bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ideational foundations of social democratic austerity in the context of the great recession
Authors: Bremer Björn , McDaniel Sean 
Published: January 2019

AbstractThe ‘austerity settlement’ has come to define the post-crisis European political economy. Since 2010, parties from across Europe’s political mainstream have implemented austerity and despite the apparent conflict with the interests of their traditional constituents, even social democratic parties have acquiesced to this settlement. However, within the existing literature ‘social democratic austerity’ is currently under-theorized as it is assumed to involve a rather straightforward adaptation of social democrats to neo- and/or ordoliberal ideas. Utilizing rich and original evidence from over 60 elite interviews with key social democratic stakeholders in France, Germany and the UK, this article contests this view. It demonstrates instead that a distinct set of ideas based on New Keynesianism, supply-side economics, and the social investment paradigm provide the ideational foundations for social democratic austerity post-crisis. Understanding this, it is argued, is critical in order to fully appreciate how and why austerity has become dominant in post-crisis Europe.
Phosphorylation of mitochondrial matrix proteins regulates their selective mitophagic degradation
Authors: Kolitsida Panagiota , Zhou Jianwen , Rackiewicz Michal , Nolic Vladimir , Dengjel Jörn , Abeliovich Hagai 
Published: January 2019

AbstractMitophagy is an important quality control mechanism in eukaryotic cells, and defects in mitophagy correlate with aging phenomena and neurodegenerative disorders. It is known that different mitochondrial matrix proteins undergo mitophagy with very different rates, but to date the mechanism underlying this selectivity at the individual protein level has remained obscure. We now present evidence indicating that protein phosphorylation within the mitochondrial matrix plays a mechanistic role in regulating selective mitophagic degradation in yeast, via involvement of the Aup1 mitochondrial protein phosphatase, as well as two known matrix-localized protein kinases, Pkp1 and Pkp2. By focusing on a specific matrix phosphoprotein reporter, we also demonstrate that phospho-mimetic and non-phosphorylatable point mutations at known phosphosites in the reporter increased or decreased its tendency to undergo mitophagy. Finally, we show that phosphorylation of the reporter protein is dynamically regulated during mitophagy, in an Aup1-dependent manner. Our results indicate that structural determinants on a mitochondrial matrix protein can govern its mitophagic fate, and that protein phosphorylation regulates these determinants.Significance statementMitochondrial dysfunction underlies many age-related human pathologies. In normal cells, defective mitochondria are often degraded by mitophagy, a process in which these mitochondria are engulfed in autophagosomes and sent for degradation in the lysosome/vacuole. Surprisingly, studies on mitophagy in diverse eukaryotic organisms reveal an unexpected dimension of protein-level selectivity, wherein individual protein species exhibit divergent rates of mitophagic degradation. In this manuscript, we show that this surprising intra-mitochondrial selectivity can be generated by differential phosphorylation of individual mitochondrial protein species, and we identify mitochondrial phosphatases and kinases which contribute to this regulation. By identifying a mechanism which regulates the intra-mitochondrial selectivity of mitophagic degradation, our findings open the door to potential manipulation of the quality control process in the future.
EK-DRD: a comprehensive database for drug repositioning inspired by experimental knowledge
Authors: Zhao Chongze , Dai Xi , Li Yecheng , Guo Qingqing , Zhang Jianhua , Zhang Xiaotong , Wang Ling 
Published: January 2019

