bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plastid genomics of Nicotiana (Solanaceae): insights into molecular evolution, positive selection and the origin of the maternal genome of Aztec tobacco (Nicotiana rustica)
Authors: Mehmood Furrukh , Abdullah  , Ubaid Zartasha , Shahzadi Iram , Ahmed Ibrar , Waheed Mohammad Tahir , Poczai Péter , Mirza Bushra 
Published: January 2020

AbstractThe genus Nicotiana of the family Solanaceae, commonly referred to as tobacco plants, are a group cultivated as garden ornamentals. Besides their use in the worldwide production of tobacco leaves, they are also used as evolutionary model systems due to their complex development history, which is tangled by polyploidy and hybridization. Here, we assembled the plastid genomes of five tobacco species, namely N. knightiana, N. rustica, N. paniculata, N. obtusifolia and N. glauca. De novo assembled tobacco plastid genomes showed typical quadripartite structure, consisting of a pair of inverted repeats (IR) regions (25,323–25,369 bp each) separated by a large single copy (LSC) region (86,510 –86,716 bp) and a small single copy (SSC) region (18,441–18,555 bp). Comparative analyses of Nicotiana plastid genomes showed similar GC content, gene content, codon usage, simple sequence repeats, oligonucleotide repeats, RNA editing sites and substitutions with currently available Solanaceae genomes sequences. We identified twenty highly polymorphic regions mostly belonging to intergenic spacer regions (IGS), which could be appropriate for the development of robust and cost-effective markers to infer the phylogeny of genus Nicotiana and family Solanaceae. Our comparative plastid genome analysis revealed that the maternal parent of the tetraploid N. rustica was the common ancestor of N. paniculata and N. knightiana, and the later species is more closely related to N. rustica. The relaxed molecular clock analyses estimated that the speciation event between N. rustica and knightiana appeared 0.56 Ma (HPD 0.65–0.46). The biogeographical analysis showed a south-to-north range expansion and diversification for N. rustica and related species, where N. undulata and N. paniculata evolved in North/Central Peru, while N. rustica developed in Southern Peru and separated from N. knightiana, which adapted to the Southern coastal climatic regimes. We further inspected selective pressure on protein-coding genes among tobacco species to determine if this adaptation process affected the evolution of plastid genes. These analyses indicated that four genes involved in different plastid functions, such as DNA replication (rpoA) and photosynthesis (atpB, ndhD and ndhF), came under positive selective pressure as a result of specific environmental conditions. Genetic mutations of the following genes might have contributed to the survival and better adaptation during the evolutionary history of tobacco species.
Characterizing dysbiosis of gut microbiome in PD: Evidence for overabundance of opportunistic pathogens
Authors: Wallen Zachary D , Appah Mary , Dean Marissa N , Sesler Cheryl L , Factor Stewart A , Molho Eric , Zabetian Cyrus P , Standaert David G , Payami Haydeh 
Published: January 2020

AbstractIn Parkinson’s disease (PD), gastrointestinal features are common and often precede the motor signs. Braak and colleagues proposed that PD may start in the gut, triggered by a pathogen, and spread to the brain. Numerous studies have examined the gut microbiome in PD, all found it to be altered, but found inconsistent results on associated microorganisms. Studies to date have been small (N=20 to 306) and are difficult to compare or combine due to varied methodology. We conducted a microbiome-wide association study (MWAS) with two large datasets for internal replication (N=333 and 507). We used uniform methodology when possible, interrogated confounders, and applied two statistical tests for concordance, followed by correlation network analysis to infer interactions. Fifteen genera were associated with PD at a microbiome-wide significance level, in both datasets, with both methods, with or without covariate adjustment. The associations were not independent, rather represented 3 clusters of co-occurring microorganisms. Cluster 1 was composed of opportunistic pathogens; all were elevated in PD. Cluster 2 were short-chain-fatty-acid producing bacteria; all were reduced in PD. Cluster 3 were carbohydrate-metabolizing probiotics; elevated in PD. Depletion of anti-inflammatory short-chain-fatty-acid producing bacteria and elevated levels of probiotics are confirmatory. Overabundance of opportunistic pathogens is a novel finding and their identity provides a lead to experimentally test their role in PD.
Regulation of perceptual learning by chronic chemogenetic manipulation of parvalbumin-positive interneurons
Authors: Cisneros-Franco J. Miguel , Thomas Maryse E. , Regragui Itri , Lane Conor P. , Ouellet Lydia , de Villers-Sidani Étienne 
Published: January 2020

