bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcranial Direct Current Stimulation on Opium Craving, Depression, and Anxiety
Authors: Taremian Farhad , Nazari Samira , Moradveisi Latif , Moloodi Reza
Published: January 2019

Objectives

Transcranial direct current stimulation can be effective in reducing the craving for food, alcohol, and methamphetamine. Because its effects have not been tested on patients with opium use disorder, we investigated its efficacy when it is combined with a standard methadone maintenance therapy protocol.

Methods

We carried out a pretest-posttest control group method to evaluate the effect of transcranial direct current stimulation at the dorsolateral prefrontal cortex (right anodal/left cathodal) on opium craving, depression, and anxiety symptoms. We considered opium craving as a primary outcome as well as depression and anxiety symptoms as secondary outcomes. Sixty participants with opium use disorder were randomly assigned into 3 groups (n = 20 for each group): (1) an active transcranial direct current stimulation with methadone maintenance treatment (active tDCS group), (2) sham transcranial direct current stimulation with methadone maintenance treatment (sham tDCS group), and (3) only methadone maintenance treatment (methadone maintenance treatment group). All participants completed the Desire for Drug Questionnaire, Obsessive-Compulsive Drug Use Scale, Beck Depression Inventory II, and Beck Anxiety Inventory a week before and a week after the treatment. The outcomes were assessed by independent assessors who were blind to the treatment conditions.

Results

The active tDCS group had a significant reduction in opium craving, depression, and anxiety symptoms compared with the other 2 groups.

Conclusions

Our results provide a preliminary support for using the transcranial direct current stimulation along with methadone maintenance therapy in the treatment of patients with opium use disorder.
Reproductive success in the barn owl is linked to partner compatibility in glucocorticoid levels
Authors: Béziers Paul , Jenni Lukas , Roulin Alexandre , Almasi Bettina
Published: January 2019

In biparental species, reproductive success depends not only on the quality of the parents, the care they each provide and many environmental factors such as territory quality and food availability, but also on the ability of the parents to collaborate and divide reproductive tasks. Because hormones, such as corticosterone (CORT), modulate physiological and behavioural functions that are associated to reproductive success, hormonal compatibility between pair members is likely to have consequences on reproductive success. Here, we investigated in the barn owl (Tyto alba) whether baseline and stress-induced CORT levels are correlated between breeding partners and whether this correlation is associated to fitness parameters (i.e., clutch size, offspring number and body mass). We found that the combination of CORT levels in the two partners predicts reproductive parameters. Pairs with similar baseline CORT levels during incubation produced more fledglings than pairs with dissimilar baseline CORT levels. On the other hand, pairs showing dissimilar stress-induced CORT responses during the period of offspring rearing produced more fledglings than pairs with similar stress-induced responses. Offspring body mass was associated only with maternal (baseline and stress-induced) CORT levels and depended on the context with baseline CORT being potentially adjusted to environmental conditions but also to the energetic demand of reproduction. Hence, to produce large broods good quality mothers might increase their baseline CORT to meet the energetic demand of the brood, while mothers in unfavourable habitats may have smaller broods but still need to increase baseline CORT to cope with the environmental challenges. Taken together, the results show that the association between parental CORT levels and reproductive success are context-dependent and rely on the combination of parental CORT levels. Assuming that CORT levels reflect investment in parental care, our study suggests that parents coordinate their reproductive activities in a complex way to ensure a high reproductive success.
Accounting for imperfect detection in species with sessile life cycle stages: a case study of bumble bee colonies
Authors: Iles David T. , Pugesek Genevieve , Kerr Natalie Z. , Dorian Nicholas N. , Crone Elizabeth E.
Published: January 2019

For bumble bees, colonies (not individual workers) are the functional unit of the population. Estimates of colony density are thus critical for understanding population distribution and trends of this important pollinator group. Yet, surveys of bumble bee colonies and other taxa with sessile life cycle states rarely account for imperfect detection.

Here we demonstrate the use of mark-recapture methods to estimate the density of bumble bee colonies across the landscape using standardized survey protocols.

We found that the probability of detecting colonies in standardized surveys varied considerably across space, through time, and among colonies.

Using simulations, we also show that imperfect detection can obscure true variation in density among plots, or generate spurious variation in counts even when all plots have the same density. In both cases, we show that mark-recapture can be used to generate unbiased estimates of density, with relatively low search effort compared to conventional survey methods for bumble bee colonies.

Our study illustrates the advantages of mark-recapture for optimizing survey protocols for species with cryptic and sessile life cycle stages, which will be a valuable tool in ongoing studies of pollinator nesting ecology.
Use of a pandemic H1N1 strain with updated haemagglutinin and neuraminidase results in increased nasopharyngeal shedding and improved immunogenicity to Russian-backbone live attenuated influenza vaccine among children aged 2 – 4 years old: an open-label, prospective, observational, phase 4 study in The Gambia
Authors: Lindsey Benjamin B. , Jagne Ya Jankey , Armitage Edwin P. , Singanayagam Anika , Sallah Hadijatou J. , Drammeh Sainabou , Senghore Elina , Mohammed Nuredin I. , Jeffries David , Höschler Katja , Tregoning John S. , Meijer Adam , Clarke Ed , Dong Tao , Barclay Wendy , Kampmann Beate , de Silva Thushan I.
Published: January 2019

Background

Poor efficacy and effectiveness of the pandemic H1N1 (pH1N1) component in intranasal live attenuated influenza vaccine (LAIV) has been demonstrated in several studies. The reasons for this are unclear, but may be due to impaired replicative fitness of pH1N1 A/California/07/2009-like (Cal09) LAIV strains.

