bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Safety and Efficacy of Transdermal Auricular Vagal Nerve Stimulation Earbud Electrodes for Modulating Autonomic Arousal, Attention, Sensory Gating, and Cortical Brain Plasticity in Humans
Authors: Tyler William J. , Wyckoff Sarah , Hearn Taylor , Hool Nicholas 
Published: August 2019

AbstractOur work was motivated by the goal of developing a Targeted Neuroplasticity Training (TNT) method for enhancing foreign language learning. To this end, our primary effort was to evaluate new and optimized approaches to noninvasive vagal nerve stimulation (VNS). We considered several Human Factors Dimensions to develop methods that would be amenable to comfortable, everyday use in common training environments or contexts. Several approaches to noninvasive or external vagal nerve stimulation have been described. Transcutaneous modulation of the left cervical branch of the vagus nerve can be uncomfortable for users resulting in a distracting experience, which may not be ideal for augmenting plasticity during training. Transdermal auricular vagal nerve stimulation (taVNS) offers another approach by targeting nerve fibers innervating the external ear. Prior methods have described many different approached using electrode clips on the ear or stainless-steel ball electrodes, which can respectively result in mechanical discomfort and electrical stimulus discomfort due to high current densities. Other approaches use carbon-doped or conductive rubbers, which require wetting. This is problematic since small degrees of dehydration cause significant changes in the electrical impedance of the skin-electrode interface. Detailed human cadaveric studies have shown the external auditory meatus or ear canal is highly innervated by branches of the auricular vagus nerve. Therefore, we designed taVNS electrodes that were fabricated as a biocompatible, hydrogel earbud electrodes for unilateral or bilateral use. We then evaluated the safety and efficacy of these approaches across a range of stimulus frequencies and intensities. We further evaluated the influence of this approach on autonomic physiology by recording heart rate, heart rate variability, skin conductance, skin temperature, and respiration rate. We investigated attention using simultaneous EEG and pupillometry during auditory stimulation tasks. We further studied the effects on sensory gating and plasticity by examining EEG brain activity patterns obtained during auditory mismatch negativity tasks. Finally, we investigated the basic safety and tolerability of the methods and approaches. We found that a simple, dry (hydrogel), earbud electrode design is a safe and effective method for achieving taVNS. Given the safety, preliminary efficacy, and comfort outcomes observed, we conclude taVNS approaches using earbud electrodes warrant further development and investigation as a TNT tool, to mediate human-computer interactions, for brain-computer interfaces, and as medical devices for the treatment of pervasive health disorders.
Uncovering a hidden diversity: optimized protocols for the extraction of bacteriophages from soil
Authors: Göller Pauline C. , Haro-Moreno Jose M. , Rodriguez-Valera Francisco , Loessner Martin J. , Gómez-Sanz Elena 
Published: August 2019

AbstractBackgroundBacteriophages are the most numerous biological entities on earth and play a crucial role in shaping microbial communities. Investigating the bacteriophage community from soil samples will shed light not only on the yet largely unknown phage diversity, but also may result in novel insights into phage biology and functioning. Unfortunately, the study of soil viromes lags far behind any other ecological model system, due to the heterogeneous soil matrix that rises major technical difficulties in the extraction process. Resolving these technical challenges and establishing a standardized extraction protocol is therefore a fundamental prerequisite for replicable results and comparative virome studies.ResultsWe here report the optimization of protocols for extraction of bacteriophage DNA from soil preceding metagenomic analysis such that the protocol can equally be harnessed for phage isolation. As an optimization strategy, soil samples were spiked with a viral community consisting of phages from different families (106 PFU/g soil): Listeria phage ΦA511 (Myovirus), Staphylococcus phage Φ2638AΔLCR (Siphovirus), and Escherichia phage ΦT7 (Podovirus). The efficacy of bacteriophage (i) elution, (ii) filtration, (iii) concentration, and (iv) DNA extraction methods was tested. Successful extraction routes were selected based on spiked phage recovery and low bacterial 16S rRNA gene contaminants. Natural agricultural soil viromes were then extracted with the optimized methods and shotgun sequenced. Our approach yielded sufficient amounts of inhibitor-free viral DNA for non-amplification dependent sequencing and low 16S rRNA gene contamination levels (≤ 0.2 ‰). Compared to previously published protocols, the number of bacterial read contamination was decreased by 65 %. In addition, 468 novel circularized soil phage genomes in size up to 235 kb were obtained from over 29,000 manually identified viral contigs, promising the discovery of a large, previously inaccessible viral diversity.ConclusionWe have shown a dramatically enhanced extraction of the soil phage community by protocol optimization that has proven robustness in both a culture-depended as well as through metaviromic analysis. Our huge data set of manually curated soil viral contigs roughly doubles the amount of currently available soil virome data, and provide insights into the yet largely undescribed soil viral sequence space.
Asymmetrical diversification of the receptor-ligand interaction controlling self-incompatibility in Arabidopsis
Authors: Maxime Chantreau , Poux Céline , Lensink Marc F. , Brysbaert Guillaume , Vekemans Xavier , Castric Vincent 
Published: August 2019

