bluuebunny/crossref_metadata_2025_split huggingface dataset:
KnetMiner: a comprehensive approach for supporting evidence-based gene discovery and complex trait analysis across species
Authors: Hassani-Pak Keywan , Singh Ajit , Brandizi Marco , Hearnshaw Joseph , Amberkar Sandeep , Phillips Andrew L. , Doonan John H. , Rawlings Chris 
Published: April 2020

ABSTRACTGenerating new ideas and scientific hypotheses is often the result of extensive literature and database reviews, overlaid with scientists’ own novel data and a creative process of making connections that were not made before. We have developed a comprehensive approach to guide this technically challenging data integration task and to make knowledge discovery and hypotheses generation easier for plant and crop researchers. KnetMiner can digest large volumes of scientific literature and biological research to find and visualise links between the genetic and biological properties of complex traits and diseases. Here we report the main design principles behind KnetMiner and provide use cases for mining public datasets to identify unknown links between traits such grain colour and pre-harvest sprouting inTriticum aestivum, as well as, an evidence-based approach to identify candidate genes under anArabidopsis thalianapetal size QTL. We have developed KnetMiner knowledge graphs and applications for a range of species including plants, crops and pathogens. KnetMiner is the first open-source gene discovery platform that can leverage genome-scale knowledge graphs, generate evidence-based biological networks and be deployed for any species with a sequenced genome. KnetMiner is available athttp://knetminer.org.
In-depth characterization of layer 5 output neurons of the primary somatosensory cortex innervating the mouse dorsal spinal cord
Authors: Frezel N. , Platonova E. , Voigt F.F. , Mateos J.M. , Kastli R. , Ziegler U. , Karayannis T. , Helmchen F. , Wildner H. , Zeilhofer H.U. 
Published: April 2020

AbstractNeuronal circuits of the spinal dorsal horn integrate sensory information from the periphery with inhibitory and facilitating input from higher CNS areas. Most previous work focused on projections descending from the hindbrain. Less is known about inputs descending from the cerebral cortex. Here, we identified cholecystokinin (CCK) positive layer 5 pyramidal neurons of the primary somatosensory cortex (CCK+S1-CST neurons) as a major source of input to the spinal dorsal horn. We combined intersectional genetics and virus-mediated gene transfer to characterize CCK+S1-CST neurons and to define their presynaptic input and postsynaptic target neurons. We found that S1-CST neurons constitute a heterogeneous population that can be subdivided into distinct molecular subgroups. Rabies-based retrograde tracing revealed monosynaptic input from layer 2/3 pyramidal neurons, from parvalbumin (PV) positive cortical interneurons, and from thalamic relay neurons in the ventral posterolateral nucleus. WGA-based anterograde tracing identified postsynaptic target neurons in dorsal horn laminae III and IV. About 60% of these neurons were inhibitory and about 60% of all spinal target neurons expressed the transcription factor c-Maf. The heterogeneous nature of both S1-CST neurons and their spinal targets suggest complex roles in the fine-tuning of sensory processing.
Expression of a transcript encoding for cytosolic renin in the diseased human heart
Authors: Sczodrok Jaroslaw , Lutze Philipp , Staar Doreen , Dörr Marcus , Peters Jörg 
Published: April 2020

AbstractSecretory renin promotes hypertrophy, apoptosis, necrosis and fibrosis through angiotensin generation. It has been claimed that local expression of renin contributes to the deleterious effects of the renin-angiotensin system in the heart. Besides the classic renin transcript (renin-a), encoding for secretory renin, a putative brain-specific (renin-b) and a putative lung-specific (renin-c) transcript may exist in human. In contrast to secretory renin, renin-b cannot be secreted, remains within the cytosol and is imported into mitochondria. In contradiction to renin-a, renin-b exerts cardioprotective effects in hearts and in cardiac cells of the rat under ischemia related conditions. To date, available data on cardiac renin expression remain inconsistent. Nobody has yet investigated which renin transcripts are expressed in the human heart. We systematically analyzed the levels of renin transcripts using specific and sensitive nested reverse-transcriptase polymerase chain reactions (RT-PCR) in human ventricular biopsies obtained from patients with heart diseases. In the 33 biopsies available, neither the expression of classic renin-a, nor of the alternative renin-c was detected. In contrast, the renin-b transcript, which was previously classified as brain-specific, was found in 11/33 ventricular biopsies. Our data exclude the expression of secretory renin and indicate that local expression of cytosolic renin but not of secretory renin can play a functional role in the human heart.
Evaluation of DNA conservation in Nile-Saharan environment, Missiminia, in Nubia: Tracking maternal lineage of “X-Group”
Authors: Cherifi Yahia Mehdi Seddik , Amrani Selma 
Published: April 2020

