bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of orthotropic material parameters for acute, necrotic, fibrotic and remodelling myocardial infarcts in the rat
Authors: Sirry Mazin S. , Dubuis Laura , Davies Neil H. , Liao Jun , Franz Thomas
Published: September 2019

Finite element (FE) models have been effectively utilized in studying biomechanical aspects of myocardial infarction (MI). Although the rat is a widely used animal model for MI, there is a lack of material parameters based on anisotropic constitutive models for rat myocardial infarcts in literature. This study aimed at employing inverse methods to identify the parameters of an orthotropic constitutive model for myocardial infarcts in the acute, necrotic, fibrotic and remodelling phases utilizing the biaxial mechanical data developed in a previous study. FE model was developed mimicking the setup of the biaxial tensile experiment. The orthotropic case of the generalized Fung constitutive model was utilized to model the material properties of the infarct. The parameters of Fung model were optimized so that the FE solution best fitted the biaxial experimental stress-strain data. A genetic algorithm was used to minimize the objective function. Fung orthotropic material parameters for different infarct stages were identified. The FE model predictions best approximated the experimental data of the 28 days infarct stage with 3.0% mean absolute percentage error. The worst approximation was for the 7 days stage with 3.6% error. This study demonstrated that the experimental biaxial stress-strain data of healing rat infarcts could be successfully approximated using inverse FE methods and genetic algorithms. The material parameters identified in this study will provide an essential platform for FE investigations of biomechanical aspects of MI and the development of therapies.
Reduced interhemispheric and increased intrahemispheric connectivity in schizophrenia brain networks
Authors: Laton Jorne , Van Schependom Jeroen , Decoster Jeroen , Moons Tim , De Hert Marc , Nagels Guy , De Vos Maarten
Published: September 2019

Introduction

Brain connectivity is disturbed in schizophrenia, both during resting state and during active tasks. Schizophrenia is characterised by a corpus callosum pathology and an inability to suppress overstimulation, both of which relate to this disturbed connectivity. We wanted to verify whether network analysis on EEG sensor level can reveal the corpus callosum pathology in schizophrenia.

Methods

We measured 62-channel EEG on 46 schizophrenia patients and 43 healthy controls during eyes-closed and eyes-open resting-state, mismatch negativity and visual and auditory oddball. We assessed connectivity through correlation, coherence and directed transfer function (DTF) in the delta, theta, alpha, low- and high beta bands.

Results

The coherence and the DTF picked up a consistent pattern of reduced interhemispheric and enhanced intrahemispheric connectivity strength in schizophrenia in the alpha and beta band. This disturbance pattern appeared across all paradigms in the parietal and the occipital region and was generally more pronounced in the right hemisphere.

Conclusions

This is the first study to use multiple similarity measures and different tasks to confirm disturbed brain connectivity on EEG sensor level. We hypothesise that the interhemispheric reductions reflect transcallosal disconnection, while the intrahemispheric increases indicate the inability to suppress the response to stimuli.
Sex differences in interrelationships between arterial stiffness, carotid intima-media thickness, white matter hyperintensities, depression and cognition: A UK Biobank study
Authors: Tsang Ruby S. M. , Gallacher John E. , Bauermeister Sarah
Published: September 2019

Objective

To explore sex differences in the associations between arterial stiffness index, carotid intima-media thickness, white matter hyperintensities, depression and cognition.

Methods

UK Biobank is a population-based cohort study of 502,664 healthy community dwelling adults aged 37-73 years. A select number of participants were recalled to participate in an online reassessment and imaging study, both of which included repeat cognitive assessments. A total of 7,394 volunteers aged 45-73 years (55% female) participated in the imaging visit and completed the self-report mental health questionnaire in the online follow-up were included in the analyses reported here. The main outcome measure of depression was measured using the PHQ-9 and cognition was assessed through measures of reaction time, verbal-numeric reasoning and visual memory. Pulse wave velocity (PWV) was assessed non-invasively using finger photoplethysmography, carotid intima-media thickness (CIMT) with automated ultrasound, and white matter hyperintensity volume with combined T1 and T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI).

Results

Cross-sectionally, greater arterial stiffness was associated with greater depression in men but with better cognition in women. When white matter hyperintensities burden was added to the model, it mediated the relationships of carotid intima-media thickness with depression and cognition only in men.

Conclusions

We report sex differences in brain microvascular changes, depression and cognition in ageing, and suggest that they may be partly explained by sex-specific effects of vascular ageing.

Summary boxes

Section 1: What is already known on this topic

Arterial stiffness and carotid intima-media thickness are two non-invasive vascular ageing markers that have been shown to be associated with depression, cognitive impairment and dementia.

Some studies report sex differences in arterial stiffness and carotid intima-media thickness.

There is, however, a paucity of research on sex differences in the associations between these vascular ageing markers, white matter hyperintensities, depression and cognition.