Methods

In an open-label, prospective, observational, phase 4 study, we evaluated the impact of updating the pH1N1 component in the Russian-backbone trivalent LAIV from Cal09 in 2016-17 (n=118) to an A/Michigan/45/2015-like strain (A/17/New York/15/5364, NY15) in 2017-18 (n=126), on shedding and immunogenicity in Gambian children aged 2-4 years old. The study was nested within a larger randomised controlled trial investigating LAIV-microbiome interactions (ClinicalTrials.govNCT02972957).

Findings

Cal09 showed impaired nasopharyngeal shedding compared to H3N2 and influenza B, along with sub-optimal serum antibody and T-cell responses. Following the switch to NY15, a significant increase in pH1N1 shedding was seen, along with improvements in seroconversion and influenza-specific CD4+ T-cell responses. Viral kineticsin vitromirrored these findings, with NY15 showing greater replicative ability than Cal09 in human nasal epithelial cells. Persistent shedding to day 7 was independently associated with both seroconversion and CD4+ T cell response in multivariable logistic regression.

Interpretation

Our results suggest that the pH1N1 component switch in LAIV may have overcome problems in prior formulations. LAIV effectiveness against pH1N1 should therefore improve in upcoming influenza seasons. Our data also highlight the importance of evaluating replicative fitness, in addition to antigenicity, when selecting annual LAIV components and design of potentially more effective vaccines.

Funding

The Wellcome Trust.
Sequence based mapping identifiesAWNS1, a candidate transcription repressor underlying awn suppression at theB1locus in wheat
Authors: DeWitt Noah , Guedira Mohammed , Lauer Edwin , Sarinelli Martin , Tyagi Priyanka , Fu Daolin , Hao QunQun , Murphy J. Paul , Marshall David , Akhunova Alina , Jordan Katie , Akhunov Eduard , Brown-Guedira Gina
Published: January 2019

Awns are stiff, hair-like structures that grow from the spikelets of wheat (Triticum aestivumL.) and other grasses. In wild wheat relatives, awns play a role in seed dispersal. Awn suppression in domesticated wheat, where awns are shortened or even eliminated entirely, is variably adaptive with both awned and awnless types under widespread cultivation. Although theB1locus on the long arm of chromosome 5A is a major determinant of awn suppression, no underlying gene or mechanism of action has been identified. Using association mapping, we identified a SNP marker located on the distal end of 5AL (5A28417) predictive of awn status in a panel of 640 U.S. winter wheat breeding lines, indicating thatB1was the determinant of awn suppression in this germplasm. Analysis of historical data available for the panel determined5A28417was also significantly associated with grain test weight. Evaluation of spike morphology and kernel traits was undertaken in a 341 RIL population developed from a cross between awned soft winter wheat cultivar LA95135 and awnless cultivar SS-MPV57. Awn suppression in the population co-segregated with 5A28417 and was co-located with QTL for number of spikelets per spike, kernel weight and kernel length. Fine-mapping locatedB1to a region containing only two predicted genes, including a C2H2 zinc finger transcription factor 219 bp from 5A28417 that we namedAWNS-A1. Deletions encompassing both genes were present in awned mutants of the awnless cultivar Brundage. Polymorphisms in theAWNS-A1coding region were not observed in diverse wheat germplasm. However, sequencing of wheat lines representing different marker haplotypes in the surrounding region identified a deletion 3 kb downstream ofAWNS-A1.A marker for this deletion was highly predictive of awn suppression in a collection of diverse wheat accessions, and indicates thatAWNS-A1is likely the major determinant of awn suppression in global wheat germplasm.AWNS-A1is more highly expressed in developing spikes of awnless individuals, suggesting a mechanism for awn suppression.
Development of a Prediction Model for Incident Atrial Fibrillation using Machine Learning Applied to Harmonized Electronic Health Record Data
Authors: Tiwari Premanand , Colborn Katie , Smith Derek E. , Xing Fuyong , Ghosh Debashis , Rosenberg Michael A.
Published: January 2019

