bluuebunny/crossref_metadata_2025_split huggingface dataset:
Saturation mutagenesis of disease-associated regulatory elements
Authors: Kircher Martin , Xiong Chenling , Martin Beth , Schubach Max , Inoue Fumitaka , Bell Robert J.A. , Costello Joseph F. , Shendure Jay , Ahituv Nadav 
Published: December 2018

AbstractThe majority of common variants associated with common diseases, as well as an unknown proportion of causal mutations for rare diseases, fall in noncoding regions of the genome. Although catalogs of noncoding regulatory elements are steadily improving, we have a limited understanding of the functional effects of mutations within them. Here, we performed saturation mutagenesis in conjunction with massively parallel reporter assays on 20 disease-associated gene promoters and enhancers, generating functional measurements for over 30,000 single nucleotide substitution and deletion mutations. We find that the density of putative transcription factor binding sites varies widely between regulatory elements, as does the extent to which evolutionary conservation or various integrative scores predict functional effects. These data provide a powerful resource for interpreting the pathogenicity of clinically observed mutations in these disease-associated regulatory elements, and also comprise a gold-standard dataset for the further development of algorithms that aim to predict the regulatory effects of noncoding mutations.
The genomic landscape of western South America: Andes, Amazonia and Pacific Coast
Authors: Barbieri Chiara , Barquera Rodrigo , Arias Leonardo , Sandoval José R. , Acosta Oscar , Zurita Camilo , Aguilar-Campos Abraham , Tito-Álvarez Ana M. , Serrano-Osuna Ricardo , Gray Russell , Heggarty Paul , Shimizu Kentaro K. , Fujita Ricardo , Stoneking Mark , Pugach Irina , Fehren-Schmitz Lars 
Published: December 2018

ABSTRACTStudies of Native South American genetic diversity have helped to shed light on the peopling and differentiation of the continent, but available data are sparse for the major ecogeographic domains. These include the Pacific Coast, a potential early migration route; the Andes, home to the most expansive complex societies and to one of the most spoken indigenous language families of the continent (Quechua); and Amazonia, with its understudied population structure and rich cultural diversity. Here we explore the genetic structure of 177 individuals from these three domains, genotyped with the Affymetrix Human Origins array. We infer multiple sources of ancestry within the Native American ancestry component; one with clear predominance on the Coast and in the Andes, and at least two distinct substrates in neighboring Amazonia, with a previously undetected ancestry characteristic of northern Ecuador and Colombia. Amazonian populations are also involved in recent gene-flow with each other and across ecogeographic domains, which does not accord with the traditional view of small, isolated groups. Long distance genetic connections between speakers of the same language family suggest that languages had spread not by cultural contact alone. Finally, Native American populations admixed with post-Columbian European and African sources at different times, with few cases of prolonged isolation. With our results we emphasize the importance of including under-studied regions of the continent in high-resolution genetic studies, and we illustrate the potential of SNP chip arrays for informative regional scale analysis.
Partitioning the genetic architecture of amyotrophic lateral sclerosis
Authors: Broce Iris J. , Fan Chun C. , Olney Nicholas T. , Lomen-Hoerth Catherine , Finkbeiner Steve , Atassi Nazem , Cudkowicz Merit E. , Paganoni Sabrina , Yokoyama Jennifer S. , Kao Aimee , Dillon William P. , Glastonbury Christine M. , Hess Christopher P. , Rheenen Wouter van , Veldink Jan H. , Al-Chalabi Ammar , Andreassen Ole A. , Dale Anders M. , Seeley William W. , Sugrue Leo P. , Ofori-Kuragu Aaron , Karch Celeste M. , Miller Bruce L. , Desikan Rahul S. 
Published: December 2018

