bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-depth secretome analysis ofPuccinia striiformisf. sp.triticiin infected wheat uncovers effector functions
Authors: Ozketen Ahmet Caglar , Andac-Ozketen Ayse , Dagvadorj Bayantes , Demiralay Burak , Akkaya Mahinur S. 
Published: January 2020

ABSTRACTThe importance of wheat yellow rust disease, caused byPuccinia striiformisf. sp.tritici(Pst), has increased substantially due to the emergence of aggressive newPstraces in the last couple of decades. In an era of escalating human populations and climate change, it is vital to understand the infection mechanism ofPstin order to develop better strategies to combat wheat yellow disease. This study focuses on the identification of small secreted proteins (SSPs) and candidate-secreted effector proteins (CSEPs) that are used by the pathogen to support infection and control disease development. We generatedde novoassembled transcriptomes ofPstcollected from wheat fields in central Anatolia. We inoculated both susceptible and resistant seedlings withPstand analyzed haustoria formation. At 10 days post-inoculation (dpi), we analyzed the transcriptomes and identified 10,550 Differentially Expressed Unigenes (DEGs), of which 6,220 werePst-related. Among thosePst-related genes, 230 were predicted as PstSSPs.In silicocharacterization was performed using an approach combining the transcriptomic data and data mining results to provide a reliable list to narrow down the ever-expanding repertoire of predicted effectorome. The comprehensive analysis detected 14 Differentially Expressed Small-Secreted Proteins (DESSPs) that overlapped with the genes in available literature data to serve as the best CSEPs for experimental validation. One of the CSEPs was cloned and studied to test the reliability of the presented data. Biological assays show that the randomly selected CSEP, Unigene17495 (PSTG_10917), localizes in the chloroplast and is able to suppress cell death induced by INF1 in aNicotiana benthamianaheterologous expression system.
Complex genetic network underlying the convergent of Rett Syndrome like (RTT-L) phenotype in neurodevelopmental disorders
Authors: Frankel Eric , Dodson Julius , Sharifi Megan , Pillai Roshan , Ramsey Keri , Gupta Raj , Brzezinski Molly , Venugopal Pooja , Llaci Lorida , Gerald Brittany , Mills Gabrielle , Belnap Newell , Sanchez-Castillo Meredith , Balak Chris D. , Claasen Ana M. , Szelinger Szabolcs , Jepsen Wayne M. , Siniard Ashley L. , Richholt Ryan , De Both Matt , Naymik Marcus , Schrauwen Isabelle , Piras Ignazio S. , Craig David W. , Huentelman Matthew J. , Narayanan Vinodh , Rangasamy Sampathkumar 
Published: January 2020

AbstractMutations of the X-linked gene encoding methyl-CpG-binding protein 2 (MECP2) cause classical forms of Rett syndrome (RTT) in girls. Patients with features of classical Rett syndrome, but do not fulfill all the diagnostic criteria (e.g. absence of aMECP2mutation), are defined as atypical Rett syndrome. Genes encoding for cyclin-dependent kinase-like 5 (CDKL5) and forkhead box G1 (FOXG1) are more commonly found in patients with atypical Rett syndrome. Nevertheless, a subset of patients who are recognized to have an overlapping phenotype with RTT but are lacking a mutation in a gene that causes typical or atypical RTT are described as having Rett syndrome like phenotype (RTT-L). Whole Exome Sequencing (WES) of 8 RTT-L patients from our cohort revealed mutations in the genesGABRG2, GRIN1, ATP1A2, KCNQ2, KCNB1, TCF4, SEMA6B, andGRIN2A, which are seemingly unrelated to Rett syndrome genes. We hypothesized that the phenotypic overlap in RTT and RTT-L is caused by mutations in genes that affect common cellular pathways critical for normal brain development and function. We annotated the list of genes identified causing RTT-L from peer-reviewed articles and performed a protein-protein interaction (PPI) network analysis. We also investigated their interaction with RTT (typical or atypical) genes such asMECP2, CDKL5, NTNG1, andFOXG1. We found that the RTT-L-causing genes were enriched in the biological pathways such as circadian entrainment, the CREB pathway, and RET signaling, and neuronal processes like ion transport, synaptic transmission, and transcription. We conclude that genes that significantly interact with the PPI network established by RTT genes cause RTT-L, explaining the considerable feature overlap between genes that are indicated for RTT-L and RTT.
Morphological facilitators for vocal learning explored through the syrinx anatomy of a basal hummingbird
Authors: Monte Amanda , Cerwenka Alexander F. , Ruthensteiner Bernhard , Gahr Manfred , Düring Daniel N. 
Published: January 2020

