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41.
Tinto N Zagari A Capuano M De Simone A Capobianco V Daniele G Giugliano M Spadaro R Franzese A Sacchetti L 《PloS one》2008,3(4):e1870
Background
Maturity onset diabetes of the young type 2 (or GCK MODY) is a genetic form of diabetes mellitus provoked by mutations in the glucokinase gene (GCK).Methodology/Principal Findings
We screened the GCK gene by direct sequencing in 30 patients from South Italy with suspected MODY. The mutation-induced structural alterations in the protein were analyzed by molecular modeling. The patients'' biochemical, clinical and anamnestic data were obtained. Mutations were detected in 16/30 patients (53%); 9 of the 12 mutations identified were novel (p.Glu70Asp, p.Phe123Leu, p.Asp132Asn, p.His137Asp, p.Gly162Asp, p.Thr168Ala, p.Arg392Ser, p.Glu290X, p.Gln106_Met107delinsLeu) and are in regions involved in structural rearrangements required for catalysis. The prevalence of mutation sites was higher in the small domain (7/12: ∼59%) than in the large (4/12: 33%) domain or in the connection (1/12: 8%) region of the protein. Mild diabetic phenotypes were detected in almost all patients [mean (SD) OGTT = 7.8 mMol/L (1.8)] and mean triglyceride levels were lower in mutated than in unmutated GCK patients (p = 0.04).Conclusions
The prevalence of GCK MODY is high in southern Italy, and the GCK small domain is a hot spot for MODY mutations. Both the severity of the GCK mutation and the genetic background seem to play a relevant role in the GCK MODY phenotype. Indeed, a partial genotype-phenotype correlation was identified in related patients (3 pairs of siblings) but not in two unrelated children bearing the same mutation. Thus, the molecular approach allows the physician to confirm the diagnosis and to predict severity of the mutation. 相似文献42.
Background
The extracellular enzyme cyclodextrin glucanotransferase (CGTase) synthesizes cyclic malto-oligosaccharides called cyclodextrins (CDs) from starch and related α-1,4-glucans. CGTases are produced by a variety of bacteria, mainly Bacillus species, by submerged culture in complex medium. CGTases differ in the amount and types of CDs produced. In addition, CGTase production is highly dependent on the strain, medium composition and culture conditions. Therefore we undertook this study with a newly isolated strain of Bacillus circulans. 相似文献43.
Ferrer E Sánchez J Milano A Alvarez S La Rosa R Lares M González LM Cortéz MM Dávila I Harrison LJ Parkhouse RM Gárate T 《Experimental parasitology》2012,130(1):78-85
To study diagnostic epitopes within the Taenia solium 8 kDa antigen family, six overlapping synthetic peptides from an 8 kDa family member (Ts8B2) were synthesized and evaluated by ELISA and MABA with sera from patients with neurocysticercosis (NCC), from infected pigs and from rabbits immunized with recombinant Ts8B2 protein. The pre-immune rabbit sera and the Ts8B2 recombinant protein served as negative and positive controls, respectively. A similar analysis was done with the already described antigenic peptides from another member of the 8 kDa family, highly similar to Ts8B2, the CyDA antigen. Surprisingly, neither the Ts8B2 peptides nor the CyDA peptides were recognized by infected human and porcine sera. However, the entire Ts8B2 recombinant, as well as amino and carboxy-terminal halves were recognized by the positive serum samples. The observed lack of recognition of linear Ts8B2 peptides suggests that the principal serological response to the Ts8B2 family is focused on conformational epitopes in contrast to the previously observed antigenicity of the CyDA peptides. This differential antigenicity of 8 kDa family peptides could be related with parasite antigenic variability. The fact that rabbits experimentally immunized with Ts8B2 did make anti-peptide antibodies to peptides Ts8B2-6 and CyDA-6, located in the carboxy-terminal region demonstrated that the Ts8B2 peptides are not intrinsically non-immunogenic. 相似文献
44.
Hereditary cerebral hemorrhage with amyloidosis-Dutch type is a disorder associated with a missense mutation (E693Q) in the β-amyloid (Aβ)-coding region of the amyloid precursor protein (APP). This familial disease is characterized by cognitive deficits secondary to intracerebral hemorrhage and, in some cases, progressive Alzheimer's disease (AD)-like dementia. Although this mutation was the first ever reported in the human APP gene, little is known about the molecular mechanisms underlying the direct toxic effects of this mutated Aβ on central neurons. In the present study, we assessed the role of calpain-mediated toxicity in such effects using an AD primary culture model system. Our results showed that Dutch mutant Aβ (E22Q) induced calpain-mediated cleavage of dynamin 1 and a significant decrease in synaptic contacts in mature hippocampal cultures. These synaptic deficits were similar to those induced by wild-type (WT) Aβ. In contrast, calpain-mediated tau cleavage leading to the generation of a 17-kDa neurotoxic fragment, as well as neuronal death, were significantly reduced in E22Q Aβ-treated neurons when compared with WT Aβ-treated ones. This complex regulation of the calpain-mediated toxicity pathway by E22Q Aβ could have some bearing in the pathobiology of this familial AD form. 相似文献
45.
