bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cus2 enforces the first ATP-dependent step of splicing by binding to yeast SF3b1 through a UHM-ULM interaction
Authors: Talkish Jason , Igel Haller , Hunter Oarteze , Horner Steven W. , Jeffrey Nazish N. , Leach Justin R. , Jenkins Jermaine L. , Kielkopf Clara L. , Ares Manuel 
Published: January 2019

ABSTRACTStable recognition of the intron branchpoint by the U2 snRNP to form the pre-spliceosome is the first ATP-dependent step of splicing. Genetic and biochemical data from yeast indicate that Cus2 aids U2 snRNA folding into the stem IIa conformation prior to pre-spliceosome formation. Cus2 must then be removed by an ATP-dependent function of Prp5 before assembly can progress. However, the location from which Cus2 is displaced and the nature of its binding to the snRNP are unknown. Here, we show that Cus2 contains a conserved UHM (U2AF homology motif) that binds Hsh155, the yeast homolog of human SF3b1, through a conserved ULM (U2AF ligand motif). Mutations in either motif block binding and allow pre-spliceosome formation without ATP. A 2.0 Å resolution structure of the Hsh155 ULM in complex with the UHM of Tat-SF1, the human homolog of Cus2, and complementary binding assays show that the interaction is highly similar between yeast and humans. Furthermore, Tat-SF1 enforces ATP-dependence of pre-spliceosome formation in yeast extracts, showing that it can replace Cus2 function. Cus2 is removed before pre-spliceosome formation, and both Cus2 and its Hsh155 ULM binding site are absent from available cryo-EM structure models. However, our data are consistent with the apparent location of the disordered Hsh155 ULM between the U2 stem-loop IIa and the HEAT-repeats of Hsh155 that interact with Prp5. We suggest a model in which Prp5 uses ATP to remove Cus2 from Hsh155 such that extended base pairing between U2 snRNA and the intron branchpoint can occur.
Locality sensitive hashing for the edit distance
Authors: Marçais Guillaume , DeBlasio Dan , Pandey Prashant , Kingsford Carl 
Published: January 2019

AbstractMotivationSequence alignment is a central operation in bioinformatics pipeline and, despite many improvements, remains a computationally challenging problem. Locality Sensitive Hashing (LSH) is one method used to estimate the likelihood of two sequences to have a proper alignment. Using an LSH, it is possible to separate, with high probability and relatively low computation, the pairs of sequences that do not have an alignment from those that may have an alignment. Therefore, an LSH reduces in the overall computational requirement while not introducing many false negatives (i.e., omitting to report a valid alignment). However, current LSH methods treat sequences as a bag ofk-mers and do not take into account the relative ordering ofk-mers in sequences. And due to the lack of a practical LSH method for edit distance, in practice, LSH methods for Jaccard similarity or Hamming distance are used as a proxy.ResultsWe present an LSH method, called Order Min Hash (OMH), for the edit distance. This method is a refinement of the minHash LSH used to approximate the Jaccard similarity, in that OMH is not only sensitive to thek-mer contents of the sequences but also to the relative order of thek-mers in the sequences. We present theoretical guarantees of the OMH as a gapped LSH.Contactgmarcais@cs.cmu.edu,carlk@cs.cmu.edu
Distinct characteristics of genes associated with phenome-wide variation in maize (Zea mays)
Authors: Liang Zhikai , Qiu Yumou , Schnable James C. 
Published: January 2019

