bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous and Stimulus-Driven Rhythmic Behaviors in ADHD Adults and Controls
Authors: Amrani Anat Kliger , Golumbic Elana Zion 
Published: December 2019

AbstractMany aspects of human behavior are inherently rhythmic, requiring production of rhythmic motor actions as well as synchronizing to rhythms in the environment. It is well-established that individuals with ADHD exhibit deficits in temporal estimation and timing functions, which may impact their ability to accurately produce and interact with rhythmic stimuli. In the current study we seek to understand the specific aspects of rhythmic behavior that are implicated in ADHD. We specifically ask whether they are attributed to imprecision in the internal generation of rhythms or to reduced acuity in rhythm perception. We also test key predictions of the Preferred Period Hypothesis, which suggests that both perceptual and motor rhythmic behaviors are biased towards a specific personal ‘default’ tempo. To this end, we tested several aspects of rhythmic behavior and the correspondence between them, including spontaneous motor tempo (SMT), preferred auditory perceptual tempo (PPT) and synchronization-continuations tapping in a broad range of rhythms, from sub-second to supra-second intervals. Moreover, we evaluate the intra-subject consistency of rhythmic preferences, as a means for testing the reality and reliability of personal ‘default-rhythms’. We used a modified operational definition for assessing SMT and PPT, instructing participants to tap or calibrate the rhythms most comfortable for them to count along with, to avoid subjective interpretations of the task.Our results shed new light on the specific aspect of rhythmic deficits implicated in ADHD adults. We find that individuals with ADHD are primarily challenged in producing and maintaining isochronous self-generated motor rhythms, during both spontaneous and memory-paced tapping. However, they nonetheless exhibit good flexibility for synchronizing to a broad range of external rhythms, suggesting that auditory-motor entrainment for simple rhythms is preserved in ADHD, and that the presence of an external pacer allows overcoming their inherent difficulty in self-generating isochronous motor rhythms. In addition, both groups showed optimal memory-paced tapping for rhythms near their ‘counting-based’ SMT and PPT, which were slightly faster in the ADHD group. This is in line with the predictions of the Preferred Period Hypothesis, indicating that at least for this well-defined rhythmic behavior (i.e., counting), individuals tend to prefer similar time-scales in both motor production and perceptual evaluation.
Transcription levels of a long noncoding RNA orchestrate opposing regulatory and cell fate outcomes in yeast
Authors: Moretto Fabien , Wood N. Ezgi , Chia Minghao , Li Cai , Luscombe Nicholas M. , van Werven Folkert J. 
Published: December 2019

ABSTRACTMany long noncoding RNAs (lncRNAs) actin cisthrough transcription-coupled chromatin alterations that drive changes in local gene expression. How somecis-acting lncRNAs promote and others repress gene expression remains poorly understood. Here we report that inS. cerevisiaetranscription levels of the lncRNAIRT2, located upstream in the promoter of the inducer of meiosis gene, regulate opposing chromatin and transcription states. LowIRT2transcription displays enhancer RNA-like features. At these levels,IRT2promotes histone exchange delivering acetylated histone H3 lysine 56 to chromatin thereby facilitating recruitment of a transcription factor and consequently activating transcription. Conversely, increasingIRT2transcription enhances chromatin assembly and transcriptional repression. The opposing functions ofIRT2direct a regulatory circuit, which ensures that cells expressing opposite, but not one of either, mating-type loci enter meiosis. Our data demonstrate that the transcription levels of an lncRNA are key to controlling gene expression and cell fate outcomes.
CNV-BAC: Copy Number Variation Detection in Bacterial Circular Genome
Authors: Wu Linjie , Wang Han , Xia Yuchao , Xi Ruibin 
Published: December 2019

AbstractMotivationWhole genome sequencing (WGS) is widely used for copy number variation (CNV) detection. However, for most bacteria, their circular genome structure and high replication rate make reads more enriched near the replication origin. CNV detection based on read depth could be seriously influenced by such replication bias.ResultsWe show that the replication bias is widespread using ~200 bacterial WGS data. We develop CNV-BAC that can properly normalize the replication bias as well as other known biases in bacterial WGS data and can accurately detect CNVs. Simulation and real data analysis show that CNV-BAC achieves the best performance in CNV detection compared with available algorithms.Availability and implementationCNV-BAC is available athttps://github.com/LinjieWu/CNV-BAC.Contactruibinxi@math.pku.edu.cn
Haloperidol-induced impairment on working memory capacity affecting long term memory performance: the binding hypothesis
Authors: Guarnieri Regina V. , Alves Marcus Vinicius , Nogueira Ana Maria Lemos , de Souza Silva Tudesco Ivanda , Galduróz José Carlos F. , Covolan Luciene , Bueno Orlando F. A. 
Published: December 2019

