bluuebunny/crossref_metadata_2025 huggingface dataset:
Specification and epigenetic resetting of the pig germline exhibit conservation with the human lineage
Authors: Zhu Qifan , Sang Fei , Withey Sarah , Tang Walfred , Dietmann Sabine , Klisch Doris , Ramos-Ibeas Priscila , Zhang Haixin , Requena Cristina E. , Hajkova Petra , Loose Matt , Surani M. Azim , Alberio Ramiro
Published: August 2020

Investigations on the human germline and programming are challenging due to limited access to embryonic material. However, the pig as a model may provide insight on transcriptional network and epigenetic reprogramming applicable to both species. Here we show that during the pre- and early migratory stages pig primordial germ cells (PGCs) initiate large-scale epigenetic reprogramming, including DNA demethylation involving TET-mediated hydroxylation and potentially base excision repair (BER). There is also macroH2A1 depletion and increased H3K27me3, as well as X chromosome reactivation (XCR) in females. Concomitantly, there is dampening of glycolytic metabolism genes and re-expression of some pluripotency genes like those in preimplantation embryos. We identified evolutionarily young transposable elements and gene coding regions resistant to DNA demethylation in acutely hypomethylated gonadal PGCs, with potential for transgenerational epigenetic inheritance. Detailed insights into the pig germline will likely contribute significantly to advances in human germline biology, includingin vitrogametogenesis.
The influence of eye movements and their retinal consequences on bistable motion perception
Authors: Brych Mareike , Murali Supriya , Händel Barbara
Published: August 2020

Eye related movements such as blinks and microsaccades are modulated during bistable perceptual tasks, however, the role of such movements in these purely internal perceptual switches is not known. We conducted two experiments involving an ambiguous plaid stimulus, wherein participants had to continuously report their motion percept. To dissociate the effect of blinks and microsaccades from the visual consequences of such eye movements, we added external blanks and microshifts.

Our results showed that while blanks facilitated a switch to the coherent motion percept, this was not the case for a switch to component percept. A similar difference was found with respect to blinks. While both types of perceptual switches were preceded by a decrease in blinks, only the switch to coherent percept was followed by an increase in blinks. These blink related findings, which we largely replicated and refined in a second study, indicate distinct internal processes underlying the two perceptual switches. Microsaccade rates, on the other hand, only showed a weak relation with perceptual switches but their direction was modulated by the perceived motion direction. Additionally, our data showed that microsaccades are differently modulated around internal (blinks) and external events (blanks, microshifts), indicating an interaction between different eye related movements.

This study shows that eye movements such as blinks and microsaccades are modulated by purely internal perceptual events independent of task related motor or attentional demands. Eye movements therefore can uncover distinct internal perceptual processes that might otherwise be hard to dissociate.
The Response of Culturally Important Plants to Experimental Warming and Grazing in Pakistan Himalayas
Authors: Karimi Saira , Nawaz Muhammad Ali , Naseem Saadia , Akrem Ahmed , Dangles Olivier , Ali Zahid
Published: August 2020

The response of wild plants towards climate warming is taxa specific, but overgrazing could also be a determining factor for the alpine ecosystems. Overgrazing and climate warming are important drivers of alpine grassland degradation worldwide. Local indigenous peoples will be the first impacted by such degradation due to impacts on animal production and the availability of local medicinal plants. Studies on plant responses to overgrazing and climate change are rarely performed to assess threats to these biological and cultural systems. Long-term observations or manipulative experiments are promising, but rarely use strategies to evaluate the sensitivity and vulnerability of such ecosystems to climatic change. We studied the combined effects of overgrazing and increased temperatures on culturally important medicinal plants of Khunjerab National Park, Pakistan. Three experimental treatments were used (control, warming through an open-top chamber, and exclusion of grazing animals vs. the control). These experimental plots were installed at different elevations (3352-4969 m) and were monitored routinely. Grazing reduced vegetation cover & biomass by 2.3% and 6.26%, respectively, but that was not significant due to the high variability among study plots. However, warming significantly increased the overall percentage cover and biomass of all target plant species, ranging from 1±0.6% inBistorta officinalisto 18.7 ± 4.9% inPoa alpina. Thus, warming may increase the availability of therapeutic plants for indigenous people while overgrazing would have deteriorating effects locally. This research illustrates that vegetation sensitivity to warming and overgrazing is likely to affect man– environment relationships, and traditional knowledge on a regional scale.
UsingPlasmodium knowlesias a model for screeningPlasmodium vivaxblood-stage malaria vaccine targets reveals new candidates
Authors: Ndegwa Duncan N. , Hostetler Jessica B. , Marin-Menendez Alejandro , Sanderson Theo , Mwikali Kioko , Verzier Lisa H. , Coyle Rachael , Adjalley Sophie , Rayner Julian C.
Published: August 2020