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, whose early detection could lead to significant improvements in outcomes through appropriate prescription of anticoagulation. Although a variety of methods exist for screening for AF, there is general agreement that a targeted approach would be preferred. Implicit within this approach is the need for an efficient method for identification of patients at risk. In this investigation, we examined the strengths and weaknesses of an approach based on application of machine-learning algorithms to electronic health record (EHR) data that has been harmonized to the Observational Medical Outcomes Partnership (OMOP) common data model. We examined data from a total of 2.3M individuals, of whom 1.16% developed incident AF over designated 6-month time intervals. We examined and compared several approaches for data reduction, sample balancing (re-sampling) and predictive modeling using cross-validation for hyperparameter selection, and out-of-sample testing for validation. Although no approach provided outstanding classification accuracy, we found that the optimal approach for prediction of 6-month incident AF used a random forest classifier, raw features (no data reduction), and synthetic minority oversampling technique (SMOTE) resampling (F1 statistic 0.12, AUC 0.65). This model performed better than a predictive model based only on known AF risk factors, and highlighted the importance of using resampling methods to optimize ML approaches to imbalanced data as exists in EHRs. Further studies using EHR data in other medical systems are needed to validate the clinical applicability of these findings.
Benefits of improved air quality on aging lungs – Impacts of genetics and obesity
Authors: Hüls Anke , Sugiri Dorothea , Abramson Michael J , Hoffmann Barbara , Schwender Holger , Ickstadt Katja , Krämer Ursula , Schikowski Tamara
Published: January 2019

Introduction

The beneficial effect of improving air quality on lung function in the elderly remains unclear. We examined associations between decline in air pollutants and lung function and effect modifications by genetics and BMI in elderly German women.

Methods

Data were analysed from the prospective SALIA cohort study (N=601). Spirometry was conducted at baseline (1985-1994; 55 years), in 2007-2010 and in 2012-2013. Air pollution concentrations at home addresses were determined for each time point using land-use regression models. GLI z-scores were calculated. Weighted genetic risk scores (GRS) were determined from lung function-related risk alleles and used to investigate interactions with improved air quality. Adjusted linear mixed models were fitted.

Results

Air pollution levels decreased substantially during the study period. Reduction of air pollution was associated with an increase of z-scores for FEV1 and FEV1/FVC. For a decrease of 10 μg/m3 in NO2, the z-score for FEV1 increased by 0.14 (95%CI: 0.01; 0.26). However, with an increasing number of lung function-related risk alleles, the benefit from improved air quality decreased (GRSxNO2-interaction:p=0.029). Interactions with BMI were not significant.

Conclusions

Reduction of air pollution is associated with a relative improvement of lung function in elderly women, but also depends on their genetic make-up.
Effects of Standing on Spinal Alignment and Lumbar Intervertebral Discs in Young, Healthy Individuals Determined by Positional Magnetic Resonance Imaging
Authors: Weber Christian I. , Hwang Ching-Ting , Dillen Linda R. Van , Tang Simon Y.
Published: January 2019

Traditional diagnostic imaging of the spine is performed in supine, a relatively unloaded position. However, the spine is subjected to complex loading environments in daily activities such as standing. Therefore, we seek to quantify the changes from supine to standing in the spines of young, healthy individuals in standing using a positional MRI system. This is an observational study that examined the changes in the spine and individual intervertebral discs (IVDs) during supine and standing of forty healthy participants (19 males / 21 females) without a history of low back pain. The regional lumbar spinal alignment was measured by the sagittal Cobb angle. Segmental IVD measurements included the segmental Cobb angle, anterior to posterior height (A/P) ratio, and IVD width measured at each L1/L2 - L5/S1 levels. The intra-observer intra-class correlation (ICC) consistency model showed values for measurements ranged from 0.76-0.98. The inter-observer ICC values ranged from 0.68-0.99. The Cobb angle decreased in standing. The L5/S1 segmental Cobb angle decreased in standing. The L2/L3 and L3/L4 A/P ratios increased and the L5/S1 A/P ratio decreased in standing. No differences in IVD width were observed from supine to standing. This study examined the regional lumbar spinal alignment and segmental IVD changes from supine to standing in young, healthy individuals without LBP using pMRI. In developing and validating these measurements, we have also established the normative data for healthy, asymptomatic population that could be useful for other investigations examining how individuals with spinal or IVD pathologies may adapt between supine and standing.
Enteropathogen seroepidemiology among children in low-resource settings
Authors: Arnold Benjamin F. , Martin Diana L. , Juma Jane , Mkocha Harran , Ochieng John B. , Cooley Gretchen M. , Omore Richard , Goodhew E. Brook , Morris Jamae F. , Costantini Veronica , Vinjé Jan , Lammie Patrick J. , Priest Jeffrey W.
Published: January 2019

Little is known about enteropathogen seroepidemiology among children in low-resource settings. We measured serological IgG response to eight enteropathogens (Giardia intestinalis, Cryptosporidium parvum, Entamoeba histolytica, Salmonella enterica, enterotoxigenicEscherichia coli, Vibrio cholerae, Campylobacter jejuni, norovirus) using multiplex bead assays in cohorts from Haiti, Kenya, and Tanzania. By age 2 years, most children had evidence of exposure by IgG response to the pathogens studied. We discovered a shift in IgG distributions for many pathogens as children age, caused by boosting and waning from repeated exposures, which complicates interpretation of seroprevalence among older children. Longitudinal profiles revealed important variation in enteropathogen IgG response above seropositivity cutoffs, underscoring the importance of longitudinal designs to estimate seroincidence rates as a measure of force of infection. In longitudinal cohorts there was a linear relationship between seroprevalence and prospective seroincidence rates, suggesting the two measures provide similar information about variation in pathogen transmission.
Individual differences in the effects of priors on perception: a multi-paradigm approach
Authors: Tulver Kadi , Aru Jaan , Rutiku Renate , Bachmann Talis
Published: January 2019

