bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of a common causal relationship between body mass index and inflammatory skin disease: a Mendelian Randomization study
Authors: Budu-Aggrey Ashley , Brumpton Ben , Tyrrell Jess , Watkins Sarah , Modalsli Ellen H , Celis-Morales Carlos , Ferguson Lyn D , Vie Gunnhild Åberge , Palmer Tom , Fritsche Lars G , Løset Mari , Nielsen Jonas Bille , Zhou Wei , Tsoi Lam C , Wood Andrew R , Jones Samuel E , Beaumont Robin , Saunes Marit , Romundstad Pål Richard , Siebert Stefan , McInnes Iain B , Elder James T , Smith George Davey , Frayling Timothy M , Åsvold Bjørn Olav , Brown Sara J , Sattar Naveed , Paternoster Lavinia 
Published: February 2018

ABSTRACTObjectivePsoriasis and eczema are common inflammatory skin diseases that have been reported to be associated with obesity. However, causality has not yet been established. We aimed to investigate the possible causal relationship between body mass index (BMI) and psoriasis or eczema.MethodsFollowing a review of published epidemiological evidence of the association between obesity and either psoriasis or eczema, Mendelian Randomization (MR) was used to test for a causal relationship between BMI and these inflammatory skin conditions. We used a genetic instrument comprising 97 single nucleotide polymorphisms (SNPs) associated with BMI. One-sample MR was conducted using individual-level data (401,508 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (731,021 individuals) from published BMI, psoriasis and eczema GWAS. The one-sample and two-sample MR estimates were meta-analysed using a fixed effect model. To explore the reverse causal direction, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis and eczema were used to test if inflammatory skin disease has a causal effect on BMI.ResultsPublished observational data show an association of greater BMI with both psoriasis and eczema case status. The observational associations were confirmed in UK Biobank and HUNT datasets. MR analyses provide evidence that higher BMI causally increases the odds of psoriasis (by 53% per 5 units higher BMI; OR= 1.09 (1.06 to 1.12) per 1 kg/m2; P=4.67×10-9) and eczema (by 8% per 5 units higher BMI; OR=1.02 (1.00 to 1.03) per 1 kg/m2; P=0.09). When investigating causality in the opposite direction, MR estimates provide little evidence for an effect of either psoriasis or eczema influencing BMI.ConclusionOur study, using genetic variants as instrumental variables for BMI, shows that higher BMI leads to a higher risk of inflammatory skin disease. The causal relationship was stronger for psoriasis than eczema. Therapies and life-style interventions aimed at controlling BMI or targeting the mechanisms linking obesity with skin inflammation may offer an opportunity for the prevention or treatment of these common skin diseases.
Triggering the expression of a silent gene cluster from genetically intractable bacteria results in scleric acid discovery
Authors: Alberti Fabrizio , Leng Daniel J. , Wilkening Ina , Song Lijiang , Tosin Manuela , Corre Christophe 
Published: February 2018

AbstractHerein we report a strategy for the rapid and rational characterisation of novel microbial natural products from silent gene clusters. A conserved set of five regulatory genes was used as a query to search genomic databases and identify atypical biosynthetic gene clusters (BGCs). A 20-kb BGC from the genetically intractable Streptomyces sclerotialus bacterial strain was captured using yeast-based homologous recombination and introduced into validated heterologous hosts. CRISPR/Cas9-mediated genome editing was then employed to rationally inactivate the key transcriptional repressor and trigger production of an unprecedented class of hybrid natural products exemplified by (2-(benzoyloxy)acetyl)-L-proline, named scleric acid. Subsequent rounds of CRISPR/Cas9-mediated gene deletions afforded a selection of biosynthetic gene mutant strains which led to a plausible biosynthetic pathway for scleric acid assembly. Scleric acid and a key biosynthetic intermediate were also synthesised and used as authentic standards. The assembly of scleric acid involves two unique enzymatic condensation reactions that respectively link a proline and a benzoyl residue to each end of a rare hydroxyethyl-ACP intermediate. Scleric acid was then shown to exhibit moderate activity against Mycobacterium tuberculosis, as well as modest inhibition of the cancer-associated metabolic enzyme Nicotinamide N-methyltransferase (NNMT).
Dental erosion caused by a gastrointestinal disorder in a child from the Late Holocene of Northeastern Brazil
Authors: Oliveira Rodrigo E. , Solari Ana , Silva Sergio Francisco S. M. , Martin Gabriela 
Published: February 2018