Michael S. Dahabieh Fan Huang Christophe Goncalves Raúl Ernesto Flores Gonzlez Sathyen Prabhu Alicia Bolt Erminia Di Pietro Elie Khoury John Heath Zi Yi Xu Joelle Rmy-Sarrazin Koren K. Mann Alexandre Orthwein Franois-Michel Boisvert Nancy Braverman Wilson H. Miller Sonia V. del Rincn 《Autophagy》2022,18(3):540
46.
Martha Patricia Lpez Adriana Paola Ulloa Fabio Alberto Escobar 《Biomédica : revista del Instituto Nacional de Salud》2022,42(1):159
Introduction:
Prison population is affected by tuberculosis (TB) due to prison overcrowding. This situation reflects an inequity in health, understood as an unfair and avoidable difference between individuals and populations.Objective:
To estimate the conditions of prison overcrowding as health inequity in prison population suffering from TB in Colombia during 2018.Materials and methods:
This is an ecological study to estimate inequities at the national level in prison population through the use of the World Health Organization methodology for the measurement of inequalities. Based on data from the public health surveillance system, the incidence of TB was taken as an indicator and the percentage of overcrowding as an equity stratifier. Simple and complex measures of inequality were calculated.Results:
The relative inequality between the lowest and highest quintiles of crowding showed that TB incidence among prison population with the highest crowding was 1.92 times that of the group with the lowest crowding. The inequality index identified an excess of 724 TB cases per 100,000 among those with the highest concentration of overcrowding. The health concentration index was -0.121, which shows that the incidence was concentrated in the group with the most overpopulation.Conclusion:
In Colombia, prison population in overcrowded conditions and suffering from TB has to face unfair and avoidable inequalities as compared with those not living in these conditions. Policies are required to reduce overcrowding and improve living conditions in prisons. 相似文献47.
Subregional variability in the response of New England vegetation to postglacial climate change
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48.
Adriana Kater-Kuipers Inez D. de Beaufort Robert-Jan H. Galjaard Eline M. Bunnik 《Bioethics》2020,34(7):671-678
Informed consent is a key condition for prenatal screening programmes to reach their aim of promoting reproductive autonomy. Reaching this aim is currently being challenged with the introduction of non-invasive prenatal testing (NIPT) in first-trimester prenatal screening programmes: amongst others its procedural ease—it only requires a blood draw and reaches high levels of reliability—might hinder women’s understanding that they should make a personal, informed decision about screening. We offer arguments for a renewed recognition and use of informed consent compared to informed choice, and for a focus on value-consistent choices and personalized informational preferences. We argue for a three-step counselling model in which three decision moments are distinguished and differently addressed: (1) professionals explore women’s values concerning whether and why they wish to know whether their baby has a genetic disorder; (2) women receive layered medical-technical information and are asked to make a decision about screening; (3) during post-test counselling, women are supported in decision-making about the continuation or termination of their pregnancy. This model might also be applicable in other fields of genetic (pre-test) counselling, where techniques for expanding genome analysis and burdensome test-outcomes challenge counselling of patients. 相似文献
49.
Bobin Mi Yuan Xiong Chenchen Yan Lang Chen Hang Xue Adriana C. Panayi Liangcong Hu Yiqiang Hu Wu Zhou Faqi Cao Guohui Liu 《Journal of cellular and molecular medicine》2020,24(11):6385-6396
N6-methyladenosine (m6A) modification has been reported in various diseases and implicated in increasing numbers of biological processes. However, previous studies have not focused on the role of m6A modification in fracture healing. Here, we demonstrated that m6A modifications are decreased during fracture healing and that methyltransferase-like 3 (METTL3) is the main factor involved in the abnormal changes in m6A modifications. Down-regulation of METTL3 promotes osteogenic processes both in vitro and in vivo, and this effect is recapitulated by the suppression of miR-7212-5p maturation. Further studies have shown that miR-7212-5p inhibits osteoblast differentiation in MC3T3-E1 cells by targeting FGFR3. The present study demonstrated an important role of the METTL3/miR-7212-5p/FGFR3 axis and provided new insights on m6A modification in fracture healing. 相似文献
50.
Adriana Vergs Alexandra H. Campbell Georgina Wood Lana Kajlich Aaron M. Eger Derrick Cruz Madelaine Langley Damon Bolton Melinda A. Coleman Jennifer Turpin Michaelie Crawford Nigel Coombes Adam Camilleri Peter D. Steinberg Ezequiel M. Marzinelli 《Ecological Management & Restoration》2020,21(2):74-85
Operation Crayweed focuses on the restoration of underwater forests that disappeared from the coastline of Sydney, Australia’s largest city, 40 years previously. We show how a combination of science, hands‐on restoration, community engagement and art has helped the project to reach its goals as well as raise awareness about the importance of underwater kelp forests that are experiencing global decline. 相似文献