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101.
Discovery-based science education: functional genomic dissection in Drosophila by undergraduate researchers
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Chen J Call GB Beyer E Bui C Cespedes A Chan A Chan J Chan S Chhabra A Dang P Deravanesian A Hermogeno B Jen J Kim E Lee E Lewis G Marshall J Regalia K Shadpour F Shemmassian A Spivey K Wells M Wu J Yamauchi Y Yavari A Abrams A Abramson A Amado L Anderson J Bashour K Bibikova E Bookatz A Brewer S Buu N Calvillo S Cao J Chang A Chang D Chang Y Chen Y Choi J Chou J Datta S Davarifar A Desai P Fabrikant J Farnad S Fu K Garcia E Garrone N Gasparyan S Gayda P Goffstein C Gonzalez C Guirguis M 《PLoS biology》2005,3(2):e59
102.
Azo coupling reactions of N-α-acetylhistidine, N-α-acetyltyrosine, and N-α-acetyllysine with p-methylbenzenediazonium ion were investigated as model reactions to obtain information on the relative reactivity of the histidine, tyrosine, and lysine moieties of protein, separated from structural effects. The azo coupling yields of the amino acids increased as the pH of the reaction medium was increased, indicating that the ractive species are the imidazole anion of histidine, the phenolate anion of tyrosine, and the neutral ε-amino group of lysine. It was calculated, based on percentage yields of the azo products, that the imidazole anion is more reactive than the phenolate anion and the ε-amino group, respectively. 相似文献
103.
This paper provides a brief account of 31 plants associated with herbal remedies among the Hayas, a tribe of Kagera region, Tanzania. Reports from informants were obtained during field studies in June 1987. For each species are given the botanical name, vernacular name, collection number, locality, habit, dis-tribution and medical uses. The data are compared with information from literature for medical uses, and listed isolated constituents and pharmacological effects. The Hayas have had a rich herbal folklore, but this is fading due to increasing acculturation and depletion of plant cover. 相似文献
104.
Randomized sham‐controlled trial evaluating efficacy and safety of endoscopic gastric plication for primary obesity: The ESSENTIAL trial
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Shelby Sullivan James M. Swain George Woodman Marc Antonetti Nestor De La Cruz‐Muñoz Sreeni S. Jonnalagadda Michael Ujiki Sayeed Ikramuddin Jaime Ponce Marvin Ryou Jason Reynoso Rajiv Chhabra G. Brent Sorenson Wendell K. Clarkston Steven A. Edmundowicz J. Christopher Eagon Daniel K. Mullady Daniel Leslie Thomas E. Lavin Christopher C. Thompson 《Obesity (Silver Spring, Md.)》2017,25(2):294-301
105.
M. Harunur Rashid Germano Heinzelmann Redwan Huq Rajeev B. Tajhya Shih Chieh Chang Sandeep Chhabra Michael W. Pennington Christine Beeton Raymond S. Norton Serdar Kuyucak 《PloS one》2013,8(11)
The voltage-gated potassium channel Kv1.3 is a well-established target for treatment of autoimmune diseases. ShK peptide from a sea anemone is one of the most potent blockers of Kv1.3 but its application as a therapeutic agent for autoimmune diseases is limited by its lack of selectivity against other Kv channels, in particular Kv1.1. Accurate models of Kv1.x-ShK complexes suggest that specific charge mutations on ShK could considerably enhance its specificity for Kv1.3. Here we evaluate the K18A mutation on ShK, and calculate the change in binding free energy associated with this mutation using the path-independent free energy perturbation and thermodynamic integration methods, with a novel implementation that avoids convergence problems. To check the accuracy of the results, the binding free energy differences were also determined from path-dependent potential of mean force calculations. The two methods yield consistent results for the K18A mutation in ShK and predict a 2 kcal/mol gain in Kv1.3/Kv1.1 selectivity free energy relative to wild-type peptide. Functional assays confirm the predicted selectivity gain for ShK[K18A] and suggest that it will be a valuable lead in the development of therapeutics for autoimmune diseases. 相似文献
106.