ABSTRACTA skeleton of an approximately 3-years-old sub-adult, in an excellent state of conservation, was found at the Pedra do Cachorro rock shelter - Buique, Pernambuco – Brazil, an archaeological site used as funerary place between 3875 and 575 cal years B.P. The skeleton has no signs of pathological bone changes, but its maxillary teeth show strong evidence of enamel and dentin wear caused by acid erosion, suggesting vomiting or gastroesophageal reflux episodes. The aim of this study was to describe the lesions and discuss the aetiology of these dental defects with the emphasis on the cause of the death of this individual.
Persistent cell motility requires transcriptional feedback of cytoskeletal — focal adhesion equilibrium by YAP/TAZ
Authors: Mason Devon E. , Dawahare James H. , Nguyen Trung Dung , Lin Yang , Voytik-Harbin Sherry L. , Zorlutuna Pinar , Yoder Mervin C. , Boerckel Joel D. 
Published: February 2018

AbstractCell migration initiates by traction generation through reciprocal actomyosin tension and focal adhesion reinforcement, but continued motility requires adaptive cytoskeletal remodeling and adhesion release. Here, we asked whetherde novogene expression contributes to this cytoskeletal feedback. We found that global inhibition of transcription or translation does not impair initial cell polarization or migration initiation, but causes eventual migratory arrest through excessive cytoskeletal tension and over-maturation of focal adhesions, tethering cells to their matrix. The transcriptional co-activators YAP and TAZ mediate this feedback response, modulating cell mechanics by limiting cytoskeletal and focal adhesion maturation to enable persistent cell motility and 3D vasculogenesis. Motile arrest after YAP/TAZ ablation was partially rescued by depletion of the YAP/TAZ-dependent myosin phosphatase regulator, NUAK2, or by inhibition of Rho-ROCK-myosin II. Together, these data establish a transcriptional feedback axis necessary to maintain a responsive cytoskeletal equilibrium and persistent migration.
From categories to dimensions: spatio-temporal dynamics of the cerebral representations of emotion in voice
Authors: Giordano Bruno L. , Whiting Whiting , Kriegeskorte Nikolaus , Kotz Sonja A. , Belin Pascal , Gross Joachim 
Published: February 2018

AbstractWhether the human brain represents emotional stimuli as discrete categories or continuous dimensions is still widely debated. Here we directly contrasted the power of categorical and dimensional models at explaining behavior and cerebral activity in the context of perceived emotion in the voice. We combined functional magnetic resonance imaging (fMRI) and magneto-encephalography (MEG) to measure with high spatiotemporal precision the dynamics of cerebral activity in participants who listened to voice stimuli expressing a range of emotions. The participants also provided a detailed perceptual assessment of the stimuli. By using representational similarity analysis (RSA), we show that the participants’ perceptual representation of the stimuli was initially dominated by discrete categories and an early (<200ms) cerebral response. These responses showed significant associations between brain activity and the categorical model in the auditory cortex starting as early as 77ms. Furthermore, we observed strong associations between the arousal and valence dimensions and activity in several cortical and subcortical areas at later latencies (>500ms). Our results thus show that both categorical and dimensional models account for patterns of cerebral responses to emotions in voices but with a different timeline and detail as to how these patterns evolve from discrete categories to progressively refined continuous dimensions.One Sentence Summary: Emotions expressed in the voice are instantly categorized in cortical processing and their distinct qualities are refined dimensionally only later on.
Age distributions of rare lineages reveal recent demographic history and selection
Authors: Platt Alexander , Hey Jody 
Published: February 2018