AbstractThe dopaminergic system is implicated in several cognitive processes including memory, attention and executive functions. This study was a double-blind, placebo-randomized trial designed to investigate the effect of dopamine D2receptor blockade on episodic and working memory and particularly the relationship between executive functions, working memory capacity and long-term memory (LTM). Subjects ingested a single oral dose (4 mg) of haloperidol, a dopamine D2receptor antagonist or placebo. Multiple linear regression using generalized linear models and a generalized estimating equation were used for statistical analyses. The results demonstrated that haloperidol impaired episodic memory (free recall of words and prose recall), working memory capacity-WMC (operation span task-OSPAN) and highly demanding executive functions (random number generation - RNG). In addition, it demonstrated that despite the large impairment in the RNG task performance in the haloperidol group, it did not affect episodic memory. The OSPAN task is predictive of episodic memory impairment, suggesting that memory impairments produced by haloperidol could be due in part to the impairment of WMC. As WMC partly relies on the appropriate functioning of the medial temporal lobe, probably the haloperidol-induced impairment on episodic memory through the decrease in the performance of WMC may depend on the activation of this area of the brain. The present study is relevant because it provides data on dopaminergic modulation of memory systems; suggesting that the major cause of deficits in episodic memory may be due to hippocampal function and WMC impairments, the latter more specifically with regard to controlled search and binding.
Visual feature tuning of superior colliculus neural reafferent responses after fixational microsaccades
Authors: Khademi Fatemeh , Chen Chih-Yang , Hafed Ziad M. 
Published: December 2019

AbstractThe primate superior colliculus (SC) is causally involved in microsaccade generation. Moreover, visually-responsive SC neurons across this structure’s topographic map, even at peripheral eccentricities much larger than the tiny microsaccade amplitudes, exhibit significant modulations of evoked response sensitivity when stimuli appear peri-microsaccadically. However, during natural viewing, visual stimuli are normally stably present in the environment and are only shifted on the retina by eye movements. Here we investigated this scenario for the case of microsaccades, asking whether and how SC neurons respond to microsaccade-induced image jitter. We recorded neural activity from two male rhesus macaque monkeys. Within the response field (RF) of a neuron, there was a stable stimulus consisting of a grating of one of three possible spatial frequencies. The grating was stable on the display, but microsaccades periodically jittered the retinotopic RF location over it. We observed clear short-latency visual reafferent responses after microsaccades. These responses were weaker, but earlier (relative to new fixation onset after microsaccade end), than responses to sudden stimulus onsets without microsaccades. The reafferent responses clearly depended on microsaccade amplitude, as well as microsaccade direction relative to grating orientation. Our results indicate that one way for microsaccades to influence vision is through modulating how the spatio-temporal landscape of SC visual neural activity represents stable stimuli in the environment. Such representation strongly depends on the specific pattern of temporal luminance modulations expected from the relative relationship between eye movement vector (size and direction), on the one hand, and spatial visual pattern layout, on the other.Significance statementDespite being diminutive, microsaccades still jitter retinal images. We investigated how such jitter affects superior colliculus (SC) activity. We found that SC neurons exhibit short-latency visual reafferent bursts after microsaccades. These bursts reflect not only the spatial luminance profiles of visual patterns, but also how such profiles are shifted by eye movement size and direction. These results indicate that the SC continuously represents visual patterns, even as they are jittered by the smallest possible saccades.
Anterograde Trans-Synaptic AAV Strategies for Probing Neural Circuitry
Authors: Zingg Brian , Peng Bo , Huang Junxiang J. , Tao Huizhong W. , Zhang Li I. 
Published: December 2019

SummaryElucidating the organization and function of neural circuits is greatly facilitated by viral tools that spread transsynaptically. Adeno-associated virus (AAV) has been shown to exhibit anterograde transneuronal spread. However, the synaptic specificity of the spread and its broad application in various neural circuits remain to be explored. Here, using anatomical, functional, and molecular approaches, we provide strong evidence for the specifically preferential spread of AAV1 to post-synaptically connected neurons. Besides glutamatergic synapses made onto excitatory and inhibitory neurons, AAV1 also transsynaptically spreads through GABAergic synapses and effectively tags spinal cord neurons receiving long-distance projections from various brain regions, but exhibits little or no spread through neuromodulatory projections (e.g. serotonergic, cholinergic, and noradrenergic). Combined with newly designed intersectional and sparse labeling strategies, AAV1 can be utilized to categorize neurons according to their input sources, morphological and molecular identities. These properties make AAV a unique anterograde transsynaptic tool for establishing a comprehensive cell-atlas of the brain.
A Machine Learning Approach to the Recognition of Brazilian Atlantic Forest Parrot Species
Authors: Padovese Bruno Tavares , Padovese Linilson Rodrigues 
Published: December 2019

