Adukpo Paula L. Hedley Fareed K. N. Arthur Thomas A. Gerds Severin O. Larsen Michael Christiansen Michael Theisen 《PloS one》2012,7(9)
Plasmodium falciparum malaria kills nearly a million people annually. Over 90% of these deaths occur in children under five years of age in sub-Saharan Africa. A neutrophil mediated mechanism, the antibody dependent respiratory burst (ADRB), was recently shown to correlate with protection from clinical malaria. Human neutrophils constitutively express Fc gamma receptor-FcγRIIA and FcγRIIIB by which they interact with immunoglobulin (Ig) G (IgG)-subclass antibodies. Polymorphisms in exon 4 of FCGR2A and exon 3 of FCGR3B genes encoding FcγRIIA and FcγRIIIB respectively have been described to alter the affinities of both receptors for IgG. Here, associations between specific polymorphisms, encoding FcγRIIA p.H166R and FcγRIIIB-NA1/NA2/SH variants with clinical malaria were investigated in a longitudinal malaria cohort study. FcγRIIA-p.166H/R was genotyped by gene specific polymerase chain reaction followed by allele specific restriction enzyme digestion. FCGR3B-exon 3 was sequenced in 585 children, aged 1 to 12 years living in a malaria endemic region of Ghana. Multivariate logistic regression analysis found no association between FcγRIIA-166H/R polymorphism and clinical malaria. The A-allele of FCGR3B-c.233C>A (rs5030738) was significantly associated with protection from clinical malaria under two out of three genetic models (additive: p = 0.0061; recessive: p = 0.097; dominant: p = 0.0076) of inheritance. The FcγRIIIB-SH allotype (CTGAAA) containing the 233A-allele (in bold) was associated with protection from malaria (p = 0.049). The FcγRIIIB-NA2*03 allotype (CTGCGA), a variant of the classical FcγRIIIB-NA2 (CTGCAA) was associated with susceptibility to clinical malaria (p = 0.0092). The present study is the first to report an association between a variant of FcγRIIIB-NA2 and susceptibility to clinical malaria and provides justification for further functional characterization of variants of the classical FcγRIIIB allotypes. This would be crucial to the improvement of neutrophil mediated functional assays such as the ADRB assay aimed at assessing the functionality of antibodies induced by candidate malaria vaccines. 相似文献
132.
Priscila P. Santos Fernando Oliveira Vanessa C. M. P. Ferreira Bertha F. Polegato Meliza G. Roscani Ana Angelica Fernandes Pamela Modesto Bruna P. M. Rafacho Silmeia G. Zanati Annarita Di Lorenzo Luiz S. Matsubara Sergio A. R. Paiva Leonardo A. M. Zornoff Marcos F. Minicucci Paula S. Azevedo 《PloS one》2014,9(12)
Background/Aims
Experimental and clinical studies have shown the direct toxic effects of cigarette smoke (CS) on the myocardium, independent of vascular effects. However, the underlying mechanisms are not well known.Methods
Wistar rats were allocated to control (C) and cigarette smoke (CS) groups. CS rats were exposed to cigarette smoke for 2 months.Results
After that morphometric, functional and biochemical parameters were measured. The echocardiographic study showed enlargement of the left atria, increase in the left ventricular systolic volume and reduced systolic function. Within the cardiac metabolism, exposure to CS decreased beta hydroxy acyl coenzyme A dehydrogenases and citrate synthases and increased lactate dehydrogenases. Peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) were expressed similarly in both groups. CS increased serum lipids and myocardial triacylglycerols (TGs). These data suggest that impairment in fatty acid oxidation and the accumulation of cardiac lipids characterize lipotoxicity. CS group exhibited increased oxidative stress and decreased antioxidant defense. Finally, the myocyte cross-sectional area and active Caspase 3 were increased in the CS group.Conclusion
The cardiac remodeling that was observed in the CS exposure model may be explained by abnormalities in energy metabolism, including lipotoxicity and oxidative stress. 相似文献133.