AbstractObjectiveWe assessed DNA conservation using a range of archaeological skeletal samples from Sudan (Missiminia in Upper Nubia, 350 B.C.E to 1400 C.E) from the unfavorable conditions of the Saharan milieu and humidity of the Nile valley by tracking maternal lineage on the ‘X-Group’ (Ballaneans).MethodWe were able to extract, amplify, and sequence mt-DNA HVS-I (Sanger sequencing method) from 11 petrous bone samples, eight for the X-Group set and three for the reference set (one Christian, one Late Meroitic, and one Meroitic).ResultsIt was possible to find the haplogroups (L1b, L2, L3, H2, N, T1a, X and W) and to carry out comparative data analysis in relation to haplogroup data cited in the literature. This investigation into the maternal lineage of X-Group (350 to 500 C.E.) origins allowed us to validate the efficiency of petrous bone sampling from ancient human remains from the Nile-Saharan milieu and established that the Ballaneans experienced an in-situ development with more admixture from the Levant region and North Africa.ConclusionsOur study used mt-DNA (HVS-I) to look for the biological origins of the X-Group from Upper-Nubia and demonstrated the feasibility of ancient DNA research on skeletons from the Nile-Saharan environment. The use of Next Sequencing Generation (NGS) should optimize and improve the detection of shorter DNA strands and their sequencing in complete genomes from ancient skeletal remains (petrous bones) from hot and humid environments.
Private Genomes and Public SNPs: Homomorphic encryption of genotypes and phenotypes for shared quantitative genetics
Authors: Mott Richard , Fischer Christian , Prins Pjotr , Davies Robert William 
Published: April 2020

AbstractSharing human genotype and phenotype data presents a challenge because of privacy concerns, but is essential in order to discover otherwise inaccessible genetic associations. Here we present a method of homomorphic encryption that obscures individuals’ genotypes and phenotypes and is suited to quantitative genetic association analysis. Encrypted ciphertext and unencrypted plaintext are interchangeable from an analytical perspective. This allows one to store ciphertext on public web services and share data across multiple studies, while maintaining privacy. The encryption method uses as its key a high-dimensional random linear orthogonal transformation that leaves the likelihood of quantitative trait data unchanged under a linear model with normally distributed errors. It also preserves linkage disequilibrium between genetic variants and associations between variants and phenotypes. It scrambles relationships between individuals: encrypted genotype dosages closely resemble Gaussian deviates, and in fact can be replaced by quantiles from a Gaussian with only negligible effects on accuracy. Standard likelihood-based inferences are unaffected by orthogonal encryption. These include the use of mixed linear models to control for unequal relatedness between individuals, the estimation of heritability, and the inclusion of covariates when testing for association. Orthogonal transformations can also be applied in a modular fashion that permits multi-party federated mega-analyses. Under this scheme any number of parties first agree to share a common set of genotype sites and covariates prior to encryption. Each party then privately encrypts and shares their own ciphertext, and analyses the other parties’ ciphertexts. In the absence of private variants, or knowledge of the key, we show that it is infeasible to decrypt ciphertext using existing brute-force or noise reduction attacks. Therefore, we present the method as a challenge to the community to determine its security.
People can learn new walking patterns without walking
Authors: Song Christine N. , Stenum Jan , Leech Kristan A. , Keller Chloe , Roemmich Ryan T. 
Published: April 2020