AbstractVocal learning is a rare evolutionary trait that evolved independently in three avian clades: songbirds, parrots, and hummingbirds. Although the anatomy and mechanisms of sound production in songbirds are well understood, little is known about the hummingbird’s vocal anatomy. We use high-resolution micro-computed tomography (μCT) and microdissection to reveal the three-dimensional structure of the syrinx, the vocal organ of the black jacobin (Florisuga fusca), a phylogenetically basal hummingbird species. We identify three unique features of the black jacobin’s syrinx: (i) a shift in the position of the syrinx to the outside of the thoracic cavity and the related loss of the sterno-tracheal muscle, (ii) complex intrinsic musculature, oriented dorso-ventrally, and (iii) ossicles embedded in the medial vibratory membranes. Their syrinx morphology allows vibratory decoupling, precise control of complex acoustic parameters, and a large redundant acoustic space that may be key biomechanical factors facilitating the occurrence of vocal production learning.
Exploring the potential genetic heterogeneity in the incidence of hoof and leg disorders in Austrian Fleckvieh and Braunvieh cattle
Authors: Kosinska-Selbi Barbara , Suchocki Tomasz , Egger-Danner Christa , Schwarzenbacher Hermann , Fraszczak Magdalena , Szyda Joanna 
Published: January 2020

AbstractBackgroundGenetic heterogeneity denotes the situation when different genetic architectures underlying diverse populations result in the same phenotype. In this study, we explore the nature of differences in the incidence of the number of hoof and leg disorders between Braunvieh and Fleckvieh cattle in the context of genetic heterogeneity between the breeds.ResultsDespite potentially higher power of testing due to twice as large sample size, none of the SNPs was significantly associated with the number of hoof and leg disorders in Fleckvieh, while 16 SNPs were significant in Braunvieh. The most promising candidate genes in Braunvieh are: CBLB on BTA01, which causes arthritis in rats; CAV2 on BTA04, which in effects mouse skeletal muscles; PTHLH on BTA05, which causes disease phenotypes related to the skeleton in humans, mice and zebrafish; SORCS2 on BTA06, which causes decreased susceptibility to injury in the mouse. Some of the significant SNPs (BTA01, BTA04, BTA05, BTA13, BTA16) reveal allelic heterogeneity – i.e. differences due to different allele frequencies between Fleckvieh and Braunvieh. Some of the significant regions (BTA01, BTA05, BTA13, BTA16) correlate to inter-breed differences in LD structure and may thus represent false-positive heterogeneity. However, positions on BTA06 (SORCS2), BTA14 and BTA24 mark Braunvieh-specific regions.ConclusionsWe hypothesise that the observed genetic heterogeneity of hoof and leg disorders is a by-product of multigenerational differential selection of the breeds – towards dairy production in the case of Braunvieh and towards beef production in the case of Fleckvieh. Based on the current data set it is no possibly to unequivocally confirm/exclude the hypothesis of genetic heterogeneity in the susceptibility to leg disorders between Fleckvieh and Braunvieh because only explore it through associations and not the causal mutations. Rationales against genetic heterogeneity comprise a limited power of detection of true associations as well as differences in the length of LD blocks and in linkage phase between breeds. On the other hand, multigenerational differential selection of the breeds and no systematic differences in LD structure between the breeds favour the heterogeneity hypothesis at some of the significant sites.
Retrospective Ensemble Docking of Allosteric Modulators in an Adenosine G-Protein-Coupled Receptor
Authors: Bhattarai Apurba , Wang Jinan , Miao Yinglong 
Published: January 2020