ABSTRACTThe age of an allele of a given frequency offers insight into both its function and origin, and the distribution of ages of alleles in a population conveys significant information about its history. The rarer the allele the more likely it is to reveal functional biological insight and the more recent the historical revelation. By measuring the length of the haplotype shared between an individual carrying a rare variant and its closest relative not carrying the variant we are able to approximate the age of the variant and can apply this method even when only a single copy of a variant has been sampled in a population. Applying this technique to rare variants in a large population sample from the United Kingdom, we identify historical migration from West Africa approximately 400 years ago, evidence of direct selection against novel protein-altering rare variants in individual biological pathways, continued negative frequency dependent selection on protein-altering variants in olfactory transducers and the innate immune system, and map the impact of background selection on the most recent portions of the sample genealogy.
Downgrading disease transmission risk estimates using terminal importations
Authors: Fox Spencer J , Bellan Steven E , Perkins T Alex , Johansson Michael A , Meyers Lauren Ancel 
Published: February 2018

AbstractAs emerging and re-emerging infectious diseases like dengue, Ebola, chikungunya, and Zika threaten new populations worldwide, officials scramble to assess local severity and transmissibility, with little to no epidemiological history to draw upon. Standard methods for assessing autochthonous (local) transmission risk make either indirect estimates based on ecological suitability or direct estimates only after local cases accumulate. However, an overlooked source of epidemiological data that can meaningfully inform risk assessments prior to outbreak emergence is the absence of transmission by imported cases. Here, we present a method for updatinga prioriecological estimates of transmission risk using real-time importation data. We demonstrate our method using Zika importation and transmission data from Texas in 2016, a high-risk region in the southern United States. Our updated risk estimates are lower than previously reported, with only six counties in Texas likely to sustain a Zika epidemic, and consistent with the number of autochthonous cases detected in 2017. Importation events can thereby provide critical, early insight into local transmission risks as infectious diseases expand their global reach.
The Limits to Parapatric Speciation II: Strengthening a Preexisting Genetic Barrier to Gene Flow in Parapatry
Authors: Blanckaert Alexandre , Hermisson Joachim 
Published: February 2018

AbstractParapatric speciation has recently received a lot of attention. By encompassing the whole continuum between allopatric and sympatric scenarios, it includes many potential scenarios for the evolution of new species. Building upon previous work, we investigate how a genetic barrier to gene flow, that relies on a single postzygotic genetic incompatibility, may further evolve. We consider a continent island model with three loci involved in pairwise Dobzhansky-Muller incompatibilities (DMIs). Using a deterministic and analytic approach, we derive the conditions for invasion of a new mutation and its consequences on an already existing genetic barrier to gene flow. We focus on quantifying the impact of the epistasis generated by the new mutation on the genetic barrier. We show that the accumulation of genetic incompatibilities in the presence of gene flow is a complex process, where new mutations can either strengthen or destroy a preexisting barrier. In particular, preexisting polymorphism and incompatibilities do not always facilitate the growth of the genetic barrier by accumulation of further barrier genes. Migration may disrupt the snowball effect (the accelerating rate of DMI accumulation in allopatry) because incompatibilities are directly tested by selection. Our results also show an ambiguous role of gene flow, which can either impede or facilitate the strengthening of the genetic barrier. Overall, our results illustrate how the inclusion of gene flow renders the building of a genetic barrier difficult to analyze.
Feeling the force: how pollen tubes deal with obstacles
Authors: Burri Jan T. , Vogler Hannes , Läubli Nino F. , Hu Chengzhi , Grossniklaus Ueli , Nelson Bradley J. 
Published: February 2018