Plasmodium vivaxis responsible for the majority of malaria cases outside Africa. UnlikeP. falciparum, theP. vivaxlife-cycle includes a dormant liver stage, the hypnozoite, which can cause infection in the absence of mosquito transmission. An effective vaccine againstP. vivaxblood stages would limit symptoms and pathology from such recurrent infections, and therefore could play a critical role in the control of this species. Vaccine development inP. vivax, however, lags considerably behindP. falciparum, which has many identified targets with several having transitioned to Phase II testing. By contrast only oneP. vivaxblood-stage vaccine candidate based on the Duffy Binding Protein (PvDBP), has reached Phase Ia, in large part because the lack of a continuousin vitroculture system forP. vivaxlimits systematic screening of new candidates. We used the close phylogenetic relationship betweenP. vivaxandP. knowlesi, for which anin vitroculture system in human erythrocytes exists, to test the scalability of systematic reverse vaccinology to identify and prioritiseP. vivaxblood-stage targets. A panel ofP. vivaxproteins predicted to function in erythrocyte invasion were expressed as full-length recombinant ectodomains in a mammalian expression system. Eight of these antigens were used to generate polyclonal antibodies, which were screened for their ability to recognize orthologous proteins inP. knowlesi. These antibodies were then tested for inhibition of growth and invasion of both wild typeP. knowlesiand chimericP. knowlesilines modified using CRISPR/Cas9 to exchangeP. knowlesigenes with theirP. vivaxorthologues. Candidates that induced antibodies that inhibited invasion to a similar level as PvDBP were identified, confirming the utility ofP. knowlesias a model forP. vivaxvaccine development and prioritizing antigens for further follow up.

AUTHOR SUMMARY

Malaria parasites cause disease after invading human red blood cells, implying that a vaccine that interrupts this process could play a significant role in malaria control. MultiplePlasmodiumparasite species can cause malaria in humans, and most malaria outside Africa is caused byPlasmodium vivax. There is currently no effective vaccine against the blood stage of any malaria parasite, and progress inP. vivaxvaccine development has been particularly hampered because this parasite species cannot be cultured for prolonged periods of time in the lab. We explored whether a related species,P. knowlesi, which can be propagated in human red blood cellsin vitro, can be used to screen for potentialP. vivaxvaccine targets. We raised antibodies against selectedP. vivaxproteins and testedtheir ability to recognize and preventP. knowlesiparasites from invading human red blood cells, thereby identifying multiple novel vaccine candidates.
Family variation in surface feeding behavior of steelhead fry predicts growth rate under hatchery conditions
Authors: Wrey Madeleine C. , Skaar James C. , Cates Stanley B. , Bollmann Stephanie R. , Fuentes Claudio , Blouin Michael S.
Published: August 2020

Hatchery reared salmonid fish often have lower fitness than their natural-origin counterparts when spawning in the wild. Although this difference appears to result from rapid adaptation to captivity, it is not known what traits are under selection. We hypothesize that variation in traits that confer a growth rate advantage to some individuals in the novel hatchery environment are under strong selection because survival at sea is correlated with size at release. Here we show that full sibling families of steelhead trout (Oncorhynchus mykiss) show substantial variation in propensity to feed at the surface as fry, and that the more surface-oriented families grew faster under hatchery conditions. We hypothesize that surface-oriented fry gain an initial growth advantage that persists through size at release. Because surface orientation is a correlate of generalized boldness, hatcheries may inadvertently select for that phenotype, which could explain the fitness differences observed between hatchery and natural-origin fish in the wild.
Successful introduction of the Colour Test into inexperienced settings
Authors: Klaos Kadri , Agejeva Anna , Kummik Tiina , Laks Sirje , Remets Olesja , Sasi Sirje , Tann Anneli , Viiklepp Piret , Altraja Alan
Published: August 2020

Implementation of non-commercial in-house methods into routine clinical diagnostics becomes more challenging, because these methods are not internationally standardized, most of the research in that field is underfunded and recommendations for their use is lacking. We conducted a study, where all the technicians were previously unfamiliar to the Colour Test (CT), a colorimetric redox indicator and thin-layer agar basedMycobacterium tuberculosiscomplex diagnosis and direct drug susceptibility testing (DST) method, and tested whether the performance of this in-house method is dependent on experience of the laboratory personnel.

After a two-day hands-on training, six panels of 150M. tuberculosisisolates were cultured onto CT plates prepared in-house by six technicians in two laboratories. Finally, triplicate readings of 900 CT plates resulted 18 DST patterns for each of the initial isolates. The results were compared to each other and the gold standard of BACTEC MGIT 960 DST results.

The median time to produceM. tuberculosisCT DST results for three antituberculosis drugs was 13 days. The overall ability to correctly define phenotypic resistance ranged from 94.7% for levofloxacin to 95.8% and 97.3% for isoniazid and rifampicin, respectively. The test specificities were even higher exceeding 97% for all three drugs tested. Interobserver agreement reached 100% in one of the laboratories and exceeded 97% for levofloxacin and 99% for isoniazid and rifampicin in the second laboratory.

