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111.
Natlia Erdens Maron Freitas Emily Ferreira Santos Leonardo Maia Leony ngelo Antnio Oliveira Silva Ramona Tavares Daltro Larissa de Carvalho Medrado Vasconcelos Gabriela Agra Duarte Cristiane Oliveira da Mota Edimilson Domingos Silva Paola Alejandra Fiorani Celedon Nilson Ivo Tonin Zanchin Fred Luciano Neves Santos 《PLoS neglected tropical diseases》2022,16(3)
BackgroundEnzyme-linked immunosorbent assays (ELISA) are generally the chosen test for Chagas disease (CD) diagnosis; however, its performance depends on the antigen preparation adsorbed to the solid phase, which may lead to false-positive results and cross-reactions. The use of chimeric recombinant antigens can overcome this limitation. Four chimeric antigens from Trypanosoma cruzi (IBMP-8.1, IBMP-8.2, IBMP-8.3 and IBMP-8.4) were developed and evaluated in phase I, II and III studies using indirect ELISA as diagnostic platform. However, peroxidase-labeled secondary anti-human IgG antibody, which is employed in indirect ELISAs, limits its use for the detection of species-specific and class-specific antibodies. To overcome this limitation, peroxidase-labeled antigens can be utilized, diagnosing both acute or chronic infection, in a species and immunoglobulin class-independent manner, through the use of a double-antigen sandwich ELISA (DAgS-ELISA). We aimed to evaluate and validate the diagnostic performance of the chimeric antigens IBMP-8.1, IBMP-8.2, IBMP-8.3 and IBMP-8.4 in the DAgS-ELISA platform.Methodology/Principal findingsDAgS-ELISA was optimized by checkerboard titration. In phase I study, 207 positive and 205 negative samples were evaluated. Cross-reactivity to other infections was also assessed using 68 samples. The selected conditions for the tests utilized 25 ng of antigen per well and the conjugate diluted at 1:2,000 for all molecules. In the phase I study, the areas under the curve of IBMP-8.1, IBMP-8.2, IBMP-8.3 and IBMP-8.4 were 98.7%, 99.5%, 98.6% and 98.8%, respectively. Among the positive samples, IBMP-8.1 antigen classified 53 (25.6%) as false negative, IBMP-8.2, 27 (13%), IBMP-8.3, 24 (11.6%) and IBMP-8.4, 43 (20.8%), giving sensitivities of 74.4%, 87%, 88.4% and 79.2%, respectively. The only antigen that did not reach 100% specificity was IBMP-8.3, with 96.6%. IBMP-8.3 was also the only molecule to show cross-reactivity with HTLV.Conclusions/SignificanceDAgS-ELISA is a promising tool for immunodiagnosis, and despite the high AUC values, the performance of this assay was different from the values obtained by our group when using these antigens in the indirect ELISA, for this reason, improvements are being considered to increase the sensitivity of the DAgS-ELISA. 相似文献
112.
Gabriela Roldo Correia-Costa Ilria Cristina Sgardioli Ana Paula dos Santos Tnia Kawasaki de Araujo Rodrigo Secolin Iscia Lopes-Cendes Vera Lúcia Gil-da-Silva-Lopes Trsis Paiva Vieira 《Genetics and molecular biology》2022,45(1)
Runs of homozygosity (ROH) in the human genome may be clinically relevant. The aim of this study was to report the frequency of increased ROH of the autosomal genome in individuals with neurodevelopmental delay/intellectual disability and/or multiple congenital anomalies, and to compare these data with a control group. Data consisted of calls of homozygosity from 265 patients and 289 controls. In total, 7.2% (19/265) of the patients showed multiple ROH exceeding 1% of autosomal genome, compared to 1.4% (4/289) in the control group (p=0.0006). Homozygosity ranged from 1.38% to 22.12% among patients, and from 1.53 to 2.40% in the control group. In turn, 1.9% (5/265) of patients presented ROH ≥10Mb in a single chromosome, compared to 0.3% (1/289) of individuals from the control group (p=0.0801). By excluding cases with reported consanguineous parents (15/24), the frequency of increased ROH was 3.4% (9/250) among patients and 1.7% (5/289) in the control group, considering multiple ROH exceeding 1% of the autosome genome and ROH ≥10Mb in a single chromosome together, although not statistically significant (p=0.1873). These results reinforce the importance of investigating ROH, which with complementary diagnostic tests can improve the diagnostic yield for patients with such conditions. 相似文献
113.
