bluuebunny/crossref_metadata_2025_split huggingface dataset:
FASTCAR: Rapid alignment-free prediction of sequence alignment identity scores using self-supervised general linear models
Authors: James Benjamin T. , Luczak Brian B. , Girgis Hani Z. 
Published: July 2018

AbstractMotivationPairwise alignment is a predominant algorithm in the field of bioinformatics. This algorithm is quadratic — slow especially on long sequences. Many applications utilize identity scores without the corresponding alignments. For these applications, we propose FASTCAR. It produces identity scores for pairs of DNA sequences using alignment-free methods and two self-supervised general linear models.ResultsFor the first time, the new tool can predict the pair-wise identity score in linear time and space. On two large-scale sequence databases, FASTCAR provided the best compromise between sensitivity and precision while being faster than BLAST by 40% and faster than USEARCH by 6–10 times. Further, FASTCAR is capable of producing the pair-wise identity scores of long DNA sequences — millions-of-nucleotides-long bacterial genomes; this task cannot be accomplished by any alignment-based tool.AvailabilityFASTCAR is available at https://github.com/TulsaBioinformaticsToolsmith/FASTCAR and as the Supplementary Dataset 1.Contacthani-girgis@utulsa.eduSupplementary informationSupplementary data are available online.
A positive feedback loop drives centrosome maturation in flies
Authors: Alvarez-Rodrigo Ines , Conduit Paul T. , Baumbach Janina , Novak Zsofia A. , Aydogan Mustafa G. , Wainman Alan , Raff Jordan W. 
Published: July 2018

AbstractCentrosomes are formed when mother centrioles recruit pericentriolar material (PCM) around themselves. The PCM expands dramatically as cells prepare to enter mitosis (a process termed centrosome maturation), but it is unclear how this expansion is achieved. In flies, Spd-2 and Cnn form an extensive scaffold around the mother centriole that recruits other components of the mitotic PCM, and the Polo-dependent phosphorylation of Cnn at the centrosome is crucial for scaffold assembly. Here we show that, like Cnn, Spd-2 is specifically phosphorylated at centrosomes. This phosphorylation appears to create multiple phosphorylated S-S/T(p) motifs that allow Spd-2 to recruit Polo to the expanding scaffold. If Spd-2 cannot recruit Polo to the expanding scaffold, the scaffold is initially assembled around the mother centriole, but it cannot expand outwards, and centrosome maturation fails. We conclude that Spd-2, Polo and Cnn cooperate to form a positive feedback loop that drives the dramatic expansion of the mitotic centrosome in flies.
Designing robust N-of-1 studies for precision medicine
Authors: Percha Bethany , Baskerville Edward B. , Johnson Matthew , Dudley Joel , Zimmerman Noah 
Published: July 2018

AbstractRecent advances in molecular biology, sensors, and digital medicine have led to an explosion of products and services for high-resolution monitoring of individual health. The N-of-1 study has emerged as an important methodological tool for harnessing these new data sources, enabling researchers to compare the effectiveness of health interventions at the level of a single individual. We have developed a stochastic time series model that simulates an N-of-1 study, facilitating rapid optimization of N-of-1 study designs and increasing the likelihood of study success while minimizing participant burden. Using simulation, we demonstrate how the number of treatment blocks, ordering of treatments within blocks, duration of each treatment, and sampling frequency affect our ability to detect true differences in treatment efficacy. We provide a set of recommendations for study designs based on treatment, outcome, and instrument parameters, and provide our simulation software as a supplement to the paper.
Structural Basis of ECF-σ-Factor-Dependent Transcription Initiation
Authors: Lin Wei , Mandal Sukhendu , Degen David , Cho Min Sung , Feng Yu , Das Kalyan , Ebright Richard H. 
Published: July 2018