Section 2: What this study adds

Cross-sectionally, greater arterial stiffness was associated with greater depression in men but with better cognition in women. When white matter hyperintensities burden was added to the model, it mediated the relationships of carotid intima-media thickness with depression and cognition only in men.

Our findings add to the existing evidence base of sex differences in brain microvascular changes, depression and cognition in ageing, and suggest that they may be partly explained by sex-specific effects of vascular ageing.
Characterization of the vaginal DNA virome in health and dysbiosis: an opening study in patients with non-female factor infertility
Authors: Jakobsen Rasmus R. , Haahr Thor , Humaidan Peter , Jensen Jørgen Skov , Kot Witold , Castro-Mejia Josue , Deng Ling , Leser Thomas D. , Nielsen Dennis S.
Published: September 2019

Background

Bacterial vaginosis (BV) is characterised by a reduction inLactobacillusspp. abundance and increased abundance of facultative anaerobes, likeGardnerella vaginalis. BV aetiology is not fully understood, but bacteriophages could play a pivotal role causing perturbation of the vaginal bacterial community. Here we investigate the vaginal viral community, including bacteriophages, and its association to the bacterial community and BV-status.

Methods

Vaginal samples from 48 patients undergoing IVF treatment for non-female factor infertility were subjected to metagenomic sequencing of purified virus-like particles. The vaginal viral community was characterized and correlated with BV-status, bacterial community structure and presence of key vaginal bacterial species.

Results

The majority of identified vaginal viruses belonged to the class of double-stranded DNA bacteriophages, with eukaryotic viruses constituting 4% of total reads. Clear links between viral community composition and BV (q = 0.006, R = 0.26) as well as presence ofL. crispatus(q = 0.001, R = 0.43), L. iners, Gardnerella vaginalisandAtopobium vaginaewere found (q < 0.002, R > 0.15). Interestingly, also the eukaryotic viral community was correlated with BV-status (q = 0.018, R = 0.20).

Conclusions

The vaginal virome is clearly linked with bacterial community structure and BV-status.

Clinical Trials Registration

NCT02042352.
Immunoinformatics Prediction of Epitope Based Peptide Vaccine Against Schistosoma Mansoni Fructose Bisphosphate Aldolase Protein
Authors: Elhag Mustafa , Alaagib Ruaa Mohamed , Haroun Esraa Musa , Ahmed Nagla Mohamed , Albagi Sahar Obi Abd , Hassan Mohammed A.
Published: September 2019

Schistosoma Mansonirepresents an important tropical disease that can cause schistosomiasis mostly in Africa and Middle East with high mortality rates. Moreover, no vaccine against it exists. This study predicts an effective epitope-based vaccine against Fructose 1,6 Bisphosphate Aldolase (FBA) enzyme of Schistosoma Mansoni using immunoinformatics approaches. FBA is important for production of energy required for different schistosome activities and survival. The sequences were retrieved from NCBI and several prediction tests were conducted to analyze possible epitopes for B-cell, T-cell MHC class I and II. Tertiary structure of the most promising epitopes was obtained. Two epitopes showed high binding affinity for B-cells, while four epitopes showed high binding affinity for MHCI and MHCII. The results were promising to formulate a vaccine with more than 99.5% population coverage. We hope that these promising epitopes serves as a preventive measure for the disease in the future and recommend invivo and invitro studies.
Preference and familiarity mediate spatial responses of a large herbivore to experimental manipulation of resource availability
Authors: Ranc Nathan , Moorcroft Paul R. , Hansen K. Whitney , Ossi Federico , Sforna Tobia , Ferraro Enrico , Brugnoli Alessandro , Cagnacci Francesca
Published: September 2019

The link between spatio-temporal resource patterns and movement behaviour is a key ecological process, however, limited experimental support has been produced at the home range scale. In this study, we analysed the spatial responses of a resident large herbivore (roe deerCapreolus capreolus) during anin situmanipulation of a concentrated food resource. Specifically, we experimentally altered feeding site accessibility to roe deer and recorded (for 25 animal-years) individual responses by GPS tracking. We found that, following the loss of their preferred resource, roe deer actively tracked resource dynamics leading to more exploratory movements, and larger, spatially-shifted home ranges. Then, we showed, for the first time experimentally, the importance of site fidelity in the maintenance of large mammal home ranges by demonstrating the return of individuals to their familiar, preferred resource despite the presence of alternate, equally-valuable food resources. This behaviour was modulated at the individual level, where roe deer characterised by a high preference for feeding sites exhibited more pronounced behavioural adjustments during the manipulation. Together, our results establish the connections between movement, space-use, individual preference, and the spatio-temporal pattern of resources in home ranging behaviour.
Predictive masking is associated with a system-wide reconfiguration of neural populations in the human visual cortex
Authors: Carvalho Joana , Renken Remco J. , Cornelissen Frans W.
Published: September 2019