ABSTRACTNaturally occurring functionally variable alleles in specific genes within a population allows the identification of which genes are involved in the determination of which phenotypes. The omnigenetic model proposes that essentially all genes which are expressed in relevant contexts likely play some role in determining phenotypic outcomes. Here, we develop an approach to identify genes where natural functional variation plays a role in shaping many phenotypic traits simultaneously. We demonstrate that this approach identifies a distinct set of genes relative to conventional genome wide association using data for 260 traits scored a maize diversity panel, and the genes identified using this approach are more likely to be independently validated than genes identified by convetional genome wide association. Genes identified by the new approach share a number of features with a gold standard set of genes characterized through forward genetics which separate them from both genes identified by conventional genome wide association and the overall population of annotated gene models. These features include evidence of significantly stronger purifying selection, positional conservation across the genomes of related species, greater length, and a scarcity of presence absence variation for these loci in natural populations. Genes identified by phenome-wide analyses also showed much stronger signals of GO enrichment and purification than genes identified by conventional genome wide association. Overall these findings are consistent with large subset of annotated gene models – despite support from transcriptional and homology evidence – being unlikely to play any role in determining organismal phenotypes.
IsDrosophila melanogasterStress Odorant (dSO) really an alarm pheromone?
Authors: Yost Ryley T. , Liang Emerald , Stewart Megan P. , Chui Selwyn , Greco Andrew F. , Long Shirley Q. , McDonald Ian S. , McNeil Jeremy N. , Simon Anne F. 
Published: January 2019

ABSTRACTSocial interactions are crucial for the reproduction and survival of many organisms, including those using visual, auditory and olfactory cues to signal the presence of danger.Drosophila melanogasteremits an olfactory alarm signal, termed theDrosophilastress odorant (dSO) in response to mechanical agitation or electric shock, and conspecifics avoid areas previously occupied by stressed individuals. However, the contextual, genetic and neural underpinnings of the emission of, and response to dSO, have received little attention. Using a binary choice assay, we determined that neither age and sex of emitters, nor the time of the day, affected the emission or avoidance of dSO. However, both sex and mating status affected the response to dSO. We also demonstrated that dSO was not species specific so it should not be considered a pheromone but a general alarm signal for Drosophila. However, the response levels to both intra and inter-specific cues differed between species and possible reasons for these differences are discussed.HIGHLIGHTSEmission of dSO, a highly volatile chemical blend emitted by stressed flies, is not context specificResponse to dSO is context specific, affected by factors such as age and mating status.As flies respond to volatiles for stressed heterospecifics, dSO should not be considered an alarm pheromone, but as an alarm cue.
Population history and gene divergence in Native Mexicans inferred from 76 human exomes
Authors: Ávila-Arcos María C. , McManus Kimberly F. , Sandoval Karla , Rodríguez-Rodríguez Juan Esteban , Martin Alicia R. , Luisi Pierre , Villa-Islas Viridiana , Peñaloza-Espinosa Rosenda I. , Eng Celeste , Huntsman Scott , Burchard Esteban G. , Gignoux Christopher R. , Bustamante Carlos D. , Moreno-Estrada Andrés 
Published: January 2019

AbstractNative American genetic variation remains underrepresented in most catalogs of human genome sequencing data. Previous genotyping efforts have revealed that Mexico’s indigenous population is highly differentiated and substructured, thus potentially harboring higher proportions of private genetic variants of functional and biomedical relevance. Here we have targeted the coding fraction of the genome and characterized its full site frequency spectrum by sequencing 76 exomes from five indigenous populations across Mexico. Using diffusion approximations, we modeled the demographic history of indigenous populations from Mexico with northern and southern ethnic groups splitting 7.2 kya and subsequently diverging locally 6.5 kya and 5.7 kya, respectively. Selection scans for positive selection revealed BCL2L13 and KBTBD8 genes as potential candidates for adaptive evolution in Rarámuris and Triquis, respectively. BCL2L13 is highly expressed in skeletal muscle and could be related to physical endurance, a well-known phenotype of the northern Mexico Rarámuri. The KBTBD8 gene has been associated with idiopathic short stature and we found it to be highly differentiated in Triqui, a southern indigenous group from Oaxaca whose height is extremely low compared to other native populations.
Neuropathy-related mutations alter the membrane binding properties of the human myelin protein P0 cytoplasmic tail
Authors: Raasakka Arne , Ruskamo Salla , Barker Robert , Krokengen Oda C. , Vatne Guro H. , Kristiansen Cecilie K. , Hallin Erik I. , Skoda Maximilian W.A. , Bergmann Ulrich , Wacklin-Knecht Hanna , Jones Nykola C. , Vrønning Hoffmann Søren , Kursula Petri 
Published: January 2019

