Miracle-dz/UniFAR-FTUs huggingface dataset:
Partial Cloning of Putative G-Proteins Modulating Mechanotransduction in the Ciliate Stentor

Abstract Signal transduction systems known to utilize G-proteins in higher eukaryotes undoubtedly evolved prior to the development of metazoa. Pharmacological evidence indicates that the ciliates Paramecium, Stentor, and Tetrahymena all utilize signaling systems similar to those found in mammals. However, there has been relatively little direct evidence for the existence of G-proteins in ciliates. Since highly conserved heterotrimeric G-proteins form the basis of receptor-coupled signal transduction systems in a wide variety of metazoa, it is of interest to know if these important signaling molecules were early to evolve and are present and functionally important in a wide variety of unicellular organisms. We have previously shown that mechanotransduction in Stentor is modulated by opiates in a manner that may involve pertussis toxin-sensitive G-proteins. Here we utilize drugs known to interact with G-proteins to further test for the involvement of these important signaling molecules in Stentor mechanotransduction. We present behavioral and electrophysiological data demonstrating that putative G-proteins in Stentor decrease mechanical sensitivity by modulating the mechanotransduction process. In addition, we report the partial cloning of 4 G-protein α-subunits from Stentor. We confirm that these clones are of Stentor origin and are transcribed. Furthermore, we employ antisense oligodeoxynucleotide-mediated knockout to demonstrate that these ciliate G-proteins exert a modulatory influence on Stentor behavior, and that a Gi/Go-like clone mediates the inhibitory action of β-endorphin on mechanotransduction.
Molecular Insights Into μ Opioid Pharmacology: From the Clinic to the Bench

Most of the opioids used in clinical practice exert their effects through μ opioid receptors. Yet, subtle but important pharmacological differences have been observed among the μ opioids. Their potency, effectiveness, and adverse effects can vary unpredictably among patients. These clinical differences among the μ opioids strongly argue against a single receptor mediating their actions. The cloning of the μ opioid receptor has greatly enhanced our understanding of the complexity of this system and has provided possible mechanisms to explain these observations. A single μ opioid receptor gene has been identified, but we now know that it generates a multitude of different μ opioid receptor subtypes through a mechanism commonly used to enhance protein diversity, alternative splicing. Early studies identified a number of splice variants involving the tip of the C-terminus. This region of the receptor is far away from the binding pocket, explaining why these variants still exhibit the same selectivity for μ opioids. However, the differences in structure at the C-terminus influence the activation patterns of the μ opioids. In addition, a second series of variants has been isolated that involves alternative splicing at the N-terminus. Together, these sets of μ opioid receptor splice variants may help explain the clinical variability of the μ drugs among patients and provide insights into why it is so important to individualize therapy for every patient in pain.
A MOLECULAR PHYLOGENY OF THE DOVE GENERA STREPTOPELIA AND COLUMBA

Abstract Evolutionary history of the dove genus Streptopelia has not been examined with rigorous phylogenetic methods. We present a study of phylogenetic relationships of Streptopelia based on over 3,600 base pairs of nuclear and mitochondrial gene sequences. To test for monophyly of Streptopelia, we used several other columbiform taxa, including Columba (Old and New World), Macropygia, Reinwardtoena, and the enigmatic Pink Pigeon (Nesoenas mayeri). On the basis of our analyses, Streptopelia (as currently defined) is not monophyletic; Nesoenas mayeri is the sister species to S. picturata, resulting in paraphyly of Streptopelia. Three main clades of Streptopelia are identified: (1) S. chinensis plus S. senegalensis, (2) S. picturata plus Nesoenas mayeri, and (3) all other species of Streptopelia. It is unclear whether those clades form a monophyletic group to the exclusion of Old World Columba, but several analyses produce that result. Species of Old World Columba are closely related to Streptopelia, with species of New World Columba clustering outside that group. Taxonomic changes suggested by our results include merging Nesoenas with Streptopelia and changing the generic name for New World Columba species to Patagioenas. Vocal similarities between S. picturata and N. mayeri are striking, given the general diversity of vocalizations in other species.
Characterization of the Metal Ion Binding Properties of the Hepatitis C Virus RNA Polymerase*

