bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan-vertebrate comparative genomics unmasks retrovirus macroevolution
Authors: Hayward Alexander , Cornwallis Charlie K. , Jern Patric 
Published: December 2014

SignificanceFor millions of years retroviruses, such as HIV in humans, have attacked vertebrates. Occasionally retroviruses infiltrate germ cells, incorporate themselves into the host’s genome, and transmit vertically to the host’s offspring as endogenous retroviruses (ERVs). Consequently, ERVs make up large portions of vertebrate genomes and represent a record of past host–retrovirus interactions. We developed pan-vertebrate ERV analyses to provide an overview of host–retrovirus interactions, generating insights into retroviral evolution, diversity, host-switching, and the factors influencing retroviral transmission. Astoundingly, we found over 36,000 ERV lineages across our sample of vertebrate diversity. The results provide knowledge about host–retrovirus coevolution, suggesting an unprecedented ability of retroviruses to switch between distantly related vertebrates and implying existence of additional, yet unidentified retroviruses.
HDAC inhibition imparts beneficial transgenerational effects in Huntington's disease mice via altered DNA and histone methylation
Authors: Jia Haiqun , Morris Charles D. , Williams Roy M. , Loring Jeanne F. , Thomas Elizabeth A. 
Published: December 2014

Significance
We demonstrate that histone deacetylase (HDAC) inhibition can elicit changes in DNA methylation in Huntington’s disease (HD) human fibroblasts, as well as in sperm from HD transgenic mice, in association with DNA methylation-related gene expression changes. We suggest that alterations in sperm DNA methylation lead to transgenerational effects, and, accordingly, we show that first filial generation (F1) offspring of HDAC inhibitor-treated male HD transgenic mice show improved HD disease phenotypes compared with F1 offspring from vehicle-treated male HD transgenic mice. These findings have significant implications for human health because they enforce the concept that ancestral drug exposure may be a major molecular factor that can affect disease phenotypes, yet in a positive manner. Further, we implicate Lys (K)-specific demethylase 5d expression in this phenomenon.
Evening use of light-emitting eReaders negatively affects sleep, circadian timing, and next-morning alertness
Authors: Chang Anne-Marie , Aeschbach Daniel , Duffy Jeanne F. , Czeisler Charles A. 
Published: December 2014

SignificanceThe use of light-emitting electronic devices for reading, communication, and entertainment has greatly increased recently. We found that the use of these devices before bedtime prolongs the time it takes to fall asleep, delays the circadian clock, suppresses levels of the sleep-promoting hormone melatonin, reduces the amount and delays the timing of REM sleep, and reduces alertness the following morning. Use of light-emitting devices immediately before bedtime also increases alertness at that time, which may lead users to delay bedtime at home. Overall, we found that the use of portable light-emitting devices immediately before bedtime has biological effects that may perpetuate sleep deficiency and disrupt circadian rhythms, both of which can have adverse impacts on performance, health, and safety.
Rare allele of a previously unidentified histone H4 acetyltransferase enhances grain weight, yield, and plant biomass in rice
Authors: Song Xian Jun , Kuroha Takeshi , Ayano Madoka , Furuta Tomoyuki , Nagai Keisuke , Komeda Norio , Segami Shuhei , Miura Kotaro , Ogawa Daisuke , Kamura Takumi , Suzuki Takamasa , Higashiyama Tetsuya , Yamasaki Masanori , Mori Hitoshi , Inukai Yoshiaki , Wu Jianzhong , Kitano Hidemi , Sakakibara Hitoshi , Jacobsen Steven E. , Ashikari Motoyuki 
Published: December 2014

