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71.
One of the most important scientific challenges today is the quantitative and predictive understanding of biological function. Classical mathematical and computational approaches have been enormously successful in modeling inert matter, but they may be inadequate to address inherent features of biological systems. We address the conceptual and methodological obstacles that lie in the inverse problem in biological systems modeling. We introduce a full Bayesian approach (FBA), a theoretical framework to study biological function, in which probability distributions are conditional on biophysical information that physically resides in the biological system that is studied by the scientist. 相似文献
72.
Zaida Araujo Francesca Giampietro María de los Angeles Bochichio Andrea Palacios Jenifer Dinis Jaime Isern Jacobus Henry de Waard Elsa Rada Rafael Borges Carlos Fernández de Larrea Angel Villasmil Magnolia Vanegas Jose Antonio Enciso-Moreno Manuel Alfonso Patarroyo 《Memórias do Instituto Oswaldo Cruz》2013,108(2):131-139
The goal of this study was to demonstrate the usefulness of an enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of pulmonary tuberculosis (PTB) and extrapulmonary TB (EPTB). This assay used 20 amino acid-long, non-overlapped synthetic peptides that spanned the complete Mycobacterium tuberculosis ESAT-6 and Ag85A sequences. The validation cohort consisted of 1,102 individuals who were grouped into the following five diagnostic groups: 455 patients with PTB, 60 patients with EPTB, 40 individuals with non-EPTB, 33 individuals with leprosy and 514 healthy controls. For the PTB group, two ESAT-6 peptides (12033 and 12034) had the highest sensitivity levels of 96.9% and 96.2%, respectively, and an Ag85A-peptide (29878) was the most specific (97.4%) in the PTB groups. For the EPTB group, two Ag85A peptides (11005 and 11006) were observed to have a sensitivity of 98.3% and an Ag85A-peptide (29878) was also the most specific (96.4%). When combinations of peptides were used, such as 12033 and 12034 or 11005 and 11006, 99.5% and 100% sensitivities in the PTB and EPTB groups were observed, respectively. In conclusion, for a cohort that consists entirely of individuals from Venezuela, a multi-antigen immunoassay using highly sensitive ESAT-6 and Ag85A peptides alone and in combination could be used to more rapidly diagnose PTB and EPTB infection. 相似文献
73.
Yaping Kou Guohua Ma Jaime A. Teixeira da Silva Nian Liu 《Plant Cell, Tissue and Organ Culture》2013,112(1):1-7
Curcuma attenuata is a highly valued ornamental. This study provides the first report on C. attenuata shoot organogenesis and plant regeneration. Immature anthers derived from 5 to 7?cm long inflorescences were isolated and cultured on different variations of Murashige and Skoog (MS) media to induce callus and then shoot organogenesis. When the 2-mm long anthers in which microspores were at the uninucleate developmental stage were cultured in the dark on MS medium containing 13.6???M 2,4-dichlorophenoxyacetic acid (2,4-D) and 2.3???M kinetin (KT) for 15?days and then transferred to 40???mol?m?2?s?1 fluorescent light for 30?days, the percentage callus induction reached 33.3?%. After callus was transferred to various differentiation media and cultured in the light, 33.1?% of all callus cultures could differentiate into adventitious shoots on MS medium supplemented with 22.0???M 6-benzyladenine (BA), 0.53???M ??-naphthaleneacetic acid (NAA) and 1.4???M thidiazuron (TDZ) after culturing for 60?days. Over 95?% of plantlets survived after transplanting plantlets into trays with a mixture of sand and perlite (2: 1) for 20?days. Chromosome number, determined from the root tips of young plantlets, indicated that all plantlets were diploid (2n?=?84). 相似文献
74.
Marlene M. Hao Joel C. Bornstein Pieter Vanden Berghe Alan E. Lomax Heather M. Young Jaime P.P. Foong 《Developmental biology》2013
The enteric nervous system (ENS) is a vital part of the autonomic nervous system that regulates many gastrointestinal functions, including motility and secretion. All neurons and glia of the ENS arise from neural crest-derived cells that migrate into the gastrointestinal tract during embryonic development. It has been known for many years that a subpopulation of the enteric neural crest-derived cells expresses pan-neuronal markers at early stages of ENS development. Recent studies have demonstrated that some enteric neurons exhibit electrical activity from as early as E11.5 in the mouse, with further maturation of activity during embryonic and postnatal development. This article discusses the maturation of electrophysiological and morphological properties of enteric neurons, the formation of synapses and synaptic activity, and the influence of neural activity on ENS development. 相似文献
75.
Graciela B. Arhancet Daniel P. Walker Sue Metz Yvette M. Fobian Steven E. Heasley Jeffrey S. Carter John R. Springer Darin E. Jones Michael J. Hayes Alexander F. Shaffer Gina M. Jerome Michael T. Baratta Ben Zweifel William M. Moore Jaime L. Masferrer Michael L. Vazquez 《Bioorganic & medicinal chemistry letters》2013,23(4):1114-1119
Inhibition of mPGES-1, the terminal enzyme in the arachidonic acid/COX pathway to regulate the production of pro-inflammatory prostaglandin PGE2, is considered an attractive new therapeutic target for safe and effective anti-inflammatory drugs. The discovery of a novel series of orally active, selective benzoxazole piperidinecarboxamides as mPGES-1 inhibitors is described. Structure–activity optimization of lead 5 with cyclohexyl carbinols resulted in compound 12, which showed excellent in vitro potency and selectivity against COX-2, and reasonable pharmacokinetic properties. Further SAR studies of the benzoxazole ring substituents lead to a novel series of highly potent compounds with improved PK profile, including 23, 26, and 29, which were effective in a carrageenan-stimulated guinea pig air pouch model of inflammation. Based on its excellent in vitro and in vivo pharmacological, pharmacokinetic and safety profile and ease of synthesis, compound 26 (PF-4693627) was advanced to clinical studies. 相似文献
76.