AbstractThe genetic basis of sporadic amyotrophic lateral sclerosis (ALS) is not well understood. Using large genome-wide association studies and validated tools to quantify genetic overlap, we systematically identified single nucleotide polymorphisms (SNPs) associated with ALS conditional on genetic data from 65 different traits and diseases from >3 million people. We found strong genetic enrichment between ALS and a number of disparate traits including frontotemporal dementia, coronary artery disease, C-reactive protein, celiac disease and memory function. BeyondC9ORF72, we detected novel genetic signal within numerous loci includingGIPC1, ELMO1andCOL16Aand confirmed previously reported variants, such asATXN2, KIF5A, UNC13AandMOBP.We found that ALS variants form a small-world co-expression network characterized by highly inter-connected ‘hub’ genes. This network clustered into smaller sub-networks, each associated with a unique function. Altered gene expression of several sub-networks and hubs was over-represented in neuropathological samples from ALS patients and SOD1 G93A mice. Our collective findings indicate that the genetic architecture of ALS can be partitioned into distinct components where some genes are highly important for developing disease. These findings have implications for stratification and enrichment strategies for ALS clinical trials.
Human Cytomegalovirus Genomes Sequenced Directly from Clinical Material: Variation, Multiple-Strain Infection, Recombination and Mutation
Authors: Suárez Nicolás M. , Wilkie Gavin S. , Hage Elias , Camiolo Salvatore , Holton Marylouisa , Hughes Joseph , Maabar Maha , Sreenu Vattipally B. , Dhingra Akshay , Gompels Ursula A. , Wilkinson Gavin W. G. , Baldanti Fausto , Furione Milena , Lilleri Daniele , Arossa Alessia , Ganzenmueller Tina , Gerna Giuseppe , Hubáček Petr , Schulz Thomas F. , Wolf Dana , Zavattoni Maurizio , Davison Andrew J. 
Published: December 2018

ABSTRACTThe genomic characteristics of human cytomegalovirus (HCMV) strains sequenced directly from clinical pathology samples were investigated, focusing on variation, multiple-strain infection, recombination and natural mutation. A total of 207 datasets generated in this and previous studies using target enrichment and high-throughput sequencing were analysed, in the process facilitating the determination of genome sequences for 91 strains. Key findings were that (i) it is important to monitor the quality of sequencing libraries in investigating diversity, (ii) many recombinant strains have been transmitted during HCMV evolution, and some have apparently survived for thousands of years without further recombination, (iii) mutants with non-functional genes (pseudogenes) have been circulating and recombining for long periods and can cause congenital infection and resulting clinical sequelae, and (iv) intrahost diversity in single-strain infections is much less than that in multiple-strain infections. Future population-based studies are likely to continue illuminating the evolution, epidemiology and pathogenesis of HCMV.
Community‐level economics spectrum of fine‐roots driven by nutrient limitations in subalpine forests
Authors: Li Fanglan , Hu Hui , McCormlack Michael Luke , Feng De Feng , Liu Xin , Bao Weikai 
Published: December 2018

Abstract

Fine‐root traits show remarkable variation with plant community structure and environmental shifts, but there is limited understanding of how trait covariation that exists among fine‐root traits shifts among different communities, especially in forests. We explored links among the fine‐root traits of forest communities to determine whether community root traits shift predictably according to an economics framework along environmental gradients.

Measurements of root morphology, nitrogen, phosphorus and carbon concentrations, and measures of standing root densities were collected on fine‐roots (diameter ≤ 2 mm) from 129 forest plots in five subalpine forests.

This study demonstrates an existence of a community‐level fine‐root economics spectrum (REScom) in the subalpine forests, in which specific root length was strongly and positively related to root nitrogen and phosphorus contents, but negatively related to root diameter. Soil nutrient limitation was a major driver of the REScom as changes in soil [N], [P] and [C] contents were related to changes in SRL, root [N], root [P]. Variables related to standing fine‐root length and mass were independent of the REScom and were primarily related to forest community structure, particularly in tree closure and herbaceous plant mass.