The implementation of the CT into a new laboratory was straightforward with only minimal guidance. This study proves that the CT is highly reproducible and easily interpreted by previously inexperienced personnel.
Cyp33 Binds AU-Rich RNA Motifs via an Extended Interface that Competitively Disrupts the Gene Repressive Cyp33-MLL1 Interactionin vitro
Authors: Lloyd Neil R. , Wuttke Deborah S.
Published: August 2020

Cyp33 is an essential human cyclophilin prolyl isomerase that plays myriad roles in splicing and chromatin remodeling. In addition to a canonical cyclophilin (Cyp) domain, Cyp33 contains an RNA-recognition motif (RRM) domain, and RNA-binding triggers proline isomerase activity. One prominent role for Cyp33 is through a direct interaction with the mixed lineage leukemia protein 1 (MLL1, also known as KMT2A) complex, which is a histone methyltransferase that serves as a global regulator of human transcription. MLL activity is regulated by Cyp33, which isomerizes a key proline in the linker between the PHD3 and Bromo domains of MLL1, acting as a switch between gene activation and repression. The direct interaction between MLL1 and Cyp33 is critical, as deletion of the MLL1-PHD3 domain responsible for this interaction results in oncogenesis. The Cyp33 RRM is central to these activities, as it binds both the PHD3 domain and RNA. To better understand how RNA binding drives the action of Cyp33, we performed RNA-SELEX against full-length Cyp33 accompanied by deep sequencing. We have identified an enriched Cyp33 binding motif (AAUAAUAA) broadly represented in the cellular RNA pool as well as tightly binding RNA aptamers with affinities comparable and competitive with the Cyp33 MLL1-PHD3 interaction. RNA binding extends beyond the canonical RRM domain, but not to the Cyp domain, suggesting an indirect mechanism of interaction. NMR chemical shift mapping confirms an overlapping, but not identical, interface on Cyp33 for RNA and PHD3 binding. This finding suggests RNA can disrupt the gene repressive Cyp33-MLL1 complex providing another layer of regulation for chromatin remodeling by MLL1.
Effect of oxidized β-carotene-oxygen copolymer compound on health and performance of pre- and post-weaned pigs
Authors: Van Kinh La , Riley William W. , Nickerson James G. , Vinh Doan , Van Phu Nguyen , Van Nguyen Thanh , Huyen La Thi Thanh , Burton Graham W.
Published: August 2020

The discovery that a naturally occurring, biologically active β-carotene-oxygen copolymer compound is the main product formed in spontaneously oxidized β-carotene has stimulated interest in its potential health benefits. The copolymer, formed in nature or synthetically by the air-oxidation of β-carotene, possesses beneficial immune modulating activities that previously had been attributed to β-carotene itself. Support for these benefits is provided by previous studies showing that supplementation in feed with low parts-per-million levels of copolymer-rich, fully oxidized β-carotene (OxBC) helped reduce the negative impact of subclinical necrotic enteritis in broilers and improved growth in weaned piglets. To further assess these potential benefits, two trials were conducted in swine raised under commercial conditions in Vietnam. Trial 1, a 140-day full-grow, post-wean study with 500 28-day-old pigs, compared 2, 4 or 8 ppm OxBC against both an unsupplemented and an antibiotic control group. OxBC and antibiotics each improved growth rate, feed efficiency, and body weight compared to the control (P<0.001). Animals receiving 4 and 8 ppm OxBC performed better than did animals on antibiotics (P<0.001). In starter pigs, OxBC reduced the occurrence of diarrhea dose-dependently (4 and 8 ppm) and to a greater extent than did antibiotics (P<0.001). Trial 2, a 49-day study with 420 piglets, was conducted in two-stages. In Stage 1 (pre-wean), OxBC in the transition (creep) feed produced a dose-dependent trend toward increased body weight over 21 days, reaching significance at the highest inclusion level (16 ppm) (P<0.001). In Stage 2 (post-wean), body weight gain showed a dose-dependent trend and was significant for both 8 ppm OxBC and the antibiotics at 28 days post-wean (P<0.001). Feed conversion was better at 8 ppm OxBC and for the antibiotic group (P<0.001). These findings support the concept that β-carotene-oxygen copolymers help optimize immune function, and provide validation for the effectiveness of this strategy in enhancing animal performance in the absence of in-feed antibiotics.
Hybrid diffuse optical monitoring of hemodynamic changes following acute cerebral ischemia in a porcine model
Authors: Wang Detian , Wang Long , Wang Jinyu , Gao Peng , Zhu Liguo , Li Zeren , Chen Tunan , Li Fei , Hua Feng
Published: August 2020

Rapid screening for stroke in pre-hospital settings may improve patient outcomes by allowing early deployment of thrombolytic therapies. Near-infrared hybrid diffuse optical screening devices may fill this need. This study seeks to determine whether hybrid diffuse optical measurements can measure hemodynamic changes associated with cerebral ischemia within the first few hours of the onset of acute ischemia in a large animal model. A hybrid diffuse optical device combining of near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) was fabricated to measure total hemoglobin concentration (HbT), tissue oxygen saturation (StO2) and blood flow index (BFI). Cerebral ischemia was induced by ligation of the bilateral common carotid arteries (CCA) in five miniature pigs. Additionally, a fatal stroke was induced in two pigs by injecting 5ml air emboli into both CCA. Cerebral hemodynamic parameters were monitored continuously throughout the study with the hybrid optical device. Relative changes BFI showed the good repeatability both of the ligation and fatal stroke experiments. During bilateral CCA ligation, the BFI decreased by up to about 66% of baseline values; during the fatal stroke experiment, the BFI decreased by up to about 95%, with a temporal resolution of 20 seconds. To the best of our knowledge, there are not existing methods which can measure the cerebral ischemia within the first few hours of the onset noninvasively. The MRI scanning was conducted at 24 h post injury. However, the images showed no abnormality. The results show the hybrid diffuse optical method can immediately measure the hemodynamic changes of miniature pigs in the first few hours of each single cerebral ischemia onset, and the BFI may be the promising biomarker to distinguish the cerebral ischemia and cerebral death.
KANSL1 Deficiency Causes Neuronal Dysfunction by Oxidative Stress-Induced Autophagy
Authors: Linda Katrin , Lewerissa EIly I. , Verboven Anouk H. A. , Gabriele Michele , Frega Monica , Gunnewiek Teun M. Klein , Devilee Lynn , Ulferts Edda , Oudakker Astrid , Schoenmaker Chantal , van Bokhoven Hans , Schubert Dirk , Testa Giuseppe , Koolen David A. , de Vries Bert B.A. , Kasri Nael Nadif
Published: August 2020