Juana Martinez Kritika Subramanian Daniel Margolis Elisabeth O'Dwyer Joseph Osborne Yuliya Jhanwar Himanshu Nagar Nicholas Williams Arindam RoyChoudhury Gabriela Madera John Babich Sandra Huicochea Castellanos 《Translational oncology》2022,15(1)
BackgroundThe primary objective was to compare the overall diagnostic performance, presented as detection rate of 68Ga-PSMA-HBED-CC positron emission tomography/magnetic resonance imaging (PSMA PET/MRI) versus conventional, multiparametric MRI (mpMRI) in a population of patients with biochemically recurrent prostate cancer. In conjunction with this analysis, secondary objectives included the evaluation of the detection rate stratified by PSA levels and primary treatment modality.MethodsA total of 165 PSMA PET MRI were performed from April 2018 to May 2021, of whom 108 were presenting for biochemical recurrent disease. The PSMA PET vertex to thigh were read by two different board-certified nuclear medicine physicians while the MRI head and neck, chest, abdomen, and pelvis (with dedicated, PI-RADS compliant multiparametric prostate MRI) were read by two board certified diagnostic radiologists.AnalysisPSMA PET/MRI had a higher detection rate than mpMRI when evaluating patients with biochemical recurrence (BCR) with similar results demonstrated when sub-analysis was performed using PSA levels, primary treatment modality, and time since androgen deprivation therapy. Our study also showed PSMA PET/MRI had a higher sensitivity than mpMRI.DiscussionOur findings demonstrate that PSMA PET/MRI is a better imaging modality in the detection of disease in the setting of BCR when compared to MRI alone. Combined utility with PSMA PET/MRI is a powerful tool which can aid in not only the detection of disease, but also guide in treatment planning for prostate cancer patients. 相似文献
114.
Ale Vanura Tomá ezanka Jaroslav Marlálek Karel Melzoch Gabriela Basaová Vladimir Kian 《FEMS microbiology letters》1988,49(3):411-415
Abstract In Streptomyces fradiae l -threonine is catabolized by threonine dehydratase or threonine aldolase to 2-ketobutyrate or acetaldehyde and glycine, respectively. Threonine dehydratase synthesis is repressed and its activity is inhibited by NH4 + ions. Threonine aldolase is not repressed by NH4 + ions and its activity is slightly stimulated by these ions. The addition of threonine to the medium increased pronouncedly the fraction of non-branched fatty acids with an even carbon number under conditions when threonine dehydratase was repressed and inhibited. The results indicate that threonine serves as a source of propionyl-CoA and 2-methylbutyryl-CoA and also of acetyl-CoA required for tylosin and fatty acid biosynthesis. 相似文献
115.
Chathika Krishan Weerasuriya Rebecca Claire Harris Christopher Finn McQuaid Gabriela B. Gomez Richard G. White 《PLoS computational biology》2022,18(4)
We investigated the effects of updating age-specific social contact matrices to match evolving demography on vaccine impact estimates. We used a dynamic transmission model of tuberculosis in India as a case study. We modelled four incremental methods to update contact matrices over time, where each method incorporated its predecessor: fixed contact matrix (M0), preserved contact reciprocity (M1), preserved contact assortativity (M2), and preserved average contacts per individual (M3). We updated the contact matrices of a deterministic compartmental model of tuberculosis transmission, calibrated to epidemiologic data between 2000 and 2019 derived from India. We additionally calibrated the M0, M2, and M3 models to the 2050 TB incidence rate projected by the calibrated M1 model. We stratified age into three groups, children (<15y), adults (≥15y, <65y), and the elderly (≥65y), using World Population Prospects demographic data, between which we applied POLYMOD-derived social contact matrices. We simulated an M72-AS01E-like tuberculosis vaccine delivered from 2027 and estimated the per cent TB incidence rate reduction (IRR) in 2050 under each update method. We found that vaccine impact estimates in all age groups remained relatively stable between the M0–M3 models, irrespective of vaccine-targeting by age group. The maximum difference in impact, observed following adult-targeted vaccination, was 7% in the elderly, in whom we observed IRRs of 19% (uncertainty range 13–32), 20% (UR 13–31), 22% (UR 14–37), and 26% (UR 18–38) following M0, M1, M2 and M3 updates, respectively. We found that model-based TB vaccine impact estimates were relatively insensitive to demography-matched contact matrix updates in an India-like demographic and epidemiologic scenario. Current model-based TB vaccine impact estimates may be reasonably robust to the lack of contact matrix updates, but further research is needed to confirm and generalise this finding. 相似文献
116.
117.