AbstractParvalbumin-positive (PV+) interneurons are major regulators of adult experience-dependent plasticity. Acute manipulation of PV+ cell activity before learning alters the rate of acquisition of new skills, whereas transient inactivation of PV+ cells interferes with retrieval of previously learned information. However, the effects of sustained PV+ cell manipulation throughout training remain largely unknown. Using chemogenetics in rat auditory cortex during an adaptive sound disrimination task, here we show that PV+ cells exert bidirectional control over the rate of perceptual learning. Down-regulation of PV+ cell activity accelerated learning, but increasing their activity resulted in slower learning. However, both interventions led to reduced gains in perceptual acuity by the end of training relative to controls. Furthermore, longitudinal training performance was functionally correlated with measures of neural synchrony and stimulus-specific adaptation. These findings suggest that, whereas restricting PV+ cell activity may initially facilitate training-induced plasticity, a subsequent increase in PV+ cell activity is necessary to prevent further plastic changes and consolidate learning.
Hypercluster: a python package and SnakeMake pipeline for flexible, parallelized unsupervised clustering optimization
Authors: Blumenberg Lili , Ruggles Kelly V. 
Published: January 2020

AbstractUnsupervised clustering is a common and exceptionally useful tool for large biological datasets. However, clustering requires upfront algorithm and hyperparameter selection, which can introduce bias into the final clustering labels. It is therefore advisable to obtain a range of clustering results from multiple models and hyperparameters, which can be cumbersome and slow. To streamline this process, we present hypercluster, a python package and SnakeMake pipeline for flexible and parallelized clustering evaluation and selection. Hypercluster is available on bioconda; installation, documentation and example workflows can be found at:https://github.com/ruggleslab/hypercluster.Author summaryUnsupervised clustering is a technique for grouping similar samples within a dataset. It is extremely common when analyzing big data from patient samples, or high throughput techniques like single cell RNA-seq. When researchers use unsupervised clustering, they have to select parameters that affect the final result—for instance, how many groups they expect to find or what the smallest group is allowed to be. Some methods require setting even less intuitive parameters. For most applications, it is extremely challenging to guess what the values of these parameters should be; therefore to prevent introducing bias into the final results, researchers should test many different parameters and methods to find the best groups. This process is cumbersome, slow and challenging to perform in a reproducible way. We developed hypercluster, a tool that automates this process, make it much faster, and presenting the results in a reproducible and helpful manner.
Protein Corona Composition and Dynamics on Carbon Nanotubes in Blood Plasma and Cerebrospinal Fluid
Authors: Pinals Rebecca L. , Yang Darwin , Rosenberg Daniel J. , Chaudhary Tanya , Crothers Andrew R. , Iavarone Anthony T. , Hammel Michal , Landry Markita P. 
Published: January 2020