Synthesis. These results indicate two distinct functional dimensions of community fine‐root trait variation: resource‐use efficiency via changes in root structure and construction, and separately via changes in the standing root system. Identifying shifts in allocation to and investment in fine‐roots enhances our understanding of a root and whole‐plant economics spectrum and community functioning.
‘I didn't want to pass that on to my child, being afraid to go to the dentist': making sense of oral health through narratives of connectedness over the life course
Authors: Emily Kettle Jennifer , Warren Lorna , Glenn Robinson Peter , Walls Angus , Gibson Barry John 
Published: December 2018

AbstractWhile previous sociological research on oral health has identified the relevance of personal relationships, there is more scope to analyse the mouth through a lens of connectedness. Recent qualitative interviews with 43 older people (65+) in England and Scotland found that participants constructed relational narratives to make sense of their oral health practices. By drawing on ideas of family practices, family display and personal life, we illustrate how the mouth can be understood relationally. Participants presented their own embodied experiences as connected to the actions of their parents. Narratives also reflected how, as parents and grandparents themselves, participants tried to shape the experiences of others. In this way, oral health practices were conceptualised as being about family. This can be seen in self‐narratives that demonstrated how participants located themselves as embedded in webs of ongoing relationships. We highlight the importance of narrated practices of thinking and feeling, whereby participants imagined doing oral health, and indeed family, in different ways. We thereby demonstrate how oral health practices are constituted through family connectedness and at the same time how these practices contribute to the constitution of family. Policy should therefore pay attention to family relations when promoting improvements in oral health practices.
Do Corporate Governance Analysts Matter? Evidence from the Expansion of Governance Analyst Coverage
Authors: LEHMANN NICO 
Published: December 2018

ABSTRACTThis paper examines the economic consequences of the initiation of governance analyst coverage. Governance analysts process, enhance, and disseminate governance‐related information to capital market participants via, for example, governance reports and ratings. Using an exogenous shock in the United Kingdom, I find that an increase in governance analyst coverage results in increased governance quality, improved liquidity, increased financial analyst following, and improved investor breadth. These findings are consistent with governance analysts creating value for firms via monitoring, information dissemination/production, and investor recognition.
Activity budgets for the sedentary Argentine sea bass Acanthistius patachonicus inferred from accelerometer data loggers
Authors: Beltramino Lucas E. , Venerus Leonardo A. , Trobbiani Gastón A. , Wilson Rory P. , Ciancio Javier E. 
Published: December 2018

AbstractThe amount of energy an animal uses to move may constitute a significant fraction of its energy budget, so detailed descriptions of wild animal activity budgets can help to understand the ecology of a species, both at the individual and at the population levels. The rocky‐reef fishes inhabiting the northern Patagonian gulfs of Argentina are important economic and recreational resources for which no activity or energy budgets are available. This fish assemblage may reach high aggregated biomasses (exceeding several hundreds of kilogrammes of fish distributed along a few hundred metres of linear reef ledges) and is not clear how such biomasses can be supported by the low productivity of the Patagonian coastal waters. We used animal‐attached accelerometers to characterise the behaviours and activity budgets for the most abundant and ubiquitous species of this assemblage, the Argentine sea bass or ‘Mero’ Acanthistius patachonicus (Jenyns, 1840; Osteichthyes: Serranidae). Sixteen individuals were tagged (two in captivity and 14 free‐living) and an ethogram was generated from acceleration recordings in varying environmental conditions. Two algorithms were used to classify the behaviours of wild fish. Both showed generally similar results during the cold‐water season (8–10°C), but differed slightly in the warm‐water season (16–18°C). Overall, sea bass were more active during warm season (mean time spent engaged in active behaviours; 46%, range; 24–60%). In contrast, during cold season fish only spent a mean of 29% of their time in active behaviours (range; 15–49%). No clear response to tidal state or ambient light was found, but some fish were more active during the night in the cold water season. Here, we provide the first activity budgets for the conspicuous Argentine sea bass, which contribute to our understanding of rocky‐reef fish behaviour in Patagonia.
Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus
Authors: Sutton Jessica A. , Rogers Lisa M. , Dixon Beverly R.E.A. , Kirk Leslie , Doster Ryan , Algood Holly M. , Gaddy Jennifer A. , Flaherty Rebecca , Manning Shannon D. , Aronoff David M. 
Published: December 2018