The human visual system masks the perceptual consequences of retinal or cortical lesion-induced scotomas by predicting what is missing from nearby regions of the visual field. To reveal the neural mechanisms underlying this remarkable capacity, known as predictive masking, we used fMRI and neural modeling to track changes in cortical population receptive fields (pRFs) and connectivity in response to the introduction of an artificial scotoma (AS). Consistent with predictive masking, we found that extrastriate areas increased their sampling of the V1 region outside the AS projection zone. Moreover, throughout the visual field and hierarchy, pRFs shifted their preferred position towards the AS border. A gain field model, centered at this border, accounted for these shifts, especially for extrastriate areas. This suggests that a system-wide reconfiguration of neural populations in response to a change in visual input is guided by extrastriate signals and underlies the predictive masking of scotomas.
ColocAI: artificial intelligence approach to quantify co-localization between mass spectrometry images
Authors: Ovchinnikova Katja , Rakhlin Alexander , Stuart Lachlan , Nikolenko Sergey , Alexandrov Theodore
Published: September 2019

Motivation

Imaging mass spectrometry (imaging MS) is a prominent technique for capturing distributions of molecules in tissue sections. Various computational methods for imaging MS rely on quantifying spatial correlations between ion images, referred to as co-localization. However, no comprehensive evaluation of co-localization measures has ever been performed; this leads to arbitrary choices and hinders method development.

Results

We present ColocAI, an artificial intelligence approach addressing this gap. With the help of 42 imaging MS experts from 9 labs, we created a gold standard of 2210 pairs of ion images ranked by their co-localization. We evaluated existing co-localization measures and developed novel measures using tf-idf and deep neural networks. The semi-supervised deep learning Pi model and the cosine score applied after median thresholding performed the best (Spearman 0.797 and 0.794 with expert rankings respectively). We illustrate these measures by inferring co-localization properties of 10273 molecules from 3685 public METASPACE datasets.

Availability and Implementation

https://github.com/metaspace2020/coloc

Contact

theodore.alexandrov@embl.de
Integrated Proteogenomic Deep Sequencing and Analytics Accurately Identify Non-Canonical Peptides in Tumor Immunopeptidomes
Authors: Chong Chloe , Müller Markus , Pak HuiSong , Harnett Dermot , Huber Florian , Grun Delphine , Leleu Marion , Auger Aymeric , Arnaud Marion , Stevenson Brian J. , Michaux Justine , Bilic Ilija , Hirsekorn Antje , Calviello Lorenzo , Simó-Riudalbas Laia , Planet Evarist , Lubiński Jan , Bryśkiewicz Marta , Wiznerowicz Maciej , Xenarios Ioannis , Zhang Lin , Trono Didier , Harari Alexandre , Ohler Uwe , Coukos George , Bassani-Sternberg Michal
Published: September 2019

Efforts to precisely identify tumor human leukocyte antigen (HLA) bound peptides capable of mediating T cell-based tumor rejection still face important challenges. Recent studies suggest that non-canonical tumor-specific HLA peptides that derive from annotated non-coding regions could elicit anti-tumor immune responses. However, sensitive and accurate mass-spectrometry (MS)-based proteogenomics approaches are required to robustly identify these non-canonical peptides. We present an MS-based analytical approach that characterizes the non-canonical tumor HLA peptide repertoire, by incorporating whole exome sequencing, bulk and single cell transcriptomics, ribosome profiling, and a combination of two MS/MS search tools. This approach results in the accurate identification of hundreds of shared and tumor-specific non-canonical HLA peptides and of an immunogenic peptide from a downstream reading frame in the melanoma stem cell marker gene ABCB5. It holds great promise for the discovery of novel cancer antigens for cancer immunotherapy.
The sources and transmission routes of microbial populations throughout a meat processing facility
Authors: Zwirzitz Benjamin , Wetzels Stefanie U. , Dixon Emmanuel D. , Stessl Beatrix , Zaiser Andreas , Rabanser Isabel , Thalguter Sarah , Pinior Beate , Roch Franz-Ferdinand , Strachan Cameron , Zhangellini Jürgen , Dzieciol Monika , Wagner Martin , Mann Evelyne
Published: September 2019

Microbial food spoilage is responsible for a considerable amount of waste and can cause food-borne diseases in humans, particularly in immunocompromised individuals and children. Therefore, preventing microbial food spoilage is a major concern for health authorities, regulators, consumers, and the food industry. However, the contamination of food products is difficult to control because there are several potential sources during production, processing, storage, distribution, and consumption, where microorganisms come in contact with the product. Here, we conduct the first study that uses high-throughput full-length 16S rRNA gene sequencing to provide novel insights into bacterial community structure throughout a pork processing plant. Specifically, we investigated what proportion of bacteria on meat are not animal-associated and are therefore transferred during cutting via personnel, equipment, machines, or the slaughter environment. We then created a facility-specific transmission map of bacterial flow which revealed previously unknown sources of bacterial contamination. This allowed us to pinpoint specific taxa to particular environmental sources and provide the facility with essential information for targeted disinfection. For example,Moraxellaspp., a prominent meat spoilage organism which was one of the most abundant amplicon sequence variants (ASVs) detected on the meat, was most likely transferred from the gloves of employees, a railing at the classification step, and the polishing tunnel whips. Finally, we provide evidence that 1000 sequences per sample provides a reasonable sequencing depth for microbial source tracking in food processing, suggesting that this approach could be implemented in regular monitoring systems.
Keeping up with the genomes: efficient learning of our increasing knowledge of the tree of life
Authors: Zhao Zhengqiao , Cristian Alexandru , Rosen Gail
Published: September 2019