AbstractWhen a nanoparticle enters a biological environment, the surface is rapidly coated with proteins to form a “protein corona”. Presence of the protein corona surrounding the nanoparticle has significant implications for applying nanotechnologies within biological systems, affecting outcomes such as biodistribution and toxicity. Herein, we measure protein corona formation on single-stranded DNA wrapped single-walled carbon nanotubes (ssDNA-SWCNTs), a high-aspect ratio nanoparticle ideal for sensing and delivery applications, and polystyrene nanoparticles, a model nanoparticle system. The protein corona of each nanoparticle is studied in human blood plasma and cerebrospinal fluid. We characterize corona composition by proteomic mass spectrometry to determine abundant and differentially enriched vs. depleted corona proteins. High-binding corona proteins on ssDNA-SWCNTs include proteins involved in lipid binding and transport (clusterin and apolipoprotein A-I), complement activation (complement C3), and blood coagulation (fibrinogen). Of note, albumin is the most common blood protein (55% w/v), yet exhibits low-binding affinity towards ssDNA-SWCNTs, displaying 1300-fold lower bound concentration relative to native plasma. We investigate the role of electrostatic and entropic interactions driving selective protein corona formation, and find that hydrophobic interactions drive inner corona formation, while shielding of electrostatic interactions allows for outer corona formation. Lastly, we study real-time binding of proteins on ssDNA-SWCNTs and find relative agreement between proteins that are enriched and bind strongly, such as fibrinogen, and proteins that are depleted and bind marginally, such as albumin. Interestingly, certain proteins express contrary behavior in single-protein experiments than within the whole biofluid, highlighting the importance of cooperative mechanisms driving selective corona adsorption on the SWCNT surface. Knowledge of the protein corona composition, dynamics, and structure informs translation of engineered nanoparticles fromin vitrodesign to effectivein vivoapplication.
Intraspinal stimulation with silicon-based 3D microelectrode array for bladder voiding in cats before and after spinal cord injury
Authors: Pikov Victor , McCreery Douglas B. , Han Martin 
Published: January 2020

AbstractBladder dysfunction is a significant and largely unaddressed problem for people living with spinal cord injury. Intermittent catheterization does not provide volitional control of micturition and has numerous side effects. Targeted electrical microstimulation of the spinal cord has been previously explored for restoring such volitional control in the animal model of experimental spinal cord injury. In this study, the development of the intraspinal microstimulation array technology was continued and evaluated in the feline animal model for its ability to provide more focused and reliable bladder control after a complete spinal cord transection. For the first time, the intraspinal multisite silicon array wad built using novel microfabrication processes to provide custom-designed tip geometry and 3D electrode distribution, better cost efficiency, reproducibility, scalability, and on-the-probe integration of active electronics. Long-term implantation was performed in 8 animals for a period up to 6 months, targeting the dorsal gray commissure area in the S1 sacral cord that is known to be involved in the coordination between the bladder detrusor and the external urethral sphincter. About one third of the electrode sites in the that area produced micturition-related responses. The effectiveness of stimulation increased starting from one month after spinal cord transection (as evaluated in one animal), likely due to supraspinal disinhibition of the spinal circuitry and/or hypertrophy and hyperexcitability of the spinal bladder afferents. Further studies are required to assess longer-term reliability of the developed intraspinal microstimulation array technology in preparation for eventual human translation.
BNrich: A Bayesian network approach to the pathway enrichment analysis
Authors: Maleknia Samaneh , Sharifi-Zarchi Ali , Tabar Vahid Rezaei , Namazi Mohsen , Kavousi Kaveh 
Published: January 2020

AbstractMotivationOne of the most popular techniques in biological studies for analyzing high throughput data is pathway enrichment analysis (PEA). Many researchers apply the existing methods without considering the topology of pathways or at least they have overlooked a significant part of the structure, which may reduce the accuracy and generalizability of the results. Developing a new approach while considering gene expression data and topological features like causal relations regarding edge directions will help the investigators to achieve more accurate results.ResultsWe proposed a new pathway enrichment analysis based on Bayesian network (BNrich) as an approach in PEA. To this end, the cycles were eliminated in 187 KEGG human signaling pathways concerning intuitive biological rules and the Bayesian network structures were constructed. The constructed networks were simplified by the Least Absolute Shrinkage Selector Operator (LASSO), and their parameters were estimated using the gene expression data. We finally prioritize the impacted pathways by Fisher’s Exact Test on significant parameters. Our method integrates both edge and node related parameters to enrich modules in the affected signaling pathway network. In order to evaluate the proposed method, consistency, discrimination, false positive rate and empirical P-value criteria were calculated, and the results are compared to well-known enrichment methods such as signaling pathway impact analysis (SPIA), bi-level meta-analysis (BLMA) and topology-based pathway enrichment analysis (TPEA).AvailabilityThe R package is available oncarn.
Varying co-factor requirements for MAML1-dependent transcription at different Notch-responsive target genes
Authors: Rogers Julia M. , Guo Bingqian , Egan Emily D. , Aster Jon C. , Adelman Karen , Blacklow Stephen C. 
Published: January 2020