ProblemDuring pregnancy, Group B Streptococcus (GBS) can infect fetal membranes to cause chorioamnionitis, resulting in adverse pregnancy outcomes. Macrophages are the primary resident phagocyte in extraplacental membranes. Protein kinase D (PKD) was recently implicated in mediating pro‐inflammatory macrophage responses to GBS outside of the reproductive system. This work aimed to characterize the human placental macrophage inflammatory response to GBS and address the extent to which PKD mediates such effects.MethodPrimary human placental macrophages were infected with GBS in the presence or absence of a specific, small molecule PKD inhibitor, CRT 0066101. Macrophage phenotypes were characterized by evaluating gene expression, cytokine release, assembly of the NLRP3 inflammasome, and NFκB activation.ResultsGBS evoked a strong inflammatory phenotype characterized by the release of inflammatory cytokines (TNFα, IL‐1β, IL‐6 (P ≤ 0.05), NLRP3 inflammasome assembly (P ≤ 0.0005), and NFκB activation (P ≤ 0.05). Pharmacological inhibition of PKD suppressed these responses, newly implicating a role for PKD in mediating immune responses of primary human placental macrophages to GBS.ConclusionPKD plays a critical role in mediating placental macrophage inflammatory activation in response to GBS infection.
Does the Helping Babies Breathe Programme impact on neonatal resuscitation care practices? Results from systematic review and meta‐analysis
Authors: Budhathoki Shyam Sundar , Gurung Rejina , Ewald Uwe , Thapa Jeevan , KC Ashish 
Published: December 2018

AbstractAimThis paper examines the change in neonatal resuscitation practices after the implementation of the Helping Babies Breathe (HBB) programme.MethodsA systematic review was carried out on studies reporting the impact of HBB programmes among the literature found in Medline, POPLINE, LILACS, African Index Medicus, Cochrane, Web of Science and Index Medicus for the Eastern Mediterranean Region database. We selected clinical trials with randomised control, quasi‐experimental and cross‐sectional designs. We used a data extraction tool to extract information on intervention and outcome reporting. We carried out a meta‐analysis of the extracted data on the neonatal resuscitation practices following HBB programme using Review Manager.ResultsFour studies that reported on neonatal resuscitation practices before and after the implementation of the HBB programme were identified. The pooled results showed no changes in the use of stimulation (RR‐0.54; 95% CI, 0.21–1.42), suctioning (RR‐0.48; 95% CI, 0.18–1.27) and bag‐and‐mask ventilation (RR‐0.93; 95% CI, 0.47–1.83) after HBB training. The proportion of babies receiving bag‐and‐mask ventilation within the Golden Minute of birth increased by more than 2.5 times (RR‐2.67; 95% CI, 2.17–3.28).ConclusionThe bag‐and‐mask ventilation within Golden minute has improved following the HBB programme. Implementation of HBB training improves timely initiation of bag‐and‐mask ventilation within one minute of birth.
Regulation of cardiac myocyte cohesion and gap junctions via desmosomal adhesion
Authors: Schinner Camilla , Erber Bernd M. , Yeruva Sunil , Waschke Jens 
Published: December 2018