SUMMARYExtracytoplasmic (ECF) σ factors, the largest class of alternative σ factors, are related to primary σ factors, but have simpler structures, comprising only two of the six conserved functional modules present in primary σ factors: region 2 (σR2) and region 4 (σR4). Here, we report crystal structures of transcription initiation complexes containing Mycobacterium tuberculosis RNA polymerase (RNAP), M. tuberculosis ECF σ factor σL, and promoter DNA. The structures show that σR2 and σR4 of the ECF σ factor occupy the same sites on RNAP as in primary σ factors, show that the connector between σR2 and σR4 of the ECF σ factor--although unrelated in sequence--follows the same path through RNAP as in primary σ factors, and show that the ECF σ factor uses the same strategy to bind and unwind promoter DNA as primary σ factors. The results define protein-protein and protein-DNA interactions involved in ECF-σ-factor-dependent transcription initiation.
Fitness-Dependent Recombination Can Be Evolutionarily Advantageous in Diploids: a Deterministic Mutation–Selection–Balance Model
Authors: Rybnikov Sviatoslav , Frenkel Zeev , Korol Abraham B. 
Published: July 2018

AbstractRecombination’s omnipresence in nature is one of the most intriguing problems in evolutionary biology. The question of why recombination exhibits certain general features is no less interesting than that ofwhy it exists at all. One such feature is recombination’s fitness dependence (FD). The so far developed population-genetics models have focused on the evolution of FD recombination mainly in haploids, although the empirical evidence for this phenomenon comes mostly from diploids. Using numerical analysis of modifier models for infinite panmictic populations, we show here that FD recombination can be evolutionarily advantageous in diploids subjected to purifying selection. This advantage is associated with benefits from the differential rate of disruption of lower-vshigher-fitness genotypes, that can be manifested in systems with at least three selected loci. We also show that in systems with linked modifier, an additional contribution to the evolutionary advantage of FD recombination may come from fitness-dependence of the intensity of modifier linkage to the selected system, although the contribution of the last effect vanishes with tighter linkage within the selected system. We also show that in systems with three selected loci, FD recombination may give rise to negative crossover interference, which may be beneficial by itself. Yet, the role of such FD-induced crossover interference in the evolutionary advantage of FD recombination is minor. Remarkably, FD recombination was often favored in situations where any constant non-zero recombination was rejected, implying a relaxation of the rather strict constraints on major parameters (e.g., selection intensity and epistasis) required for the evolutionary advantage of non-zero recombination formulated by classical models.
A novel bioactive molecule 5-β-Hydroxyltridecanyl benzoate identified in Pedalium Murex L. (Gokhru) fruit extracts showed antifungal activity against Sclerotinia sclerotiorum
Authors: Chaudhary Gulshan , Kaushik Nutan , Reddy Pallavolu Maheswara 
Published: July 2018

AbstractFruits of Pedalium murex known as, ‘Gokhru’ is predominantly used in Ayurveda for its aphrodisiac properties and use in treatment of urological orders. However till now, bioactivity of this fruit has not been documented for plant protection against phytopathogenes, Hence in this regard, we investigated antimicrobial activity of P. murex fruit extracts (isolated from the different agro climatic zones of India) were tested against twelve microbial phytopathogens. From 29 fruit extracts, only 13 were found to be active against three pathogens viz. Botrytis cinerea, Rhizoctonia solani, and Sclerotinia sclerotiorum. Among the nine TLC fractions only one showed presence of a single peak, thus presence of a single compound in the crude extract. Based on lower IC50 value (328 μg/ml) the crude fruit extract collected from Indore region was further characterized. Evaluation against screened phytopathogens indicates its activity. Further, structural characterization of this compound using FTIR and NMR revealed it to be a novel compound i.e. 5-β-Hydroxyl tridecanyl benzoate. Our study paves a way to investigate effective dose of P. murex fruit extracts to utilize in plant protection programs. In future, a better method is required to scale up the process of bioactive molecule (5-β-Hydroxyl tridecayl benzoate) extraction from P. murex or for its chemical synthesis.
Rudhira/BCAS3 couples microtubules and intermediate filaments to promote cell migration for angiogenic remodeling
Authors: Joshi Divyesh , Inamdar Maneesha S. 
Published: July 2018