AbstractMastermind proteins are required for transcription of Notch target genes, yet the molecular basis for mastermind function remains incompletely understood. Previous work has shown that Notch can induce transcriptional responses by binding to promoters, but more often by binding to enhancers, with HES4 and DTX1 as representative mammalian examples of promoter and enhancer responsiveness, respectively. Here, we show that mastermind dependence of the Notch response at these loci is differentially encoded in Jurkat T-ALL cells. Knockout of Mastermind-like1 (MAML1) eliminates Notch responsive activation of both these genes, and reduced target gene expression is accompanied by a decrease in H3K27 acetylation, consistent with the importance of MAML1 for p300 activity. Add-back of defined MAML1 constructs in knockout cells identifies residues 151-350 of MAML1 as essential for expression of either Notch-responsive gene. Fusion of the Notch-binding region of MAML1 to the HAT domain of p300 rescues expression of HES4 but not DTX1, suggesting that an additional activity of MAML1 is needed for gene induction at a distance. Together, these studies establish the functional importance of the MAML1151-350 region for Notch-dependent transcriptional induction, and reveal differential requirements for MAML1-dependent recruitment activities at different Notch responsive loci, highlighting the molecular complexity of NTC-stimulated transcription.
Loss of the Er81 Transcription Factor in Cholinergic Cells Alters Striatal Activity and Habit Formation
Authors: Ranjbar-Slamloo Yadollah , Ahmed Noorya Yasmin , Al Abed Alice Shaam , Gao Lingxiao , Sontani Yovina , Gauthier Alexandre R’Com-H Cheo , Arabzadeh Ehsan , Dehorter Nathalie 
Published: January 2020

SUMMARYThe finely-tuned activity of cholinergic interneurons (CINs) in the striatum is key for motor control, learning, and habit formation. Yet, the molecular mechanisms that determine their unique functional properties remain poorly explored. Using a combination of genetic and biochemical assays,in vitroandin vivophysiological characterisation, we report that selective ablation of the Er81 transcription factor leads to prominent changes in CIN molecular, morphological and electrophysiological features. In particular, the lack of Er81 amplifies intrinsic delayed-rectifier and hyperpolarization-activated currents, which subsequently alters the tonic and phasic activity of CINs. We further demonstrate that these alterations enhance their pause and time-locked responses to sensorimotor inputs in awake mice. Finally, this study reveals an Er81-dependent developmental mechanism in CINs essential for habit formation in adult mice.Highlights- The Er81 transcription factor is expressed in striatal cholinergic interneurons (CINs)- Conditional deletion of Er81 alters key molecular, morphological and electrophysiological properties of CINs in adult mice- Deletion of Er81 reduces the intrinsic excitability of CINs by upregulating delayed rectifier and hyperpolarization-activated currents- Deletion of Er81 altersin vivostriatal activity and habit formation
The origin of domestication genes in goats
Authors: Zheng Zhuqing , Wang Xihong , Li Ming , Li Yunjia , Yang Zhirui , Wang Xiaolong , Pan Xiangyu , Gong Mian , Zhang Yu , Guo Yingwei , Wang Yu , Liu Jing , Cai Yudong , Chen Qiuming , Okpeku Moses , Colli Licia , Cai Dawei , Wang Kun , Huang Shisheng , Sonstegard Tad S. , Esmailizadeh Ali , Zhang Wenguang , Zhang Tingting , Xu Yangbin , Xu Naiyi , Yang Yi , Han Jianlin , Chen Lei , Lesur Joséphine , Daly Kevin G. , Bradley Daniel G. , Heller Rasmus , Zhang Guojie , Wang Wen , Chen Yulin , Jiang Yu 
Published: January 2020