Biftu T Feng D Ponpipom M Girotra N Liang GB Qian X Bugianesi R Simeone J Chang L Gurnett A Liberator P Dulski P Leavitt PS Crumley T Misura A Murphy T Rattray S Samaras S Tamas T Mathew J Brown C Thompson D Schmatz D Fisher M Wyvratt M 《Bioorganic & medicinal chemistry letters》2005,15(13):3296-3301
Several analogs of 2,3-diaryl pyrroles were synthesized and evaluated as inhibitors of Eimeria tenella cGMP-dependent protein kinase and in in vivo anticoccidial assays. A 4-fluorophenyl group enhances both in vitro and in vivo activities. The most potent analogs are the 5-(N-methyl, N-ethyl, and N-methylazetidine methyl) piperidyl derivatives 12, 23, and 34. These compounds have a broad spectrum of activity. Based on the in vivo efficacy and cost of synthesis, the N-ethyl analog 23 was chosen as a novel anticoccidial agent for a field trial. 相似文献
134.
135.
Paula Martínez María Pilar Sáez José Amador Rubio Ester Cánovas Elena Esteban Javier Botas 《Revista espa?ola de geriatría y gerontología》2014
Objective
To review our experience on using an implantable loop recorder (ILR) in patients with recurrent falls, when an arrhythmogenic cause is suspected.Material and methods
This is a retrospective, observational study of patients with repetitive unexplained falls, suspected syncope, or electrocardiographic abnormalities. All of them had been evaluated by a cardiologist, who decided to implant a loop recorder (ILR) for an accurate diagnosis.Results
A total of 13 patients received an ILR. The average falls rate for the sample was 3.3. The mean age was 78 years, and 46% were female, with a mean follow-up period of 24 months. During this time, three patients did not suffer from a new fall. An arrhythmogenic diagnosis was obtained in 5 patients: bradycardia was identified in 4 cases, and tachycardia in one of them. The symptoms did not coincide with a documented arrhythmia in the rest of the patients.Conclusion
ILR is a helpful tool to establish an arrhythmogenic cause of unexplained and recurrent falls, in this selected sample of older adults. 相似文献136.
Kevin MacDonald Samuel Buxton Michael J. Kimber Tim A. Day Alan P. Robertson Paula Ribeiro 《PLoS pathogens》2014,10(6)
Acetylcholine is the canonical excitatory neurotransmitter of the mammalian neuromuscular system. However, in the trematode parasite Schistosoma mansoni, cholinergic stimulation leads to muscle relaxation and a flaccid paralysis, suggesting an inhibitory mode of action. Information about the pharmacological mechanism of this inhibition is lacking. Here, we used a combination of techniques to assess the role of cholinergic receptors in schistosome motor function. The neuromuscular effects of acetylcholine are typically mediated by gated cation channels of the nicotinic receptor (nAChR) family. Bioinformatics analyses identified numerous nAChR subunits in the S. mansoni genome but, interestingly, nearly half of these subunits carried a motif normally associated with chloride-selectivity. These putative schistosome acetylcholine-gated chloride channels (SmACCs) are evolutionarily divergent from those of nematodes and form a unique clade within the larger family of nAChRs. Pharmacological and RNA interference (RNAi) behavioral screens were used to assess the role of the SmACCs in larval motor function. Treatment with antagonists produced the same effect as RNAi suppression of SmACCs; both led to a hypermotile phenotype consistent with abrogation of an inhibitory neuromuscular mediator. Antibodies were then generated against two of the SmACCs for use in immunolocalization studies. SmACC-1 and SmACC-2 localize to regions of the peripheral nervous system that innervate the body wall muscles, yet neither appears to be expressed directly on the musculature. One gene, SmACC-1, was expressed in HEK-293 cells and characterized using an iodide flux assay. The results indicate that SmACC-1 formed a functional homomeric chloride channel and was activated selectively by a panel of cholinergic agonists. The results described in this study identify a novel clade of nicotinic chloride channels that act as inhibitory modulators of schistosome neuromuscular function. Additionally, the iodide flux assay used to characterize SmACC-1 represents a new high-throughput tool for drug screening against these unique parasite ion channels. 相似文献
137.