ABSTRACTSummaryDrug repositioning, or the identification of new indications for approved therapeutic drugs, has gained substantial traction with both academics and pharmaceutical companies because it reduces the cost and duration of the drug development pipeline and it reduces the likelihood of unforeseen adverse events. So far, there has not been a systematic effort to identify such opportunities, in part because of the lack of a comprehensive resource for an enormous amount of unsystematic drug repositioning information to support scientists who could benefit from this endeavor. To address this challenge, we developed a new database, Experimental Knowledge-Based Drug Repositioning Database (EK-DRD) by using text and data mining, as well as manual curation. EK-DRD contains experimentally validated drug repositioning annotation for 1861 FDA-approved and 102 withdrawn small molecule drugs. Annotation was done at four levels, using 70,212 target assay records, 3999 cell assay records, 585 organism assay records, and 8910 clinical trial records. Additionally, approximately 1799 repositioning protein or target sequences coupled with 856 related diseases and 1332 pathways are linked to the drug entries. Our web-based software displays a network for integrative relationships between drugs, their repositioning targets, and related diseases. The database is fully searchable and supports extensive text, sequence, chemical structure, and relational query searches.AvailabilityEK-DRD is freely available at http://www.idruglab.com/drd/index.php.Contactlingwang@scut.edu.cn.
Molecular Logic of Spinocerebellar Tract Neuron Diversity and Connectivity
Authors: Baek Myungin , Menon Vilas , Jessell Thomas M. , Hantman Adam W. , Dasen Jeremy S. 
Published: January 2019

AbstractCoordinated motor behaviors depend on feedback communication between peripheral sensory systems and central circuits in the brain and spinal cord. Relay of muscle and tendon-derived sensory information to the CNS is facilitated by functionally and anatomically diverse groups of spinocerebellar tract neurons (SCTNs), but the molecular logic by which SCTN diversity and connectivity is achieved is poorly understood. We used single cell RNA sequencing and genetic manipulations to define the mechanisms governing the molecular profile and organization of SCTN subtypes. We found that SCTNs relaying proprioceptive sensory information from limb and axial muscles are generated through segmentally-restricted actions of specific Hox genes. Loss of Hox function disrupts SCTN subtype-specific transcriptional programs, leading to defects in the connections between proprioceptive sensory neurons, SCTNs, and the cerebellum. These results indicate that Hox-dependent genetic programs play essential roles in the assembly of the neural circuits required for proprioception.
Fungal Communities in Soybean Cyst Nematode-Infested Soil under Long Term Corn and Soybean Monoculture and Crop Rotation
Authors: Strom Noah , Hu Weiming , Haarith Deepak , Chen Senyu , Bushley Kathryn 
Published: January 2019

AbstractCorn (Zea mays) and soybean (Glycine max) production forms an integral part of economies worldwide, but yields are limited by biotic and abiotic factors associated with short rotations and long-term monocultures. In this study, a long-term rotation study site with corn and soybean planted in annual rotation, five-year rotation, and long-term monoculture was utilized to examine the relationships between crop sequences, soil fungal communities, soybean cyst nematode (SCN, Heterodera glycines) densities, soil properties, and crop yields. High throughput sequencing of the ITS1 region of fungal rDNA revealed that soil fungal community structure varied significantly by crop sequence, with fungal communities under five consecutive years of monoculture becoming progressively similar to communities in long-term monoculture plots associated with their respective crop hosts. Total alpha diversity was greater under corn, but patterns of diversity and relative abundance of specific functional groups differed by crop host, with more pathotrophs proliferating under soybean and more saprotrophs and symbiotrophs proliferating under corn. Soil phosphorus (P) varied significantly by crop sequence, with lower levels of P corresponding with relative abundance of Glomerales, Paraglomerales, and Sebacinales and higher levels of P corresponding with relative abundance of Mortierellales. Soil density of the SCN was positively correlated with relative abundance and diversity of nematode-trapping fungi and with relative abundance of many potential nematode egg parasites. These results suggest several possible explanations for the improved yields associated with crop rotation, including decreased pathogen pressure, modification of soil properties, and increased diversity of soil fungal communities. Future research should investigate the potential of nematode-trapping fungi to regulate SCN densities and examine the relationships between soil P and specific arbuscular mycorrhizal and mortierellalean fungi associated with corn and soybean hosts.
Effects of α-tubulin acetylation on microtubule structure and stability
Authors: Eshun-Wilson Lisa , Zhang Rui , Portran Didier , Nachury Maxence , Toso Dan , Lohr Thomas , Vendruscolo Michele , Bonomi Massimiliano , Fraser James S. , Nogales Eva 
Published: January 2019