It is a computational challenge for current metagenomic classifiers to keep up with the pace of training data generated from genome sequencing projects, such as the exponentially-growing NCBI RefSeq bacterial genome database. When new reference sequences are added to training data, statically trained classifiers must be rerun on all data, resulting in a highly inefficient process. The rich literature of “incremental learning” addresses the need to update an existing classifier to accommodate new data without sacrificing much accuracy compared to retraining the classifier with all data. We demonstrate how classification improves over time by incrementally training a classifier on progressive RefSeq snapshots and testing it on: (a) all known current genomes (as a ground truth set) and (b) a real experimental metagenomic gut sample. We demonstrate that as a classifier model’s knowledge of genomes grows, classification accuracy increases. The proof-of-concept naïve Bayes implementation, when updated yearly, now runs in 1/4th of the non-incremental time with no accuracy loss. In conclusion, it is evident that classification improves by having the most current knowledge at its disposal. Therefore, it is of utmost importance to make classifiers computationally tractable to keep up with the data deluge.
Test-statistic correlation and data-row correlation
Authors: Zhuo Bin , Jiang Duo , Di Yanming
Published: September 2019

When a statistical test is repeatedly applied to rows of a data matrix—such as in differential-expression analysis of gene expression data, correlations among data rows will give rise to correlations among corresponding test statistic values. Correlations among test statistic values create many inferential challenges in false-discovery-rate control procedures, gene-set enrichment analysis, or other procedures aiming to summarize the collection of test results. To tackle these challenges, researchers sometimes will—explicitly or implicitly—use the correlations (e.g., as measured by the Pearson correlation coefficients) among the data rows to approximate the correlations among the corresponding test statistic values. We show that, however, such approximations are only valid under limited settings. We investigate the relationship between the correlation coefficient between a pair of test statistics (test-statistic correlation) and the correlation coefficient between the two corresponding data rows (data-row correlation). We derive an analytical formula for the test-statistic correlation as a function of the data-row correlation for a general class of test statistics: in particular, two-sample t-test is a special case. The analytical formula implies that the test-statistic correlation is generally weaker than the corresponding data-row correlation, and in general, the latter will not well approximate the former when the involved null hypotheses are false. We verify our analytical results through simulations.
Motion Displaces Population Receptive Fields in the Direction Opposite to Motion
Authors: Schneider Marian , Marquardt Ingo , Sengupta Shubharthi , De Martino Federico , Goebel Rainer
Published: September 2019

Motion signals can bias the perceived position of visual stimuli. While the apparent position of a stimulus is biased in the direction of motion, electro-physiological studies have shown that the receptive field (RF) of neurons is shifted in the direction opposite to motion, at least in cats and macaque monkeys. In humans, it remains unclear how motion signals affect population RF (pRF) estimates. We addressed this question using psychophysical measurements and functional magnetic resonance imaging (fMRI) at 7 Tesla. We systematically varied two factors: the motion direction of the carrier pattern (inward, outward and flicker motion) and the contrast of the mapping stimulus (low and high stimulus contrast). We observed that while physical positions were identical across all conditions, presence of low-contrast motion, but not high-contrast motion, shifted perceived stimulus position in the direction of motion. Correspondingly, we found that pRF estimates in early visual cortex were shifted against the direction of motion for low-contrast stimuli but not for high stimulus contrast. We offer an explanation in form of a model for why apertures are perceptually shifted in the direction of motion even though pRFs shift in the opposite direction.
Specific nanoscale synaptic reshuffling and control of short-term plasticity following NMDAR- and P2XR-dependent Long-Term Depression
Authors: Compans Benjamin , Martineau Magalie , Klaassen Remco V. , Bartol Thomas M. , Butler Corey , Kechkar Adel , Perrais David , Sejnowski Terrence J. , Sibarita Jean-Baptiste , Smit August B. , Choquet Daniel , Hosy Eric
Published: September 2019