The severe acute respiratory syndrome coronavirus (SARS-CoV) envelope spike (S) glycoprotein is responsible for the fusion between the membranes of the virus and the target cell. In the case of the S2 domain of protein S, it has been found a highly hydrophobic and interfacial domain flanked by the heptad repeat 1 and 2 regions; significantly, different peptides pertaining to this domain have shown a significant leakage effect and an important plaque formation inhibition, which, similarly to HIV-1 gp41, support the role of this region in the fusion process. Therefore, we have carried out a study of the binding and interaction with model membranes of a peptide corresponding to segment 1073–1095 of the SARS-CoV S glycoprotein, peptide SARSL in the presence of different membrane model systems, as well as the structural changes taking place in both the lipid and the peptide induced by the binding of the peptide to the membrane. Our results show that SARSL strongly partitions into phospholipid membranes and organizes differently in lipid environments, displaying membrane activity modulated by the lipid composition of the membrane. These data would support its role in SARS-CoV mediated membrane fusion and suggest that the region where this peptide resides could be involved in the merging of the viral and target cell membranes. 相似文献
77.
Skeletal muscle formation during development and the adult mammal consists of a highly organised and regulated the sequence of cellular processes intending to form or repair muscle tissue. This sequence includes, cell proliferation, migration, and differentiation. Proteoglycans (PGs), macromolecules formed by a core protein and glycosaminoglycan chains (GAGs) present a great diversity of functions explained by their capacity to interact with different ligands and receptors forming part of their signalling complex and/or protecting them from proteolytic cleavage. Particularly attractive is the function of the different types of PGs present at the neuromuscular junction (NMJ). This review is focussed on the advances reached to understand the role of PGs during myogenesis and skeletal muscular dystrophies. 相似文献
78.
Donna J. Shaver Kristen M. Hart Ikuko Fujisaki Cynthia Rubio Autumn R. Sartain Jaime Peña Patrick M. Burchfield Daniel Gomez Gamez Jaime Ortiz 《Ecology and evolution》2013,3(7):2002-2012
For many marine species, locations of key foraging areas are not well defined. We used satellite telemetry and switching state‐space modeling (SSM) to identify distinct foraging areas used by Kemp's ridley turtles (Lepidochelys kempii) tagged after nesting during 1998–2011 at Padre Island National Seashore, Texas, USA (PAIS; N = 22), and Rancho Nuevo, Tamaulipas, Mexico (RN; N = 9). Overall, turtles traveled a mean distance of 793.1 km (±347.8 SD) to foraging sites, where 24 of 31 turtles showed foraging area fidelity (FAF) over time (N = 22 in USA, N = 2 in Mexico). Multiple turtles foraged along their migratory route, prior to arrival at their “final” foraging sites. We identified new foraging “hotspots” where adult female Kemp's ridley turtles spent 44% of their time during tracking (i.e., 2641/6009 tracking days in foraging mode). Nearshore Gulf of Mexico waters served as foraging habitat for all turtles tracked in this study; final foraging sites were located in water <68 m deep and a mean distance of 33.2 km (±25.3 SD) from the nearest mainland coast. Distance to release site, distance to mainland shore, annual mean sea surface temperature, bathymetry, and net primary production were significant predictors of sites where turtles spent large numbers of days in foraging mode. Spatial similarity of particular foraging sites selected by different turtles over the 13‐year tracking period indicates that these areas represent critical foraging habitat, particularly in waters off Louisiana. Furthermore, the wide distribution of foraging sites indicates that a foraging corridor exists for Kemp's ridleys in the Gulf. Our results highlight the need for further study of environmental and bathymetric components of foraging sites and prey resources contained therein, as well as international cooperation to protect essential at‐sea foraging habitats for this imperiled species. 相似文献
79.
Gene flow through dispersal has traditionally been thought to function as a force opposing evolutionary differentiation. However, directional gene flow may actually reinforce divergence of populations in close proximity. This study documents the phenotypic differentiation over more than two decades in body size (tarsus length) at a very short spatial scale (1.1 km) within a population of pied flycatchers Ficedula hypoleuca inhabiting deciduous and coniferous habitats. Unlike females, males breeding in the deciduous forest were consistently larger than those from the managed coniferous forest. This assortment by size is likely explained by preset habitat preferences leading to dominance of the largest males and exclusion of the smallest ones toward the nonpreferred coniferous forest coupled with directional dispersal. Movements of males between forests were nonrandom with respect to body size and flow rate, which might function to maintain the phenotypic variation in this heritable trait at such a small spatial scale. However, a deeply rooted preference for the deciduous habitat might not be in line with its quality due to the increased levels of breeding density of hole‐nesting competitors therein. These results illustrate how eco‐evolutionary scenarios can develop under directional gene flow over surprisingly small spatial scales. Our findings come on top of recent studies concerning new ways in which dispersal and gene flow can influence microevolution. 相似文献