ABSTRACTAcetylation of K40 in α-tubulin is the sole post-translational modification to mark the luminal surface of microtubules. It is still controversial whether its relationship with microtubule stabilization is correlative or causative. We have obtained high-resolution cryo-electron microscopy reconstructions of pure samples of αTAT1-acetylated and SIRT2-deacetylated microtubules to visualize the structural consequences of this modification and reveal its potential for influencing the larger assembly properties of microtubules. We modeled the conformational ensembles of the unmodified and acetylated states by using the experimental cryo-EM density as the structural restraint in molecular dynamics simulations. We found that acetylation alters the conformational landscape of the flexible loop that contains αK40. Modification of αK40 reduces the disorder of the loop and restricts the states that it samples. We propose that the change in conformational sampling that we describe, at a location very close to the lateral contacts site, is likely to affect microtubule stability and function.
Non-invasive characterization of human bone marrow by cell free messenger-RNA reveals response to growth factor stimulation and hematopoietic reconstitution after transplantation
Authors: Ibarra Arkaitz , Zhao Yue , Salathia Neeraj S. , Zhuang Jiali , Huang Vera , Acosta Alexander D. , Aballi Jonathan , Toden Shusuke , Karns Amy P. , Purnajo Intan , Parks Julianna R. , Guo Lucy , Mason James , Sigal Darren , Nova Tina S. , Quake Stephen R. , Nerenberg Michael 
Published: January 2019

AbstractCirculating cell free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, the biological origin of cf-mRNA is still not well understood, limiting the clinical applications of this technology. Here, we use the bone marrow (BM) and pharmacologic manipulation of its resident cells as a window to study the origin of cf-mRNA. Using NGS-based profiling, we show that cf-mRNA is enriched in transcripts derived from the BM compared to circulating cells. Further, BM ablation experiments followed by hematopoietic stem cell transplants in cancer patients show that cf-mRNA levels reflect the transcriptional activity of BM resident hematopoietic lineages during marrow reconstitution. Finally, by stimulating specific BM cell populations in vivo using growth factor therapeutics (i.e. EPO, G-CSF), we show that cf-mRNA reveals dynamic functional changes in growing cell types, suggesting that, unlike other cell-free nucleic acids, cf-mRNA is secreted from living cells, rather than exclusively from apoptotic cells. Our results shed new light on the biology of cf-mRNA and demonstrate its potential applications in clinical practice.
DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract
Authors: Blackburn Alexandria T.M. , Bekheirnia Nasim , C. Uma Vanessa , Rosenfeld Jill A. , Bainbridge Matthew N. , Yang Yaping , Liu Pengfei , Madan-Khetarpal Suneeta , Delgado Mauricio R. , Hudgins Louanne , Krantz Ian , Rodriguez-Buritica David , G. Wheeler Patricia , Gazali Lihadh Al , Mohamed Al Shamsi Aisha Mohamed Saeed , Gomez-Ospina Natalia , Chao Hsiao-Tuan , Mirzaa Ghayda M. , Scheuerle Angela E. , Kukolich Mary K , Scaglia Fernando , Eng Christine , Braun Michael C. , Lamb Dolores J. , Miller Rachel K. , Bekheirnia Mir Reza 
Published: January 2019