Identification of the pgmG Gene, Encoding a Bifunctional Protein with Phosphoglucomutase and Phosphomannomutase Activities, in the Gellan Gum-Producing Strain Sphingomonas paucimobilis ATCC 31461 总被引:2,自引:0,他引:2 下载免费PDF全文
Paula A. Videira Luísa L. Cortes Arsnio M. Fialho Isabel S-Correia 《Applied microbiology》2000,66(5):2252-2258
The pgmG gene of Sphingomonas paucimobilis ATCC 31461, the industrial gellan gum-producing strain, was cloned and sequenced. It encodes a 50,059-Da polypeptide that has phosphoglucomutase (PGM) and phosphomannomutase (PMM) activities and is 37 to 59% identical to other bifunctional proteins with PGM and PMM activities from gram-negative species, including Pseudomonas aeruginosa AlgC. Purified PgmG protein showed a marked preference for glucose-1-phosphate (G1P); the catalytic efficiency was about 50-fold higher for G1P than it was for mannose-1-phosphate (M1P). The estimated apparent Km values for G1P and M1P were high, 0.33 and 1.27 mM, respectively. The pgmG gene allowed the recovery of alginate biosynthetic ability in a P. aeruginosa mutant with a defective algC gene. This result indicates that PgmG protein can convert mannose-6-phosphate into M1P in the initial steps of alginate biosynthesis and, together with other results, suggests that PgmG may convert glucose-6-phosphate into G1P in the gellan pathway. 相似文献
138.
Martine de Boer Maaike te Lintel Hekkert Jiang Chang Bibi S. van Thiel Leonie Martens Maxime M. Bos Marion G. J. de Kleijnen Yanto Ridwan Yanti Octavia Elza D. van Deel Lau A. Blonden Renata M. C. Brandt Sander Barnhoorn Paula K. Bautista-Niño Ilona Krabbendam-Peters Rianne Wolswinkel Banafsheh Arshi Mohsen Ghanbari Christian Kupatt Leon J. de Windt A. H. Jan Danser Ingrid van der Pluijm Carol Ann Remme Monika Stoll Joris Pothof Anton J. M. Roks Maryam Kavousi Jeroen Essers Jolanda van der Velden Jan H. J. Hoeijmakers Dirk J. Duncker 《Aging cell》2023,22(3):e13768
139.
Daniel Ruivo Marques Paula Castilho Ana Allen Gomes Anabela Pereira 《Chronobiology international》2019,36(4):541-547
It is well established in the literature that morning-type individuals present better health indicators than evening-types. Mindfulness is considered an adaptive self-regulation skill associated with well-being and physical and mental health. However, there is scarce studies that relate chronotype and mindfulness. Thus, in this research, our aim was to study the relationship between chronotype and mindfulness-related variables. For this purpose, a sample composed of 483 participants from the community was recruited through an online survey and invited to fill out the Five Facet Mindfulness Questionnaire, the Self-Compassion Scale, and the Composite Morningness Scale. Regarding mindfulness measure, the results indicated that morning-types presented higher levels of “acting with awareness” than intermediate and evening-types. Additionally, as to self-compassion measure, morning-types presented higher levels of “mindfulness” and “overall self-compassion” than intermediate and evening-types. The remaining associations examined were not statistically significant. In sum, the morning-types showed higher scores in some of the mindfulness and self-compassion scales which seem to suggest that this morningness tendency may function as protective factor concerning eventual disorders´ development. Nonetheless, more systematic studies are needed to better understand this association and subsequently foster changes for psychological intervention. 相似文献
140.
Carolina P. Bellusci Carlos Rocco Paula Aulicino Debora Mecikovsky Verónica Curras Soledad Hegoburu Guillermo F. Bramuglia Rosa Bologna Luisa Sen Andrea Mangano 《Gene》2013