Autophagy is a finely tuned process of programmed degradation and recycling of proteins and cellular components, which is crucial in neuronal function and synaptic integrity. Mounting evidence implicates chromatin remodelling in fine-tuning autophagy pathways. However, this epigenetic regulation is poorly understood in neurons. Here, we investigate the role in autophagy of KANSL1, a member of the nonspecific lethal complex, which acetylates histone H4 on lysine 16 (H4K16ac) to facilitate transcriptional activation. Loss-of-function of KANSL1 is strongly associated with the neurodevelopmental disorder Koolen-de Vries Syndrome (KdVS).

Starting from KANSL1-deficient human induced-pluripotent stem cells, both from KdVS patients and genome-edited lines, we identified superoxide dismutase 1, an antioxidant enzyme, to be significantly decreased, leading to a subsequent increase in oxidative stress and autophagosome accumulation. In KANSL1-deficient neurons, autophagosome accumulation at excitatory synapses resulted in reduced synaptic density, reduced AMPA receptor-mediated transmission and impaired neuronal network activity. Furthermore, we found that increased oxidative stress-mediated autophagosome accumulation leads to increased mTOR activation and decreased lysosome function, further preventing the clearing of autophagosomes. Finally, by pharmacologically reducing oxidative stress, we could rescue the aberrant autophagosome formation as well as synaptic and neuronal network activity in KANSL1-deficient neurons. Our findings thus point towards an important relation between oxidative stress-induced autophagy and synapse function, and demonstrate the importance of H4K16ac-mediated changes in chromatin structure to balance reactive oxygen species- and mTOR-dependent autophagy.
Identifying Transcriptomic Correlates of Histology using Deep Learning
Authors: Badea Liviu , Stănescu Emil
Published: August 2020

Linking phenotypes to specific gene expression profiles is an extremely important problem in biology, which has been approached mainly by correlation methods or, more fundamentally, by studying the effects of gene perturbations. However, genome-wide perturbations involve extensive experimental efforts, which may be prohibitive for certain organisms. On the other hand, the characterization of the various phenotypes frequently requires an expert’s subjective interpretation, such as a histopathologist’s description of tissue slide images in terms of complex visual features (e.g. ‘acinar structures’). In this paper, we use Deep Learning to eliminate the inherent subjective nature of these visual histological features and link them to genomic data, thus establishing a more precisely quantifiable correlation between transcriptomes and phenotypes. Using a dataset of whole slide images with matching gene expression data from 39 normal tissue types, we first developed a Deep Learningtissue classifierwith an accuracy of 94%. Then we searched forgenes whose expression correlates with features inferred by the classifierand demonstrate that Deep Learning can automatically derive visual (phenotypical) features that are well correlated with the transcriptome and thereforebiologically interpretable. As we are particularly concerned withinterpretabilityandexplainabilityof the inferred histological models, we also developvisualizationsof the inferred features and compare them with gene expression patterns determined by immunohistochemistry. This can be viewed as a first step toward bridging the gap between the level of genes and the cellular organization of tissues.
Horizontal gene transfer becomes disadvantageous in rapidly fluctuating environments
Authors: Goyal Akshit , Gelbwaser-Klimovsky David , Gore Jeff
Published: August 2020

Horizontal gene transfer (HGT) allows organisms to share genetic material with non-offspring, and is typically considered beneficial for evolving populations. Recent unexplained observations suggest that HGT rates in nature are linked with environmental dynamics, being high in static environments but surprisingly low in fluctuating environments. Here, using a geometric model of adaptation, we show that this trend might arise from evolutionary constraints. During adaptation in our model, a population of phenotype vectors aligns with a potentially fluctuating environmental vector while experiencing mutation, selection, drift and HGT. Simulations and theory reveal that HGT shapes a trade-off between the adaptation speed of populations and their fitness. This trade-off gives rise to an optimal HGT rate which decreases sharply with the rate of environmental fluctuations. Our results are consistent with data from natural populations, and strikingly suggest that HGT may sometimes carry a significant disadvantage for populations.
Exploring the Causal Effects of Shear Stress Associated DNA Methylation on Cardiovascular Risk
Authors: Methorst Ruben , de Borst Gert Jan , Pasterkamp Gerard , van der Laan Sander W.
Published: August 2020

Background and aims

Atherosclerosis is a lipid-driven inflammatory disease presumably initiated by endothelial activation. Low vascular shear stress is known for its ability to activate endothelial cells. Differential DNA methylation (DNAm) is a relatively unexplored player in atherosclerotic disease development and endothelial dysfunction. Literature search revealed that expression of 11 genes have been found to be associated with differential DNAm due to low shear stress in endothelial cells. We hypothesized a causal relationship between DNAm of shear stress associated genes in human carotid plaque and increased risk of cardiovascular disease.