ABSTRACTHumans can learn many new walking patterns. People have learned to snowshoe up mountains, racewalk marathons, and march in precise synchrony. But what is required to learn a new walking pattern? Here, we demonstrate that people can learn new walking patterns without actually walking. Through a series of experiments, we observe that stepping with only one leg can facilitate learning of an entirely new walking pattern (i.e., split-belt treadmill walking). We find that the nervous system learns from the relative motion between the legs – whether or not both legs are moving – and can transfer this learning to novel gaits. We also show that locomotor learning requires active movement: observing another person adapt their gait did not result in significantly faster learning. These findings reveal that people can learn new walking patterns without bilateral gait training, as stepping with one leg can facilitate adaptive learning that transfers to novel gait patterns.
Mutant EGFR is a preferred SMURF2 substrate of ubiquitination: role in enhanced receptor stability and TKI sensitivity
Authors: Ray Paramita , Raghunathan Krishnan , Ahsan Aarif , Allam Uday Sankar , Shukla Shirish , Basrur Venkatesha , Veatch Sarah , Lawrence Theodore S. , Nyati Mukesh K. , Ray Dipankar 
Published: April 2020

ABSTRACTWe previously reported that differential protein degradation of TKI-sensitive [L858R, del(E746-A750)] and resistant (T790M) epidermal growth factor receptor (EGFR) mutants upon erlotinib treatment correlates with drug sensitivity. However, the molecular mechanism remains unclear. We also reported SMAD ubiquitination regulatory factor 2 (SMURF2) ligase activity is important in stabilizing EGFR. Here, usingin vitroandin vivoubiquitination assays, mass spectrometry, and super-resolution microscopy, we show SMURF2-EGFR functional interaction is critical in receptor stability and TKI sensitivity. We found that L858R/T790M EGFR is a preferred substrate of SMURF2-UBCH5 (an E3-E2) complex-mediated K63-linked polyubiquitination, which preferentially stabilizes mutant receptor. We identified four lysine (K) residues (K721, 846, 1037 and 1164) as the sites of ubiquitination and replacement of K to acetylation-mimicking asparagine (Q) at K1037 position in L858R/T790M background converts the stable protein sensitive to erlotinib-induced degradation. Using STochastic Optical Reconstruction Microscopy (STORM) imaging, we show that SMURF2 presence allows longer membrane retention of activated EGFR upon EGF treatment, whereas, siRNA-mediatedSMURF2knockdown fastens receptor endocytosis and lysosome enrichment. In an erlotinib-sensitive PC9 cells, SMURF2 overexpression increased EGFR levels with improved erlotinib tolerance, whereas,SMURF2knockdown decreased EGFR steady state levels in NCI-H1975 and PC9-AR cells to overcome erlotinib and AZD-9291 resistance respectively. Additionally, by genetically altering the SMURF2-UBCH5 complex formation destabilized EGFR. Together, we propose that SMURF2-mediated preferential polyubiquitination of L858R/T790M EGFR may be competing with acetylation-mediated receptor internalization to provide enhanced receptor stability and that disruption of the E3-E2 complex may be an attractive alternate to overcome TKI resistance.
miTAR: a hybrid deep learning-based approach for predicting miRNA targets
Authors: Gu Tongjun , Zhao Xiwu , Barbazuk William Bradley , Lee Ji-Hyun 
Published: April 2020

AbstractmicroRNAs (miRNAs) are a major type of small RNA that alter gene expression at the post-transcriptional or translational level. They have been shown to play important roles in a wide range of biological processes. Many computational methods have been developed to predict targets of miRNAs in order to understand miRNAs’ function. However, the majority of the methods depend on a set of pre-defined features that require considerable effort and resources to compute, and these methods often do not effectively on the prediction of miRNA targets. Therefore, we developed a novel hybrid deep learning-based approach that is capable to predict miRNA targets at a higher accuracy. Our approach integrates two deep learning methods: convolutional neural networks (CNNs) that excel in learning spatial features, and recurrent neural networks (RNNs) that discern sequential features. By combining CNNs and RNNs, our approach has the advantages of learning both the intrinsic spatial and sequential features of miRNA:target. The inputs for the approach are raw sequences of miRNA and gene sequences. Data from two latest miRNA target prediction studies were used in our study: the DeepMirTar dataset and the miRAW dataset. Two models were obtained by training on the two datasets separately. The models achieved a higher accuracy than the methods developed in the previous studies: 0.9787 vs. 0.9348 for the DeepMirTar dataset; 0.9649 vs. 0.935 for the miRAW dataset. We also calculated a series of model evaluation metrics including sensitivity, specificity, F-score and Brier Score. Our approach consistently outperformed the current methods. In addition, we compared our approach with earlier developed deep learning methods, resulting in an overall better performance. Lastly, a unified model for both datasets was developed with an accuracy higher than the current methods (0.9545). We named the unified model miTAR for miRNA target prediction. The source code and executable are available athttps://github.com/tjgu/miTAR.
Experience-independent transformation of single-cell 3D genome structure and transcriptome during postnatal development of the mammalian brain
Authors: Tan Longzhi , Ma Wenping , Wu Honggui , Zheng Yinghui , Xing Dong , Chen Ritchie , Li Xiang , Daley Nicholas , Deisseroth Karl , Xie X. Sunney 
Published: April 2020