The anatomy and ontogeny of the gynoecium and nutlets of two Bulbostylis species with different micro-morphology, Bulbostylis capillaris sensu Barros and B. major, were analyzed. The specific aim of this work was to identify which part of the pericarp determines the differences in the nutlet surface between these two species. We found that pre-fertilization development is the same in both species, with differences between species appearing only after fertilization. In the nutlet of B. major, the exocarp forms a tuberculate primary sculpture that has nipple-like protuberances consisting of one conoidal silica body per cell, whereas the secondary sculpture is micro-granulose and is constituted by the cuticle. In the nutlet of B. capillaris, the primary sculpture is granulose and is formed by the presence of starch granules in the exocarp that do not degrade, whereas the secondary sculpture is smooth. 相似文献
118.
Hyperkalemic periodic paralysis M1592V mutation modifies activation in human skeletal muscle Na+ channel 总被引:1,自引:0,他引:1
Rojas Cecilia V.; Neely Alan; Velasco-Loyden Gabriela; Palma Veronica; Kukuljan Manuel 《American journal of physiology. Cell physiology》1999,276(1):C259
Mutations in thehuman skeletal muscle Na+ channelunderlie the autosomal dominant disease hyperkalemic periodic paralysis (HPP). Muscle fibers from affected individuals exhibit sustained Na+ currents thought to depolarizethe sarcolemma and thus inactivate normalNa+ channels. We expressed humanwild-type or M1592V mutant-subunits with the 1-subunitin Xenopus laevis oocytes and recordedNa+ currents using two-electrodeand cut-open oocyte voltage-clamp techniques. The most prominentfunctional difference betweenM1592V mutant and wild-typechannels is a 5- to 10-mV shift in the hyperpolarized direction of thesteady-state activation curve. The shift in the activation curve forthe mutant results in a larger overlap with the inactivation curve thanthat observed for wild-type channels. Accordingly, the current throughM1592V channels displays a larger noninactivating component than does that through wild-type channels atmembrane potentials near 40 mV. The functional properties of theM1592V mutant resemble those ofthe previously characterized HPPT704M mutant. Both clinicallysimilar phenotypes arise from mutations located at a distance from theputative voltage sensor of the channel. 相似文献
119.
Dutka P Szydłowska M Chodorowski Z Rybakowska I Nagel-Starczynowska G Kaletha K 《Molecular and cellular biochemistry》2004,262(1-2):119-126
AMP-deaminase (EC 3.5.4.6) is an enzyme of nucleotide breakdown involved in regulation of adenine nucleotide pool in mammalian cells. Reaction catalysed by AMP-deaminase constitutes a rate-limiting step in adenine nucleotide catabolism in liver. In this study kinetic and regulatory properties of AMP-deaminase purified from normal and cirrhotic human liver were investigated. In comparison to AMP-deaminase extracted from the normal human liver, AMP-deaminase extracted from the cirrhotic liver was less sensitive towards substrate analogues, and only a very limited response towards pH and adenylate energy charge changes tested for enzyme isolated from this tissue source had been observed. At physiological pH 7.0, in the absence and in the presence of important allosteric effectors (ATP, ADP, GTP and orthophosphate), AMP-deaminases from the two sources studied manifested different regulatory profiles, with half-saturation constant (S0.5) values being distinctly higher for the enzyme extracted from the pathological organ. In contrast to AMP-deaminase isolated from the normal, healthy liver, where presence of relatively large (68 kDa) protein fragment was also detected, only smaller protein fragments were identified, while SDS-PAG electrophoresis of AMP-deaminase isolated from the cirrhotic liver was performed. The obtained results indicate clearly that advanced proteolytic processes occurring in the cirrhotic liver may affect structural integrity of AMP-deaminase studied, making enzyme less active and less sensitive to regulatory action of important allosteric effectors. 相似文献
120.
The cyanobacterial flora of maritime Antarctica appears to contain many endemic species and only few cosmopolitan or wider-distributed taxa. Several morphospecies that have been erroneously identified in the past following available keys from temperate or tropical zones belong in fact to little-known and poorly described Antarctic cyanobacteria. Here we describe the taxonomy of one such example, the colonial species Gloeocapsopsis aurea . This cyanobacterium produces irregular, packet-like colonies that form black mats, films and crusts. Based on analysis of algal samples from Punta Cierva (Antarctic Peninsula) and King George Island (South Shetland Islands), this taxon is widely distributed in coastal, deglaciated areas of the maritime Antarctic. It is an important, often dominating, ecotype, mostly colonising irrigated rocks but also found in a variety of other aquatic and semi-aquatic habitats under a wide range of conductivities, pH and nutrient regimes. 相似文献