ABSTRACTPurposeHaploinsufficiency of DYRK1A causes a recognizable clinical syndrome. The goal of this paper is to investigate congenital anomalies of the kidney and urinary tract (CAKUT) and genital defects (GD) in patients with DYRK1A mutations.MethodsA large database of clinical exome sequencing (ES) was queried for de novo DYRK1A mutations and CAKUT/GD phenotypes were characterized. Xenopus laevis (frog) was chosen as a model organism to assess Dyrk1a’s role in renal development.ResultsPhenotypic details and mutations of 19 patients were compiled after an initial observation that one patient with a de novo pathogenic mutation in DYRK1A had GD. CAKUT/GD data were available from 15 patients, 11 of whom present with CAKUT/GD. Studies in Xenopus embryos demonstrate that knockdown of Dyrk1a disrupts the development of segments of developing embryonic nephrons, which ultimately give rise to the entire genitourinary (GU) tract. These defects could be rescued by co-injecting wildtype human DYRK1A RNA, but not with truncated DYRK1AR205* RNA.ConclusionEvidence supports routine GU screening of all individuals with de novo DYRK1A pathogenic variants to ensure optimized clinical management. Collectively, the reported clinical data and loss of function studies in Xenopus substantiate a novel role for DYRK1A in GU development.
Evolutionary Dynamics Do Not Motivate a Single-Mutant Theory of Human Language
Authors: de Boer Bart , Thompson Bill , Ravignani Andrea , Boeckx Cedric 
Published: January 2019

AbstractOne of the most controversial hypotheses in cognitive science is the Chomskyan evolutionary conjecture that language arose instantaneously in our species as the result of a single staggeringly fortuitous mutation. Here we analyze the evolutionary dynamics implied by this hypothesis, which has never been formalized. The theory supposes the emergence and fixation of a single mutant (capable of the syntactic operationMerge) during a narrow historical window as a result of frequency-independent selection under a huge fitness advantage in a population of an effective size that is standardly assumed to have been no larger than ~15 000 early humans. We examine this proposal by combining diffusion analysis and extreme value theory to derive a probabilistic formulation of its dynamics. Perhaps counter-intuitively, a macro-mutation is much more unlikelya priorithan multiple mutations with smaller fitness effects, yet both hypotheses predict fixation with high conditional probability. The consequences of this asymmetry have not been accounted for previously. Our results diffuse any suggestion that evolutionary reasoning provides an independent rationale for the controversial single-mutant theory of language.Significance statementIn recent years, Chomsky and colleagues have sought support for their minimalist theory of the language faculty from evolutionary considerations. They have argued for a spontaneous emergence of a mutation conferring an advantage for thought independent of communication. Here for the first time a formalization of this view is offered, and contrasted with a more gradual evolutionary scenario. The outcome of our analysis argues against the Chomskyan view.
Shoot-to-root translocation of the jasmonate precursor 12-oxo-phytodienoic acid (OPDA) coordinates plant growth responses following tissue damage
Authors: Schulze Adina , Zimmer Marlene , Mielke Stefan , Stellmach Hagen , Melnyk Charles W. , Hause Bettina , Gasperini Debora 
Published: January 2019

ABSTRACTMulticellular organisms rely upon the movement of signaling molecules across cells, tissues and organs to communicate among distal sites. In plants, herbivorous insects, necrotrophic pathogens and mechanical wounding stimulate the activation of the jasmonate (JA) pathway, which in turn triggers the transcriptional changes necessary to protect plants against those challenges, often at the expense of growth. Although previous evidence indicated that JA species can translocate from damaged into distal sites, the identity of the mobile compound(s), the tissues through which they translocate and the consequences of their relocation remain unknown. Here, we demonstrated that endogenous JA species generated after shoot injury translocate to unharmed roots via the phloem vascular tissue in Arabidopsis thaliana. By wounding wild-type shoots of chimeric plants and by quantifying the relocating compounds from their JA-deficient roots, we uncovered that the JA-Ile precursor 12-oxo-phytodienoic acid (OPDA) is a mobile JA species. Our data also showed that OPDA is a primary mobile compound relocating to roots where, upon conversion to the bioactive hormone, it induces JA-mediated gene expression and root growth inhibition. Collectively, our findings reveal the existence of long-distance transport of endogenous OPDA which serves as a communication molecule to coordinate shoot-to-root responses, and highlight the importance of a controlled distribution of JA species among organs during plant stress acclimation.
Genome structure predicts modular transcriptome responses to genetic and environmental conditions
Authors: Mark Stephanie , Weiss Joerg , Sharma Eesha , Liu Ting , Wang Wei , Claycomb Julie M. , Cutter Asher D. 
Published: January 2019