AbstractBlood vessel formation requires endothelial cell (EC) migration that depends on dynamic remodeling of the cytoskeleton. Rudhira/Breast Carcinoma Amplified Sequence 3 (BCAS3) is a cytoskeletal protein essential for EC migration and sprouting angiogenesis during mouse development and implicated in metastatic disease. Here, we report that Rudhira mediates cytoskeleton organization and dynamics during EC migration. Rudhira binds to both microtubules and Vimentin intermediate filaments (IFs) and stabilizes microtubules. Rudhira depletion impairs cytoskeletal crosstalk, microtubule stability and hence focal adhesion disassembly. The BCAS3 domain of Rudhira is necessary and sufficient for microtubule-IF crosslinking and cell migration. Pharmacologically restoring microtubule stability rescues gross cytoskeleton organization and angiogenic sprouting in Rudhira depleted cells. Our study identifies the novel and essential role of Rudhira in cytoskeletal crosstalk and assigns function to the conserved BCAS3 domain. Targeting Rudhira could allow tissue-restricted cytoskeleton modulation to control cell migration and angiogenesis in development and disease.
Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: The case of hypertrophic cardiomyopathy
Authors: Walsh Roddy , Mazzarotto Francesco , Whiffin Nicola , Buchan Rachel , Midwinter William , Wilk Alicja , Li Nicholas , Felkin Leanne , Ingold Nathan , Govind Risha , Ahmad Mian , Mazaika Erica , Allouba Mona , Zhang Xiaolei , Marvao Antonio de , Day Sharlene M , Ashley Euan , Colan Steven D , Michels Michelle , Pereira Alexandre C , Jacoby Daniel , Ho Carolyn Y , Thomson Kate L , Watkins Hugh , Barton Paul JR , Olivotto Iacopo , Cook Stuart A , Ware James S 
Published: July 2018

ABSTRACTBackgroundInternational guidelines for variant interpretation in Mendelian disease set stringent criteria to report a variant as (likely) pathogenic, prioritising control of false positive rate over test sensitivity and diagnostic yield. Genetic testing is also more likely informative in individuals with well-characterised variants from extensively studied European-ancestry populations. Inherited cardiomyopathies are relatively common Mendelian diseases that allow empirical calibration and assessment of this framework.ResultsWe compared rare variants in large hypertrophic cardiomyopathy (HCM) cohorts to reference populations to identify variant classes with high prior likelihoods of pathogenicity, as defined by etiological fraction (EF). Analysis of variant distribution identified regions in which variants are significantly enriched in cases and variant location was a better discriminator of pathogenicity than generic computational functional prediction algorithms. Non-truncating variant classes with an EF≥0.95, and therefore clinically actionable, were identified in 5 established HCM genes. Applying this approach leads to an estimated 14-20% increase in cases with actionable HCM variants.ConclusionsWhen found in a patient confirmed to have disease, novel variants in some genes and regions are empirically shown to have a sufficiently high probability of pathogenicity to support a “likely pathogenic” classification, even without additional segregation or functional data. This could increase the yield of high confidence actionable variants, consistent with the framework and recommendations of current guidelines. The techniques outlined offer a consistent, unbiased and equitable approach to variant interpretation for Mendelian disease genetic testing. We propose adaptations to ACMG/AMP guidelines to incorporate such evidence in a quantitative and transparent manner.
Application of an Interpretable Classification Model on Early Folding Residues during Protein Folding
Authors: Bittrich Sebastian , Kaden Marika , Leberecht Christoph , Kaiser Florian , Villmann Thomas , Labudde Dirk 
Published: July 2018

AbstractBackgroundMachine learning strategies are prominent tools for data analysis. Especially in life sciences, they have become increasingly important to handle the growing datasets collected by the scientific community. Meanwhile, algorithms improve in performance, but also gain complexity, and tend to neglect interpretability and comprehensiveness of the resulting models.ResultsGeneralized Matrix Learning Vector Quantization (GMLVQ) is a supervised, prototype-based machine learning method and provides comprehensive visualization capabilities not present in other classifiers which allow for a fine-grained interpretation of the data. In contrast to commonly used machine learning strategies, GMLVQ is well-suited for imbalanced classification problems which are frequent in life sciences. We present a Weka plug-in implementing GMLVQ. The feasibility of GMLVQ is demonstrated on a dataset of Early Folding Residues (EFR) that have been shown to initiate and guide the protein folding process. Using 27 features, an area under the receiver operating characteristic of 76.6% was achieved which is comparable to other state-of-the-art classifiers.ConclusionsThe application on EFR prediction demonstrates how an easy interpretation of classification models can promote the comprehension of biological mechanisms. The results shed light on the special features of EFR which were reported as most influential for the classification: EFR are embedded in ordered secondary structure elements and they participate in networks of hydrophobic residues. Visualization capabilities of GMLVQ are presented as we demonstrate how to interpret the results.
Selective auxin agonists induce specific AUX/IAA protein degradation to modulate plant development
Authors: Vain Thomas , Raggi Sara , Ferro Noel , Barange Deepak Kumar , Kieffer Martin , Ma Qian , Doyle Siamsa M. , Thelander Mattias , Pařízková Barbora , Novák Ondřej , Ismail Alexandre , Enquist Per Anders , Rigal Adeline , Łangowska Małgorzata , Harborough Sigurd Ramans , Zhang Yi , Ljung Karin , Callis Judy , Almqvist Fredrik , Kepinski Stefan , Estelle Mark , Pauwels Laurens , Robert Stéphanie 
Published: July 2018