The present study investigated individual differences in how much subjects rely on prior information, such as expectations or knowledge, when faced with perceptual ambiguity. The behavioural performance of forty-four participants was measured on four different visual paradigms (Mooney face recognition, illusory contours, blur detection and representational momentum) in which priors have been shown to affect perception. In addition, questionnaires were used to measure autistic and schizotypal traits in the non-clinical population. We hypothesized that someone who in the face of ambiguous or noisy perceptual input relies heavily on priors, would exhibit this tendency across a variety of tasks. This general pattern would then be reflected in high pairwise correlations between the behavioural measures and an emerging common factor. On the contrary, our results imply that there is no single factor that explains the individual differences present in the aforementioned tasks, as further evidenced by the overall lack of robust correlations between the separate paradigms. Instead, a two-factor structure reflecting differences in the hierarchy of perceptual processing was the best fit for explaining the individual variance in these tasks. This lends support to the notion that mechanisms underlying the effects of priors likely originate from several independent sources and that it is important to consider the role of specific tasks and stimuli more carefully when reporting effects of priors on perception.
The KZFP/KAP1 system controls transposable elements-embedded regulatory sequences in adult T cells
Authors: Marzetta Flavia , Simó-Riudalbas Laia , Duc Julien , Planet Evarist , Verp Sonia , Turelli Priscilla , Trono Didier
Published: January 2019

Transposable elements-embedded regulatory sequences (TEeRS) are subjected to early embryonic repression through sequence-specific recruitment of KRAB zinc finger proteins (KZFPs), their cofactor KAP1/TRIM28 and associated chromatin modifiers. This modulates the TEeRS-mediated regulation of gene expression in embryonic stem cells (ESCs) and leads to DNA methylation-induced silencing. However, KZFPs are broadly expressed in adult tissues, suggesting that they control TEeRS throughout life. Confirming this hypothesis, we reveal here that the KZFP/KAP1 system exerts a highly dynamic control of TEeRS in adult human CD4+ T lymphocytes. First, we observed that in these cells many TEs are still bound by KAP1, the recruitment of which is dynamically regulated upon T cell receptor stimulation. Second, we found that KAP1 depletion induces broad transcriptional alterations in T cells, with de-repression of TE-based regulatory elements leading to the illegitimate activation of nearby genes. Finally, we show that the tissue-restricted expression of KZFPs correlates with KAP1-mediated lineage-specific chromatin signatures and transcriptional repression. These data support a model where TE-targeting KZFPs and KAP1 are important regulators of gene expression in adult human cells.
Acute Myeloid Leukemia Driven by the CALM-AF10 Fusion Gene is Dependent on BMI1
Authors: Barbosa Karina , Ghosh Anwesha , Deshpande Anagha , Chen Bo-Rui , Sun Younguk , Weetall Marla , Armstrong Scott A. , Bohlander Stefan K. , Deshpande Aniruddha J.
Published: January 2019

A subset of acute myeloid and lymphoid leukemia cases harbor a t(10;11)(p13;q14) translocation resulting in the CALM-AF10 fusion gene. Standard chemotherapeutic strategies are often ineffective in treating patients with CALM-AF10 fusions. Hence, there is an urgent need to identify molecular pathways dysregulated in CALM-AF10-positive leukemias which may lay the foundation for novel targeted therapies. Here we demonstrate that the Polycomb Repressive Complex 1 geneBMI1is consistently overexpressed in adult and pediatric CALM-AF10-positive leukemias. We demonstrate that geneticBmi1depletion abrogates CALM-AF10-mediated transformation of murine hematopoietic stem and progenitor cells (HSPCs). Furthermore, CALM-AF10-positive murine and human AML cells are profoundly sensitive to the small-molecule BMI1 inhibitor PTC209 as well as to PTC596, a compound in clinical development that has been shown to result in downstream degradation of BMI1 protein. PTC-596 significantly prolongs survival of mice injected with a human CALM-AF10 cell line in a xenograft assay. In summary, these results validate BMI1 as abonafidecandidate for therapeutic targeting in AML with CALM-AF10 rearrangements.
Distinct genetic signatures of cortical and subcortical regions associated with human memory
Authors: Tan Pin Kwang , Ananyev Egor , Hsieh Po-Jang (Brown)
Published: January 2019

Despite the discovery of gene variants linked to memory performance, understanding the genetic basis of human memory remains a challenge. Here, we devised a framework combining human transcriptome data and a functional neuroimaging map to uncover the genetic signatures of memory in functionally-defined cortical and subcortical memory regions. Results were validated with animal literature and our framework proved to be highly effective and specific to the targeted cognitive function versus a control function. Genes preferentially expressed in cortical memory regions are linked to associative learning and ribosome biogenesis. Genes expressed in subcortical memory regions are associated with synaptic signaling and epigenetic processes. Cortical and subcortical regions share a number of memory-related biological processes and genes, e.g. translational initiation and GRIN1. Thus, cortical and subcortical memory regions exhibit distinct genetic signatures that potentially reflect functional differences in health and disease, and propose gene candidates for the targeted treatment of memory disorders.
Landscape-scale simulations as a tool in multi-criteria decision making for agri-environment schemes
Authors: Topping Chris J. , Dalby Lars , Valdez Jose W.
Published: January 2019