SUMMARYBoth transcription and 3D organization of the mammalian genome play critical roles in neurodevelopment and its disorders. However, 3D genome structures of single brain cells have not been solved; little is known about the dynamics of single-cell transcriptome and 3D genome after birth. Here we generate a transcriptome atlas of 3,517 cells and a 3D genome atlas of 3,646 cells from the developing mouse cortex and hippocampus, using our high-resolution MALBAC-DT and Dip-C methods. In adults, 3D genome “structure types” delineate all major cell types, with high correlation between A/B compartments and gene expression. During development, both transcriptome and 3D genome are extensively transformed in the first postnatal month. In neurons, 3D genome is rewired across multiple scales, correlated with gene expression modules and independent of sensory experience. Finally, we examine allele-specific structure of imprinted genes, revealing local and chromosome-wide differences. These findings uncover a previously unknown dimension of neurodevelopment.HIGHLIGHTSTranscriptomes and 3D genome structures of single brain cells (both neurons and glia) in the developing mouse forebrainCell type identity encoded in the 3D wiring of the mammalian genome (“structure types”)Major transformation of both transcriptome and 3D genome during the first month of life, independent of sensory experienceAllele-specific 3D structure at 7 imprinted gene loci, including one that spans a whole chromosome
Disinhibition of the orbitofrontal cortex biases decision making in obesity
Authors: Seabrook Lauren T. , Naef Lindsay , Baimel Corey , Judge Allap K. , Kenney Tyra , Ellis Madelyn , Tayyab Temoor , Armstrong Mataea , Qiao Min , Floresco Stan B , Borgland Stephanie L. 
Published: April 2020

AbstractThe lateral orbitofrontal cortex (lOFC) receives sensory information about food and integrates these signals with expected outcomes to guide future actions, and thus may play a key role in a distributed network of neural circuits that regulate feeding behaviour. Here, we reveal a novel role for the lOFC in the cognitive control of behaviour in obesity. Food-seeking behaviour is biased in obesity such that in male obese mice, behaviours are less flexible to changes in the perceived value of the outcome. Obesity is associated with reduced lOFC inhibitory drive, and chemogenetic reduction in GABAergic neurotransmission in the lOFC induces obesity-like impairments in goal-directed behaviour. Conversely, pharmacological or optogenetic restoration of inhibitory neurotransmission in the lOFC of obese mice reinstates flexible behaviour. Our results indicate that obesity-induced disinhibition of the lOFC leads to a failure to update changes in the value of food with satiety, which in turn may influence how individuals make decisions in an obesogenic environment.
STEP inhibition prevents Aβ-mediated damage in dendritic complexity and spine density in Alzheimer’s disease.
Authors: Chatterjee Manavi , Kwon Jeemin , Benedict Jessie , Kamceva Marija , Kurup Pradeep , Lombroso Paul J. 
Published: April 2020

AbstractLoss of dendritic spines and decline of cognitive function are hallmarks of patients with Alzheimer’s disease (AD). Previous studies have shown that AD pathophysiology involves increased expression of a central nervous system-enriched protein tyrosine phosphatase called STEP (STriatal-Enriched protein tyrosine Phosphatase). STEP opposes the development of synaptic strengthening by dephosphorylating substrates, including GluN2B, Pyk2 and ERK1/2. Genetic reduction of STEP as well as pharmacological inhibition of STEP improves cognitive function and hippocampal memory in the 3xTg AD mouse model. Here, we show that the improved cognitive function is accompanied by an increase in synaptic connectivity in cell cultures as well as in the triple transgenic AD mouse model, further highlighting the potential of STEP inhibitors as a therapeutic agent.
What do women know about breast density? A public screening program perspective
Authors: Robertson Monique , Darcey Ellie C , Dench Evenda K , Keogh Louise , McLean Kirsty , Pirikahu Sarah , Saunders Christobel , Thompson Sandra , Woulfe Catherine , Wylie Elizabeth , Stone Jennifer 
Published: April 2020