HighlightPollen tubes literally feel their way through their environment to avoid obstacles as they deliver male gametes to the ovule. We measured their force sensitivity to understand this remarkable behavior.AbstractPhysical forces are involved in the regulation of plant development and morphogenesis by translating mechanical stress into the modification of physiological processes, which, in turn, can affect cellular growth. Pollen tubes are tip-growing cells that provide an ideal system to study processes induced by exposure to mechanical stress. We combined a lab-on-a-chip device with cellular force microscopy to mimic and quantify the forces that are involved in pollen tube navigation upon confronting mechanical obstacles. Several stages of obstacle avoidance were identified, including force perception, growth adjustment, and penetration. We have experimentally determined the perceptive force, which is the force threshold at which the pollen tube senses the obstacle, forLilium longiflorumandArabidopsis thaliana. In addition, we provide evidence that pollen tubes are capable of penetrating narrow gaps by increasing turgor pressure. Taken together, our data indicate that pollen tubes sense physical barriers and actively adjust their growth behavior to overcome them.
Somatic nicotinic acetylcholine receptors control the activity of dopamine neurons and reward-related behaviors
Authors: Cuttoli Romain Durand-de , Mondoloni Sarah , Marti Fabio , Lemoine Damien , Naudé Jérémie , d’Izarny-Gargas Thibaut , Pons Stéphanie , Maskos Uwe , Trauner Dirk , Kramer Richard H. , Faure Philippe , Mourot Alexandre 
Published: February 2018

SummaryDopamine (DA) neurons of the ventral tegmental area (VTA) integrate cholinergic inputs to regulate key functions such as motivation and goal-directed behaviors. Yet the temporal dynamic range and mechanism of action of acetylcholine (ACh) on the modulation of VTA circuits and reward-related behaviors are not known. Here we used a chemical-genetic approach for rapid and precise optical manipulation of nicotinic neurotransmission in VTA neurons in vivo. We provide direct evidence that the ACh tone fine-tunes the firing properties of VTA DA neurons through somatic β2-containing (β2*) nicotinic ACh receptors (nAChRs). Furthermore, locally photo-antagonizing these receptors in the VTA was sufficient to reversibly switch nicotine reinforcement on and off. By enabling control of nicotinic transmission in targeted brain circuits, this technology will help unravel the various physiological functions of nAChRs and may assist in the design of novel therapies relevant to neuropsychiatric disorders.
Genetic variants associated with Alzheimer's disease confer different cerebral cortex cell-type population structure
Authors: Li Zeran , Del-Aguila Jorge L , Dube Umber , Budde John , Martinez Rita , Black Kathleen , Xiao Qingli , Cairns Nigel J. ,   the Dominantly Inherited Alzheimer Network (DIAN), Dougherty Joseph D. , Lee Jin-Moo , Morris John C , Bateman Randall J. , Karch Celeste M. , Cruchaga Carlos , Harari Oscar 
Published: February 2018

AbstractAlzheimer’s disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, the effects of brain cellular composition are often ignored in high-throughput molecular studies. We developed and optimized a cell-type specific expression reference panel and employed digital deconvolution methods to determine brain cellular distribution in three independent transcriptomic studies. We found that neuronal and astrocyte proportions differ between healthy and diseased brains and also among AD cases that carry specific genetic risk variants. Brain carriers of pathogenic mutations in APP, PSEN1 or PSEN2 presented lower neurons and higher astrocytes proportions compared to sporadic AD. Similarly, the APOE ε4 allele also showed decreased neurons and increased astrocytes compared to AD non-carriers. On the contrary, carriers of variants in TREM2 risk showed a lower degree of neuronal loss than matched AD cases in multiple independent studies. These findings suggest that genetic risk factors associated with AD etiology have a specific imprinting in the cellular composition of AD brains. Our digital deconvolution reference panel provides an enhanced understanding of the fundamental molecular mechanisms underlying neurodegeneration, enabling the analysis of large bulk RNA-seq studies for cell composition, and suggests that correcting for the cellular structure when performing transcriptomic analysis will lead to novel insights of AD.
Reversion of the photoperiod dependence of flowering in rice with synthetic Hd1-microProteins
Authors: Eguen Tenai , Ariza Jorge Gomez , Bhati Kaushal Kumar , Sun Bin , Fornara Fabio , Wenkel Stephan 
Published: February 2018