Increasing concerns over the environmental impacts of agriculture in Europe has led to the introduction of agri-environment schemes (AES) to help mitigate biodiversity loss. However, effectiveness of AES has been mixed and only partially successful in achieving desired outcomes. To improve effectiveness and reduce high costs, multi-criteria decision analysis (MCDA) can help support decision-making and determine the most effective management action. Although MCDA has great potential for evaluating policy measures, it rarely considers the context-dependency of species responses to management practices across different landscapes. Landscape simulations can, therefore, be valuable for reducing the uncertainties when predicting the consequences of management actions. A potential suitable simulation system is the Animal, Landscape, and Man Simulation System (ALMaSS), a mechanistic simulation with can improve MCDA with the automatic integration of a species ecology and behaviour and landscape context. The aim of this study was to demonstrate the effectiveness of ALMaSS in evaluating AES management practices across different landscapes and estimate their ability to achieve the proposed conservation outcomes of three typical species of conservation interest. In this study, the effect of a particular management strategy on a species was dependent on the landscape context, in our case, a combination of landscape structure and the type and distribution of farms, and varied depending on the metrics being measured. Although we did not aim to make recommendations of particular management strategies, we demonstrate how simulations can be used for MCDA to select between management strategies with different costs. Despite the complexity of ALMaSS models, the simulation results provided are easy to interpret. Landscape simulations, such as ALMaSS, can be an important tool in multi-criteria decision making by simulating a wide range of managements and contexts and provide supporting information for filtering management options based on specific conservation goals.
Thalamus drives two complementary input strata of the neocortex in parallel
Authors: Egger R. , Narayanan R.T. , Udvary D. , Bast A. , Guest J.M. , Das S. , de Kock C.P.J. , Oberlaender M.
Published: January 2019

Sensory information enters the neocortex via thalamocortical axons that define the major ‘input’ layer 4. The same thalamocortical axons, however, additionally innervate the deep ‘output’ layers 5/6. How such bistratification impacts cortical processing remains unknown. Here, we find a class of neurons that cluster specifically around thalamocortical axons at the layer 5/6 border. We show that these border stratum cells are characterized by extensive horizontal axons, that they receive strong convergent input from the thalamus, and that this input is sufficient to drive reliable sensory-evoked responses, which precede those in layer 4. These cells are hence strategically placed to amplify and relay thalamocortical inputs across the cortical area, for example to drive the fast onsets of cortical output patterns. Layer 4 is therefore not the sole starting point of cortical processing. Instead, parallel activation of layer 4 and the border stratum is necessary to broadcast information out of the neocortex.
A new Image Segmentation Algorithm with Applications in Confocal Microscopy Analysis
Authors: Sánchez-Aragón M. , Casares F.
Published: January 2019

Gene regulatory networks (GRNs) represent the molecular interactions that govern the behavior of cells in tissues during development. The building and analysis of GRNs require quantitative information on gene expression from tissues. Laser Scanning Confocal Microscopy (LSCM) is commonly used to obtain such information, where immunofluorescence signal can be used as a correlate of gene expression or protein levels. However, a critical step for the extraction of this information is the segmentation of LSCM digital images. Popular segmentation algorithms are frequently based on watershed methods. Here we present an algorithm for the 3D segmentation ofnucleifrom LSCM (x,y,z) image stacks based on regional merging and graph contractions. This algorithm outperforms watershed methods, especially when the density of images along the z-axis is low and there is a high nuclear signal crowding. In addition, it reduces the parameterization since no filter is needed in order to prevent signal noise side effects (e.g. oversegmentation). Based on this algorithm, we developed an application (iFLIC, immunoFLuorescence Imaging Cytometry tool) for the Java Virtual Machine (JVM). The application supports basic operations for reading, writing and filtering 8-bit depth multicolor TIFF image formats, including indexed file directories (IFD), which are provided by the Java Advanced Imaging (JAI) library. It also provides with basic 3D-rendering and ROI specification that make extensive use of the Java3D library. iFLIC is also a plugin based application powered by the Java Plugin Platform (JPF), so each specific operation is declared as a unique command associated to one plugin and linked to a common interface. Results from segmentation can be exported both as TIFF images and a descriptive file format (iFLIC format)
Rapidly processed stool swabs approximate stool microbiota profiles
Authors: Bokulich Nicholas A. , Maldonado Juan , Kang Dae-Wook , Krajmalnik-Brown Rosa , Caporaso J. Gregory
Published: January 2019