The hepatitis C virus nonstructural 5B protein (NS5B) protein has been shown to require either magnesium or manganese for its RNA-dependent RNA polymerase activity. As a first step toward elucidating the nature and the role(s) of the metal ions in the reaction chemistry, we have utilized endogenous tryptophan fluorescence to quantitate the interactions of magnesium and manganese ions with this protein. The association of either Mg2+ or Mn2+ ions with the enzyme resulted in a decrease in the intensity of the tryptophan emission spectrum. This decrease was used to determine the apparent dissociation constants for both ions. The apparent K d values for the binding of Mg2+ and Mn2+ ions to the free enzyme were 3.1 and 0.3 mm, respectively. Dual ligand titration experiments demonstrated that both ions bind to a single common site, for which they compete. The kinetics of real time metal ion binding to the NS5B protein were also investigated. Based on the results of our fluorescence and near-UV circular dichroism experiments, we show that NS5B undergoes conformational changes upon the binding of metal ions. However, this process does not significantly stimulate the binding to the RNA or NTP substrates. We envisage that the ion-induced conformational change is a prerequisite for catalytic activity by both correctly positioning the side chains of the residues located in the active site of the enzyme and also contributing to the stabilization of the intermediate transition state.
[Combined glaucoma and diabetic retinopathy screening in Burgundy].

INTRODUCTION The aim of this study was to evaluate the yield of glaucoma and ocular hypertension (OHT) screening in association with diabetic retinopathy (DR) screening in a rural population. PATIENTS AND METHODS 676 patients were screened between 2004 and 2005. The four departments the Burgundy region were visited, divided into 39 areas with sparse medical services. Each patient had fundus photographs taken with a nonmydriatic camera and IOP measurement in each eye with a noncontact tonometer. Optic discs were classified into suspect or normal. RESULTS On the 676 screened patients, 41 presented an anomaly (6.1%): 31 with OHT (4.6%), 7 with a suspect optic disc (1.0%), and 3 with both anomalies (0.4%). After further control, we finally found 4 cases of OHT (0.6%) and 8 cases of glaucoma (1.2%). This screening program allowed the diagnosis of 2 new cases of OHT (0.3%) and 4 new cases of glaucoma (0.6%). DISCUSSION This screening improved the quality of the ophthalmic follow-up in rural areas for diabetics. Furthermore, it is a simple and not more expensive way to screen for OHT and glaucoma in these populations. CONCLUSION The itinerant screening of OHT and glaucoma combined with a diabetic retinopathy screening is effective. The screening campaign was renewed for 2 years in semi-rural zones.
Multicolor Stationary Light

