bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of the nitric oxide‐cGMP pathway in age‐related cardiovascular disease: Focus on phosphodiesterase‐1 and soluble guanylate cyclase
Authors: Golshiri Keivan , Ataei Ataabadi Ehsan , Portilla Fernandez Eliana C. , Jan Danser A. H. , Roks Anton J. M. 
Published: September 2019

AbstractAmong ageing‐related illnesses, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality causing one‐third of all deaths worldwide. Ageing evokes a number of functional, pharmacological and morphological changes in the vasculature, accompanied by a progressive failure of protective and homeostatic mechanisms, resulting in target organ damage. Impaired vasomotor, proliferation, migration, antithrombotic and anti‐inflammatory function in both the endothelial and vascular smooth muscle cells are parts of the vascular ageing phenotype. The endothelium regulates these functions by the release of a wide variety of active molecules including endothelium‐derived relaxing factors such as nitric oxide, prostacyclin (PGI2) and endothelium‐derived hyperpolarization (EDH). During ageing, a functional decay of the nitric oxide pathway takes place. Nitric oxide signals to VSMC and other important cell types for vascular homeostasis through the second messenger cyclic guanosine monophosphate (cGMP). Maintenance of proper cGMP levels is an important goal in sustainment of proper vascular function during ageing. For this purpose, different components can be targeted in this signalling system, and among them, phosphodiesterase‐1 (PDE1) and soluble guanylate cyclase (sGC) are crucial. This review focuses on the role of PDE1 and sGC in conditions that are relevant for vascular ageing.
Administering elections in a digital age: Online voting in Ontario municipalities
Authors: Goodman Nicole , Spicer Zachary 
Published: September 2019

AbstractTo date, online voting studies have focused on impacts on political behaviour and voting security. Analyses of impacts on administrators and electoral governance remain sparse internationally and are relegated to overviews in technical reports in Canada (Pammett and Goodman 2013; Goodman and Pyman 2016). Drawing on an original survey of local administrators in Ontario following the 2014 municipal elections, this article explores how online voting impacts election administration. Findings suggest strong satisfaction with online voting, citizen‐centered rationales for adoption, and key differences in challenges and cost based on municipal size. We conclude with implications for the local governance of elections as technology plays a greater role in voting processes.
Evidence for a role of autoinflammation in early-phase psoriasis
Authors: Fanoni D , Venegoni L , Vergani B , Tavecchio S , Cattaneo A , Leone B E , Berti E , Marzano A V 
Published: September 2019

Summary
Psoriasis is a common, inflammatory immune-mediated skin disease mainly presenting with plaques whose pathogenesis is based on the central role of the interleukin (IL)-23/IL-17 axis. However, the mechanisms acting in papular lesions of early-phase psoriasis are not fully understood. The aim of this study was to assess the involvement of autoinflammation, a state of sterile inflammation mainly driven by IL-1 over-production that has been recently hypothesized to act in the early phase of disease. Lesional skin of 10 patients with recent onset, untreated psoriasis has been investigated for expression of IL-1β, IL-17, IL-23 and other cytokines involved in the disease in comparison with normal skin of 10 healthy controls using a protein array method. Immunohistochemical phenotyping of inflammatory infiltrate and co-localization experiments with immunofluorescence confocal microscopy were conducted. IL-1β was significantly more expressed in psoriasis than in normal skin (P &lt; 0·0001). The chemokine IL-8 was also over-expressed in psoriasis (P = 0·03) while IL-12, IL-17, IL-23, tumour necrosis factor-α and interferon-γ were only slightly more expressed in psoriasis than in normal skin, without reaching statistical significance. The inflammatory infiltrate consisted mainly of neutrophils with a relevant number of macrophages and dendritic cells and only scattered, predominantly T helper 1 lymphocytes. IL-1β co-localized mainly with CD66b, a neutrophil marker, suggesting that neutrophils were the major source of this cytokine. IL-1β over-expression in combination with low expression of cytokines that are predominant in late-phase plaque psoriasis may support the role of autoinflammation in early-phase disease, possibly paving the way to randomized trials with IL-1 antagonists.
Growth factor and receptor malfunctions associated with human genetic deafness
Authors: Naz Sadaf , Friedman Thomas B. 
Published: September 2019