AbstractAuxin phytohormones control most aspects of plant development through a complex and interconnected signaling network. In the presence of auxin, AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) transcriptional repressors are targeted for degradation by the SKP1-CULLIN1-F-BOX (SCF) ubiquitin-protein ligases containing TRANSPORT INHIBITOR RESISTANT 1/AUXIN SIGNALING F-BOX (TIR1/AFB). CULLIN1-neddylation is required for SCFTIR1/AFBfunctionality as exemplified by mutants deficient in the NEDD8-activating enzyme subunit AUXIN-RESISTANT 1 (AXR1). Here, we report a chemical biology screen that identifies small molecules requiring AXR1 to modulate plant development. We selected four molecules of interest, RubNeddin1 to 4 (RN1 to 4), among which RN3 and RN4 trigger selective auxin responses at transcriptional, biochemical and morphological levels. This selective activity is explained by their ability to promote the interaction between TIR1 and a specific subset of AUX/IAA proteins, stimulating the degradation of particular AUX/IAA combinations. Finally, via a genetic screen using RN4, we revealed that the chromatin remodeling ATPase BRAHMA is implicated in auxin-mediated apical hook development. These results demonstrate the power of selective auxin agonists to dissect auxin perception for plant developmental functions.
Quantifying the effects of head movement on magnetic resonance spectroscopy estimates of gamma-aminobutyric acid
Authors: Cui Edward D. , Maddock Richard J. , Buonocore Michael H. , Ozturk Meric , Yoon Jong H. 
Published: July 2018

AbstractThere has been keen interest in measuring in vivo GABA. However, GABA signal is low and typically measured using techniques vulnerable to the confounding effects of in-scanner head movement. This issue is particularly problematic for clinical studies since it may lead to Type I or II error in testing for group differences. While solutions to mitigate the effects of movement have been proposed, fundamental and largely unexamined issues are the nature and scale of this effect. We developed a method to quantify and characterize head movement during GABA spectroscopy and found that two parameters of movement, displacement and instantaneous movement, were inversely correlated with and accounted for 12.1% and 20.2% variance of GABA estimates respectively. We conclude that head movement can significantly affect GABA measurements and the application of methods to account for movement may improve of GABA measurement accuracy and the detection of true group differences in clinical studies.
IPSE, a urogenital parasite-derived immunomodulatory protein, ameliorates ifosfamide-induced hemorrhagic cystitis through downregulation of pro-inflammatory pathways
Authors: Mbanefo Evaristus C. , Le Loc , Zee Rebecca , Banskota Nirad , Ishida Kenji , Pennington Luke F. , Odegaard Justin I. , Jardetzky Theodore S. , Alouffi Abdulaziz , Falcone Franco H. , Hsieh Michael H. 
Published: July 2018