AbstractBackgroundThis study assesses knowledge of breast density, one of breast cancer’s strongest risk factors, in women attending a public mammographic screening program in Western Australia that routinely notifies women if they have dense breasts.MethodsSurvey data was collected from women who were notified they have dense breasts and women who had not (controls). Descriptive data analysis was used to summarize responses.ResultsOf the 6183 women surveyed, over 85% of notified women knew that breast density makes it difficult to see cancer on a mammogram (53.9% in controls). A quarter of notified women knew that having dense breasts puts women at increased risk for breast cancer (13.2% in controls). Overall, 50.1% of notified women indicated that they thought the amount of information provided was “just right” and 24.9% thought it was “too little”, particularly women notified for the first time (32.1%).ConclusionThe main message of reduced sensitivity of mammography in women with dense breasts provided by the screening program appears to be getting though. However, women are largely unaware that increased breast density is associated with increased risk. Women notified of having dense breasts for the first time could potentially benefit from additional information.
Alpha oscillations do not implement gain control in early visual cortex but rather gating in parieto-occipital regions
Authors: Zhigalov Alexander , Jensen Ole 
Published: April 2020

AbstractSpatial attention provides a mechanism for respectively enhancing relevant and suppressing irrelevant information. While it is well-established that attention modulates oscillations in the alpha band, it remains unclear if alpha oscillations are involved in directly modulating the neuronal excitability associated with the allocation of spatial attention. In this study in humans, we utilized a novel broadband frequency (60 – 70 Hz) tagging paradigm to quantify neuronal excitability in relation to alpha oscillations in a spatial attention paradigm. We used magnetoencephalography to characterize ongoing brain activity as it allows for localizing the sources of both the alpha and frequency tagging responses. We found that attentional modulation of alpha power and the frequency tagging response are uncorrelated over trials. Importantly, the neuronal sources of the tagging response were localized in early visual cortex (V1) whereas the sources of the alpha activity were identified around parieto-occipital sulcus. Moreover, we found that attention did not modulate the latency of the frequency tagged responses. Our findings point to alpha band oscillations serving a downstream gating role rather than implementing gain control of excitability in early visual regions.Significance StatementBy combining magnetoencephalography and a novel broadband frequency tagging approach, we show that spatial attention differently modulates alpha oscillations and neuronal excitability. Importantly, the sources of the alpha oscillations and tagging responses were spatially distinct and the alpha power and tagging response were not related over trials. These results are inconsistent with previous ideas suggesting that alpha oscillations are involved in gain control of early sensory regions; rather alpha oscillations are involved in the allocation of neuronal resources in downstream regions.
The effect of servant leadership, perceived organizational support, job satisfaction and job embeddedness on turnover intentions
Authors: Huning Tobias M. , Hurt Kevin J. , Frieder Rachel E. 
Published: April 2020

PurposeThe purpose of this study is to provide insights into the effect of servant leadership on turnover intentions. The authors investigate the mediating effects of perceived organizational support (POS), job embeddedness and job satisfaction on the relationship between servant leadership and turnover intentions. In doing so, the authors seek to make the following contributions. First, the authors seek to provide additional empirical evidence for servant leadership as an effective organizational theory. Additionally, the authors seek to establish POS, embeddedness and job satisfaction as underlying mechanisms that transmit the positive effects of servant leadership.Design/methodology/approachThe data were collected from a paper and pencil survey questionnaire provided to employees of different organizations in a metropolitan area in the southeastern United States. The sample consisted of 150 participants; complete (listwise) data were available for 115 participants.FindingsThe study shows that POS and embeddedness are mediating mechanisms through which servant leadership is related to employee turnover intentions. The authors found POS and job embeddedness to be significant mediating constructs which help explain the nature of the relationship between servant leadership and turnover intentions.Originality/valueBy investigating these constructs in the present framework, we help to provide answers to the questions of how and why servant leadership affects employee outcomes. These answers are an important step towards more fully understanding the complex ways by which followers respond to servant leadership.