Methods

Using Mendelian randomisation (MR) analysis, we explored the potential causal role of DNAm of shear stress associated genes on cardiovascular disease risk. We used genetic and DNAm data of 442 carotid endarterectomy derived advanced plaques from the Athero-Express Biobank Study for quantitative trait loci (QTL) discovery and performed MR analysis using these QTLs and GWAS summary statistics of coronary artery disease (CAD) and ischemic stroke (IS).

Results

We discovered 9 methylation QTLs in plaque for differentially methylated shear stress associated genes. We found no significant effect of shear stress gene promotor methylation and increased risk of CAD and IS.

Conclusions

Differential methylation of shear stress associated genes in advanced atherosclerotic plaques in unlikely to increase cardiovascular risk.

Highlights

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Plaque-derived DNA methylation in shear stress associated genes shows no significant effect on cardiovascular disease

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Genetic variants in shear stress associated genes affect DNA methylation in human carotid plaque

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Human validation of atherosclerotic associated genes in murine models
Memory Trace Imbalance in Reinforcement and Punishment Systems Can Reinforce Implicit Choices Leading to Obsessive-Compulsive Behavior
Authors: Sakai Yuki , Sakai Yutaka , Abe Yoshinari , Narumoto Jin , Tanaka Saori C.
Published: August 2020

We may view most of our daily activities as rational action selections; however, we sometimes reinforce maladaptive behaviors despite having explicit environmental knowledge. In this study, we model obsessive-compulsive disorder (OCD) symptoms as implicitly learned maladaptive behaviors. Simulations in the reinforcement learning framework show that agents implicitly learn to respond to intrusive thoughts when the memory trace signal for past actions decays differently for positive and negative prediction errors. Moreover, this model extends our understanding of therapeutic effects of behavioral therapy in OCD. Using empirical data, we confirm that patients with OCD show extremely imbalanced traces, which are normalized by serotonin enhancers. We find that healthy participants also vary in their obsessive-compulsive tendencies, consistent with the degree of imbalanced traces. These behavioral characteristics can be generalized to variations in the healthy population beyond the spectrum of clinical phenotypes.
Convergent acoustic community structure in South Asian dry and wet grassland birds
Authors: Lahiri Sutirtha , Pathaw Nafisa A. , Krishnan Anand
Published: August 2020

Although the study of bird acoustic communities has great potential to provide valuable conservation data, many aspects of their assembly and dynamics remain poorly understood. Grassland habitats in South Asia comprise distinct biomes with a unique avifauna, presenting an opportunity to address how community-level patterns in acoustic signal space arise. Similarity in signal space of different grassland bird communities may be due to phylogenetic similarity, or because different bird groups partition the acoustic resource, resulting in convergent distributions in signal space. Here, we quantify the composition, signal space and phylogenetic diversity of bird acoustic communities from the dry semiarid grasslands of Northwest India and the wet floodplain grasslands of Northeast India. We find that acoustic communities occupying these distinct biomes exhibit convergent signal space. However, dry grasslands exhibit higher phylogenetic diversity, and the two communities are not phylogenetically more similar than expected by chance. The Sylvioidea encompasses half the species in the wet grassland acoustic community, with an expanded signal space compared to the dry grasslands. Thus, dry and wet grassland communities are convergent in signal space despite differences in phylogenetic diversity. We therefore hypothesize that different clades colonizing grasslands partition the acoustic resource, resulting in convergent community structure across biomes. Many of the birds we recorded are highly threatened, and acoustic monitoring will support conservation measures in these imperiled, yet poorly-studied habitats.
Improving prediction and assessment of global wildfires using neural networks
Authors: Joshi Jaideep , Sukumar Raman
Published: August 2020

Fires determine vegetation patterns, impact human societies, and provide complex feedbacks into the global climate system. Empirical and process-based models differ in their scale and mechanistic assumptions, giving divergent predictions of fire drivers and extent. Especially, the role of anthropogenic drivers remains less understood. Taking a data-driven approach, we use an artificial neural network to learn region-specific relationships between fire and its socio-environmental drivers across the globe. As a result, our models achieve higher predictability than previously reported, with global spatial correlation of 0.92, temporal correlation of 0.76, interannual correlation of 0.69, and grid-cell level correlation of 0.6, between predicted and observed burned area. Our analysis reveals universal global patterns in fire-climate interactions, coupled with strong regional differences in fire-human relationships. Given the current socio-anthropogenic conditions, Equatorial Asia, southern Africa, and Australia show a strong sensitivity of fire extent to temperature whereas northern Africa shows a strong negative sensitivity. Overall, forests and shrublands, show a stronger sensitivity of burned area to temperature compared to savannas, potentially weakening their status as carbon sinks under future climate-change scenarios.
Multiomics analysis reveals extensive epigenome remodeling during cortical development
Authors: Noack Florian , Vangelisti Silvia , Carido Madalena , Chong Faye , Bonev Boyan
Published: August 2020

