bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue-Specific Transcriptomics in the Field CricketTeleogryllus oceanicus
Authors: Bailey Nathan W , Veltsos Paris , Tan Yew-Foon , Millar A Harvey , Ritchie Michael G , Simmons Leigh W 
Published: February 2013

AbstractField crickets (family Gryllidae) frequently are used in studies of behavioral genetics, sexual selection, and sexual conflict, but there have been no studies of transcriptomic differences among different tissue types. We evaluated transcriptome variation among testis, accessory gland, and the remaining whole-body preparations from males of the field cricket, Teleogryllus oceanicus. Non-normalized cDNA libraries from each tissue were sequenced on the Roche 454 platform, and a master assembly was constructed using testis, accessory gland, and whole-body preparations. A total of 940,200 reads were assembled into 41,962 contigs, to which 36,856 singletons (reads not assembled into a contig) were added to provide a total of 78,818 sequences used in annotation analysis. A total of 59,072 sequences (75%) were unique to one of the three tissues. Testis tissue had the greatest proportion of tissue-specific sequences (62.6%), followed by general body (56.43%) and accessory gland tissue (44.16%). We tested the hypothesis that tissues expressing gene products expected to evolve rapidly as a result of sexual selection—testis and accessory gland—would yield a smaller proportion of BLASTx matches to homologous genes in the model organism Drosophila melanogaster compared with whole-body tissue. Uniquely expressed sequences in both testis and accessory gland showed a significantly lower rate of matching to annotated D. melanogaster genes compared with those from general body tissue. These results correspond with empirical evidence that genes expressed in testis and accessory gland tissue are rapidly evolving targets of selection.
A Compendium of Caenorhabditis elegans RNA Binding Proteins Predicts Extensive Regulation at Multiple Levels
Authors: Tamburino Alex M , Ryder Sean P , Walhout Albertha J M 
Published: February 2013

Abstract
Gene expression is regulated at multiple levels, including transcription and translation, as well as mRNA and protein stability. Although systems-level functions of transcription factors and microRNAs are rapidly being characterized, few studies have focused on the posttranscriptional gene regulation by RNA binding proteins (RBPs). RBPs are important to many aspects of gene regulation. Thus, it is essential to know which genes encode RBPs, which RBPs regulate which gene(s), and how RBP genes are themselves regulated. Here we provide a comprehensive compendium of RBPs from the nematode Caenorhabditis elegans (wRBP1.0). We predict that as many as 887 (4.4%) of C. elegans genes may encode RBPs ~250 of which likely function in a gene-specific manner. In addition, we find that RBPs, and most notably gene-specific RBPs, are themselves enriched for binding and modification by regulatory proteins, indicating the potential for extensive regulation of RBPs at many different levels. wRBP1.0 will provide a significant contribution toward the comprehensive delineation of posttranscriptional regulatory networks and will provide a resource for further studies regulation by RBPs.
Redundant Canonical and NoncanonicalCaenorhabditis elegansp21-Activated Kinase Signaling Governs Distal Tip Cell Migrations
Authors: Peters Eldon C , Gossett Andrea J , Goldstein Bob , Der Channing J , Reiner David J 
Published: February 2013

Abstractp21-activated kinases (Paks) are prominent mediators of Rac/Cdc42-dependent and -independent signaling and regulate signal transduction and cytoskeletal-based cell movements. We used the reproducible migrations of the Caenorhabditis elegans gonadal distal tip cells to show that two of the three nematode Pak proteins, MAX-2 and PAK-1, function redundantly in regulation of cell migration but are regulated by very different mechanisms. First, we suggest that MAX-2 requires CED-10/Rac function and thus functions canonically. Second, PIX-1 and GIT-1 function in the same role as PAK-1, and PAK-1 interaction with PIX-1 is required for PAK-1 activity; thus, PAK-1 functions noncanonically. The human Pak-Pix-Git complex is central to noncanonical Pak signaling and requires only modest Rac/CDC-42 input. Unlike the human complex, our results suggest that the C. elegans Pak-Pix-Git complex requires PAK-1 kinase domain activity. This study delineates signaling network relationships in this cell migration model, thus providing potential further mechanistic insights and an assessment of total Pak contribution to cell migration events.
Caenorhabditis elegans POT-1 and POT-2 Repress Telomere Maintenance Pathways
Authors: Shtessel Ludmila , Lowden Mia Rochelle , Cheng Chen , Simon Matt , Wang Kyle , Ahmed Shawn 
Published: February 2013