Quantum coherence and interference (Scully & Zubairy, 1997) are leading edge topics in quantum optics and laser physics, and have led to many important novel effects, such as coherent population trapping (CPT) (Arimondo & Orriols, 1976; Alzetta et al., 1976; Gray et al., 1978), lasing without inversion (LWI) (Harris, 1989; Scully et al., 1989; Padmabandu et al., 1996), electromagnetically induced transparency (EIT) (Boller et al., 1991; Harris, 1997; Ham et al., 1997; Phillips et al., 2003; Fleischhauer et al., 2005; Marangos, 1998), high refractive index without absorption (Scully, 1991; Scully & Zhu 1992; Harris et al., 1990), giant Kerr nonlinear effect (Schmidt & Imamoglu, 1996), and so on. In particular, EIT, which can dramatically modify the absorption and dispersion characteristics of an optical medium, plays an important role in quantum optics. In the last two decades, EIT has attracted great attention and has been successfully applied to ultraslow and stopping light (Kasapi et al., 1995; Hau et al., 1999; Kocharovskaya et al., 2001; Liu et al., 2001; Turukhin et al., 2002), quantum switching (Ham & Hemmer, 2000), quantum memory (Ham et al., 1997; ibid., 1998), quantum entanglement generation (Lukin & Imamoglu, 2000), and quantum computing (Lukin & Imamoglu, 2001). It is well established that light is the fastest information carrier in nature. However, controlling light for localized application is very difficult. Thus, manipulation of light velocity becomes a crucial task in optical and quantum information processing (Nielsen & Chuang, 2000). Recently light localization using EIT has been demonstrated for stationary light (Bajcsy et al., 2003). Stationary light gives novel effects to nonlinear quantum optics in the context of lengthening light-matter interaction time. Compared with ultraslow light, where the medium’s length is a limiting factor, stationary light is free from spatial constraint. For example, the interaction time using ultraslow light in a semiconductor quantum dot, whose spatial dimension is less than a few tens of nanometers, is much less than nanosecond. By using a stationary light technique, however, we can enormously increase the interaction time of the light with such a nano optical medium. In this chapter, we discuss stationary light based on the EIT-induced ultraslow light phenomenon. We theoretically investigate how to dynamically manipulate multicolor (MC) stationary light in the multi double lambda-type system by simply changing the parameters of control fields, and demonstrate ultralong trapping of light, which is different from the conventional quantum mapping phenomenon. Quantum coherent control of the stationary light has potential applications to various quantum optical processing such as quantum nondemolition measurement and quantum wavelength conversion.
Fair Resource Allocation in Self-Organizing Heterogeneous Networks With Imperfect Connections

Interference management by controlling the transmission powers is crucial for unveiling the potential of heterogeneous networks. Power allocation has mostly been investigated using ideal communication links, where it is generally assumed that information can be relayed perfectly between base stations. The impact of delays and time-outs during communication is not well understood. We propose a model with nonideal links and a power adjustment algorithm for heterogeneous networks. Contrary to the power allocation approaches in the literature, channel state information is not required for power adjustment. The convergence properties of the proposed algorithm are investigated using tools from switched system theory and it is shown to converge to the max–min solution even with nonideal communication links. The simulation results are in agreement with the theoretical analysis.
Development of a Prediction Model for Post-Concussive Symptoms following Mild Traumatic Brain Injury: A TRACK-TBI Pilot Study.

Post-concussive symptoms occur frequently after mild traumatic brain injury (mTBI) and may be categorized as cognitive, somatic, or emotional. We aimed to: 1) assess whether patient demographics and clinical variables predict development of each of these three symptom categories, and 2) develop a prediction model for six-month post-concussive symptoms. MTBI patients (Glasgow Coma Scale score 13-15) from the prospective multicenter Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot study (2010-2012) who completed the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) at six-months post-injury were included. Linear regression was utilized to determine the predictive value of candidate predictors for cognitive, somatic, and emotional subscales individually as well as the overall RPQ. The final prediction model was developed using Lasso shrinkage and bootstrap validation. We included 277 mTBI patients (70% male, median age 42y). No major differences in the predictive value of our set of predictors existed for the cognitive, somatic, and emotional subscales, and therefore one prediction model for the RPQ total scale was developed. Years of education, pre-injury psychiatric disorders and prior TBI were the strongest predictors of six-month post-concussive symptoms. The total set of predictors explained 21% of the variance, which decreased to 14% after bootstrap validation. Demographic and clinical variables at baseline are predictive of six-month post-concussive symptoms following mTBI, however these variables explain less than one-fifth of the total variance in outcome. Model refinement with larger datasets, more granular variables, and objective biomarkers are needed before implementation in clinical practice.
The Construct and Predictive Validity of a Dynamic Assessment of Young Children Learning to Read: Implications for RTI Frameworks