AbstractUnderstanding the plasticity, robustness, and modularity of transcriptome expression to genetic and environmental conditions is crucial to deciphering how organisms adapt in nature. To test how genome architecture influences transcriptome profiles, we quantified expression responses for distinct temperature-adapted genotypes of the nematodeCaenorhabditis briggsaewhen exposed to chronic temperature stresses throughout development. We found that 56% of the 8795 differentially-expressed genes show genotype-specific changes in expression in response to temperature (genotype-by-environment interactions, GxE). Most genotype-specific responses occur under heat stress, indicating that cold versus heat stress responses involve distinct genomic architectures. The 22 co-expression modules that we identified differ in their enrichment of genes with genetic versus environmental versus interaction effects, as well as their genomic spatial distributions, functional attributes, and rates of molecular evolution at the sequence level. Genes in modules enriched for simple effects of either genotype or temperature alone tend to evolve especially rapidly, consistent with disproportionate influence of adaptation or weaker constraint on these subsets of loci. Chromosome scale heterogeneity in nucleotide polymorphism, however, rather than the scale of individual genes, predominate as the source of genetic differences among expression profiles, and natural selection regimes are largely decoupled between coding sequences and non-coding flanking sequences that containcis-regulatory elements. These results illustrate how the form of transcriptome modularity and genome structure contribute to predictable profiles of evolutionary change.
Evaluating comparative performance of Indian engineering educational institutes based on TQM criteria for internal benchmarking
Authors: Mehta Namish , Diwakar Nilesh , Arya Rajeev 
Published: January 2019

Purpose
The purpose of this paper is to provide a framework for designing a multiple performance measurement tool for evaluating, comparing and benchmarking the working of engineering educational institutes in a group based on total quality management (TQM) criteria and performance measurement criterion, respectively.

Design/methodology/approach
Proposed framework is based on fuzzy analytic hierarchy process (FAHP) which takes in to account the fuzziness of human opinion for realistic outcome and generalization of the results. Based on the proposed framework a case study was conducted on engineering institutes of central India for collecting data and analyzing the current practices followed in these institutes. A relationship among TQM implementation criterion was developed, their respective weights derived and then institutes were ranked.

Findings
It was found that the rank of institutions based on both the criterion is same, which indicates that the institutes having better TQM implementation have better performance.

Research limitations/implications
The research in this paper is limited to Indian scenario; studies in other countries and sectors may be conducted to compare the results obtained.

Practical implications
The results will help policy makers in identifying institutions having poor performance in the region.

Originality/value
The paper is navel in its attempt to provide a model based on TQM criteria for evaluating the working of engineering educational institutes in a group in terms of their relative weightage and benchmark.
Is it always this cold? Chilly interpersonal climates as a barrier to the well-being of early-career women faculty in STEM
Authors: Miner Kathi N. , January Samantha C. , Dray Kelly K. , Carter-Sowell Adrienne R. 
Published: January 2019

PurposeThe purpose of this project was to examine the extent to which early-career women faculty in science, technology, engineering and math (STEM) experience working in a chilly interpersonal climate (as indicated by experiences of ostracism and incivility) and how those experiences relate to work and non-work well-being outcomes.Design/methodology/approachData came from a sample of 96 early-career STEM faculty (Study 1) and a sample of 68 early-career women STEM faculty (Study 2). Both samples completed online surveys assessing their experiences of working in a chilly interpersonal climate and well-being.FindingsIn Study 1, early-career women STEM faculty reported greater experiences of ostracism and incivility and more negative occupational well-being outcomes associated with these experiences compared to early-career men STEM faculty. In Study 2, early-career women STEM faculty reported more ostracism and incivility from their male colleagues than from their female colleagues. Experiences of ostracism (and, to a lesser extent, incivility) from male colleagues also related to negative occupational and psychological well-being outcomes.Originality/valueThis paper documents that exposure to a chilly interpersonal climate in the form of ostracism and incivility is a potential explanation for the lack and withdrawal of junior women faculty in STEM academic fields.