Significance
Grain weight is an important crop yield component; however, its underlying regulatory mechanisms are largely unknown. Here, we identify a grain-weight quantitative trait locus (QTL) in rice encoding a new-type GNAT-like protein that harbors intrinsic histone acetyltransferase activity (OsglHAT1). Elevated OsglHAT1 expression enhances grain weight and yield by enlarging spikelet hulls via increasing cell number and accelerating grain filling, and increases global acetylation levels of histone H4. Our findings reveal the first example, to our knowledge, of a QTL for a yield component trait being due to a chromatin modifier that has the potential to improve crop high-yield breeding.
A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome
Authors: Bowles Nicole P. , Karatsoreos Ilia N. , Li Xiaosong , Vemuri V. Kiran , Wood Jodi-Anne , Li Zhiying , Tamashiro Kellie L. K. , Schwartz Gary J. , Makriyannis Alexandros M. , Kunos George , Hillard Cecilia J. , McEwen Bruce S. , Hill Matthew N. 
Published: December 2014

Significance
Obesity and associated metabolic disorders (e.g., cardiovascular disease and type 2 diabetes) are major public health concerns. These disorders result, in part, from hormonal dysregulation, particularly of glucocorticoids (GCs; central regulators of metabolism and adipogenesis). The specific mechanisms by which GCs modulate these processes remain largely unknown, but GCs increase production of endocannabinoids—potent central and peripheral regulators of appetite, energy balance, and metabolism. Our results show that sustained exposure to GCs produces obesity and metabolic syndrome through a peripheral endocannabinoid mechanism. These data further our understanding of the role of endocannabinoid signaling to promote not only diet-induced, but also, hormonal-mediated obesity and support the argument that peripheral blockade of endocannabinoid signaling could be a potential treatment for obese conditions.
Only three driver gene mutations are required for the development of lung and colorectal cancers
Authors: Tomasetti Cristian , Marchionni Luigi , Nowak Martin A. , Parmigiani Giovanni , Vogelstein Bert 
Published: December 2014

Significance
The number of driver events required for human tumorigenesis has remained one of the fundamental issues in cancer research since the seminal studies of Armitage and Doll. This question has become even more important with the recent genome-wide sequencing studies of cancer, whose major goal is the identification of the driver genes responsible for tumor initiation and progression. By using a novel approach that combines conventional epidemiologic studies with genome-wide sequencing data, we show that only three sequential mutations are required to develop lung and colon adenocarcinomas, a number that is lower than what is typically thought to be required for the formation of cancers of these and other organs. This finding has important implications for the design of future cancer genome-sequencing efforts.
PBOOST: a GPU-based tool for parallel permutation tests in genome-wide association studies
Authors: Yang Guangyuan , Jiang Wei , Yang Qiang , Yu Weichuan 
Published: December 2014

Abstract
Motivation: The importance of testing associations allowing for interactions has been demonstrated by Marchini et al. (2005). A fast method detecting associations allowing for interactions has been proposed by Wan et al. (2010a). The method is based on likelihood ratio test with the assumption that the statistic follows the χ2 distribution. Many single nucleotide polymorphism (SNP) pairs with significant associations allowing for interactions have been detected using their method. However, the assumption of χ2 test requires the expected values in each cell of the contingency table to be at least five. This assumption is violated in some identified SNP pairs. In this case, likelihood ratio test may not be applicable any more. Permutation test is an ideal approach to checking the P-values calculated in likelihood ratio test because of its non-parametric nature. The P-values of SNP pairs having significant associations with disease are always extremely small. Thus, we need a huge number of permutations to achieve correspondingly high resolution for the P-values. In order to investigate whether the P-values from likelihood ratio tests are reliable, a fast permutation tool to accomplish large number of permutations is desirable.
Results: We developed a permutation tool named PBOOST. It is based on GPU with highly reliable P-value estimation. By using simulation data, we found that the P-values from likelihood ratio tests will have relative error of &gt;100% when 50% cells in the contingency table have expected count less than five or when there is zero expected count in any of the contingency table cells. In terms of speed, PBOOST completed 107 permutations for a single SNP pair from the Wellcome Trust Case Control Consortium (WTCCC) genome data (Wellcome Trust Case Control Consortium, 2007) within 1 min on a single Nvidia Tesla M2090 device, while it took 60 min in a single CPU Intel Xeon E5-2650 to finish the same task. More importantly, when simultaneously testing 256 SNP pairs for 107 permutations, our tool took only 5 min, while the CPU program took 10 h. By permuting on a GPU cluster consisting of 40 nodes, we completed 1012 permutations for all 280 SNP pairs reported with P-values smaller than 1.6×10−12 in the WTCCC datasets in 1 week.
Availability and implementation: The source code and sample data are available at http://bioinformatics.ust.hk/PBOOST.zip.
Contact: gyang@ust.hk; eeyu@ust.hk
Supplementary information: Supplementary data are available at Bioinformatics online.
Clinic staff attitudes towards the use of mHealth technology to conduct perinatal depression screenings: a qualitative study
Authors: Pineros-Leano Maria , Tabb Karen M , Sears Heather , Meline Brandon , Huang Hsiang 
Published: December 2014