Studies of the intestinal microbiome commonly utilize stool samples to measure microbial composition in the distal gut. However, collection of stool can be difficult from some subjects under certain experimental conditions. In this study we validate the use of swabs of fecal matter to approximate measurements of microbiota in stool using 16S rRNA gene Illumina amplicon sequencing, and evaluate the effects of shipping time at ambient temperatures on accuracy. Results indicate that swab samples reliably replicate stool microbiota bacterial composition, alpha diversity, and beta diversity when swabs are processed quickly (< 2 days), but sample quality quickly degrades after this period, accompanied by increased abundances of Enterobacteriaceae. Fresh swabs appear to be a viable alternative to stool sampling when standard collection methods are challenging, but extended exposure to ambient temperatures prior to processing threatens sample integrity.
Widespread selection for high and low secondary structure in coding sequences across all domains of life
Authors: Gebert Daniel , Jehn Julia , Rosenkranz David
Published: January 2019

Codon composition, GC-content and local RNA secondary structures can have a profound effect on gene expression and mutations affecting these parameters, even though they do not alter the protein sequence, are not neutral in terms of selection. Although evidence exists that in some cases selection favors more stable RNA secondary structures, we currently lack a concrete idea of how many genes are affected within a species, and if this is a universal phenomenon in nature.

We searched for signs of structural selection in a global manner, analyzing a set of one million coding sequences from 73 species representing all domains of life, as well as viruses, by means of our newly developed software PACKEIS. We show that codon composition and amino acid identity are main determinants of RNA secondary structure. In addition, we show that the arrangement of synonymous codons within coding sequences is non-random, yielding extremely high, but also extremely low secondary structures significantly more often than expected by chance.

Together, we demonstrate that selection for high and low secondary structure is a widespread phenomenon. Our results provide another line of evidence that synonymous mutations are less neutral than commonly thought, which is of importance for many evolutionary models.
Risks to pollinators from different land-use transitions: bee species’ responses to agricultural expansion show strong phylogenetic signal
Authors: Palma Adriana De , Kuhlmann Michael , Pearse William D. , Flynn Emma , Roberts Stuart P.M. , Potts Simon G. , Purvis Andy
Published: January 2019

Bee species worldwide are facing a future of further land-use change and intensification. Populations of closely-related species with similar ecological characteristics are likely to respond similarly to such pressures. Such phylogenetic signal in species’ responses could undermine the stability of pollination services in agricultural and natural systems. We use abundance data from a global compilation of bee assemblages in different land uses to assess the sensitivity of 573 bee species to agricultural expansion, intensification and urbanization; and combine the results with the Bee Tree of Life to assess phylogenetic signal. In addition, we assess whether variation in species’ sensitivity to land-use change is better explained by phylogenetic or available functional trait differences. Bee species show strong phylogenetic signal in sensitivity to agricultural land expansion but only a weak signal in sensitivity to agricultural intensification and urbanisation. Sensitivities were usually best explained by a combination of functional and phylogenetic distances. This finding suggests that the commonly-recorded traits, despite being meaningful as functional response traits, do not capture all important determinants of bee species’ vulnerability or resistance. However, it also suggests that model-based predictions of the sensitivity of poorly known species may be sufficient to help guide conservation efforts.
Transcriptomic correlates of electrophysiological and morphological diversity within and across neuron types
Authors: Bomkamp Claire , Tripathy Shreejoy , Bengtsson Gonzales Carolina , Hjerling Leffler Jens , Craig Ann Marie , Pavlidis Paul
Published: January 2019

In order to further our understanding of how gene expression contributes to key functional properties of neurons, we combined publicly accessible gene expression, electrophysiology, and morphology measurements to identify cross-cell type correlations between these data modalities. Building on our previous work using a similar approach, we distinguished between correlations which were "class-driven," meaning those that could be explained by differences between excitatory and inhibitory cell classes, and those that reflected graded phenotypic differences within classes. Taking cell class identity into account increased the degree to which our results replicated in an independent dataset as well as their correspondence with known modes of ion channel function based on the literature. We also found a smaller set of genes whose relationships to electrophysiological or morphological properties appear to be specific to either excitatory or inhibitory cell types. Next, using data from Patch-seq experiments, allowing simultaneous single-cell characterization of gene expression and electrophysiology, we found that some of the gene-property correlations observed across cell types were further predictive of within-cell type heterogeneity. In summary, we have identified a number of relationships between gene expression, electrophysiology, and morphology that provide testable hypotheses for future studies.
Transcriptome analysis of the Molecular Mechanism underlying Immunity- and Reproduction trade-off in Locusta migratoria Infected by Micrococcus luteus
Authors: Wang Shaohua , Liu Xiaojun , Xia Zhiyong , Xie Guoqiang , Tang Bin , Wang Shigui
Published: January 2019