AbstractSchwann cells myelinate selected axons in the peripheral nervous system (PNS) and contribute to fast saltatory conduction via the formation of compact myelin, in which water is excluded from between tightly adhered lipid bilayers. Peripheral neuropathies, such as Charcot-Marie-Tooth disease (CMT) and Dejerine-Sottas syndrome (DSS), are incurable demyelinating conditions that result in pain, decrease in muscle mass, and functional impairment. Many Schwann cell proteins, which are directly involved in the stability of compact myelin or its development, are subject to mutations linked to these neuropathies. The most abundant PNS myelin protein is protein zero (P0); point mutations in this transmembrane protein cause CMT subtype 1B and DSS. P0 tethers apposing lipid bilayers together through its extracellular immunoglobulin-like domain. Additionally, P0 contains a cytoplasmic tail (P0ct), which is membrane-associated and contributes to the physical properties of the lipid membrane. Six CMT- and DSS-associated missense mutations have been reported in P0ct. We generated recombinant disease mutant variants of P0ct and characterized them using biophysical methods. Compared to wild-type P0ct, some mutants have negligible differences in function and folding, while others highlight functionally important amino acids within P0ct. For example, the D224Y variant of P0ct induced tight membrane multilayer stacking. Our results show a putative molecular basis for the hypermyelinating phenotype observed in patients with this particular mutation and provide overall information on the effects of disease-linked mutations in a flexible, membrane-binding protein segment.
Septin 9-containging filaments and Golgi assembly depend on two polybasic domains
Authors: Omrane Mohyeddine , Camara Amanda S. , Taveneau Cyntia , Benzoubir Nassima , Tubiana Thibault , Yua Jinchao , Guérois Raphaël , Samuel Didier , Goud Bruno , Poüs Christian , Bressanelli Stéphane , Garratt Richard C. , Thiam Abdou Rachid , Gassama-Diagne Ama 
Published: January 2019

AbstractSeptins are GTP-binding proteins involved in several membrane remodeling mechanisms. They associate with membranes, presumably by using a polybasic domain (PB1) that interacts with phosphoinositides (PIs). Membrane-bound septins assemble into microscopic structures that regulate membrane shape. How septins exactly interact with PIs, assemble, and shape membranes is weakly understood. Here, we found that septin 9 has a second polybasic domain (PB2) conserved in the human septin family. Similarly to PB1, PB2 binds specifically to PIs, and both domains are critical for septin filament formation. However, septin 9 membrane association does not depend on these PB domains but on putative PB-adjacent amphipathic helices. The presence of the PB domains guarantees the protein enrichment to PI-contained membranes, which is critical for PI-enriched organelles. In particular, we found that septin 9 PB domains control the assembly and functionality of the Golgi apparatus. Our findings bring novel insights into the role of septins in organelle morphology.HighlightsTwo polybasic domains mediate septin 9 interaction with PIsHuman septins have amphipathic helices suitable for binding membraneSeptin 9 polybasic domains mediate septin high order structure formationMutation or depletion of septin polybasic domains induce Golgi fragmentation
Energy Landscape of the Domain Movement in Staphylococcus aureus UDP-N-acetylglucosamine 2-epimerase
Authors: de Azevedo Erika Chang , Nascimento Alessandro S. 
Published: January 2019