Barry R. Zeebèrg Ralph C. Reid Katherine A. Murphy Richard C. Reba 《Bulletin of mathematical biology》1988,50(5):423-444
A simplified one-dimensional model system was used to test the possibility that physically realistic parameters would lead
to the prediction of microscopic heterogeneity of radioligand distribution in the brain and that microscopic heterogeneity
of radioligand and neuroreceptor distribution could influence the macroscopically observedin vivo kinetics. The model was represented mathematically by a partial differential equation which is similar to the heat diffusion
equation, but with special boundary conditions. The equation was solved analytically under the condition of negligible receptor
occupancy by inversion of the Laplace transform and in the more general case of arbitrary receptor occupancy by cubic spline
approximation. In simulations with physically reasonable values for rate constants and parameters, we find that significant
radioligand gradients can occur. Thus, the level of radioligand in the immediate vicinity of the receptor may be substantially
different from the average level in a macroscopically measured region of interest.
In order to analyze the simulated data, we derived a rigorous steady-state solution, including both a statement of necessary
and sufficient conditions for the validity of the steady-state approximation as well as a demonstration of the proper technique
for assessing the consistency of the derived parameter with the requirements of the approximation. The radioligand heterogeneity
leads to significant errors in the parameters estimated in the steady-state kinetic analysis. In particular, the pseudo first-order
rate constant for radioligand-neuroreceptor association, which is often used as a measure of the total amount of neuroreceptor,
is underestimated. The first-order rate constant for radioligand-neuroreceptor dissociation is also underestimated. These
effects can partially account for the experimentally-observed discrepancy betweenin vivo andin vitro estimates of these kinetic parameters. 相似文献
107.
Divya Chhabra Sunita Sharma Alvin T Kho Roger Gaedigk Carrie A Vyhlidal J Steven Leeder Jarrett Morrow Vincent J Carey Scott T Weiss Kelan G Tantisira Dawn L DeMeo 《Epigenetics》2014,9(11):1473-1484
In utero smoke exposure has been shown to have detrimental effects on lung function and to be associated with persistent wheezing and asthma in children. One potential mechanism of IUS effects could be alterations in DNA methylation, which may have life-long implications. The goal of this study was to examine the association between DNA methylation and nicotine exposure in fetal lung and placental tissue in early development; nicotine exposure in this analysis represents a likely surrogate for in-utero smoke. We performed an epigenome-wide analysis of DNA methylation in fetal lung tissue (n = 85, 41 smoke exposed (48%), 44 controls) and the corresponding placental tissue samples (n = 80, 39 smoke exposed (49%), 41 controls) using the Illumina HumanMethylation450 BeadChip array. Differential methylation analyses were conducted to evaluate the variation associated with nicotine exposure. The most significant CpG sites in the fetal lung analysis mapped to the PKP3 (P = 2.94 × 10−03), ANKRD33B (P = 3.12 × 10−03), CNTD2 (P = 4.9 × 10−03) and DPP10 (P = 5.43 × 10−03) genes. In the placental methylome, the most significant CpG sites mapped to the GTF2H2C and GTF2H2D genes (P = 2.87 × 10−06 − 3.48 × 10−05). One hundred and one unique CpG sites with P-values < 0.05 were concordant between lung and placental tissue analyses. Gene Set Enrichment Analysis demonstrated enrichment of specific disorders, such as asthma and immune disorders. Our findings demonstrate an association between in utero nicotine exposure and variable DNA methylation in fetal lung and placental tissues, suggesting a role for DNA methylation variation in the fetal origins of chronic diseases. 相似文献
108.