AbstractHow two-components genetic systems accumulate evolutionary novelty and become diversified in the course of evolution is a fundamental problem in evolutionary systems biology. In the Brassicaceae, self-incompatibility (SI) is a spectacular example of a diversified allelic series in which numerous highly diverged receptor-ligand combinations are segregating in natural populations. However, the evolutionary mechanisms by which new SI specificities arise in the first place have remained elusive. Usingin plantaancestral protein resurrection, we demonstrate that two allelic variants currently segregating as distinct receptor-ligand combinations diverged through an asymmetrical process whereby one variant has retained the same recognition specificity as the (now extinct) ancestor, while the other has functionally diverged and now represents a novel specificity no longer recognized by the ancestor. Examination of the structural determinants of the shift in binding specificity suggests that allosteric changes may be an important source of evolutionary novelty in this highly diversified receptor-ligand system.
Including variability in air temperature warming scenarios in a lake simulation model highlights uncertainty in predictions of cyanobacteria
Authors: Krinos Arianna I. , Farrell Kaitlin J. , Daneshmand Vahid , Subratie Kensworth C. , Figueiredo Renato J. , Carey Cayelan C. 
Published: August 2019

AbstractDespite growing evidence that climate change will increase temperature variability and the frequency of temperature extremes, many modeling studies that analyze the effects of warming scenarios on cyanobacteria in lakes examine uniform warming temperature scenarios without including any variability. Here, we used the one-dimensional hydrodynamic General Lake Model coupled to Aquatic EcoDynamics modules (GLM-AED) to simulate 11 years of nitrogen-fixing and non-nitrogen-fixing cyanobacterial biomass in Lake Mendota (Madison, WI, USA). We developed climate scenarios with either uniform (constant) warming or variable warming based on random sampling of daily air temperatures from either a normal or Poisson probability distribution. We found that while the median cyanobacterial biomass among repeated simulations for each of the years was similar regardless of whether or not air temperature variability was included in the climate scenarios, the randomly-sampled air temperature distribution scenarios exhibited much greater variability in the year-to-year cyanobacterial biomass estimates. Our results suggest that including temperature variability in climate scenarios may substantially change our understanding of how climate warming may alter cyanobacterial blooms over yearly to decadal time scales. To more effectively predict the range of possible future cyanobacterial dynamics, both the magnitude and variability of warming must be considered when developing climate scenarios for lake modeling studies.
An integrated population model for estimating the relative effects of natural and anthropogenic factors on a threatened population of Pacific trout
Authors: Scheuerell Mark D. , Ruff Casey P. , Anderson Joseph H. , Beamer Eric M. 
Published: August 2019