AbstractA variety of different signaling pathways are necessary for development and maintenance of the human auditory system. Normal hearing allows for the detection of soft sounds within the frequency range of 20 to 20 000 Hz, but more importantly to perceive the human voice frequency band of 250 to 6000 Hz. Loss of hearing is common, and is a clinically heterogeneous disorder that can be caused by environmental factors such as exposure to loud noise, infections and ototoxic drugs. In addition, variants of hundreds of genes have been reported to disrupt processes required for hearing. Noncoding regulatory variants and variants of additional genes necessary for hearing remain to be discovered as many individuals with inherited deafness are without a genetic diagnosis, despite the advent of whole exome sequencing. Here, we discuss in detail some of these deafness‐causing variants of genes encoding a ligand or its receptor. Spotlighted in this review are three growth factor‐receptor‐pairs EDN3/EDNRB, HGF/MET and JAG/NOTCH, which individually are necessary for normal hearing. We also offer our perspective on unanswered questions, future challenges and potential opportunities for treatments emerging from molecular genetic and mechanistic studies of deafness due to these causes.
Lots of loss with little scrutiny: The attrition of habitat critical for threatened species in Australia
Authors: Ward Michelle S. , Simmonds Jeremy S. , Reside April E. , Watson James E. M. , Rhodes Jonathan R. , Possingham Hugh P. , Trezise James , Fletcher Rachel , File Lindsey , Taylor Martin 
Published: September 2019

AbstractAustralia has one of the worst extinction rates of any nation, yet there has been little assessment of the effect of its flagship environmental legislation, the Environment Protection and Biodiversity Conservation Act 1999 (EPBC Act), to prevent species extinction. By coupling remotely sensed forest and woodland data with the distributions of 1,638 terrestrial threatened species, terrestrial migratory species, and threatened ecological communities, we quantified the loss of potential habitat and communities since the EPBC Act came into force in 2000. We found that over 7.7 million ha of potential habitat and communities were cleared in the period 2000–2017. Of this clearing, over 93% was not referred to the Federal Government for assessment, meaning the loss was not scrutinized under the EPBC Act. While 1,390 (84%) species suffered loss, Mount Cooper striped skink, Keighery's macarthuria, and Southern black‐throated finch lost 25, 23, and 10% of potential habitat, respectively. Iconic Australian species, such as koala, also lost ~1 million ha (2.3%) of potential habitat. Our analysis showed that the EPBC Act is ineffective at protecting potential habitat for terrestrial threatened species, terrestrial migratory species, or threatened ecological communities. We recommend that when scientifically determinable, critical habitat is demarcated for listed species and communities, which provides absolute protection that is enforced, monitored, and investigated by the regulator. Without a fundamental change in how environmental law is enforced, Australia faces an increasing extinction rate.
Allometry of reaching and contact structures in Kukulcania hibernalis (Araneae: Filistatidae)
Authors: Barrantes Gilbert , Madrigal‐Brenes Ruth 
Published: September 2019