Despite huge advances in stem-cell, single-cell and epigenetic technologies, the precise molecular mechanisms that determine lineage specification remain largely unknown. Applying an integrative multiomics approach, e.g. combining single-cell RNA-seq, single-cell ATAC-seq together with cell-type-specific DNA methylation and 3D genome measurements, we systematically map the regulatory landscape in the mouse neocortexin vivo. Our analysis identifies thousands of novel enhancer-gene pairs associated with dynamic changes in chromatin accessibility and gene expression along the differentiation trajectory. Crucially, we provide evidence that epigenetic remodeling generally precedes transcriptional activation, yet true priming appears limited to a subset of lineage-determining enhancers. Notably, we reveal considerable heterogeneity in both contact strength and dynamics of the generally cell-type-specific enhancer-promoter contacts. Finally, our work suggests a so far unrecognized function of several key transcription factors which act as putative “molecular bridges” and facilitate the dynamic reorganization of the chromatin landscape accompanying lineage specification in the brain.
The Vagus Nerve Mediates the Physiological but not Pharmacological Effects of PYY3-36on Food Intake
Authors: Alonso A Martin , Cork SC , Ma Y , Arnold M , Herzog H , Bloom SR , Distaso W , Murphy KG , Salem V
Published: August 2020

Peptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity mediated by the neuropeptide Y (NPY) Y2 receptor (Y2R). However, the neuronal pathways by which PYY3-36acts to supress appetite are unclear. Determining how the PYY3-36system physiologically regulates food intake may help exploit its therapeutic potential. Here we demonstrate that germline and post-natal targeted knockdown of the Y2R in the afferent vagus nerve inhibits the anorectic effects of physiologically-released PYY3-36, but not peripherally-administered higher doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is compensated for in the germline model. Loss of vagal Y2R signalling also alters meal patterning and accelerates gastric emptying. These results may facilitate the design of PYY-based anti-obesity agents.

Abstract Figure
mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2
Authors: Hassert Mariah , Geerling Elizabeth , Stone E. Taylor , Steffen Tara L. , Feldman Madi S. , Class Jacob , Richner Justin M. , Brien James D. , Pinto Amelia K.
Published: August 2020

The novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in nearly 20 million infections across the globe, as of August 2020. Critical to the rapid evaluation of vaccines and antivirals is the development of tractable animal models of infection. The use of common laboratory strains of mice to this end is hindered by significant divergence of the angiotensin-converting enzyme 2 (ACE2), which is the receptor required for entry of SARS-CoV-2. In the current study, we designed and utilized an mRNA-based transfection system to induce expression of the hACE2 receptor in order to confer entry of SARS-CoV-2 in otherwise non-permissive cells. By employing this expression system in an in vivo setting, we were able to interrogate the adaptive immune response to SARS-CoV-2 in type 1 interferon receptor deficient mice. In doing so, we showed that the T cell response to SARS-CoV-2 is enhanced when hACE2 is expressed during infection. Moreover, we demonstrated that these responses are preserved in memory and are boosted upon secondary infection. Interestingly, we did not observe an enhancement of SARS-CoV-2 specific antibody responses with hACE2 induction. Importantly, using this system, we functionally identified the CD4+ and CD8+ peptide epitopes targeted during SARS-CoV-2 infection in H2brestricted mice. Antigen-specific CD8+ T cells in mice of this MHC haplotype primarily target peptides of the spike and membrane proteins, while the antigen-specific CD4+ T cells target peptides of the nucleocapsid, membrane, and spike proteins. The functional identification of these T cell epitopes will be critical for evaluation of vaccine efficacy in murine models of SARS-CoV-2. The use of this tractable expression system has the potential to be used in other instances of emerging infections in which the rapid development of an animal model is hindered by a lack of host susceptibility factors.
Sex and estrogen receptor β have modest effects on gene expression in the mouse brain posterior cortex
Authors: Fels Jasmine A , Casalena Gabriella A , Manfredi Giovanni
Published: August 2020

Introduction

Sex differences in brain cortical function affect cognition, behavior, and susceptibility to neural diseases, but the molecular basis of sexual dimorphism in cortical function is still largely unknown. Estrogen and estrogen receptors (ERs), specifically ERβ, the most abundant ER in the cortex, may play a role in determining sex differences in gene expression, which could underlie functional sex differences. However, further investigation is needed to address brain region specificity of the effects of sex and ERβ on gene expression. The goal of this study was to investigate sex differences in gene expression in the mouse posterior cortex, where sex differences in transcription have never been examined, and to determine how genetic ablation of ERβ affects transcription.

Methods

In this study, we performed unbiased transcriptomics on RNA from the posterior cortex of adult wild-type and ERβ knockout mice (n=4/sex/genotype). We used unbiased clustering to analyze whole-transcriptome changes between the groups. We also performed differential expression analysis on the data using DESeq2 to identify specific changes in gene expression.

Results

We found only 27 significantly differentially expressed genes (DEGs) in wild-type (WT) males vs females, of which 17 were autosomal genes. Interestingly, in ERβKO males vs females all the autosomal DEGs were lost. Gene Ontology analysis of the subset of DEGs with sex differences only in the WT cortex revealed a significant enrichment of genes annotated with the function ‘cation channel activity’. Moreover, within each sex we found only a few DEGs in ERβKO vs WT mice (8 and 5 in males and females, respectively).