Abstract

Background.
The use of mHealth technology is an innovative approach for screening low-income mothers for depression. Past studies show that the use of technology removes barriers such as literacy issues, language challenges, concerns about privacy and lack of transportation and can also increase reliability. However, little is known about staff attitudes and perceptions towards using mHealth technology for screening low-income women for depression in clinics.

Methods.
Four focus groups were conducted with staff members in a supplemental nutrition program for women, infants and children located in a public health clinic. A semi-structured focus group interview guide was used to examine staff perceptions related to depression screening with tablet technology. All interviews were audio recorded and transcribed verbatim. Thematic analysis was used to analyse all focus group data.

Results.
Three major benefits and two major barriers were found. The benefits of using technology for perinatal depression screenings were reduction of literacy and language barriers, reduction of redundancy and errors and increased privacy for clients. The barriers were increased network issues and responsibility for technology, which included fear of the devices being lost, stolen or broken.

Implications.
Before implementing mHealth tablet technology for depression screening in a public health clinic, it is important to address the concerns of staff members to make the transition more effective. This study provides timely information on staff-perceived benefits and barriers when implementing mHealth technology in a public health setting.
Rifampicin and rifapentine significantly reduce concentrations of bedaquiline, a new anti-TB drug
Authors: Svensson Elin M. , Murray Stephen , Karlsson Mats O. , Dooley Kelly E. 
Published: December 2014

AbstractObjectivesBedaquiline is the first drug of a new class approved for the treatment of TB in decades. Bedaquiline is metabolized by cytochrome P450 (CYP) 3A4 to a less-active M2 metabolite. Its terminal half-life is extremely long (5–6 months), complicating evaluations of drug–drug interactions. Rifampicin and rifapentine, two anti-TB drugs now being optimized to shorten TB treatment duration, are potent inducers of CYP3A4. This analysis aimed to predict the effect of repeated doses of rifampicin or rifapentine on the steady-state pharmacokinetics of bedaquiline and its M2 metabolite from single-dose data using a model-based approach.MethodsPharmacokinetic data for bedaquiline and M2 were obtained from a Phase I study involving 32 individuals each receiving two doses of bedaquiline, alone or together with multiple-dose rifampicin or rifapentine. Sampling was performed over 14 days following each bedaquiline dose. Pharmacokinetic analyses were performed using non-linear mixed-effects modelling. Models were used to simulate potential dose adjustments.ResultsRifamycin co-administration increased bedaquiline clearance substantially: 4.78-fold [relative standard error (RSE) 9.10%] with rifampicin and 3.96-fold (RSE 5.00%) with rifapentine. Induction of M2 clearance was equally strong. Average steady-state concentrations of bedaquiline and M2 are predicted to decrease by 79% and 75% when given with rifampicin or rifapentine, respectively. Simulations indicated that increasing the bedaquiline dosage to mitigate the interaction would yield elevated M2 concentrations during the first treatment weeks.ConclusionsRifamycin antibiotics reduce bedaquiline concentrations substantially. In line with current treatment guidelines for drug-susceptible TB, concomitant use is not recommended, even with dose adjustment.
Pollen feeding proteomics: salivary proteins of the passion flower butterfly,Heliconius melpomene
Authors: Harpel Desiree , Cullen Darron A. , Ott Swidbert , Jiggins Chris D. , Walters James R. 
Published: December 2014