AbstractAimsMutations in desmosomal proteins can induce arrhythmogenic cardiomyopathy with life‐threatening arrhythmia. Previous data demonstrated adrenergic signalling to be important to regulate desmosomal cohesion in cardiac myocytes. Here, we investigated how signalling pathways including adrenergic signalling, PKC and SERCA regulate desmosomal adhesion and how this controls gap junctions (GJs) in cardiac myocytes.MethodsImmunostaining, Western blot, dissociation assay and multi‐electrode array were applied in HL‐1 cardiac myocytes to evaluate localization, expression and function of desmosomal and GJ components. cAMP levels were determined by ELISA.ResultsActivation of PKC by PMA or adrenergic signalling increased cell cohesion and desmoglein‐2 and desmoplakin localization at cell‐cell junctions, whereas tryptophan (Trp) treatment to inhibit cadherin binding or inhibition of SERCA by thapsigargin reduced cell cohesion, while cAMP elevation rescued this effect. Despite no changes in protein expression, accumulation of GJ protein connexin‐43 was detectable at cell‐cell contacts in parallel to increased cohesion. Disruption of cell cohesion by Trp, PMA or thapsigargin impaired conduction of excitation comparable to GJ inhibition. cAMP elevation was effective to improve arrhythmia after Trp treatment. Weakened cell cohesion by Trp or depletion of desmoglein‐2 or plakoglobin blocked signalling via the β1‐adrenergic receptor. Moreover, silencing of desmosomal proteins increased arrhythmia and reduced conduction velocity, which were rescued by cAMP elevation.ConclusionThese data demonstrate the interplay of GJs, desmosomes and the β1‐adrenergic receptor with regulation of their function by cell cohesion, adrenergic and PKC signalling or SERCA inhibition. These results support the identification of new targets to treat arrhythmogenic cardiomyopathy.
Glacial and climate history of the last 24 000 years in the Polar Ural Mountains, Arctic Russia, inferred from partly varved lake sediments
Authors: Regnéll Carl , Haflidason Haflidi , Mangerud Jan , Svendsen John Inge 
Published: December 2018

We present a well‐dated, high‐resolution and continuous sediment record spanning the last c. 24 000 years from lake Bolshoye Shchuchye located in the Polar Ural Mountains, Arctic Russia. This is the first continuous sediment succession reaching back into the Last Glacial Maximum (LGM) ever retrieved from this region. We reconstruct the glacial and climate history in the area since the LGM based on sedimentological and geochemical analysis of a 24‐m‐long sediment core. A robust chronology was established using a combination of AMS 14C‐dating, the position of the Vedde Ash and varve counting. The varved part of the sediment core spans across the LGM from 24 to 18.7 cal. ka BP. We conclude that the lake basin remained ice‐free throughout the LGM, but that mountain glaciers were present in the lake catchment. A decrease in both glacial varve preservation and sedimentation rate suggests that these glaciers started to retreat c. 18.7 cal. ka BP and had disappeared from the catchment by 14.35 cal. ka BP. There are no indications of glacier regrowth during the Younger Dryas. We infer a distinct climatic amelioration following the onset of the Holocene and an Early to Middle Holocene thermal optimum between 10–5 cal. ka BP. Our results provide a long‐awaited continuous and high‐resolution record of past climate that supplements the existing, more fragmentary data from moraines and exposed strata along river banks and coastal cliffs around the Russian Arctic.
Political budget cycles, incumbency advantage, and propaganda
Authors: Bohn Frank 
Published: December 2018

AbstractThis paper combines incumbency advantage and political budget cycle theory. An opportunistic politician is given two instruments: deficit‐financed transfers and propaganda. Unlike earlier analytical models, but in accordance with the empirical literature, government manipulations do actually improve re‐election chances. However, the optimal level of government manipulation depends on country characteristics, in particular the competence dispersion among potential candidates. This may explain why it is easier to detect political budget cycles in, for instance, developing countries or new democracies. Results are robust to alternative competence distribution and propaganda cost assumptions.
Assessing the density of honey bee colonies at ecosystem scales
Authors: Utaipanon Patsavee , Schaerf Timothy M. , Oldroyd Benjamin P. 
Published: December 2018

1. Information about the density of wild honey bee (Apisspp.) colonies in an ecosystem is central to understanding the functional role of honey bees in that ecosystem, necessary for effective biosecurity response planning, and useful for determining whether pollination services are adequate. However, direct visual surveys of colony locations are not practical at ecosystem scales. Thus, indirect methods based on population genetic analysis of trapped males have been proposed and implemented.2. In this review, indirect methods of assessment of honey bee colony densities are described, which can be applied at ecosystem scales. The review also describes how to trap males in the field using the Williams drone trap (or virgin queens) the appropriate genetic markers and statistical analyses, and discusses issues surrounding sample size.3. The review also discusses some outstanding issues concerning the methods and the conversion of estimated colony number to colony density per km2. The appropriate conversion factor will require further research to determine the area over which a drone trap draws drones.