Conclusions

Overall, our results suggest that in the adult mouse posterior cortex there are surprisingly few sex differences in gene expression, and those that exist are mainly related to cation channel activity. Additionally, they indicate that brain region-specific functional effects of ERβ may be largely post-transcriptional.
Genome-based targeted sequencing as a reproducible microbial community profiling assay
Authors: Benjamino Jacquelynn , Leopold Benjamin , Phillips Daniel , Adams Mark D.
Published: August 2020

Current sequencing-based methods for profiling microbial communities rely on marker gene (e.g. 16S rRNA) or metagenome shotgun sequencing (mWGS) analysis. We present a new approach based on highly multiplexed oligonucleotide probes designed from reference genomes in a pooled primer-extension reaction during library construction to derive relative abundance data. This approach, termed MA-GenTA: Microbial Abundances from Genome Tagged Analysis, enables quantitative, straightforward, cost-effective microbiome profiling that combines desirable features of both 16S rRNA and mWGS strategies. To test the utility of the MA-GenTA assay, probes were designed for 830 genome sequences representing bacteria present in mouse stool specimens. Comparison of the MA-GenTA data with mWGS data demonstrated excellent correlation down to 0.01% relative abundance and a similar number of organisms detected per sample. Despite the incompleteness of the reference database, NMDS clustering based on the Bray-Curtis dissimilarity metric of sample groups was consistent between MA-GenTA, mWGS and 16S rRNA datasets. MA-GenTA represents a potentially useful new method for microbiome community profiling based on reference genomes.
Antioxidant activity and zebrafish teratogenicity of hydroalcoholicMoringa oleiferaL. leaf extracts
Authors: Mohamad Shariff Nurul Fatin Syazleen , Singgampalam Thangam , Ng Chean Hui , Kue Chin Siang
Published: August 2020

Purpose

Moringa oleifera(MO) is a herbal remedy that is rich in essential amino acids and phytochemicals in the leaves, seeds and pods. It is becoming a famous food in various ethnic groups, and the consumption is increasing worldwide. However, there is no safety profile of the hydroalcoholic MO leaf extracts, or documented teratogenicity aspect. This study was sought to compare the antioxidant activity and the teratogenicity of hydroalcoholic MO leaf extracts in the zebrafish embryo.

Design/methodology/approach

MO leaves were extracted with aqueous alcohols (ethanol or methanol: water, 80:20 v/v) using the Soxhlet method. The antioxidant capacity was determined using DPPH assay. The concentrations of extracts ranging from 3 to 1,000 µg/mL were used to examine the toxicity and teratogenicity on the zebrafish embryo.

Findings

Both hydroalcoholic MO leaf extracts were positive for alkaloids, terpenoids, steroids, tannins, flavonoids, phenols, coumarins, quinones and glycosides, except saponins only absent in aqueous methanol extract. The antioxidant capacity based on lC50, was 15.92 ± 3.62 mg/mL for aqueous methanolic and 25.28 ± 2.89 mg/mL for aqueous ethanolic extract. For acute toxicity, the aqueous methanolic extract has lower LC50(163.87 ± 12.88 µg/mL) compared to aqueous ethanolic extract (337.48 ± 30.04 µg/mL). The embryo treated with aqueous methanolic extract showed phenotypic defect but not on the aqueous ethanolic extract.

Originality/value

This study suggests that aqueous methanol of MO leaves extract has better antioxidant capacity compared to ethanol, and ethanolic leaf extract is safer (higher LC50 and no teratogenicity) than methanolic extract.
Current mode fractional order PID control of wind-based quadratic boost converter inverter system with enhanced time response
Authors: J. Nandha Gopal , N.B. Muthuselvan
Published: August 2020

Purpose

The purpose of this paper is to enhance the response of quadratic boost converter inverter system (QBCIS) and also investigate proportional integral (PI) and fractional order proportional integral derivative (FOPID)-based space vector modulation inverter (SVMI) systems.

Design/methodology/approach

This paper presents modern expansion in control methods and power electronics have created wind-based AC to AC converters that relays to AC drives. The process includes the flow of quadratic boost converter (QBC) and SVMI locate their technique in associating permanent magnet synchronous generator and three phase load. This effort conveys with digital simulation using MATLAB/Simulink and hardware implementation of current mode wind-based QBCIS.

Findings

The direct current (DC) output from the rectifier is boosted using Quadratic Boost Converter (QBC). The DC yield of QBC is provided to the SVMI. The alternating current (AC) yield voltage is attained by using three-phase filter. The investigations are done with PI and FOPID-based SVMI systems. Current mode FOPID control is proposed to improve the time response of QBCIS system.

Originality/value

The simulation results are compared with the hardware results of QBCIS. The results of the comparison of PI with FOPID controlled by converters are made to show the improvement in terms of settling time and steady-state error.
Development of buck power converter circuit with ANN RL algorithm intended for power industry
Authors: Purohit Chandra Shekher , Manna Saibal , Mani Geetha , Stonier Albert Alexander
Published: August 2020

Purpose

This paper aims to deal with application of artificial intelligence for solving real time control complication adhered with the controlled operation of a buck power converter. This type of converter finds application for power conversion at various levels for the direct current-direct current power industry to step down the input voltage.