SUMMARYRice (Oryza sativa) is a facultative short-day plant that flowers very late when grown in non-inductive long day conditions. Photoperiod-dependent flowering in rice is regulated by heading date (Hd1) which acts as both an activator and repressor of flowering in a day length-dependent manner. In order to regulate flowering of rice in long days (LD), overexpression of a synthetic Hd1miP, which is capable of interacting with Hd1, was employed. Transgenic Hd1miP rice plants flowered significantly earlier when grown in LD compared to SD, showing that synthetic microProteins can be used to revert short-day plants to long-day plants. Yield analysis revealed that although the OX-Hd1miP grains are comparable to WT in terms of the size of the grains produced, OX-Hd1miP plants like hd1 knockout plants, are compromised in the number of grains produced and the grain maturity rate, suggesting an additional unrecognized role of Hd1 in grain maturity.
Supply chain performance measures and metrics: a bibliometric study
Authors: Mishra Deepa , Gunasekaran Angappa , Papadopoulos Thanos , Dubey Rameshwar 
Published: February 2018

Purpose
The purpose of this paper is to review the existing literature on supply chain performance measures and metrics (PMMs). It provides a critical evaluation of 234 articles published in past 24 years.

Design/methodology/approach
The paper examines the studies published from 1991 to 2014 by adopting the bibliometric technique of citation and co-citation analysis.

Findings
The analysis of the results indicate that the number of articles on supply chain PMMs is increasing at its fastest pace in the past few years. Furthermore, the study identifies some of the most influential articles on performance measurement and metrics. Finally, it concludes that there has been a transition from traditional to more sophisticated performance measurement system.

Research limitations/implications
This study focuses only on supply chain performance measurement and metrics and excludes research on performance management and control. Thus, researchers may explore and extend this area of research.

Originality/value
To the knowledge of the authors, this is the first study to review the literature on supply chain PMMs by using citation and co-citation analysis. The study includes 234 articles over the time of 24 years (1991-2014).
Differential impact of short-term and long-term group incentives
Authors: Han Kyongji , Kim Andrea 
Published: February 2018

PurposeThe purpose of this paper is to investigate the additive and differential effects of short-term-oriented group incentives (STOGIs) and long-term-oriented group incentives (LTOGIs) on psychological ownership and organizational commitment.Design/methodology/approachThis study analyzed data from 17,255 US employees in the 2005 data set of the National Bureau of Economic Research Shared Capitalism Research.FindingsBoth additive indices of group incentives have direct positive relationships with psychological ownership and organizational commitment, as well as indirect positive relationships with organizational commitment through psychological ownership. STOGIs have a stronger relationship with organizational commitment and LTOGIs have a stronger relationship with psychological ownership.Originality/valueThe value of this research lies in exploring the differential effects of short-and long-term group incentives, which provides new insight into the theory of group incentives and practical implications for their effective utilization.
The use of management control and performance measurement systems in SMEs
Authors: Pešalj Biljana , Pavlov Andrey , Micheli Pietro 
Published: February 2018

Purpose
The purpose of this paper is to respond to recent calls for understanding how multiple management control (MC) and performance measurement (PM) systems are used simultaneously for managing performance, particularly in the context of small- and medium-sized enterprises (SMEs).

Design/methodology/approach
Data are collected during an in-depth case study of MC and PM and management practices in a Dutch SME using multiple data sources and elicitation methods, including interviews and participant observations.

Findings
This study identifies managerial practices that enable the interplay of the four control systems – beliefs, boundaries, diagnostic and interactive – helping the organization manage organizational tensions in relation to short- and long-term focus, predictable goal achievement and search for new opportunities, internal and external focus, and control and creativity.

Research limitations/implications
This paper advances the research on integrating multiple aspects of performance management, particularly technical and social. This research is based on a single case study; future qualitative and quantitative studies could explore the interplay between the four control systems in other settings and explore the relationship between control systems and leadership style.

Practical implications
Managing performance requires active and continuous use of all four control systems. This is particularly salient in SMEs where less formal controls play a key role and where balance needs to be ensured despite the lack of managerial processes and capabilities.

Originality/value
The findings advance PM and management theory and practice in the context of SMEs.