AbstractIfosfamide and other oxazaphosphorines can result in hemorrhagic cystitis, a constellation of complications caused by acrolein metabolites. We previously showed that a single dose of IPSE, a schistosome-derived host modulatory protein, can ameliorate ifosfamide-related cystitis; however, the exact mechanisms underlying this urotoxic effect and its prevention are not fully understood. To provide insights into IPSE’s protective mechanism, we undertook transcriptional profiling of bladders from ifosfamide-treated mice, with or without IPSE pretreatment. Following ifosfamide challenge, there was upregulation of a range of pro-inflammatory genes. The pro-inflammatory pathway involving the IL-1β, TNFαand IL-6 triad via NFκB and STAT3 signaling pathways was identified as the key driver of inflammation. The NRF2-mediated oxidative stress response pathway, which regulates bothHmox1-mediated heme homoeostasis and expression of antioxidant enzymes, was highly activated. Anti-inflammatory and cellular proliferation cascades implicated in tissue repair, namely Wnt, Hedgehog and PPAR pathways, were downregulated. IPSE administration before ifosfamide injection resulted in significant downregulation of major proinflammatory pathways including the triad of IL-1β, TNFαand IL-6 pathways, the interferon signaling pathway, and less apparent reduction in oxidative stress responses. Taken together, we have identified signatures of acute phase inflammation and oxidative stress responses in the ifosfamide-injured bladder, which are reversed by pretreatment with IPSE, a parasite derived anti-inflammatory molecule. In addition to providing new insights into the underlying mechanism of IPSE’s therapeutic effects, this work has revealed several pathways that could be therapeutically targeted to prevent and treat ifosfamide-induced hemorrhagic cystitis.
The genetic prehistory of the Andean highlands 7,000 Years BP though European contact
Authors: Lindo John , Haas Randall , Hofman Courtney , Apata Mario , Moraga Mauricio , Verdugo Ricardo , Watson James T. , Llave Carlos Viviano , Witonsky David , Pacheco Enrique Vargas , Villena Mercedes , Soria Rudy , Beall Cynthia , Warinner Christina , Novembre John , Aldenderfer Mark , Di Rienzo Anna 
Published: July 2018

AbstractThe peopling of the Andean highlands above 2500m in elevation was a complex process that included cultural, biological and genetic adaptations. Here we present a time series of ancient whole genomes from the Andes of Peru, dating back to 7,000 calendar years before present (BP), and compare them to 64 new genome-wide genetic variation datasets from both high and lowland populations. We infer three significant features: a split between low and high elevation populations that occurred between 9200-8200 BP; a population collapse after European contact that is significantly more severe in South American lowlanders than in highland populations; and evidence for positive selection at genetic loci related to starch digestion and plausibly pathogen resistance after European contact. Importantly, we do not find selective sweep signals related to known components of the human hypoxia response, which may suggest more complex modes of genetic adaptation to high altitude.One Sentence SummaryAncient DNA from the Andes reveals a complex picture of human adaptation from early settlement to the colonial period.
Consumer willingness to pay for low acrylamide content
Authors: Harkness Caroline , Areal Francisco 
Published: July 2018

Purpose
Acrylamide is a common dietary exposure present in many baby foods. Evidence of acrylamide causing tumours in rodents has led to the chemical being classified as “probably carcinogenic to humans” by the International Agency for Research on Cancer. The purpose of this paper is to examine consumers’ willingness to pay (WTP) for a reduction in the acrylamide content of baby food and, therefore, a reduction in the risk of cancer.

Design/methodology/approach
A discrete choice experiment is conducted on UK consumers incorporating different levels of seven attributes: packaging, production method (organic, GM and conventional), acrylamide level, sugar, salt, one of five portions of fruit and vegetable per day and price. Consumer WTP for low acrylamide content is estimated using a mixed logit model.

Findings
The empirical results indicate consumers assign a high value to safer baby food, with low acrylamide content. The WTP premium for baby food with low acrylamide (105 per cent) is the highest of all attributes assessed. Consumers also have a preference for organic baby food, in contrast to an aversion towards GM. The study results indicate that reducing the acrylamide content in baby food is desirable for consumers.

Originality/value
This is the first study to estimate consumers’ WTP for reducing the acrylamide content of baby food in the UK. Existing research has been limited to examining the exposure of young children, in addition to the potential health risks.
Business model innovation for sustainability: a food start-up case study
Authors: Franceschelli Maria Vittoria , Santoro Gabriele , Candelo Elena 
Published: July 2018

Purpose
The purpose of this paper is to investigate and present the way in which a food start-up can develop business model innovations, taking into account the importance of social and environmental issues.

Design/methodology/approach
The authors studied an Italian pizzeria, implementing the illustrative single-case study methodology, to answer the research question: “how can food start-ups develop a sustainable business model innovation?”

Findings
The study highlights sustainable elements for each component of the business model configuration provided by Osterwalder to provide a deeper view of the sustainable business model concept.

Originality/value
The study contributes to the extant research introducing the concept of sustainable innovation within the business model literature. It concludes that, within the food industry, especially for start-ups, the development of sustainable business model innovation is particularly important because the industry is itself linked with nature and human respect. Moreover, it suggests a methodological analysis of the business model configuration, which will help to develop clearer and more accurate and influential research.