Long-Term Potentiation (LTP) and Long-Term Depression (LTD) of excitatory synaptic transmission are considered as cellular basis of learning and memory. These two forms of synaptic plasticity have been mainly attributed to global changes in the number of synaptic AMPA-type glutamate receptor (AMPAR) through a regulation of the diffusion/trapping balance at the PSD, exocytosis and endocytosis. While the precise molecular mechanisms at the base of LTP have been intensively investigated, the ones involved in LTD remains elusive. Here we combined super-resolution imaging technique, electrophysiology and modeling to describe the various modifications of AMPAR nanoscale organization and their effect on synaptic transmission in response to two different LTD protocols, based on the activation of either NMDA receptors or P2X receptors. While both type of LTD are associated with a decrease in synaptic AMPAR clustering, only NMDAR-dependent LTD is associated with a reorganization of PSD-95 at the nanoscale. This change increases the pool of diffusive AMPAR improving synaptic short-term facilitation through a post-synaptic mechanism. These results demonstrate that specific dynamic reorganization of synapses at the nanoscale during specific LTD paradigm allows to improve the responsiveness of depressed synapses.
Stability of excitatory structural connectivity predicts the probability of CA1 pyramidal neurons to become engram neurons
Authors: Castello-Waldow Tim P. , Weston Ghabiba , Chenani Alireza , Loewenstein Yonatan , Chen Alon , Attardo Alessio
Published: September 2019

Neurons undergoing activity-dependent plasticity represent experience and are functional for learning and recall thus they are considered cellular engrams of memory. Although increase in excitability and stability of structural synaptic connectivity have been implicated in the formation and persistance of engrams, the mechanisms bringing engrams into existence are still largely unknown. To investigate this issue, we tracked the dynamics of structural excitatory synaptic connectivity of hippocampal CA1 pyramidal neurons over two weeks using deep-brain two-photon imaging in live mice. We found that neurons that will prospectively become part of an engram display higher stability of connectivity than neurons that will not. A novel experience significantly stabilizes the connectivity of non-engram neurons. Finally, the density and survival of dendritic spines negatively correlates to freezing to the context but not to the tone in a trace fear conditioning learning paradigm.
A two-stage approach to identifying and validating modifiable factors for the prevention of depression
Authors: Choi Karmel W. , Stein Murray B. , Nishimi Kristen , Ge Tian , Coleman Jonathan R.I. , Chen Chia-Yen , Ratanatharathorn Andrew , Zheutlin Amanda B. , Dunn Erin C. ,   23andMe Research Team,   Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Breen Gerome , Koenen Karestan C. , Smoller Jordan W.
Published: September 2019

Background

Although depression is recognized as the leading cause of disability worldwide, decades of research have identified few actionable preventive factors. Using phenotypic and genomic data from the UK Biobank, we took advantage of a unique opportunity to screen a wide range of potentially modifiable factors that could offset known risk factors for depression.

Methods

We curated baseline data on more than 100 lifestyle and environmental factors in participants’ lives, including behavioral (e.g., exercise, sleep, media use, diet), social (e.g., support, activities), and environmental (e.g., greenspace, pollution) variables. In a follow-up survey, participants reported on their traumatic life experiences and mental health, including depression. Polygenic risk scores for depression were generated based on large-scale genome-wide association results. Excluding those meeting criteria for depression at baseline, we identified at-risk individuals at high predicted probability (> 90th percentile) for clinically significant depression at follow-up based on their (i) polygenic risk, or (ii) reported traumatic life events. Using a factors-wide design corrected for multiple testing and adjusted for potential confounders, we identified modifiable factors associated with follow-up depression in the full sample and among at-risk individuals. Using a two-sample Mendelian randomization (MR) design, we then examined which significant factors showed potential causal influences on depression risk, or vice versa.

Results

A range of baseline modifiable factors were prospectively associated with follow-up depression, including factors related to social engagement, physical activity, media use, and diet. MR follow-up analyses provided further support for the effects of social support-seeking, TV use, and other factors on depression risk.

Conclusion

As the field increasingly quantifies the role of genetic factors in complex conditions such as depression, knowledge of modifiable factors that could offset one’s genetic risk has become highly relevant. Here, we present an approach to screening for potentially modifiable factors that may offset the risk of depression in general and among at-risk individuals. In light of the burden of disease associated with depression and the urgent need for actionable preventive strategies, this approach could help prioritize candidates for follow-up studies including clinical trials for depression prevention.
N-acetyl-L-leucine treatment attenuates neuronal cell death and suppresses neuroinflammation after traumatic brain injury in mice
Authors: Sarkar Chinmoy , Hegdekar Nivedita , Lipinski Marta M.
Published: September 2019

Traumatic brain injury (TBI) is a major cause of mortality and long-term disability around the world. Even mild to moderate TBI can lead to lifelong neurological impairment due to acute and progressive neurodegeneration and neuroinflammation induced by the injury. Thus, the discovery of novel treatments which can be used as early therapeutic interventions following TBI is essential to restrict neuronal cell death and neuroinflammation. In this study, we demonstrate that orally administered treatment with N-acetyl-L-leucine (NALL) led to attenuation of cell death and reduced the expression of neuroinflammatory markers after controlled cortical impact (CCI) induced experimental TBI in mice. Our data indicate that partial restoration of autophagy flux mediated by NALL may account for the positive effect of treatment in the injured mouse brain. Taken together, our study indicates treatment with NALL would be expected to be beneficial in restricting neuronal death and hence improving neurological function after injury, and is a promising novel, neuroprotective drug candidate for the treatment of TBI.
Genomewide association study reveals transient loci underlying the genetic architecture of biomass accumulation under cold stress in Sorghum
Authors: Shakoor Nadia , Agnew Erica , Ziegler Greg , Lee Scott , Lizárraga César , Fahlgren Noah , Baxter Ivan , Mockler Todd C.
Published: September 2019