AbstractGoat domestication was critical for agriculture and civilization, but its underlying genetic changes and selection regimes remain unclear. Here we analyze the genomes of worldwide domestic goats, wild caprid species and historical remains, providing evidence of an ancient introgression event from a West Caucasian tur-like species to the ancestor of domestic goats. One introgressed locus with a strong signature of selection harbors the MUC6 gene which encodes a gastrointestinally secreted mucin. Experiments revealed that the nearly fixed introgressed haplotype confers enhanced immune resistance to gastrointestinal pathogens. Another locus with a strong signal of selection may be related to behavior. The selected alleles at these two loci emerged in domestic goats at least 7,200 and 8,100 years ago, respectively, and increased to high frequencies concurrent with the expansion of the ubiquitous modern mitochondrial haplogroup A. Tracking these archaeologically cryptic evolutionary transformations provides new insights into the mechanism of animal domestication.One Sentence SummaryGoat domestication mainly focused on immune and neural genes, with adaptive leaps driven by introgression and selection.
A Pathway and Network Oriented Approach to Enlighten Molecular Mechanisms of Type 2 Diabetes Using Multiple Association Studies
Authors: Bakir-Gungor Burcu , Yazici Miray Unlu , Goy Gokhan , Temiz Mustafa 
Published: January 2020

AbstractDiabetes Mellitus (DM) is a group of metabolic disorder that is characterized by pancreatic dysfunction in insulin producing beta cells, glucagon secreting alpha cells, and insulin resistance or insulin in-functionality related hyperglycemia. Type 2 Diabetes Mellitus (T2D), which constitutes 90% of the diabetes cases, is a complex multifactorial disease. In the last decade, genome-wide association studies (GWASs) for type 2 diabetes (T2D) successfully pinpointed the genetic variants (typically single nucleotide polymorphisms, SNPs) that associate with disease risk. However, traditional GWASs focus on the ‘the tip of the iceberg’ SNPs, and the SNPs with mild effects are discarded. In order to diminish the burden of multiple testing in GWAS, researchers attempted to evaluate the collective effects of interesting variants. In this regard, pathway-based analyses of GWAS became popular to discover novel multi-genic functional associations. Still, to reveal the unaccounted 85 to 90% of T2D variation, which lies hidden in GWAS datasets, new post-GWAS strategies need to be developed. In this respect, here we reanalyze three meta-analysis data of GWAS in T2D, using the methodology that we have developed to identify disease-associated pathways by combining nominally significant evidence of genetic association with the known biochemical pathways, protein-protein interaction (PPI) networks, and the functional information of selected SNPs. In this research effort, to enlighten the molecular mechanisms underlying T2D development and progress, we integrated different in-silico approaches that proceed in top-down manner and bottom-up manner, and hence presented a comprehensive analysis at protein subnetwork, pathway, and pathway subnetwork levels. Our network and pathway-oriented approach is based on both the significance level of an affected pathway and its topological relationship with its neighbor pathways. Using the mutual information based on the shared genes, the identified protein subnetworks and the affected pathways of each dataset were compared. While, most of the identified pathways recapitulate the pathophysiology of T2D, our results show that incorporating SNP functional properties, protein-protein interaction networks into GWAS can dissect leading molecular pathways, which cannot be picked up using traditional analyses. We hope to bridge the knowledge gap from sequence to consequence.