Abstract
Telomeres are composed of simple tandem DNA repeats that protect the ends of linear chromosomes from replicative erosion or inappropriate DNA damage response mechanisms. The mammalian Protection Of Telomeres (POT1) protein interacts with single-stranded telomeric DNA and can exert positive and negative effects on telomere length. Of four distinct POT1 homologs in the roundworm Caenorhabditis elegans, deficiency for POT-1 or POT-2 resulted in progressive telomere elongation that occurred because both proteins negatively regulate telomerase. We created a POT-1::mCherry fusion protein that forms discrete foci at C. elegans telomeres, independent of POT-2, allowing for live analysis of telomere dynamics. Transgenic pot-1::mCherry repressed telomerase in pot-1 mutants. Animals deficient for pot-1, but not pot-2, displayed mildly enhanced telomere erosion rates in the absence of the telomerase reverse transcriptase, trt-1. However, trt-1; pot-1 double mutants exhibited delayed senescence in comparison to trt-1 animals, and senescence was further delayed in trt-1; pot-2; pot-1 triple mutants, some of which survived robustly in the absence of telomerase. Our results indicate that POT-1 and POT-2 play independent roles in suppressing a telomerase-independent telomere maintenance pathway but may function together to repress telomerase.
RNA Polymerase II Mutations Conferring Defects in Poly(A) Site Cleavage and Termination inSaccharomyces cerevisiae
Authors: Kubicek Charles E , Chisholm Robert D , Takayama Sachiko , Hawley Diane K 
Published: February 2013

AbstractTranscription termination by RNA polymerase (Pol) II is an essential but poorly understood process. In eukaryotic nuclei, the 3′ ends of mRNAs are generated by cleavage and polyadenylation, and the same sequence elements that specify that process are required for downstream release of the polymerase from the DNA. Although Pol II is known to bind proteins required for both events, few studies have focused on Pol II mutations as a means to uncover the mechanisms that couple polyadenylation and termination. We performed a genetic screen in the yeast Saccharomyces cerevisiae to isolate mutations in the N-terminal half of Rpb2, the second largest Pol II subunit, that conferred either a decreased or increased response to a well-characterized poly(A) site. Most of the mutant alleles encoded substitutions affecting either surface residues or conserved active site amino acids at positions important for termination by other RNA polymerases. Reverse transcription polymerase chain reaction experiments revealed that transcript cleavage at the poly(A) site was impaired in both classes of increased readthrough mutants. Transcription into downstream sequences beyond where termination normally occurs was also probed. Although most of the tested readthrough mutants showed a reduction in termination concomitant with the reduced poly(A) usage, these processes were uncoupled in at least one mutant strain. Several rpb2 alleles were found to be similar or identical to published mutants associated with defective TFIIF function. Tests of these and additional mutations known to impair Rpb2−TFIIF interactions revealed similar decreased readthrough phenotypes, suggesting that TFIIF may have a role in 3′ end formation and termination.
Saccharomyces cerevisiaeGenetics Predicts Candidate Therapeutic Genetic Interactions at the Mammalian Replication Fork
Authors: van Pel Derek M , Stirling Peter C , Minaker Sean W , Sipahimalani Payal , Hieter Philip 
Published: February 2013

AbstractThe concept of synthetic lethality has gained popularity as a rational guide for predicting chemotherapeutic targets based on negative genetic interactions between tumor-specific somatic mutations and a second-site target gene. One hallmark of most cancers that can be exploited by chemotherapies is chromosome instability (CIN). Because chromosome replication, maintenance, and segregation represent conserved and cell-essential processes, they can be modeled effectively in simpler eukaryotes such as Saccharomyces cerevisiae. Here we analyze and extend genetic networks of CIN cancer gene orthologs in yeast, focusing on essential genes. This identifies hub genes and processes that are candidate targets for synthetic lethal killing of cancer cells with defined somatic mutations. One hub process in these networks is DNA replication. A nonessential, fork-associated scaffold, CTF4, is among the most highly connected genes. As Ctf4 lacks enzymatic activity, potentially limiting its development as a therapeutic target, we exploited its function as a physical interaction hub to rationally predict synthetic lethal interactions between essential Ctf4-binding proteins and CIN cancer gene orthologs. We then validated a subset of predicted genetic interactions in a human colorectal cancer cell line, showing that siRNA-mediated knockdown of MRE11A sensitizes cells to depletion of various replication fork-associated proteins. Overall, this work describes methods to identify, predict, and validate in cancer cells candidate therapeutic targets for tumors with known somatic mutations in CIN genes using data from yeast. We affirm not only replication stress but also the targeting of DNA replication fork proteins themselves as potential targets for anticancer therapeutic development.
Genome-Wide Copy Number Variant Analysis in Inbred Chickens Lines With Different Susceptibility to Marek’s Disease
Authors: Luo Juan , Yu Ying , Mitra Apratim , Chang Shuang , Zhang Huanmin , Liu George , Yang Ning , Song Jiuzhou 
Published: February 2013