Immune response and reproductive success are two of the main energy-consuming processes in living organisms. However, it is unclear which process is prioritized when both are required. Therefore, the present study was designed to examine this question using one of the world’s most destructive agricultural pests, the migratory locust Locusta migratoria. Transcripts from the ovaries and fat bodies of newly emerged locusts were analyzed, using RNA-seq based transcriptome and qualitative real-time PCR, at 4 h and 6 d after being infected with the gram-positive bacteria Microcroccus luteus, and changes in the main biological pathways involved in reproduction and immunization were analyzed using bioinformatics. At 4 h after infection, 348 and 133 transcripts were up- and down-regulated, respectively, whereas 5699 and 44 transcripts were up- and down-regulated, respectively, at 6 d after infection. Meanwhile, KEGG analysis indicated that vital pathways related with immunity and reproduction, such as Insulin resistance, FoxO signaling, Lysosome, mTOR signaling, and Toll-like receptor signaling pathways were up-regulated. Among the differentially expressed genes, 22 and 17 were related to immunity and reproduction, respectively, and the expression levels of PPO1 and antimicrobial peptide defensin 3 were increased (log2FC = 5.93 and 6.75, respectively), whereas those of VgA and VgB were reduced (log2FC = −17.82 and −18.13, respectively). These results indicated that that locusts allocate energy and resources to maintain their own survival by increasing immune response when dealing with both immune and reproductive processes. The present study provides the first report of expression levels for genes related with reproduction and immunity in locusts, thereby providing a reference for future studies, as well as theoretical guidance for investigations of locust control.
Global and regional white matter development in early childhood
Authors: Reynolds Jess E. , Grohs Melody N. , Dewey Deborah , Lebel Catherine
Published: January 2019

White matter development continues throughout childhood and into early adulthood, but few studies have examined early childhood, and the specific trajectories and regional variation in this age range remain unclear. The aim of this study was to characterize developmental trajectories and sex differences of white matter in typically developing young children. Three hundred and ninety-six diffusion tensor imaging datasets from 120 children (57 male) aged 2-8 years were analyzed using tractography. Fractional anisotropy (FA) increased and mean diffusivity (MD) decreased in all white matter tracts by 5-15% over the 6-year period, likely reflecting increases in myelination and axonal packing. Males showed steeper slopes in a number of brain areas. Overall, early childhood is associated with substantial development of all white matter and appears to be an important period for the development of occipital and limbic connections, which showed the largest changes. This study provides a detailed characterization of age-related white matter changes in early childhood, offering baseline data that can be used to understand cognitive and behavioural development, as well as to identify deviations from normal development in children with various diseases, disorders, or brain injuries.
Direct binding of the flexible C-terminal segment of periaxin to β4 integrin suggests a molecular basis for CMT4F
Authors: Raasakka Arne , Linxweiler Helen , Brophy Peter J , Sherman Diane L , Kursula Petri
Published: January 2019

The process of myelination in the nervous system requires coordinated formation of both transient and stable supramolecular complexes. Myelin-specific proteins play key roles in these assemblies, which may link membranes to each other or connect the myelinating cell cytoskeleton to the extracellular matrix. The myelin protein periaxin is known to play an important role in linking the Schwann cell cytoskeleton to the basal lamina through membrane receptors, such as the dystroglycan complex. Mutations that truncate periaxin from the C terminus cause demyelinating peripheral neuropathy, Charcot-Marie-Tooth disease type 4F, indicating a function for the periaxin C-terminal region in myelination. We identified the cytoplasmic domain of β4 integrin as a specific high-affinity binding partner for periaxin. The C-terminal region of periaxin remains unfolded and flexible when bound to the third fibronectin type III domain of β4 integrin. Our data suggest that periaxin is able to link the Schwann cell cytoplasm to the basal lamina through a two-pronged interaction via different membrane protein complexes, which bind close to the N and C terminus of this elongated, flexible molecule.
Comparisons of dual isogenic human iPSC pairs identify functional alterations directly caused by an epilepsy associatedSCN1Amutation
Authors: Xie Yunyao , Ng Nathan N. , Safrina Olga S. , Ramos Carmen M. , Ess Kevin C. , Schwartz Philip H. , Smith Martin A. , O’Dowd Diane K.
Published: January 2019

Over 1250 mutations inSCN1A, the Nav1.1 voltage-gated sodium channel gene, are associated with seizure disorders including GEFS+. To evaluate how a specific mutation, independent of genetic background, causes seizure activity we generated two pairs of isogenic human iPSC lines by CRISPR/Cas9 gene editing. One pair is a control line from an unaffected sibling, and the mutated control carrying the GEFS+ K1270TSCN1Amutation. The second pair is a GEFS+ patient line with the K1270T mutation, and the corrected patient line. By comparing the electrophysiological properties in inhibitory and excitatory iPSC-derived neurons from these pairs, we found the K1270T mutation causes cell type-specific alterations in sodium current density and evoked firing, resulting in hyperactive neural networks. We also identified differences associated with genetic background and interaction between the mutation and genetic background. Comparisons within and between dual pairs of isogenic iPSC-derived neuronal cultures provide a novel platform for evaluating cellular mechanisms underlying a disease phenotype and for developing patient-specific anti-seizure therapies.
Scavenging of reactive dicarbonyls with 2-hydroxybenzylamine reduces atherosclerosis in hypercholesterolemic Ldlr−/− mice
Authors: Tao Huan , Huang Jiansheng , Yancey Patricia G. , Yermalitsky Valery , Blakemore John L. , Zhang Youmin , Ding Lei , Zagol-Ikapitte Irene , Amarnath Venkataraman , Boutaud Olivier , Oates John A. , Roberts L. Jackson , Davies Sean S. , Linton MacRae F.
Published: January 2019