AbstractBackgroundEnsemble docking has proven useful in drug discovery and development. It increases the hit rate by incorporating receptor flexibility into molecular docking as demonstrated on important drug targets including G-protein-coupled receptors (GPCRs). Adenosine A1receptor (A1AR) is a key GPCR that has been targeted for treating cardiac ischemia-reperfusion injuries, neuropathic pain and renal diseases. Development of allosteric modulators, compounds binding to distinct and less conserved GPCR target sites compared with agonists and antagonists, has attracted increasing interest for designing selective drugs of the A1AR. Despite significant advances, more effective approaches are needed to discover potent and selective allosteric modulators of the A1AR.MethodsEnsemble docking that integrates Gaussian accelerated molecular dynamic (GaMD) simulations and molecular docking usingAutodockhas been implemented for retrospective docking of known positive allosteric modulators (PAMs) in the A1AR.ResultsEnsemble docking outperforms docking of the receptor cryo-EM structure. The calculated docking enrichment factors (EFs) and the area under the receiver operating characteristic curves (AUC) are significantly increased.ConclusionsReceptor ensembles generated from GaMD simulations are able to increase the success rate of discovering PAMs of A1AR. It is important to account for receptor flexibility through GaMD simulations and flexible docking.General SignificanceEnsemble docking is a promising approach for drug discovery targeting flexible receptors.
A population-level statistic for assessing Mendelian behavior of genotyping-by-sequencing data from highly duplicated genomes
Authors: Clark Lindsay V. , Mays Wittney , Lipka Alexander E. , Sacks Erik J. 
Published: January 2020

AbstractBackgroundGiven the economic and environmental importance of allopolyploids and other species with highly duplicated genomes, there is a need for methods to distinguish paralogs, i.e. duplicate sequences within a genome, from Mendelian loci, i.e. single copy sequences that pair at meiosis. The ratio of observed to expected heterozygosity is an effective tool for filtering loci but requires genotyping to be performed first at a high computational cost, whereas counting the number of sequence tags detected per genotype is computationally quick but very ineffective in inbred or polyploid populations. Therefore, new methods are needed for filtering paralogs.ResultsWe introduce a novel statistic,Hind/HE, that uses the probability that two reads sampled from a genotype will belong to different alleles, instead of observed heterozygosity. The expected value ofHind/HEis the same across all loci in a dataset, regardless of read depth or allele frequency. In contrast to methods based on observed heterozygosity, it can be estimated and used for filtering loci prior to genotype calling. In addition to filtering paralogs, it can be used to filter loci with null alleles or high overdispersion, and identify individuals with unexpected ploidy and hybrid status. We demonstrate that the statistic is useful at read depths as low as five to 10, well below the depth needed for accurate genotype calling in polyploid and outcrossing species.ConclusionsOur methodology for estimatingHind/HEacross loci and individuals, as well as determining reasonable thresholds for filtering loci, is implemented in polyRAD v1.6, available athttps://github.com/lvclark/polyRAD. In large sequencing datasets, we anticipate that the ability to filter markers and identify problematic individuals prior to genotype calling will save researchers considerable computational time.
SnpReady for Rice (SR4R) Database
Authors: Yan Jun , Zou Dong , Li Chen , Zhang Zhang , Song Shuhui , Wang Xiangfeng 
Published: January 2020

AbstractThe information commons for rice (IC4R) database is a collection of ∼18 million SNPs (single nucleotide polymorphisms) identified by the resequencing of 5,152 rice accessions. Although IC4R offers ultra-high density rice variation map, these raw SNPs are not readily usable for the public. To satisfy different research utilizations of SNPs for population genetics, evolutionary analysis, association studies and genomic breeding in rice, the raw genotypic data of the 18 million SNPs were processed by unified bioinformatics pipelines. The outcomes were used to develop a daughter database of IC4R – SnpReady for Rice (SR4R). The SR4R presents four reference SNP panels, including 2,097,405 hapmapSNPs after data filtration and genotype imputation, 156,502 tagSNPs selected from linkage disequilibrium (LD)-based redundancy removal, 1,180 fixedSNPs selected from genes exhibiting selective sweep signatures, and 38 barcodeSNPs selected from DNA fingerprinting simulation. SR4R thus offers a highly efficient rice variation map that combines reduced SNP redundancy with extensive data describing the genetic diversity of rice populations. In addition, SR4R provides rice researchers with a web-interface that enables them to browse all four SNP panels, use online toolkits, and retrieve the original data and scripts for a variety of population genetics analyses on local computers. The SR4R is freely available to academic users athttp://sr4r.ic4r.org/.
Voluntary actions modulate perception and neural representation of action-consequences in a hand-dependent manner
Authors: B. Buaron , D. Reznik , R. Gilron , R. Mukamel 
Published: January 2020