AbstractStaphylococcus aureus is an important cause of resistant healthcare-associated infections. It has been shown that the Wall Teichoic Acid (WTA) may be an important drug target acting on antibiotic-resistant cells. The UDP-N-Acetylglucosamine 2-epimerase, MnaA, is one of the first enzymes on the pathway for the biosynthesis of the WTA. Here, detailed molecular dynamics simulations of S. aureus MnaA were used to characterize the conformational changes that occur in the presence of UDP and UDP-GlcNac and also the energetic landscape associated with these changes. Using different simulation techniques, such as ABMD and GAMD, it was possible to assess the energetic profile for the protein with and without ligands in its active site. We found that there is a dynamic energy landscape that has its minimum changed by the presence of the ligands, with a closed structure of the enzyme being more frequently observed for the bound state while the unbound enzyme favors an opened conformation. Further structural analysis indicated that positively charged amino acids associated with UDP and UDP-GlcNac interactions play a major role in the enzyme opening movement. Finally, the energy landscape profiled in this work provides important conclusions for the design of inhibitor candidates targeting S. aureus MnaA.
Towards a low CO2 emission building material employing bacterial metabolism in a two-step process of limestone dissolution and recrystallization: The bacterial system and prototype production
Authors: Røyne Anja , Phua Yi Jing , Le Simone Balzer , Eikjeland Ina Grosås , Josefsen Kjell Domaas , Markussen Sidsel , Myhr Anders , Throne-Holst Harald , Sikorski Pawel , Wentzel Alexander 
Published: January 2019

AbstractThe production of concrete for construction purposes is a major source of anthropogenic CO2 emissions. One promising avenue towards a more sustainable construction industry is to make use of naturally occurring mineral-microbe interactions, such as microbial-induced carbonate precipitation (MICP), to produce solid materials. In this paper, we present a new process where calcium carbonate in the form of powdered limestone is transformed to a binder material (termed BioZEment) through microbial dissolution and recrystallization. For the dissolution step, a suitable bacterial strain, closely related to Bacillus pumilus, was isolated from soil near a limestone quarry. We show that this strain produces organic acids from glucose, inducing the dissolution of calcium carbonate in an aqueous slurry of powdered limestone. In the second step, the dissolved limestone solution is used as the calcium source for MICP in sand packed syringe moulds. The amounts of acid produced and calcium carbonate dissolved are shown to depend on the amount of available oxygen as well as the degree of mixing. Precipitation is induced through the pH increase caused by the hydrolysis of urea, mediated by the enzyme urease, which is produced in situ by the bacterium Sporosarcina pasteurii DSM33. The degree of successful consolidation of sand by BioZEment was found to depend on both the amount of urea and the amount of glucose available in the dissolution reaction.
Adherence rate to iron folic acid supplementation among pregnant women
Authors: Niguse Wondwossen 
Published: January 2019

AbstractIntroductionGlobally 41.8% of pregnant women are anemic with the highest proportion affected in developing countries. Nationally, only 0.4% of the pregnant women take Iron supplements more than 90 days of the recommended 180 days. In Oromiya region 75.3% of pregnant women do not take any iron tablets or syrup during their last pregnancy, while 10.8% take for less than 60 days, 0.4% took for 60-89 days and only 0.3% took for 90 days or more.ObjectiveTo assess the adherence rate to iron and folic acid supplements among pregnant women attending antenatal clinics in Asella Town, south east EthiopiaMethod and materialsInstitution based cross-sectional quantitative study design was conducted in Asella town from September 2015 to June 2016. A purposive sampling technique used to select the health institution. There are six health institutions selected for this study. The sample size 317 was selected with systematic random sampling method. Ten percent of pre-test was conducted in one institution which is not included in data collection. Data were collected using structured pre-tested questionnaire. Before data collection verbal consent was obtained. The collected data were analyzed using Epi-data and SPSS version 22.00 packages.ResultThe study revealed that Out of 317 pregnant women 296 (93%) responded to the questioner. The study revealed that 177 (59.8%) of pregnant mothers in the town adhered to the iron/folic acid supplement.Conclusion and recommendationAdherence of iron/folic acid supplementation found in this study is very low. Consequently, maternal education, adequate supplement supply to the health facility, early starting antenatal visit, and health education on duration of supplementation
BIN1 protein isoforms are differentially expressed in astrocytes, neurons, and microglia: neuronal and astrocyte BIN1 implicated in Tau pathology
Authors: Taga Mariko , Petyuk Vladislav A , White Charles , Marsh Galina , Ma Yiyi , Klein Hans-Ulrich , Connor Sarah M , Khairallah Anthony , Olah Marta , Schneider Julie , Ransohoff Richard , Bennett David A , Crotti Andrea , Bradshaw Elizabeth M , De Jager Philip L 
Published: January 2019