Sorghum bicolor is a promising cellulosic feedstock crop for bioenergy because of its potential for high biomass yields. However, in its early growth phases, sorghum is sensitive to cold stress, preventing early planting in temperate environments. Cold temperature adaptability is vital for the successful cultivation of both bioenergy and grain sorghum at higher latitudes and elevations, and for early season planting or to extend the growing season. Identification of genes and alleles that enhance biomass accumulation of sorghum grown under early cold stress would enable the development of improved bioenergy sorghum through breeding or genetic engineering. We conducted image-based phenotyping on 369 accessions from the sorghum Bioenergy Association Panel (BAP) in a controlled environment with early cold treatment. The BAP is a collection of densely genotyped and racially, geographically, and phenotypically diverse accessions. The plants were weighed, watered, and imaged daily to measure growth dynamics and water use efficiency (WUE). Daily, non-destructive imaging allowed for a temporal analysis of growth-related traits in response to cold stress. We performed a genome-wide association study (GWAS) to identify candidate genomic intervals and genes controlling response to early cold stress. GWAS identified transient quantitative trait loci (QTL) strongly associated with each growth-related trait, permitting an investigation into the genetic basis of cold stress response at different stages of development. The analysis identified a priori and novel candidate genes associated with growth-related traits and the temporal response to cold stress.

SIGNIFICANCE STATEMENT

Genome-wide association study of bioenergy sorghum accessions phenotyped under early season cold stress revealed transient QTLs for highly heritable biomass and growth-related traits that appeared as the temperature increased and plants developed. Sorghum accessions clustered into multiple groups for each heritable trait with distinct growth profiles. GWAS identified candidate genes associated with growth traits and cold stress responses. The top-performing accessions with the highest growth-related trait values over time and temperature shifts will be useful for further genetic analysis and breeding or engineering efforts directed at biomass yield enhancements.
“Bolder” together – response to human social cues in free-ranging dogs
Authors: Bhattacharjee Debottam , Sau Shubhra , Bhadra Anindita
Published: September 2019

Interspecific interactions within an ecosystem have different direct and indirect effects on the two interacting species. In the urban environment, humans are a part of an interaction network of several species. While indirect human influence on different urban species has been measured extensively, experimental studies concerning direct human influence are lacking. In this study, we tested interactions between groups of urban free-ranging dogs (Canis lupus familiaris) and solitary unfamiliar humans in ecologically relevant contexts. We provided different sets of dogs with four commonly used human social cues (neutral, friendly, low and high impact threatening) to understand their responses at the group-level and identify potential inter-individual differences. Finally, we compared data from a previous study to investigate the differences in behavioural outcomes between solitary and groups of dogs while interacting with humans. The study not only strengthens the idea of situation-relevant responsiveness in free-ranging dogs but also highlights the minute differences between solitary and group-level reactions in the form of higher approach and less anxious behaviour of groups towards the unfamiliar human. Additionally, we report inter-individual differences and the effect of sex while responding to the threatening cues. Our study suggests a direct benefit of group-living over a solitary lifestyle in free-ranging dogs while interacting with humans in the streets.

Summary statement

Free-ranging dogs can benefit by living in groups over a solitary lifestyle while interacting with unfamiliar humans in urban habitats irrespective of having significant inter-individual differences.
Trading water for carbon: Sustained photosynthesis at the cost of increased water loss during high temperatures in a temperate forest
Authors: Griebel Anne , Bennett Lauren T. , Metzen Daniel , Pendall Elise , Lane Patrick N.J. , Arndt Stefan K.
Published: September 2019

Forest carbon and water fluxes are often assumed to be coupled as a result of stomatal regulation during dry conditions. However, recent observations have indicated increased transpiration rates during isolated heat waves across a range of eucalypt species under experimental and natural conditions, with inconsistent effects on photosynthesis (ranging from an increase to a near total decline). To improve the empirical basis for understanding carbon and water fluxes in forests under hotter and drier climates, we measured the water use of dominant trees, and the ecosystem-scale carbon and water exchange in a mature temperate eucalypt forest over three summer seasons. The forest maintained photosynthesis within 16% of peak photosynthesis rates during all conditions, despite up to 70% reductions in canopy conductance during a 5-day heatwave. While carbon and water fluxes both decreased by 16% on exceptionally dry summer days, GPP was sustained at the cost of up to 74% increased water loss on the hottest days and during the heatwave. This led to ∼40% variation in ecosystem water use efficiency over the three summers, and ∼two-fold differences depending on the way water use efficiency is calculated. Furthermore, the forest became a net source of carbon following a 137% increase in ecosystem respiration during the heat wave, highlighting that the potential for temperate eucalypt forests to remain net carbon sinks under future climates will depend not only on their potential to maintain photosynthesis during higher temperatures, but also on responses of ecosystem respiration to changes in climate.