Abstract
Breeding of genetically resistant chickens to Marek’s disease (MD) is a vital strategy to poultry health. To find the markers underlying the genetic resistance to MD, copy number variation (CNV) was examined in inbred MD-resistant and -susceptible chicken lines. A total of 45 CNVs were found in four lines of chickens, and 28 were potentially involved in immune response and cell proliferation, etc. Importantly, two CNVs related with MD resistance were transmitted to descendent recombinant congenic lines that differ in susceptibility to MD. Our findings may lead to better strategies for genetic improvement of disease resistance in poultry.
Effect of Iron Deficiency Anemia in Pregnancy on Child Mental Development in Rural China
Authors: Chang Suying , Zeng Lingxia , Brouwer Inge D. , Kok Frans J. , Yan Hong 
Published: February 2013

OBJECTIVE:
To determine the impact of iron deficiency anemia (IDA) in pregnancy on young child development.

METHODS:
A 2-year follow-up of 850 children born to women who participated in a double-blind cluster randomized controlled trial of prenatal micronutrient supplementation in western rural China. These women were randomly assigned to receive either daily folic acid, iron/folic acid (60 mg iron), or multiple micronutrients (with 30 mg iron) during pregnancy. Children were categorized into the prenatal-IDA and prenatal–non-IDA groups based on the mother’s hemoglobin in the third trimester. Each group contained 3 subgroups based on mother’s treatment: folic acid, iron/folic acid, and multiple micronutrients. Bayley scales of infant development were administered to the children to assess their development at 3, 6, 12, 18, and 24 months of age.

RESULTS:
Compared with the prenatal–non-IDA group, the prenatal-IDA group showed a significantly lower mental development index at 12, 18, and 24 months of age. The adjusted mean difference was 5.8 (95% confidence interval [CI], 1.1–10.5), 5.1 (95% CI, 1.2–9.0), and 5.3 (95% CI, 0.9–9.7), respectively. Further analysis showed that the mental development indexes in the prenatal-IDA group and prenatal–non-IDA group were similar with supplementation of iron/folic acid but were significantly lower in the prenatal-IDA group with supplementation of folic acid or multiple micronutrients.

CONCLUSIONS:
Prenatal IDA in the third trimester is associated with mental development of the child. However, prenatal supplementation with sufficient iron protects child development even when the woman’s IDA was not properly corrected in pregnancy.
Cost-Effectiveness of the School-Based Asthma Therapy (SBAT) Program
Authors: Noyes Katia , Bajorska Alina , Fisher Susan , Sauer Joseph , Fagnano Maria , Halterman Jill S. 
Published: February 2013

BACKGROUND AND OBJECTIVE:Impoverished urban children suffer disproportionately from asthma and underuse preventive asthma medications. The objective of this study was to examine cost-effectiveness (CE) of the School-Based Asthma Therapy (SBAT) program compared with usual care (UC).METHODS:The analysis was based on the SBAT trial, including 525 children aged 3 to 10 years attending urban preschool or elementary school who were randomized to either UC or administration of 1 dose of preventive asthma medication at school by the school nurse each school day. The primary outcome was the mean number of symptom-free days (SFDs). The impact of the intervention on medical costs was estimated by using parent-reported child health services utilization data and average national reimbursement rates. We estimated the cost of running the program using wages for program staff. Productivity costs were estimated by using value of parent lost time due to child illness. CE of the SBAT program compared with UC was evaluated based on the incremental CE ratio.RESULTS:The health benefit of the intervention was equal to ∼158 SFD gained per each 30-day period (P &lt; .05) per 100 children. The programmatic expenses summed to an extra $4822 per 100 children per month. The net saving due to the intervention (reduction in medical costs and parental productivity, and improvement in school attendance) was $3240, resulting in the incremental cost-savings difference of $1583 and CE of $10 per 1 extra SFD gained.CONCLUSIONS:The SBAT was effective and cost-effective in reducing symptoms in urban children with asthma compared with other existing programs.
US Prevalence and Trends in Tobacco Smoke Exposure Among Children and Adolescents With Asthma
Authors: Kit Brian K. , Simon Alan E. , Brody Debra J. , Akinbami Lara J. 
Published: February 2013