SummaryAssessing the degree to which at-risk species are regulated by density dependent versus density independent factors is often complicated by incomplete or biased information. If not addressed in an appropriate manner, errors in the data can affect estimates of population demographics, which may obfuscate the anticipated response of the population to a specific action.We developed a Bayesian integrated population model that accounts explicitly for interannual variability in the number of reproducing adults and their age structure, harvest, and environmental conditions. We apply the model to 41 years of data for a population of threatened steelhead troutOncorhynchus mykissusing freshwater flows, ocean indices, and releases of hatchery-born conspecifics as covariates.We found compelling evidence that the population is under strong density dependence, despite being well below its historical population size. In the freshwater portion of the lifecycle, we found a negative relationship between productivity (offspring per parent) and peak winter flows, and a positive relationship with summer flows. We also found a negative relationship between productivity and releases of hatchery conspecifics. In the marine portion of the lifecycle, we found a positive correlation between productivity and the North Pacific Gyre Oscillation. Furthermore, harvest rates on wild fish have been sufficiently low to ensure very little risk of overfishing.Synthesis and applications.The evidence for density dependent population regulation, combined with the substantial loss of juvenile rearing habitat in this river basin, suggests that habitat restoration could benefit this population of at-risk steelhead. Our results also imply that hatchery programs for steelhead need to be considered carefully with respect to habitat availability and recovery goals for wild steelhead. If releases of hatchery steelhead have indeed limited the production potential of wild steelhead, there are likely significant tradeoffs between providing harvest opportunities via hatchery steelhead production, and achieving wild steelhead recovery goals.
Multipotent radial glia progenitors and fate-restricted intermediate progenitors sequentially generate diverse cortical interneuron types
Authors: Kelly Sean M. , Raudales Ricardo , Moissidis Monika , Kim Gukham , Huang Z. Josh 
Published: August 2019

SUMMARYGABAergic interneurons deploy numerous inhibitory mechanisms that regulate cortical circuit operation, but the developmental programs that generate diverse interneuron types remain not well understood. We carried out a comprehensive genetic fate mapping of the radial glial progenitors (RGs) and intermediate progenitors (IP) in the medial ganglionic eminence (MGE). We reveal thatNkx2.1+RGs are multipotent and mediate two consecutive waves of neurogenesis, each sequentially generating different sets of interneuron types that laminate the neocortex in an inside-out-inside order. The first wave is restricted to the caudal MGE, has limited neurogenic capacity, and involves mostly apical IPs. The second wave initiates throughout the MGE and features a large set of fate-restricted basal IPs that amplify and diversify interneurons. Chandelier cells are generated toward the end of each wave and laminate in an outside-in order. Therefore, separate pools of multipotent RGs deploy temporal cohorts of IPs to sequentially generate diverse interneuron types.
Selection on mutators is not frequency-dependent
Authors: Raynes Yevgeniy , Weinreich Daniel M. 
Published: August 2019

AbstractThe evolutionary fate of mutator mutations – i.e., genetic variants that raise the genome-wide mutation rate – in asexual populations is often described as being frequency (or number) dependent. This common intuition suggests that mutators can invade a population by hitchhiking with a sweeping beneficial mutation, but only when sufficiently frequent to produce such a mutation before non-mutators do. Here, we use stochastic, agent-based simulations to show that neither the strength nor the sign of selection on mutators depend on their initial frequency, and while the overall probability of hitchhiking increases predictably with frequency, the per-capita probability of fixation remains unchanged.
Polygenic Hyperlipidemias and Coronary Artery Disease Risk
Authors: Ripatti Pietari , Rämö Joel T , Mars Nina J , Söderlund Sanni , Benner Christian , Surakka Ida , Kiiskinen Tuomo , Havulinna Aki S , Palta Priit , Freimer Nelson B , Salomaa Veikko , Pirinen Matti , Palotie FinnGen Aarno , Taskinen Marja-Riitta , Ripatti Samuli 
Published: August 2019

AbstractBackgroundHyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). Monogenic familial hypercholesterolemia associates with higher increase in CAD risk than expected from a single LDL-C measurement, likely due to lifelong cumulative exposure to high LDL-C. It remains unclear to what extent a high polygenic load of LDL-C or TG-increasing variants associates with increased CAD risk.Methods and ResultsWe derived polygenic risk scores (PRS) with ∼6M variants for LDL-C and TG with weights from a UK biobank-based genome-wide association study with ∼500K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the FINRISK cohort, and to CAD risk in 135 300 individuals (13 695 CAD cases) from the FinnGen project.In FINRISK, LDL-C ranged from 2.83 (95% CI 2.79-2.89) to 3.80 (3.72-3.88) and TG from 0.99 (0.95-1.01) to 1.52 (1.48-1.58) mmol/l between the lowest and highest 5% of the respective PRS distributions. The corresponding CAD prevalences ranged from 8.2% to 12.7% for the LDL-C PRS and from 8.2% to 12.1% for the TG PRS in FinnGen. Furthermore, CAD risk was 1.36-fold higher (OR, 95% CI 1.24-1.49) for the LDL-C PRS and 1.31-fold higher (1.20-1.44) for the TG PRS for those with the PRS >95thpercentile vs those without. These estimates were only slightly attenuated when adjusting for a CAD PRS (OR 1.26 [95% CI 1.15-1.39] for LDL-C and 1.21 [1.10-1.32] for TG PRS).ConclusionsThe CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and mostly independent of a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing more direct guidance for clinical translation.
Enduring consequences of perinatal fentanyl exposure in mice
Authors: Alipio Jason B. , Brockett Adam T. , Fox Megan E. , Tennyson Stephen S. , deBettencourt Coreylyn A. , El-Metwally Dina , Francis Nikolas A. , Kanold Patrick O. , Lobo Mary Kay , Roesch Matthew R. , Keller Asaf 
Published: August 2019

AbstractOpioid use by pregnant women is an understudied consequence associated with the opioid epidemic, resulting in a rise in the incidence of neonatal opioid withdrawal syndrome (NOWS), and lifelong neurobehavioral deficits that result from perinatal opioid exposure. There are few preclinical models that accurately recapitulate human perinatal drug exposure, and few focus on fentanyl, a potent synthetic opioid that is a leading driver of the opioid epidemic. To investigate the consequences of perinatal opioid exposure, we administered fentanyl to mouse dams in their drinking water throughout gestation and until litters were weaned at postnatal day (PD) 21. Fentanyl-exposed dams delivered smaller litters, and had higher litter mortality rates compared to controls. Metrics of maternal care behavior were not affected by the treatment, nor were there differences in dams’ weight or liquid consumption throughout gestation and 21 days postpartum. Twenty-four hours after weaning and drug cessation, perinatal fentanyl-exposed mice exhibited signs of spontaneous somatic withdrawal behavior, and sex-specific weight fluctuations that normalized in adulthood. At adolescence (PD 35) they displayed elevated anxiety-like behaviors and decreased grooming, assayed in the elevated plus maze and sucrose splash tests. Finally, by adulthood (PD 55) they displayed impaired performance in a two-tone auditory discrimination task. Collectively, our findings suggest that perinatal fentanyl exposed mice exhibit somatic withdrawal behavior and changes across the lifespan reminiscent of humans born with NOWS.
Population-Level Disease Dynamics Reflect Individual Heterogeneities in Transmission
Authors: Siva-Jothy Jonathon A. , White Lauren A. , Craft Meggan E. , Vale Pedro F. 
Published: August 2019

AbstractHost heterogeneity in disease transmission is widespread and presents a major hurdle to predicting and minimizing pathogen spread. Using theDrosophila melanogastermodel system infected withDrosophilaC virus, we integrate experimental measurements of individual host heterogeneity in social aggregation, virus shedding, and disease-induced mortality into an epidemiological framework that simulates outbreaks of infectious disease. We use these simulations to calculate individual variation in disease transmission and apportion this variation to specific components of transmission: social network degree distribution, infectiousness, and infection duration. The experimentally-observed variation produces substantial differences in individual transmission potential, providing evidence for genetic and sex-specific effects on disease dynamics at a population level. Manipulating variation in social network connectivity, infectiousness, and infection duration in simulated populations reveals that these components affect disease transmission in clear and distinct ways. We consider the implications of this genetic and sex-specific variation in disease transmission and discuss implications for appropriate control methods given the relative contributions made by social aggregation, virus shedding, and infection duration to transmission in other host-pathogen systems.
Resting-state and task-based centrality of dorsolateral prefrontal cortex predict resilience to inhibitory repetitive transcranial magnetic stimulation
Authors: Fitzsimmons Sophie M.D.D. , Douw Linda , van den Heuvel Odile A. , van der Werf Ysbrand D. , Vriend Chris 
Published: August 2019

AbstractBackgroundRepetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties.Objective/HypothesisA previous study by our group showed that ‘virtually lesioning’ the left dorsolateral prefrontal cortex (dlPFC; important for cognitive flexibility) using inhibitory rTMS reduced performance on a set-shifting task. We aimed to determine whether this behavioural response was related to topological features of pre-TMS resting-state and task-based functional networks.MethodsInhibitory (1Hz) rTMS was applied to the left dlPFC in 16 healthy participants, and to the vertex in 17 participants as a control condition. Participants performed a set-shifting task during fMRI at baseline and directly after a single rTMS session 1-2 weeks later. Functional network topology measures were calculated from resting-state and task-based fMRI scans using graph theoretical analysis.ResultsThe dlPFC-stimulated group, but not the vertex group, showed reduced set shifting performance after rTMS associated with lower task-based betweenness centrality of the dlPFC at baseline (p=.030) and a smaller reduction in task-based betweenness centrality after rTMS (p=.024). Reduced repeat trial accuracy after rTMS was associated with higher baseline resting state node strength of the dlPFC (p=.017).ConclusionsOur results suggest that behavioural response to inhibitory rTMS to the dlPFC is dependent on baseline functional network features. Individuals with more globally integrated stimulated regions show greater resilience to inhibitory rTMS, while individuals with more locally well-connected regions show greater vulnerability.HighlightsFunctional brain network properties predict behavioural response to 1Hz DLPFC rTMSGlobally integrated stimulated regions are resilient to effects of inhibitory rTMSSegregated, locally well-connected regions are vulnerable to inhibitory rTMSChange in performance after rTMS correlates with change in network properties
The abundance and diversity of West Nile virus mosquito vectors in two Regional Units of Greece during the onset of the 2018 transmission season
Authors: Bisia Marina , Jeffries Claire L , Lytra Ioanna , Michaelakis Antonios , Walker Thomas 
Published: August 2019

AbstractBackgroundWest Nile virus (WNV) is a zoonotic arbovirus of great medical and veterinary importance, threatening the health of humans and equines worldwide. Mosquitoes belonging to the Culex (Cx.) pipiens complex are major vectors but numerous other mosquito species have also been implicated as vectors of WNV. Due to variations in blood-feeding behaviour, the different biotypes and hybrids of Cx. pipiens influence the transmission of WNV, from enzootic cycles (between mosquitoes and birds), to spill-over transmission to humans and equines.MethodsIn this study, mosquitoes were collected and analysed from two regional units (RUs) of Greece with reported cases of WNV within the past 4 years; Palaio Flairo and Argolida (in Attica and Peloponnese regions, respectively). Collections using different types of mosquito surveillance traps were undertaken in May-June 2018 during the early period of the WNV transmission season.ResultsA total of 1062 mosquitoes were collected, with Biogents Sentinel traps (BG traps) collecting both a greater number of mosquitoes across all species and Cx. pipiens complex individuals than Centres for Disease Control miniature light traps (CDC traps) or Heavy Duty Encephalitis Vector Survey traps (EVS traps). Identification of collected mosquitoes (using both morphological keys and molecular barcoding) confirmed the presence of additional species including Aedes (Ae.) albopictus, Ae. caspius and Culiseta (Cs.) longiareolata. The prevalence of Cx. pipiens biotypes in the RU of Palaio Faliro was 54.5% pipiens type, 20.0% molestus type and 25.5% hybrids. In the RU of Argolida, the collection comprised 68.1% pipiens type, 8.3% molestus type and 23.6% hybrids. Screening individual unfed female mosquitoes for WNV (molecular xenomonitoring) resulted in detection in three females of the pipiens type and in one hybrid; all collected from the RU of Argolida.ConclusionsAs hybrids play an important role in spill-over transmission of WNV to humans and equines, these findings highlight the importance of undertaking entomological surveillance programs incorporating molecular xenomonitoring at the onset of the transmission season to provide an early warning system for health authorities aiming to prevent WNV outbreaks in Greece.