Key Points

GPP of temperate eucalypts was sustained at the cost of increased water use during hot periods, but both fluxes decreased during dry periods.

WUE estimates for the same period differed up to two-fold depending on the way it was calculated.

Doubling of ecosystem respiration turned the forest from a net sink into a net source of carbon during a longer heatwave.
Germline RNA helicases couple RNA binding to P granule assembly at nuclear periphery
Authors: Chen Wenjun , Hu Yabing , Lang Charles , Brown Jordan S , Song Xiaoyan , Munro Ed , Bennett Karen , Zhang Donglei , Lee Heng-Chi
Published: September 2019

P granules are phase-separated liquid droplets that play important roles in the maintenance of the germ cell fate in C. elegans. The localization and formation of P granules are highly dynamic, but mechanisms that regulate such processes remain poorly understood. Here we show that germline RNA helicases (GLHs) control the formation and disassembly of germ granules through their binding and release of RNAs, respectively. In addition, the FGG repeats in the GLHs promote the formation of germ granules at the perinucleus. Proteomic analyses of a mutation that traps RNA-bound GLH-1 complex revealed transient interactions of GLH-1 with several Argonautes and RNA binding proteins. Finally, we found that defects in perinuclear P granule formation correlate with the fertility defects observed in various GLH mutants. Together, our results highlight the versatile roles of RNA helicases in controlling the formation of liquid droplets in space and time.
The co-stimulation of anti-CD28 and IL-2 enhances the sensitivity of ELISPOT assays for detection of neoantigen-specific T cells in PBMC
Authors: Tang Yunxia , Zhu Linnan , Xu Qumiao , Zhang Xiuqing , Li Bo , Lee Leo J.
Published: September 2019

Neoantigen-based cancer immunotherapies hold the promise of being a truly personalized, effective treatment for diverse cancer types. ELISPOT assays, as a powerful experimental technique, can verify the existence of antigen specific T cells to support basic clinical research and monitor clinical trials. However, despite the high sensitivity of ELISPOT assays, detecting immune responses of neoantigen specific T cells in a patient or healthy donor’s PBMCs is still extremely difficult, since the frequency of these T cells can be very low. We developed a novel experimental method, by co-stimulation of T cells with anti-CD28 and IL-2 at the beginning of ELISPOT, to further increase the sensitivity of ELISPOT and mitigate the challenge introduced by low frequency T cells. Under the optimal concentration of 1μg/mL for anti-CD28 and 1U/ml for IL-2, our new method can increase sensitivity by up to 5 folds comparing to a conventional ELISPOT, and outperforms other cytokine stimulation alternatives. To the best of our knowledge, this is the first report that the co-stimulation of anti-CD28 and IL-2 is able to significantly improve the sensitivity of ELISPOT assays, indicating that anti-CD28 and IL-2 signaling can act in synergy to lower the T cell activation threshold and trigger more neoantigen-specific T cells.
Association between the 4p16 genomic locus and different types of congenital heart disease: results from adult survivors in the UK Biobank
Authors: Córdova-Palomera Aldo , Priest James R.
Published: September 2019

Congenital heart disease is the most common birth defect in newborns and the leading cause of death in infancy, affecting nearly 1% of live births. A locus in chromosome 4p16, adjacent to MSX1 and STX18, has been associated with atrial septal defects (ASD) in multiple European and Chinese cohorts. Here, genotyping data from the UK Biobank was used to test for associations between this locus and congenital heart disease in adult survivors of left ventricular outflow tract obstruction (n=164) and ASD (n=223), with a control sample of 332,788 individuals, and a meta-analysis of the new and existing ASD data was performed.

The results show an association between the previously reported markers at 4p16 and risk for either ASD or left ventricular outflow tract obstruction, with effect sizes similar to the published data (OR between 1.27-1.45; all p<0.05). Differences in allele frequencies remained constant through the studied age range (40-70 years), indicating that the variants themselves do not drive lethal genetic defects. Meta-analysis shows an OR of 1.35 (95% CI: 1.25-1.46; p<10−4) for the association with ASD.

The findings show that the genetic associations with ASD can be generalized to adult survivors of both ASD and left ventricular lesions. Although the 4p16 associations are statistically compelling, the mentioned alleles confer only a small risk for disease and their frequencies in this adult sample are the same as in children, likely limiting their clinical significance. Further epidemiological and functional studies may elicit factors triggering disease in interaction with the risk alleles.
Unsupervised Clusterless Decoding using a Switching Poisson Hidden Markov Model
Authors: Ackermann Etienne , Kemere Caleb T. , Cunningham John P.
Published: September 2019