OBJECTIVE:To examine exposure to tobacco smoke products (TSPs), environmental tobacco smoke (ETS), and in-home smoke among youth with asthma in the United States.METHODS:Nationally representative, cross-sectional data from 2250 youth aged 4 to 19 years with current asthma in the 1988–1994, 1999–2004, and 2005–2010 National Health and Nutrition Examination Survey (NHANES) were analyzed. Outcomes were use of TSPs (serum cotinine level &gt;10 ng/mL or self-reported recent use of cigarettes, cigars, or pipes) and, among non-TSP users, ETS exposure (serum cotinine ≥0.05 ng/mL) and in-home smoke exposure (reported). Multiple logistic regression analyses assessed the associations between the outcomes and age, gender, race/ethnicity, and family income.RESULTS:Among adolescents (aged 12–19 years) with asthma in 2005–2010, 17.3% reported TSP use. Among youth (aged 4–19 years) with asthma who did not use TSPs, 53.2% were exposed to ETS and 17.6% had in-home smoke exposure. Among low-income youth, 70.1% and 28.1% had exposure to ETS and in-home smoke, respectively. After controlling for sociodemographic factors, higher prevalence of exposure to ETS and in-home smoke persisted among low-income youth. Between 1988–1994 and 2005–2010, there was a decline in ETS and in-home smoke exposure (both P &lt; .001).CONCLUSIONS:ETS exposure among youth with asthma declined between 1988–1994 and 2005–2010, but a majority remained exposed in 2005–2010, with higher exposure among low-income youth. More than 1 in 6 youth with asthma in 2005–2010 were exposed to in-home smoke and a similar portion of adolescents used TSPs.
Comparative Effectiveness of Interventions for Children Exposed to Nonrelational Traumatic Events
Authors: Forman-Hoffman Valerie L. , Zolotor Adam J. , McKeeman Joni L. , Blanco Roberto , Knauer Stefanie R. , Lloyd Stacey W. , Fraser Jenifer Goldman , Viswanathan Meera 
Published: February 2013

OBJECTIVES:To assess the effectiveness of interventions targeting traumatic stress among children exposed to nonrelational traumatic events (eg, accidents, natural disasters, war).METHODS:We assessed research on psychological and pharmacological therapy as part of an Agency for Healthcare Research and Quality–commissioned comparative effectiveness review. We conducted focused searches of Medline, Cochrane Library, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, International Pharmaceutical Abstracts, and Web of Science. Two trained reviewers independently selected, extracted data from, and rated the risk of bias of relevant trials and systematic reviews. We used qualitative rather than quantitative analysis methods because of statistical heterogeneity, insufficient numbers of similar studies, and variation in outcome reporting.RESULTS:We found a total of 21 trials and 1 cohort study of medium or low risk of bias from our review of 6647 unduplicated abstracts. We generally did not find studies that attempted to replicate findings of effective interventions. In the short term, no pharmacotherapy intervention demonstrated efficacy, and only a few psychological treatments (each with elements of cognitive behavioral therapy) showed benefit. The body of evidence provides little insight into how interventions to treat children exposed to trauma might influence healthy long-term development.CONCLUSIONS:Our findings serve as a call to action: Psychotherapeutic intervention may be beneficial relative to no treatment in children exposed to traumatic events. Definitive guidance, however, requires far more research on the comparative effectiveness of interventions targeting children exposed to nonrelational traumatic events.
Suspended particles in wastewater: their optical, sedimentation and acoustical characterization and modeling
Authors: Pallarès A. , François P. , Pons M.-N. , Schmitt P. 
Published: February 2013