AbstractLarge part of the morphological diversity observed across taxa is attributed to the effect of sexual selection; and the static allometry of these structures vary largely from highly positive to negative, depending on their function, and position on the animal's body. In arthropods, information of how sexually selected contact and reaching male structures use during courtship scale on body size is scarce. We tested two complementary hypotheses: the reaching structure hypothesis and the contact‐function hypothesis, in the spider Kukulcania hibernalis. We used the length of the proximal segments of the male pedipalp to test the reaching structure hypothesis, and claw features to test the contact‐function hypothesis. Our results support both hypotheses. Small males have disproportionally longer pedipalps (highly negative allometry) than large males, increasing the probability of small‐bodied males to inseminate even large females. We also found that both distal contact and noncontact homologous structures scaled shallow (slope < 1) on body size, but allometry was significantly shallower for contact than for noncontact distal structures, providing support to the contact‐function hypothesis, and allowing teasing apart the effect of sexual selection on distal contact structures with dual functions.
Processing of performance errors predicts memory formation: Enhanced feedback‐related negativities for corrected versus repeated errors in an associative learning paradigm
Authors: de Bruijn Ellen R. A. , Mars Rogier B. , Hester Rob 
Published: September 2019

AbstractLearning from errors or negative feedback is crucial for adaptive behavior. FMRI studies have demonstrated enhanced anterior cingulate cortex activity for errors that were later corrected versus repeated errors even when a substantial delay between the error and the opportunity to correct was introduced. We aimed at identifying the electrophysiological correlates of these processes by investigating the feedback‐related negativity (FRN) and stimulus‐locked P3. Participants had to learn and recall the location of 2‐digit targets over consecutive rounds. Feedback was provided in two steps, first a color change indicated a correct or incorrect response (feedback phase) followed by presentation of the correct digit information (re‐encoding phase). Behaviorally, participants improved performance from the first to the third round. FRN amplitudes time‐locked to feedback were enhanced for corrected compared to repeated errors. The P3 in response to re‐encoding did not differ between the two error types. The finding that FRN amplitudes positively predicted memory performance is consistent with the idea that the FRN reflects prediction errors and the need for enhanced cognitive control. Interestingly, this happens early during feedback processing and not at a later time point when re‐encoding of correct information takes place. The prediction error signal reflected in the FRN is usually elicited by performance errors, but may thus also play a role in preparing/optimizing the system for memory formation. This supports the existence of a close link between action control and memory processes even when there is a substantial delay between error feedback and the opportunity to correct the error.
Understanding the effect of competition during evolutionary radiations: an integrated model of phenotypic and species diversification
Authors: Aristide Leandro , Morlon Hélène 
Published: September 2019

AbstractCompetition can drive macroevolutionary change, for example during adaptive radiations. However, we still lack a clear understanding of how it shapes diversification processes and patterns. To better understand the macroevolutionary consequences of competition, as well as the signal left on phylogenetic data, we developed a model linking trait evolution and species diversification in an ecological context. We find four main results: first, competition spurs trait diversity but not necessarily species richness; second, competition produces slowdowns in species diversification even in the absence of explicit ecological limits, but not in phenotypic diversification even in the presence of such limits; third, early burst patterns do not provide a reliable way of testing for adaptive radiations; and fourth, looking for phylogenetic signal in trait data and support for phenotypic models incorporating competition is a better alternative. Our results clarify the macroevolutionary consequences of competition and could help design more powerful tests of adaptive radiations in nature.
Combining genetic crosses and pool targeted DNA‐seq for untangling genomic variations associated with resistance to multiple insecticides in the mosquito Aedes aegypti
Authors: Cattel Julien , Faucon Frédéric , Le Péron Bastien , Sherpa Stéphanie , Monchal Marie , Grillet Lucie , Gaude Thierry , Laporte Frederic , Dusfour Isabelle , Reynaud Stéphane , David Jean‐Philippe 
Published: September 2019