AbstractEvoked neural activity in sensory regions, and perception of sensory stimuli, are modulated when the stimuli are the consequence of voluntary movement as opposed to an external source. It has been suggested that such modulations are due to efference copies of the motor command that are sent to relevant sensory regions during voluntary movement. Given the anatomical-functional laterality bias of the motor system, it is plausible that the pattern of such behavioral and neural sensory modulations will exhibit a similar bias, depending on the effector that was used to trigger the stimulus (e.g. right / left hand). Here we examined this issue in the visual domain using behavioral and neural measures (fMRI). Healthy participants judged the relative brightness of identical visual stimuli that were either self-triggered (using right or left hand button presses), or triggered by the computer. By presenting stimuli to either the right or left visual field, we biased visual-evoked responses to left / right visual cortex. We found stronger perceptual modulations when the triggering hand was ipsi (rather than contra) lateral to the stimulated visual field. At the neural level, we found that despite identical physical properties of the visual consequence, evoked fMRI responses in right and left visual cortices differentiate the identity of the triggering hand (left / right). Our findings support a model in which voluntary actions induce sensory modulations that follow the anatomical-functional bias of the motor system.
Activation of Src-family kinases orchestrate secretion of flaviviruses by targeting mature progeny virions to secretory autophagosomes
Authors: Li Ming Yuan , Naik Trupti Shivaprasad , Siu Lewis Yu Lam , Acuto Oreste , Spooner Eric , Wang Peigang , Yang Xiaohan , Lin Yongping , Bruzzone Roberto , Ashour Joseph , Sanyal Sumana 
Published: January 2020

SummaryAmong the various host cellular processes that are hijacked by flaviviruses, very few mechanisms have been described with regard to viral secretion. Here we investigated how flaviviruses exploit the Src family kinases (SFKs) for exit from infected cells. We isolated three members of the SFK family – Src, Fyn and Lyn – that were specifically activated during secretion of Dengue and Zika or their corresponding virus like particles (VLPs). Pharmacological inhibition or genetic depletion of the SFKs blocked virus secretion, most significantly upon Lyn-deficiency. Lyn-/-cells were severely impaired in virus release, and were rescued when reconstituted with wild-type Lyn, but not a kinase- or palmitoylation-deficient Lyn mutant. We further established that Lyn, via its palmitoylation-dependent membrane association, triggered post-Golgi virus transport in specialised Rab11 and Transferrin receptor positive organelles resembling secretory autophagosomes, and distinct from conventional exocytic vesicles. In the absence of Lyn activity or its aberrant membrane association, virions were sorted into the lysosomal pathway for degradation. This mode of export was specifically triggered by processed, and mature, but not by furin-resistant virus particles, and occurred with significantly faster kinetics than the conventional secretory pathway. Our study therefore charts a previously undiscovered Lyn-dependent exit strategy, triggered by flaviviruses in secretory autophagosomes that might enable them to evade circulating antibodies and dictate tissue tropism.
Embodied Spatial Knowledge Acquisition in Immersive Virtual Reality: Comparison to Map Exploration
Authors: König Sabine U. , Keshava Ashima , Clay Viviane , Rittershofer Kirsten , Kuske Nicolas , König Peter 
Published: January 2020

AbstractInvestigating spatial learning in virtual environments allows studying different sources of information under controlled conditions. We built a virtual environment in the style of a European village and investigated spatial knowledge acquisition by experience in the virtual environment and by the use of an interactive map. We tested knowledge of cardinal directions, building-to-building orientation, and judgment of direction between buildings. We find that judgment of directions was more accurate after virtual reality exploration than after map exploration, and the opposite results were observed for knowledge of cardinal directions and relative orientation between buildings. Further, the alignment effect was confined to the map exploration condition. Taken together, our results suggest that the source of spatial exploration differentially influenced spatial knowledge acquisition.
Increased resolution of African Swine Fever Virus genome patterns based on profile HMM protein domains
Authors: Masembe Charles , Phan My V.T. , Robertson David L. , Cotten Matthew 
Published: January 2020