Wastewater regulation and treatment is still a major concern in planetary pollution management. Some pollutants, referred to as particulate matter, consist of very small particles just suspended in the water. Various techniques are used for the suspended particles survey. Few of them are able to provide real-time data. The development of new, real time instruments needs the confrontation with real wastewater. Due its instability, the modeling of wastewater in terms of suspended solids was explored.
Knowing the description of real wastewater, we tried to produce a synthetic mixture made of basic organic ingredients. A good agreement in terms of turbidity and settling velocity was observed between the artificial wastewater matrix and the real one. The investigation of the individual contribution of the different compounds to the acoustical signal showed a more complex dependance. Thus the modeling of wastewater with reference to turbidity and settling velocity is not sufficient to describe it acoustically. Further studies should lead to a good comparison of the acoustical and turbidity behavior of wastewater.
The Effect of Continuous Auditing on the Relationship between Internal Audit Sourcing and the External Auditor's Reliance on the Internal Audit Function
Authors: Davidson Bruce I. , Desai Naman K. , Gerard Gregory J. 
Published: February 2013

ABSTRACT
Prior research indicates that external auditors are willing to rely to a greater extent on the work of the internal audit (IA) function when the function has been outsourced, or co-sourced, as opposed to maintained in-house. This article addresses the extent to which this relationship between IA sourcing and external auditor reliance is moderated by the use of continuous auditing. One hundred forty-two auditors, all CPAs, participated in an experiment in which we manipulated both IA sourcing type (in-house versus outsourced) and audit type (periodic versus continuous) and measured ratings of external auditor reliance on the IA function. Results indicate that when the IA function uses periodic auditing, external auditors rely more on an outsourced function than an in-house function. However, when the IA function uses continuous auditing, external auditors do not differ in reliance on an outsourced or in-house function. The prior literature suggests that outsourcing an IA function can lead to higher levels of external auditor reliance and subsequently lower external audit costs. The results here suggest that maintaining the IA function in-house and employing continuous auditing may lead to similar external audit effects.
Evaluation of the effects of a killed whole-cell vaccine against Mycobacterium avium subsp paratuberculosis in 3 herds of dairy cattle with natural exposure to the organism
Authors: Knust Barbara , Patton Elisabeth , Ribeiro-Lima João , Bohn Jeff J. , Wells Scott J. 
Published: February 2013

Abstract
Objective—To evaluate effects of vaccination with a killed whole-cell vaccine against Mycobacterium avium subsp paratuberculosis (MAP) on fecal shedding of the organism, development of clinical paratuberculosis (Johne's disease [JD]), milk production, measures of reproduction, and within-herd longevity of dairy cattle naturally exposed to MAP.
Design—Controlled clinical trial.
Animals—200 vaccinated and 195 unvaccinated (control) dairy cows from 3 herds in Wisconsin.
Procedures—Every other heifer calf born in each herd received the MAP vaccine; 162 vaccinates and 145 controls that had ≥ 1 lactation were included in analyses. Bacteriologic culture of fecal samples for MAP was performed annually for 7 years; results were confirmed via histologic methods and PCR assay. Production records and culture results were evaluated to determine effects of vaccination on variables of interest in study cows. Annual whole-herd prevalence of MAP shedding in feces was also determined.
Results—Vaccinates had a significantly lower hazard of testing positive for MAP via culture of fecal samples than did controls over time (hazard ratio, 0.57; 95% confidence interval, 0.34 to 0.97). Fewer vaccinates developed clinical JD than did controls (n = 6 and 12, respectively), but these differences were nonsignificant. Overall within-herd longevity, total milk production, and calving-to-conception intervals were similar between vaccinates and controls. In all herds, prevalence of MAP shedding in feces decreased over time.
Conclusions and Clinical Relevance—Vaccination with a killed whole-cell MAP vaccine appeared to be an effective tool as part of a program to control the spread of JD in dairy cattle.
Mapping a medical curriculum using a learning objectives database - Lessons learned at the University of Munich
Authors: Hege Inga , Fischer Martin R. 
Published: February 2013

Abstract
A curriculum map gives an overall overview about a curriculum and what is taught where, when and how. At the medical faculty of the Ludwig-Maximilians-University in Munich (LMU) a curriculum mapping tool based on learning objectives was introduced some years ago. Since that time teachers could document the learning objectives of their courses in a standardised way. In this article we describe the status quo of our efforts and the challenges to implement such learning-objective-based
curriculum map that reflects the overall curriculum at our faculty.