AbstractIn addition to combating vector‐borne diseases, studying the adaptation of mosquitoes to insecticides provides a remarkable example of evolution‐in‐action driving the selection of complex phenotypes. Actually, most resistant mosquito populations show multi‐resistance phenotypes as a consequence of the variety of insecticides employed and of the complexity of selected resistance mechanisms. Such complexity makes the identification of alleles conferring resistance to specific insecticides challenging and prevents the development of molecular assays to track them in the field. Here we showed that combining simple genetic crosses with pool targeted DNA‐seq can enhance the specificity of resistance allele's detection while maintaining experimental work and sequencing effort at reasonable levels. A multi‐resistant population of the mosquito Aedes aegypti was exposed to three distinct insecticides (deltamethrin, bendiocarb and fenitrothion), and survivors to each insecticide were crossed with a susceptible strain to generate three distinct lines. F2 individuals from each line were then segregated based on their survival to two insecticide doses. Hundreds of genes covering all detoxifying enzymes and insecticide targets together with more than 7,000 intergenic regions equally spread over mosquito genome were sequenced from pools of F0 and F2 individuals unexposed or surviving insecticide. Differential coverage analysis identified 39 detoxification enzymes showing an increased gene copy number in association with resistance. Combining an allele frequency filtering approach with a Bayesian FST‐based genome scan identified multiple genomic regions showing strong selection signatures together with 50 nonsynonymous variations associated with resistance. This study provides a simple and cost‐effective approach to improve the specificity of resistance allele's detection in multi‐resistant populations while reducing false positives frequently arising when comparing populations showing divergent genetic backgrounds. The identification of novel DNA resistance markers opens new opportunities for improving the tracking of insecticide resistance in the field.
Multifocal outbreak of equine influenza in vaccinated horses in Argentina in 2018: Epidemiological aspects and molecular characterisation of the involved virus strains
Authors: Olguin‐Perglione C. , Vissani M. A. , Alamos F. , Tordoya M. S. , Barrandeguy M. 
Published: September 2019

SummaryBackgroundEquine influenza is an important cause of respiratory disease of horses worldwide. The equine influenza virus (EIV) undergoes antigenic drift through the accumulation of amino acid substitutions in the viral proteins, which may lead to vaccine breakdown.ObjectivesTo describe the epidemiological findings and the molecular characteristics of the EIV detected during the multifocal outbreak that occurred in Argentina between March and July 2018 and evidence a vaccine breakdown.Study designObservational, descriptive study.MethodsVirus was detected in nasopharyngeal swabs using real‐time reverse transcriptase PCR (RT‐PCR). Nucleotide and deduced amino acid sequences of the haemagglutinin (HA) and neuraminidase (NA) genes were obtained from EIV positive nasopharyngeal swabs, and phylogenetic analysis was undertaken. Amino acid sequences were compared against the current World Organisation for Animal Health (OIE)‐recommended Florida clade 1 vaccine strain and strain components of vaccines used in Argentina. Serum samples were tested using haemagglutination inhibition test.ResultsEquine influenza virus infection was confirmed using real‐time RT‐PCR and serological testing. The phylogenetic analysis of the HA and NA genes revealed that all the EIV identified during the outbreak belong to the H3N8 subtype, Florida clade 1. Multiple amino acid changes, some of them at antigenic sites, were observed in the circulating virus when compared with the strains included in the most commonly used vaccine in Argentina. Seventy‐six percent of the affected horses had been vaccinated with this vaccine, suggesting the occurrence of vaccine breakdown.Main limitationsThe study does not include antigenic characterisation and full genome sequencing of Argentinian strains, that could provide additional information.ConclusionsThe occurrence of this multifocal equine influenza outbreak in regularly vaccinated horses is a field evidence of vaccine breakdown, reinforcing the necessity of keeping vaccine strains updated according to OIE recommendations. It also underlines the importance of the implementation of appropriate quarantine measures and restriction of horse movement in the face of disease.
The role of topical probiotics in skin conditions: A systematic review of animal and human studies and implications for future therapies
Authors: Knackstedt Rebecca , Knackstedt Thomas , Gatherwright James 
Published: September 2019