ABSTRACTAfrican Swine Fever Virus (ASFV) was originally described in Africa almost 100 years ago and is now spreading uncontrolled across Europe and Asia and threatening to destroy the domestic pork industry. Neither effective antiviral drugs nor a protective vaccine are currently available. Efforts to understand the basis for viral pathogenicity and the development of attenuated potential vaccine strains are complicated by the large and complex ASFV genome. We report here a novel method of documenting viral diversity based on profile Hidden Markov Model domains on a genome scale. The method can be used to infer genomic relationships independent of genome alignments and also reveal ASFV genome sequence differences that alter the presence of functional protein domains in the virus. We show that the method can quickly identify differences and shared patterns between virulent and attenuated ASFV strains and will be a useful tool for developing much-needed vaccines and antiviral agents to help control this virus. The tool is rapid to run and easy to implement, readily available as a simple Docker image.
Avid binding by B cells to thePlasmodiumcircumsporozoite protein repeat suppresses responses to protective subdominant epitopes
Authors: Lewis Fiona J. , Chatterjee Deepyan , Kaczmarski Joe , Gao Xin , Cai Yeping , McNamara Hayley A. , Sutton Henry J. , Jackson Colin J. , Cockburn Ian A. 
Published: January 2020

AbstractAntibodies targeting the NANP/NVDP repeat domain of thePlasmodium falciparumcircumsporozoite protein (CSPRepeat) can confer protection against malaria. However, it has also been suggested that this repeat domain exists as a decoy that distracts the immune system from mounting protective responses targeting other domains of CSP. Here we show that B cell responses to the repeat domain are indeed ∼10 fold higher than responses to the N- and C-terminal regions of CSP after sporozoite immunization. We investigated the role of the number of CSPRepeat-specific naïve precursor B cells and high avidity binding by B cells in driving the immunodominance of the CSPRepeat. Using adoptive transfer of germline precursors specific for the CSPRepeat, we found that increasing precursor number did indeed increase the responses to the repeat region, but not to the detriment of responses to other epitopes. To investigate the role of avid binding by B cells to the CSPRepeatin driving immunodominance we generated CSP9: a truncated CSP molecule with just 9 NANP repeats. Compared to near full length CSP molecules, CSP9 induced lower BCR signalling in CSPRepeat-specific cells and induced stronger responses to non-repeat epitopes. Finally, we found mice immunized with CSP9 molecules were strongly protected against mosquito bite challenge. Collectively these data demonstrate that the CSPRepeatdoes function as an immunodominant decoy and that truncated CSP molecules may be a promising avenue for future malaria vaccines.Significance StatementMalaria kills approximately 420,000 individuals each year(1). Our best vaccine, RTS,S/AS01 is based on the circumsporozoite protein that coasts the surface of the parasite. However, this vaccine is only partially protective. Here we show that responses to a repeat region in the circumsporozoite dominate the immune response. However, immunizing with a circumsporozoite protein with a shortened repeat region induces a more diverse immune response, which could be an avenue to make better malaria vaccines.
Evaluating crystallographic likelihood functions using numerical quadratures
Authors: Zwart Petrus H. , Perryman Elliott D. 
Published: January 2020

AbstractIntensity-based likelihood functions in crystallographic applications have the potential to enhance the quality of structures derived from marginal diffraction data. Their usage however is complicated by the ability to efficiently compute these targets functions. Here a numerical quadrature is developed that allows for the rapid evaluation of intensity-based likelihood functions in crystallographic applications. By using a sequence of change of variable transformations, including a non-linear domain compression operation, an accurate, robust, and efficient quadrature is constructed. The approach is flexible and can incorporate different noise models with relative ease.
Shotgun Proteomics of non-depleted and depleted hemolymph of humanSchistosomiasis snail vector; Biomphalaria glabrata, revealed vital immune related proteins
Authors: Otarigho Benson , Falade Mofolusho , William Castro-Borges 
Published: January 2020

AbstractBackgroundBiomphalaria glabratais an important host in the transmission of human schistosomiasis in the Caribbean and South America. There are serious setbacks in the current control measures, hence need to explore alternatives.ObjectiveTo unveilBiomphalaria glabratahemolymph proteome for possible detailed knowledge of its immunity in host-pathogen relationship.MethodsIn this study we performed a shotgun proteomic and bioinformatic analyses of the non-depleted and depleted [0.5 and 0.75% Trifluoroacetic acid (TFA) depletion] hemolymph ofB. glabrata(LE strain).ResultsOur analysis was able to mine a total of 148 proteins from the hemolymph. The highest number of protein (148) was obtained from the 0.5% TFA-depleted sample, followed by 62 proteins from the 0.75% TFA-depleted sample and only 59 from non-depleted hemolymph.ConclusionMost of these proteins are novel and some of them may perform an important role in the immunity of this snail against invading pathogens.