AbstractIdentified as an Alzheimer’s disease (AD) susceptibility gene by genome wide-association studies, BIN1 has 10 isoforms that are expressed in the Central Nervous System (CNS). The distribution of these isoforms in different cell types, as well as their role in AD pathology still remains unclear. Utilizing antibodies targeting specific BIN1 epitopes in human postmortem tissue and analyzing RNA expression data from purified microglia, we identified three isoforms expressed specifically in neurons (isoforms 1, 2 and 3) and four isoforms expressed in microglia (isoforms 6, 9, 10 and 12). The abundance of selected peptides, which correspond to groups of BIN1 protein isoforms, was measured in dorsolateral prefrontal cortex, and their relation to neuropathological features of AD was assessed. Peptides contained in exon 7 of BIN1’s N-BAR domain were found to be significantly associated with AD-related traits and, particularly, tau pathology. Since only isoforms 1, 2 and 3 contain exon 7, it appears that decreased protein expression of the N-BAR domain of BIN1 is associated with greater accumulation of tau pathology and subsequent cognitive decline, with astrocytic rather than neuronal BIN1 being the more likely culprit. These effects are independent of the BIN1 AD risk variant, suggesting that targeting specific BIN1 isoforms might be a novel therapeutic approach to prevent the accumulation of tau pathology.
Support, training readiness and learning motivation in determining intention to transfer
Authors: Kim Eun-Jee , Park Sunyoung , Kang Hye-Seung (Theresa) 
Published: January 2019

Purpose
The purpose of this study is to augment knowledge of how work environment and personal characteristics affect intention to transfer in a work context. This study aims to investigate the factors that can influence intention to transfer training in a professional development training context. The study examined the predictive capacity of organizational support, supervisor support, training readiness and learning motivation on transfer intention among the study respondents.

Design/methodology/approach
Data were collected from teachers in secondary schools in the USA. The structural equation modeling method was adopted to analyze 216 responses using a self-report survey.

Findings
We found that (a) organizational support was directly associated with supervisor support for training, (b) supervisor support for training significantly influenced training readiness and motivation to learn, (c) training readiness positively affected motivation to learn, and (d) motivation to learn positively influenced intention to transfer. In addition, supervisor support mediated the relationships between organizational support and training readiness and between organizational support and motivation to learn. Training readiness linked intention to transfer and motivation to learn. Motivation to learn also played a mediating role in the relationship between supervisor support and intention to transfer.

Originality/value
Our findings add to the academic work on training transfer by empirically analyzing how both the environment (e.g. organizational support) and individual factors (e.g. learning motivation) influence employees’ intention to transfer. In particular, we investigated the potential impact of both organizational support and supervisory support on intentions to transfer, compared to previous studies emphasizing only supervisory support to improve training outcomes.
Understanding pro-environmental workplace behavior: a comparative study
Authors: Tezel Ecem , Giritli Heyecan 
Published: January 2019

PurposeThis paper aims to fulfill the gap in existing knowledge of determinants of pro-environmental behavior (PEB) in the workplace and the influence of sustainability certificates on occupants’ PEBs in workplace settings.Design/methodology/approachA questionnaire survey with a total of 95 respondents from both certified and noncertified office buildings was conducted. Two independent sample comparisons were executed to understand the influence of sustainable building certificates on occupants’ environmental values, beliefs, awareness and PEBs.FindingsEcocentric value, belief and awareness were found as the predictors of pro-environmental workplace behavior. Certified office occupants showed higher awareness about buildings’ environmentally oriented characteristics. Despite higher awareness, certified office occupants revealed less PEB compared to those who work in noncertified office buildings.Originality/valueThis study determined the influencing factors on PEBs in workplaces and PEB differences between certified and noncertified building occupants. Less PEBs of occupants in certified offices signify the misperception of individuals about sustainable buildings and the need for more informative training about sustainability issues in the society. This result also draws academic attention to sustainable building evaluation practices and provides certain insights for more occupant integrated evaluation alternative for sustainable buildings.