Spike sorting is a standard preprocessing step to obtain ensembles of single unit data from multiunit, multichannel recordings in neuroscience. However, more recently, some researchers have started doing analyses directly on the unsorted data. Here we present a new computational model that is an extension of the standard (unsupervised) switching Poisson hidden Markov model (where observations are time-binned spike counts from each of N neurons), to a clusterless approximation in which we observe only a d-dimensional mark for each spike. Such an unsupervised yet clusterless approach has the potential to incorporate more information than is typically available from spike-sorted approaches, and to uncover temporal structure in neural data without access to behavioral correlates. We show that our approach can recover model parameters from simulated data, and that it can uncover task-relevant structure from real neural data.
Within-Host Diversity and Vertical Transmission of Group B Streptococcus Among Mother-infant Dyads in The Gambia
Authors: Foster-Nyarko Ebenezer , Senghore Madikay , Kwambana-Adams Brenda A. , Alikhan Nabil-Fareed , Ravi Anuradha , Jafali James , Jawneh Kaddijatou , Jah Amara , Jarju Maimuna , Ceesay Fatima , Bojang Sainabou , Worwui Archibald , Odutola Aderonke , Ogundare Ezra , Pallen Mark J. , Ota Martin , Antonio Martin
Published: September 2019

Introduction

Understanding mother-to-infant transmission of Group B Streptococcus (GBS) is vital to the prevention and control of GBS disease. We investigated the transmission and phylogenetic relationships of mothers colonised by GBS and their infants in a peri-urban setting in The Gambia.

Methods

We collected nasopharyngeal swabs from 35 mother-infant dyads at weekly intervals from birth until six weeks post-partum. GBS was isolated by conventional microbiology techniques. Whole-genome sequencing was performed on GBS isolates from one mother-infant dyad (dyad 17).

Results

We recovered 85 GBS isolates from the 245 nasopharyngeal swabs. GBS was isolated from 16.33% and 18.37% of sampled mothers and infants, respectively. In 87% of cultured swabs, the culture status of an infant agreed with that of the mother (Kappa p-value <0.001). In dyad 17, phylogenetic analysis revealed within-host strain diversity in the mother and clone to her infant.

Conclusion

GBS colonisation in mothers presents a significant risk of colonisation in their infants. We confirm vertical transmission from mother to child in dyad 17, accompanied by within-host diversity.
Predicting the impacts of sea level rise in sea turtle nesting habitat on Bioko Island, Equatorial Guinea
Authors: Veelenturf Callie A. , Sinclair Elizabeth M. , Paladino Frank V. , Honarvar Shaya
Published: September 2019

Sea level is expected to rise 44 to 74 cm by the year 2100, which may have critical, previously un-investigated implications for sea turtle nesting habitat on Bioko Island, Equatorial Guinea. This study investigates how nesting habitat will likely be lost and altered with various increases in sea level, using global sea level rise (SLR) predictions from the Intergovernmental Panel on Climate Change. Beach profiling datasets from Bioko’s five southern nesting beaches were used in GIS to create models to estimate habitat loss with predicted increases in sea level by years 2046-2065 and 2081-2100. The models indicate that an average of 62% of Bioko’s current nesting habitat could be lost by 2046-2065 and 87% by the years 2081-2100. Beach D is predicted to be the least vulnerable to increases in sea level. Erosion and tall vegetation berms have been documented on Beaches A and B, causing green turtles to nest uncharacteristically in front of the vegetation line. Development plans are currently underway for Beach D. With Beach D being the least susceptible to future increases in sea level, development and anthropogenic encroachment here would be especially detrimental to nesting turtle populations. Identified habitat sensitivities to SLR will be used to inform the government of Equatorial Guinea to consider the vulnerability of their resident turtle populations and projected climate change implications when planning for future development. To our knowledge this is the first study to predict the impacts of SLR on sea turtle nesting habitat in Africa.
Proprioceptive accuracy in immersive virtual reality: A developmental perspective
Authors: Valori Irene , McKenna-Plumley Phoebe E. , Bayramova Rena , Callegher Claudio Zandonella , Altoè Gianmarco , Farroni Teresa
Published: September 2019

Proprioceptive development relies on a variety of sensory inputs, among which vision is hugely dominant. Focusing on the developmental trajectory underpinning the integration of vision and proprioception, the present research explores how this integration is involved in interactions with Immersive Virtual Reality (IVR) by examining how proprioceptive accuracy is affected byage, perception, andenvironment. Individuals from 4 to 43 years old completed a self-turning task which asked them to manually return to a previous location with different sensory modalities available in both IVR and reality. Results were interpreted from an exploratory perspective using Bayesian model comparison analysis, which allows the phenomena to be described using probabilistic statements rather than simplified reject/not-reject decisions. The most plausible model showed that 4–8-year-old children can generally be expected to make more proprioceptive errors than older children and adults. Across age groups, proprioceptive accuracy is higher when vision is available, and is disrupted in the visual environment provided by the IVR headset. We can conclude that proprioceptive accuracy mostly develops during the first eight years of life and that it relies largely on vision. Moreover, our findings indicate that this proprioceptive accuracy can be disrupted by the use of an IVR headset.