The pathogenesis of atherosclerosis may be accelerated by oxidative stress, which produces lipid peroxidation. Among the products of lipid peroxidation are highly reactive dicarbonyls including isolevuglandins (IsoLGs) and malondialdehyde (MDA) that covalently modify proteins. We investigated the impact of treatment with the dicarbonyl scavenger, 2-hydroxybenzylamine (2-HOBA) on HDL function and atherosclerosis in hyperlipidemic Ldlr−/− mice, a model of familial hypercholesterolemia (FH). Compared to mice treated with vehicle, 2-HOBA significantly decreased atherosclerosis in hypercholesterolemic Ldlr−/− mice by 31% in the proximal aortas and 60% in en face aortas, in the absence of changes in blood lipid levels. 2-HOBA reduced MDA content in HDL and LDL. Consuming a western diet increased plasma MDA-apoAI adduct levels in Ldlr−/− mice. 2-HOBA inhibited MDA-apoAI formation and increased the capacity of the mouse HDL to reduce macrophage cholesterol stores. Importantly, 2-HOBA reduced the MDA- and IsoLG-lysyl content in atherosclerotic aortas in Ldlr−/− mice. Furthermore, 2-HOBA diminished oxidative stress-induced inflammatory responses in macrophages, reduced the number of TUNEL-positive cells in atherosclerotic lesions by 72%, and decreased serum proinflammatory cytokines. Furthermore, 2-HOBA enhanced efferocytosis and promoted characteristics of stable plaque formation in mice as evidenced by a 69% (p<0.01) reduction in necrotic core and by increased collagen content (2.7-fold) and fibrous cap thickness (2.1-fold). HDL from patients with FH had increased MDA content resulting in a reduced ability of FH-HDL to decrease macrophage cholesterol content versus controls. Our results demonstrate that dicarbonyl scavenging with 2-HOBA has multiple atheroprotective effects on lipoproteins and reduces atherosclerosis in a murine model of FH, supporting its potential as a novel therapeutic approach for the prevention and treatment of human atherosclerotic cardiovascular disease.

Abbreviations

2-HOBA, 2-hydroxybenzylamine; 4-HOBA, 4-hydroxybenzylamine; MDA, malondialdehyde; 4-HNE, 4-hydroxynonenal; IsoLGs, isolevuglandins; HDL, high-density lipoproteins; LDL, lowdensity lipoprotein; LDLR, low-density lipoprotein receptor; ApoAI, apolipoprotein AI; ApoB, apolipoprotein B; ROS, reactive oxygen species; IL, interleukin.
Domain-specific working memory, but not dopamine-related genetic variability, shapes reward-based motor learning
Authors: Holland Peter , Codol Olivier , Oxley Elizabeth , Taylor Madison , Hamshere Elizabeth , Joseph Shadiq , Huffer Laura , Galea Joseph M.
Published: January 2019

The addition of rewarding feedback to motor learning tasks has been shown to increase the retention of learning, spurring interest in the possible utility for rehabilitation. However, laboratory-based motor tasks employing rewarding feedback have repeatedly been shown to lead to great inter-individual variability in performance. Understanding the causes of such variability is vital for maximising the potential benefits of reward-based motor learning. Thus, using a large cohort (n=241) we examined whether spatial (SWM), verbal (VWM) and mental rotation (RWM) working memory capacity and dopamine-related genetic profiles were associated with performance in two reward-based motor tasks. The first task assessed participant’s ability to follow a hidden and slowly shifting reward region based on hit/miss (binary) feedback. The second task investigated participant’s capacity to preserve performance with binary feedback after adapting to the rotation with full visual feedback. Our results demonstrate that higher SWM is associated with greater success and a greater capacity to reproduce a successful motor action, measured as change in reach angle following reward. Whereas higher RWM was predictive of an increased propensity to express an explicit strategy when required to make large adjustments in reach angle. Therefore, both SWM and RWM were reliable predictors of success during reward-based motor learning. Change in reach direction following failure was also a strong predictor of success rate, although we observed no consistent relationship with any type of working memory. Surprisingly, no dopamine-related genotypes predicted performance. Therefore, working memory capacity plays a pivotal role in determining individual ability in reward-based motor learning.

Significance statement

Reward-based motor learning tasks have repeatedly been shown to lead to idiosyncratic behaviours that cause varying degrees of task success. Yet, the factors determining an individual’s capacity to use reward-based feedback are unclear. Here, we assessed a wide range of possible candidate predictors, and demonstrate that domain-specific working memory plays an essential role in determining individual capacity to use reward-based feedback. Surprisingly, genetic variations in dopamine availability were not found to play a role. This is in stark contrast with seminal work in the reinforcement and decision-making literature, which show strong and replicated effects of the same dopaminergic genes in decision-making. Therefore, our results provide novel insights into reward-based motor learning, highlighting a key role for domain-specific working memory capacity.