The purpose of this study was to examine the construct and predictive validity of a dynamic assessment (DA) of decoding learning. Students (N = 318) were assessed in the fall of first grade on an array of instruments that were given in hopes of forecasting responsiveness to reading instruction. These instruments included DA as well as one-point-in-time (static) measures of early alphabetic knowledge, rapid automatized naming (RAN), phonemic awareness, oral vocabulary, listening comprehension, attentive behavior, and hyperactive or impulsive behavior. An IQ test was administered in spring of second grade. Measures of reading outcomes administered in spring of first grade were accuracy and fluency of word identification skills and reading comprehension. Factor analysis using principal axis factor extraction indicated that DA loaded on a first factor that also included language abilities and IQ, which the authors refer to as the “language, IQ, and DA” factor. It was relatively distinct from two additional factors: (a) “speeded alphabetic knowledge and RAN” and (b) “task-oriented behavior. ” A three-level (children nested within classroom; classrooms nested within school) random intercept model with fixed effects predictors suggested that DA differed from word attack in predicting future reading skill and that DA was a significant predictor of responsiveness to instruction, contributing unique variance to end-of-first-grade word identification and reading comprehension beyond that explained by other well-established predictors of reading development.
Effects of dietary protein-energy interrelationships on Holstein steer performance and ruminal bacterial fermentation in continuous culture.

In vivo and in vitro 3 x 2 factorial experiments were conducted concurrently to evaluate the incorporation of 0, 15, or 30% sugar beet pulp (SBP) as an energy source in diets fed to growing Holstein steers with either soybean meal (SBM) or alcohol-treated, defatted soybean flakes (ATSBF) as primary supplemental protein sources. Three groups of 42 Holstein steers each were fed six different diets from 54 kg initial BW to 320 kg in three experimental periods. There were no overall SBP level x protein source interactions (P greater than .05). Beet pulp level tended to decrease ADG (linear, P = .05) and increase feed/gain (linear, P less than .05) and DMI (quadratic, P less than .05). Each grower diet was used in a substrate for ruminal microbial metabolism in six dual-flow, continuous-culture fermenters. Organic matter and carbohydrate digestion were similar (P greater than .05) among diets. Increasing dietary levels of SBP caused a concomitant increase (P less than .05) in acetate and decrease (P less than .05) in butyrate and isobutyrate concentrations. Beet pulp level x protein source interactions (P less than .05) were observed for CP degradation, ammonia and nonammonia N, and dietary N flow. Crude protein degradation was higher (P less than .05) for the 0% SBP with SBM diet (81.3%) than for the 30% SBP with ATSBF diet (64.4%). Efficiency of bacterial synthesis was similar (P greater than .05) among diets. Results indicated that SBP is an effective dietary energy source for high-energy grower diets at 15 or 30% of the DM but may cause a decrease in some performance traits. There were no nutritional benefits of using ATSBF vs SBM as the supplemental N source.
Relationship Between Visual-Motor Integration and Spatial Organization of Written Language and Math

Purpose. The relationship between visual-motor integration and academic achievement is not clearly understood. The purpose of this study was to assess the type and frequency of errors made by children with poor visual-motor integration during a written language and math task. Methods. Eighteen children with normal visual-motor integration (≥36%) and 19 children with low visual-motor integration (≤16%) participated in the study. The two groups had similar ages, gender profiles, and cognitive and reading levels. Each group copied and solved math problems and copied a written passage. The errors for the math and writing task were combined into a total error score, and the time taken to complete each task was combined into a total time score. Results. The low visual-motor integration group made more errors than the normal visual-motor integration group. However, the time taken to copy both tasks was not different between the two groups. A secondary analysis of the errors revealed that alignment of numbers (p = 0.02), organization of math problems (p = 0.05), and spacing errors of letters and words (p = 0.01) were more common in the low visual-motor integration group. Conclusions. The results suggest that reduced visual-motor integration may contribute to poor spatial organization of written work.
Targeting Plasmodium ligands on mosquito salivary glands and midgut with a phage display peptide library