Ria Gupta Aayushi Mittal Vishesh Agrawal Sushant Gupta Krishan Gupta Rishi Raj Jain Prakriti Garg Sanjay Kumar Mohanty Riya Sogani Harshit Singh Chhabra Vishakha Gautam Tripti Mishra Debarka Sengupta Gaurav Ahuja 《The Journal of biological chemistry》2021,297(2)
The molecular mechanisms of olfaction, or the sense of smell, are relatively underexplored compared with other sensory systems, primarily because of its underlying molecular complexity and the limited availability of dedicated predictive computational tools. Odorant receptors (ORs) allow the detection and discrimination of a myriad of odorant molecules and therefore mediate the first step of the olfactory signaling cascade. To date, odorant (or agonist) information for the majority of these receptors is still unknown, limiting our understanding of their functional relevance in odor-induced behavioral responses. In this study, we introduce OdoriFy, a Web server featuring powerful deep neural network–based prediction engines. OdoriFy enables (1) identification of odorant molecules for wildtype or mutant human ORs (Odor Finder); (2) classification of user-provided chemicals as odorants/nonodorants (Odorant Predictor); (3) identification of responsive ORs for a query odorant (OR Finder); and (4) interaction validation using Odorant–OR Pair Analysis. In addition, OdoriFy provides the rationale behind every prediction it makes by leveraging explainable artificial intelligence. This module highlights the basis of the prediction of odorants/nonodorants at atomic resolution and for the ORs at amino acid levels. A key distinguishing feature of OdoriFy is that it is built on a comprehensive repertoire of manually curated information of human ORs with their known agonists and nonagonists, making it a highly interactive and resource-enriched Web server. Moreover, comparative analysis of OdoriFy predictions with an alternative structure-based ligand interaction method revealed comparable results. OdoriFy is available freely as a web service at https://odorify.ahujalab.iiitd.edu.in/olfy/. 相似文献
109.
Formin proteins modulate both nucleation and elongation of actin filaments through processive movement of their dimeric formin homology 2 (FH2) domains with filament barbed ends. Mammals possess at least 15 formin genes. A subset of formins termed "diaphanous formins" are regulated by autoinhibition through interaction between an N-terminal diaphanous inhibitory domain (DID) and a C-terminal diaphanous autoregulatory domain (DAD). Here, we found several striking features for the mouse formin, INF2. First, INF2 interacted directly with actin through a region C-terminal to the FH2. This second interacting region sequesters actin monomers, an activity that is dependent on a WASP homology 2 (WH2) motif. Second, the combination of the FH2 and C-terminal regions of INF2 resulted in its curious ability to accelerate both polymerization and depolymerization of actin filaments. The mechanism of the depolymerization activity, which is novel for formin proteins, involves both the monomer binding ability of the WH2 and a potent severing activity that is dependent on covalent attachment of the FH2 to the C terminus. Phosphate inhibits both the depolymerization and severing activities of INF2, suggesting that phosphate release from actin subunits in the filament is a trigger for depolymerization. Third, INF2 contains an N-terminal DID, and the WH2 motif likely doubles as a DAD in an autoinhibitory interaction. 相似文献
110.
Photorhabdus temperata strain K122 exhibited oral toxicity against Prays oleae with an LC50 of 58.1 x 10(6) cells ml(-1). Recombinant P. temperata strains expressing the cry1Aa and/or cry1Ia genes of Bacillus thuringiensis have been constructed. The two cry genes, encoding delta-endotoxins, were placed under the control of the lac promoter and IPTG dependent expression in P. temperata was demonstrated. The presence of the cry genes in K122 resulted in a clear improvement of oral toxicity. This improvement was of 6.2-, 6.6-, and 14.6-fold for the strains K122(pBCcry1Aa), K122(pBScry1Ia), and K122(pBCcry1Aa + pBScry1Ia), respectively. Furthermore, determination of the Synergistic Factor between Cry1Aa and Cry1Ia showed that they act synergistically. This work demonstrates that the heterologous expression of B. thuringiensis cry genes in P. temperata can be used to improve and broaden its host range for insect control. 相似文献