AbstractWhile most adult Lepidoptera use flower nectar as their primary food source, butterflies in the genusHeliconiushave evolved the novel ability to acquire amino acids from consuming pollen.Heliconiusbutterflies collect pollen on their proboscis, moisten the pollen with saliva, and use a combination of mechanical disruption and chemical degradation to release free amino acids that are subsequently re-ingested in the saliva. Little is known about the molecular mechanisms of this complex pollen feeding adaptation. Here we report an initial shotgun proteomic analysis of saliva fromHeliconius melpomene. Results from liquid-chromatography tandem mass-spectrometry confidently identified 31 salivary proteins, most of which contained predicted signal peptides, consistent with extracellular secretion. Further bioinformatic annotation of these salivary proteins indicated the presence of four distinct functional classes: proteolysis (10 proteins), carbohydrate hydrolysis (5), immunity (6), and “housekeeping”(4). Additionally, six proteins could not be functionally annotated beyond containing a predicted signal sequence. The presence of several salivary proteases is consistent with previous demonstrations thatHeliconiussaliva has proteolytic capacity. It is likely these proteins play a key role in generating free amino acids during pollen digestion. The identification of proteins functioning in carbohydrate hydrolysis is consistent withHeliconiusbutterflies consuming nectar, like other lepidopterans, as well as pollen. Immune-related proteins in saliva are also expected, given that ingestion of pathogens is a very likely route to infection. The few “housekeeping” proteins are likely not true salivary proteins and reflect a modest level of contamination that occurred during saliva collection. Among the unannotated proteins were two sets of paralogs, each seemingly the result of a relatively recent tandem duplication. These results offer a first glimpse into the molecular foundation ofHeliconiuspollen feeding and provide a substantial advance towards comprehensively understanding this striking evolutionary novelty.
Crystallization and preliminary X-ray analysis of the type IV restriction endonuclease ScoMcrA fromStreptomyces coelicolor, which cleaves both Dcm-methylated DNA and phosphorothioated DNA
Authors: Liu Guang , Zhang Zhenyi , Zhao Gong , Deng Zixin , Wu Geng , He Xinyi 
Published: December 2014

ScoMcrA is a type IV modification-dependent restriction endonuclease found in the model strainStreptomyces coelicolor. Unlike type I, II and III restriction endonucleases, which cleave unmodified DNA, type IV restriction endonucleases cleave modified DNA, including methylated, hydroxymethylated, glucosyl-hydroxymethylated and phosphorothioated DNA. ScoMcrA targets both Dcm-methylated DNA and phosphorothioated DNA, and makes double-strand breaks 16–28 nt away from the modified nucleotides or the phosphorothioate links. However, the mechanism by which ScoMcrA recognizes these two entirely different types of modification remains unclear. In this study, the ScoMcrA protein was overexpressed, purified and crystallized. The crystals diffracted to 3.35 Å resolution and belonged to space groupP212121. The unit-cell parameters were determined to bea= 130.19,b= 139.36,c= 281.01 Å, α = β = γ = 90°. These results will facilitate the detailed structural analysis of ScoMcrA and further elucidation of its biochemical mechanism.
Pakistan Accumulators (PVT) Limited (PAL) – a third world perspective
Authors: Hussain Umer 
Published: December 2014

Subject area
Operational Management, Strategic Management and Marketing Management.