Despite vast efforts and expenditures in the past few decades, malaria continues to kill millions of persons every year, and new approaches for disease control are urgently needed. To complete its life cycle in the mosquito, Plasmodium, the causative agent of malaria, has to traverse the epithelia of the midgut and salivary glands. Although strong circumstantial evidence indicates that parasite interactions with the two organs are specific, hardly any information is available about the interacting molecules. By use of a phage display library, we identified a 12-aa peptide—salivary gland and midgut peptide 1 (SM1)—that binds to the distal lobes of the salivary gland and to the luminal side of the midgut epithelium, but not to the midgut surface facing the hemolymph or to ovaries. The coincidence of the tissues with which parasites and the SM1 peptide interact suggested that the parasite and peptide recognize the same surface ligand. In support of this hypothesis, the SM1 peptide strongly inhibited Plasmodium invasion of salivary gland and midgut epithelia. These experiments suggest a new strategy for the genetic manipulation of mosquito vectorial capacity.
Assessing the goodness of fit of personal risk models

We describe a flexible family of tests for evaluating the goodness of fit (calibration) of a pre‐specified personal risk model to the outcomes observed in a longitudinal cohort. Such evaluation involves using the risk model to assign each subject an absolute risk of developing the outcome within a given time from cohort entry and comparing subjects’ assigned risks with their observed outcomes. This comparison involves several issues. For example, subjects followed only for part of the risk period have unknown outcomes. Moreover, existing tests do not reveal the reasons for poor model fit when it occurs, which can reflect misspecification of the model's hazards for the competing risks of outcome development and death. To address these issues, we extend the model‐specified hazards for outcome and death, and use score statistics to test the null hypothesis that the extensions are unnecessary. Simulated cohort data applied to risk models whose outcome and mortality hazards agreed and disagreed with those generating the data show that the tests are sensitive to poor model fit, provide insight into the reasons for poor fit, and accommodate a wide range of model misspecification. We illustrate the methods by examining the calibration of two breast cancer risk models as applied to a cohort of participants in the Breast Cancer Family Registry. The methods can be implemented using the Risk Model Assessment Program, an R package freely available at http://stanford.edu/~ggong/rmap/. Copyright © 2014 John Wiley & Sons, Ltd.
Early embryonic expression of FGF4/6/9 gene and its role in the induction of mesenchyme and notochord in Ciona savignyi embryos

the morpholino oligo and synthetic Cs-FGF4/6/9 mRNA. Downregulation of b -catenin nuclear localization resulted in the absence of mesenchyme cell differentiation due to failure of the formation of signal-producing endodermal cells. Injection of synthetic Cs-FGF4/6/9 mRNA in b -catenin-downregulated embryos evoked mesenchyme cell differentiation. These results strongly suggest that Cs-FGF4/6/9 produced by endodermal cells acts an inductive signal for the differentiation of mesenchyme cells. On the other hand, the role of Cs-FGF4/6/9 in the induction of notochord cells is partial; the initial process of the induction was inhibited by Cs-FGF4/6/9 morpholino oligo, but notochord-speciﬁc genes were expressed later to form a partial notochord.
A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression.

OBJECTIVE This study was an evaluation of the omega-3 fatty acid docosahexaenoic acid (DHA) for the treatment of major depression. METHOD Thirty-six depressed patients were randomly assigned to receive DHA, 2 g/day, or placebo for 6 weeks. Response was defined a priori as a > or =50% reduction in the score on the Montgomery-Asberg Depression Rating Scale. Thirty-five participants were evaluable; 18 received DHA, and 17 received placebo. RESULTS Response rates were 27.8% in the DHA group and 23.5% in the placebo group. The difference in response rates between groups did not reach statistical significance. CONCLUSIONS This trial failed to show a significant effect of DHA monotherapy in subjects with major depression.