Design/methodology/approach

Use of ANN-RL (Artificial Neural Networks- Reinforcement Learning)-based control algorithm to control buck power converter shows robustness against parameter and load variation. Because of non-linearity instigated by element used for switching, control of this converter becomes an arduous control predicament. All the classical control techniques are based on an approximate linear model of the step down converter and these techniques fail to handle actual non-linearity.

Findings

In this paper, a reinforcement learning-based algorithm has been used to handle and control buck power converter output voltage, without approximating the model of converter. The non-linearity instigated in converter is subjected to state of switch. Model of buck power converter is defined as a multi-step decision problem so that it can be solved using mathematical model of Markov decision process (MDP) and, in turn, reinforcement learning can be implemented. As MDP model is available for a discrete state system so model of converter has to be discretized and then value iteration is applied and output is analyzed. Load regulation and integral time absolute error analysis is done to show efficacy of this technique.

Originality/value

To mitigate the effect of discretization function approximation using neural network is applied. MATrix LABoratory has been used for implementation and result indicates an improvement in the overall response.
Haar wavelets collocation method for a system of nonlinear singular differential equations
Authors: Verma Amit K. , Kumar Narendra , Tiwari Diksha
Published: August 2020

Purpose

The purpose of this paper is to propose an efficient computational technique, which uses Haar wavelets collocation approach coupled with the Newton-Raphson method and solves the following class of system of Lane–Emden equations:

−(tk1y′(t))′=t−ω1f1(t,y(t),z(t)),

−(tk2z′(t))′=t−ω2f2(t,y(t),z(t)),where t > 0, subject to the following initial values, boundary values and four-point boundary values:

y(0)=γ1, y′(0)=0, z(0)=γ2, z′(0)=0,

y′(0)=0, y(1)=δ1, z′(0)=0, z(1)=δ2,

y(0)=0, y(1)=n1z(v1), z(0)=0, z(1)=n2y(v2),where

n1,n2,v1,v2∈(0,1) and

k1≥0, k2≥0, ω1<1, ω2<1, γ1, γ2, δ1, δ2 are real constants.

Design/methodology/approach

To deal with singularity, Haar wavelets are used, and to deal with the nonlinear system of equations that arise during computation, the Newton-Raphson method is used. The convergence of these methods is also established and the results are compared with existing techniques.

Findings

The authors propose three methods based on uniform Haar wavelets approximation coupled with the Newton-Raphson method. The authors obtain quadratic convergence for the Haar wavelets collocation method. Test problems are solved to validate various computational aspects of the Haar wavelets approach. The authors observe that with only a few spatial divisions the authors can obtain highly accurate solutions for both initial value problems and boundary value problems.

Originality/value

The results presented in this paper do not exist in the literature. The system of nonlinear singular differential equations is not easy to handle as they are singular, as well as nonlinear. To the best of the knowledge, these are the first results for a system of nonlinear singular differential equations, by using the Haar wavelets collocation approach coupled with the Newton-Raphson method. The results developed in this paper can be used to solve problems arising in different branches of science and engineering.
How the C-suite is embracing Agile
Authors: Denning Stephen
Published: August 2020

Purpose

The authors reviews the leadership responsibilities involved in managing an organization that practices Agile management.

Design/methodology/approach

Outlines the best practices of major corporations that have adopted Agile processes both for teams and C-suite leadership.

Findings

Agile leaders spend less time reviewing the work of subordinates. They add value by adapting corporate strategies, leading critical agile teams, spending time with customers, mentoring individuals and coaching teams.

Practical implications

It is the C-suite leadership’s responsibility to establish and maintain a hierarchy of competence rather than a bureaucratic hierarchy of authority.

Originality/value

Describes how top management at some of the world’s largest and most successful corporations are adopting Agile practices to spur innovation and promote continuously adding customer vale.
Impact of team design and technical factors on team cohesion
Authors: Dey Chitra , M.P. Ganesh
Published: August 2020

Purpose

Based on the interpersonal interaction perspective of team cohesion, this study aims to examine the effects of team boundedness, formal coordination and organization tenure diversity on both task and social cohesion. The authors test for the interaction effect of organization tenure diversity on the relationships between the independent variables and the dimensions of team cohesion.

Design/methodology/approach

Data was collected from 111 software development teams and aggregated to the team level. Common latent factor test for common method bias showed no significant bias. Structural equation modelling (SEM) was used to test all the hypotheses.

Findings

SEM results show that team boundedness and formal coordination have positive and significant association with both dimensions of team cohesion. Formal coordination was found to be a stronger positive predictor for task cohesion than for social cohesion. Organization tenure diversity was found to be a stronger negative predictor for social cohesion than for task cohesion. Organization tenure diversity in the team moderates the relationship between formal coordination and task cohesion.

Research limitations/implications

The data was collected using a cross-sectional design. However, the authors have mitigated the effect of common method variance by adopting both procedural and statistical methods.

Originality/value

This paper expands extant literature by examining the antecedents of two important components of team cohesion, task and social cohesion. The authors proposed and found that the independent variables have different impacts on task and social cohesion. This study furthers both theory and practice by considering team boundedness as a variable of interest and its impact on internal team dynamics.