Study level/applicability
The case can be taught in introductory marketing courses and management and organizational policy course and in advanced level in promotion, distribution channels, marketing research, consumer behavior and brand management courses at graduate level. Importance of market and technological research; first mover advantage and disadvantages in new market segment; importance of competition in a market; use of PESTL analysis before pursuing for any segment; types of growth strategies which could be used that is Broad base or Narrow base; how company uses marketing mix strategy; and how managers make decision in dynamic environment (contingency theory approach).

Case overview
This case study relates to a real-life situation the data was collected from primary and secondary sources between 2012 and 2013. The case is of a company Pakistan Accumulators (PAL), having less than 18 years of experience, has been able to grow successfully in the dynamic environment of Pakistan. The decline of the private businesses in Pakistan due to the energy crisis has popped up a new need of power generation alternative equipment in the country. PAL, which is a privately owned company, suppliers of automotive batteries, Uninterruptable Power System (UPS) batteries, lead acid batteries and rechargeable batteries has been able to manage the growth of 20 per cent per year. In this case study, we have highlighted only one market segment of the company that is of UPS batteries, we have focused on what is the future prospect of this particular segment, its attractiveness. Also, the area of focus was the new market segments which can be targeted by the company. Basic issues of the case study: calculation of the market segment value of UPS industry; identification and solution of different challenges faced by PAL in the dynamic Pakistani market (contingency theory); recognition of different future growth prospects for PAL.

Expected learning outcomes
The basic objective of this case is to enhance the analytical and qualitative skills of the students by giving them the real-life perspective of a company working successfully in country like Pakistan which is facing economic and political crises. This case can also be used for understanding the problems of third-world markets and how company can pursue successfully in the long–term.

Supplementary materials
Teaching notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.
Co‐evolution of foraging behaviour in herbivores and their natural enemies predicts multifunctionality of herbivore‐induced plant volatiles
Authors: Yoneya Kinuyo , Miki Takeshi 
Published: December 2014

SummaryHerbivorous arthropods often induce phenotypic changes in plants of terrestrial systems, which include increased direct resistance to herbivores. In addition, infested plants release quantitatively and qualitatively different volatiles from those of uninfested plants, which are so‐called herbivore‐induced plant volatiles (HIPVs). Due toHIPVs, plants are more conspicuous to herbivorous arthropods and their natural enemies (carnivorous arthropods) than uninfested plants, thus acting as foraging cues in tri‐trophic systems.Intriguingly, herbivore and natural enemy responses toHIPVs are highly diverse. Whether they are attracted or repelled byHIPVs depend on the plant–herbivore–natural enemy species combination, suggesting aHIPVmultifunctionality. We hypothesized that co‐evolutionary diversification of foraging strategies in herbivores and natural enemies, where arthropods adapted to diverse plant ecological traits, served to explainHIPVmultifunctionality.We developed a food chain model of plant–herbivore–natural enemy to test our hypothesis, where plants exhibited three different states and different apparency (uninfested < lightly infested < highly infested) and quality (lightly infested > highly infested). The shifts between plant states were mediated by herbivore life cycle, interactions among herbivores, natural enemies and plant reproduction.The natural enemy evolutionary stable strategy (ESS) was predicted to choose the lightly and heavily infested plants in broad ranges of induced direct resistance and plant apparency (HIPVlevels), implying thatHIPVs acted as the induced indirect resistance. The corresponding herbivoreESSwas to choose (or avoid)HIPVs whenHIPVlevels were low (or high). When the induced direct resistance was very high and thus herbivore quality was low, natural enemies tended to avoid increasedHIPVs with increasing herbivory levels. This was associated with herbivoreESSchoice forHIPVs, leading to intraspecific enemy‐free space. These predictedESSdiversities explained observed herbivore and natural enemy responses toHIPVs in several contrasting plant systems, including willow trees, lima bean and wild tobacco.Our findings suggest that non‐lethal herbivory and variations in induced plant responses are key mechanisms for evolutionary diversification of animal foraging behaviour and thus structure of ecological networks.