AbstractThere is increasing evidence that the intestinal microbiome plays an important role in modulating systemic inflammation and disease. Oral probiotics can modulate the intestinal microbiome and have demonstrated to be efficacious in treating topical skin conditions, such as atopic dermatitis, acne and rosacea. By proxy, exogenous application to the skin of probiotics should also promote a positive bacterial balance to mitigate or potentially eliminate pathologic conditions. The goal of this article was to provide a systematic review of studies that have investigated the role of topical probiotics in mitigating skin conditions. Additionally, skin conditions where dysbiosis has been identified but topical probiotics have not been investigated are discussed. We hope this review both analyses the evidence for the role that topical probiotics could play in topical skin conditions and highlights additional areas in need of research and exploration.
Tree growth declines and mortality were associated with a parasitic plant during warm and dry climatic conditions in a temperate coniferous forest ecosystem
Authors: Bell David M. , Pabst Robert J. , Shaw David C. 
Published: September 2019

AbstractInsects and pathogens are widely recognized as contributing to increased tree vulnerability to the projected future increasing frequency of hot and dry conditions, but the role of parasitic plants is poorly understood even though they are common throughout temperate coniferous forests in the western United States. We investigated the influence of western hemlock dwarf mistletoe (Arceuthobium tsugense) on large (≥45.7 cm diameter) western hemlock (Tsuga heterophylla) growth and mortality in a 500 year old coniferous forest at the Wind River Experimental Forest, Washington State, United States. We used five repeated measurements from a long‐term tree record for 1,395 T. heterophylla individuals. Data were collected across a time gradient (1991–2014) capturing temperature increases and precipitation decreases. The dwarf mistletoe rating (DMR), a measure of infection intensity, varied among individuals. Our results indicated that warmer and drier conditions amplified dwarf mistletoe effects on T. heterophylla tree growth and mortality. We found that heavy infection (i.e., high DMR) resulted in reduced growth during all four measurement intervals, but during warm and dry intervals (a) growth declined across the entire population regardless of DMR level, and (b) both moderate and heavy infections resulted in greater growth declines compared to light infection levels. Mortality rates increased from cooler‐wetter to warmer‐drier measurement intervals, in part reflecting increasing mortality with decreasing tree growth. Mortality rates were positively related to DMR, but only during the warm and dry measurement intervals. These results imply that parasitic plants like dwarf mistletoe can amplify the impact of climatic stressors of trees, contributing to the vulnerability of forest landscapes to climate‐induced productivity losses and mortality events.
Potential of the Community Counts registry to characterize rare bleeding disorders
Authors: Gupta Sweta , Acharya Suchitra , Roberson Christopher , Lail Alice , Soucie J. Michael , Shapiro Amy 
Published: September 2019

AbstractIntroductionRare bleeding disorders (RBDs) comprise of heterogeneous coagulation factor deficiencies and platelet disorders that are underreported worldwide.AimFirst report on RBD data from United States haemophilia treatment center network (USHTCN).MethodsA national surveillance system for the federally recognized USHTCN developed in collaboration with the Centers for Disease Control and Prevention (CDC) and American Thrombosis and Haemostasis Network (ATHN) was queried for patients with RBDs. Patient counts were extracted from the HTC Population Profile (HTC PP) component including limited data on patients followed through the USHTCN, and from the Registry component, including patient authorized, detailed clinical data. The prevalence of RBDs in the United States was estimated based on the HTC PP data and compared to the expected national prevalence based on data extrapolated from Orphanet, an international registry.ResultsBased on the estimated prevalence of RBD in the overall 2017 US population, the cases in the HTC network were lower than expected for FI, FII, FX, and FV + FVIII deficiencies by 36%, 61%, 75% and 94%, respectively, and higher than expected for FXIII, FV, FVII, and FXI deficiencies by 7%, 14%, 33% and 185%, respectively. The proportion of RBD patients reported in the HTC PP, enrolled in the Registry, was 10.8%.ConclusionsThere is a clear need to identify individuals with RBDs who could benefit from the comprehensive care provided in the USHTCN. In addition, increased enrolment of people with all RBDs in the Registry is needed to improve knowledge of treatment outcomes of patients with RBDs in the United States.