AbstractAvian survey is a time-consuming and challenging task, often being conducted in remote and sometimes inhospitable locations. In this context, the development of automated acoustic landscape monitoring systems for bird survey is essential. We conducted a comparative study between two machine learning methods for the detection and identification of 2 endangered Brazilian bird species from the Psittacidae species, theAmazona brasiliensisand theAmazona vinacea. Specifically, we focus on the identification of these 2 species in an acoustic landscape where similar vocalizations from other Psittacidae species are present. A 3-step approach is presented, composed of signal segmentation and filtering, feature extraction, and classification. In the feature extraction step, the Mel-Frequency Cepstrum Coefficients features were extract and fed to the Random Forest Algorithm and the Multilayer Perceptron for training and classifying acoustic samples. The experiments showed promising results, particularly for the Random Forest algorithm, achieving accuracy of up to 99%. Using a combination of signal segmentation and filtering before the feature extraction steps greatly increased experimental results. Additionally, the results show that the proposed approach is robust and flexible to be adopted in passive acoustic monitoring systems.
Object novelty and value coding segregate across functionally connected brain networks
Authors: Ghazizadeh Ali , Fakharian MohammadAmin , Amini Arash , Griggs Whitney , Leopold David A. , Hikosaka Okihide 
Published: December 2019

AbstractNovel and valuable objects are motivationally attractive for animals including primates. However, little is known about how novelty and value processing is organized across the brain. We used fMRI in macaques to map brain activity to fractal patterns varying in either novelty or value dimensions in the context of functionally connected brain networks determined at rest. Results show unique combinations of novelty and value coding across the brain networks. Networks in the ventral temporal cortex and in the parietal cortex showed preferential coding of novelty and value dimensions, respectively, while a wider network composed of temporal and prefrontal areas (TP network), along with functionally connected portions of the striatum, amygdala, and claustrum, responded to both dimensions with similar activation dynamics. Our results support emergence of a common currency signal in the TP network that may underlie the common attitudes toward novel and valuable objects.
Identifying triplex binding rulesin vitroleads to creation of a new synthetic regulatory toolin vivo
Authors: Kaufmann Beate , Willinger Or , Eden Noa , Kermas Lisa , Anavy Leon , Solomon Oz , Atar Orna , Yakhini Zohar , Goldberg Sarah , Amit Roee 
Published: December 2019

SummaryNature provides a rich toolbox of dynamic nucleic acid structures that are widespread in cells and affect multiple biological processes1. Recently, non-canonical structures gained renewed scientific and biotechnological interest2,3. One particularly intriguing form of such structures are triplexes4in which a single-stranded nucleic acid molecule interacts via Hoogsteen bonds with a DNA/RNA double helix5. Despite extensive researchin vitro6–9, the underlying rules for triplex formation remain debated and evidence for triplexesin vivois circumstantial10–12. Here, we demonstrate the development of a deep-sequencing platform termed Triplex-Seq to systematically refine the DNA triplex code and identify high affinity triplex forming oligo (TFO) variants. We identified a preference for short G-rich motifs using an oligo-library with a mix of all four bases. These high-information content motifs formed specific high-affinity triplexes in a pH-independent manner and stability was increased with G-rich double-stranded molecules. We then conjugated one high-affinity and one low-affinity variant to a VP48 peptide and studied these synthetic biomolecules in mammalian cells. Using these peptide-oligo constructs (POCs), we demonstrated possible triplex-induced down-regulation activity in 544 differentially expressed genes. Our results show that deep-sequencing platforms can substantially expand our understanding of triplex binding rules, which in turn has led to the development of a functional non-genetically encoded regulatory tool forin vivoapplications.
Elaboration of the corticosteroid synthesis pathway in primates through a multi-step enzyme
Authors: Olson-Manning Carrie F. 
Published: December 2019

AbstractMetabolic networks are complex cellular systems dependent on the interactions among, and regulation of, the enzymes in the network. However, the mechanisms that lead to the expansion of networks are not well understood. While gene duplication is a major driver of the expansion and functional evolution of metabolic networks, the effect and fate of retained duplicates in a network is poorly understood. Here, I study the evolution of an enzyme family that performs multiple subsequent enzymatic reactions in the corticosteroid pathway in primates to illuminate the mechanisms that shape network components following duplication. The products of the pathway (aldosterone, corticosterone, and cortisol) are steroid hormones that regulate metabolism and stress in tetrapods. These steroids are synthesized by a multi-step enzyme Cytochrome P450 11B (CYP11B) that performs subsequent steps on different carbon atoms of the steroid derivatives. Through ancestral state reconstruction andin vitrocharacterization, I find the ancestor of the CYP11B1 and CYP11B2 paralogs (in primates) had moderate ability to synthesize cortisol and aldosterone. Following duplication in the primate lineage the CYP11B1 homolog specialized on the production of cortisol while its paralog, CYP11B2, maintained its ability to perform multiple subsequent steps as in the ancestral pathway. Unlike CYP11B1, CYP11B2 could not specialize on the production of aldosterone because it is constrained to perform earlier steps in the corticosteroid synthesis pathway to achieve the final product aldosterone. These results suggest that pathway context, along with tissue-specific regulation, both play a role in shaping potential outcomes of metabolic network elaboration.
Multi-Parametric Profiling of Endothelial Cell Networks Reveals Functional Role of Glutamate Receptors in Angiogenesis
Authors: Sailem Heba Z. , Haj Zen Ayman Al 
Published: December 2019

AbstractAngiogenesis plays a key role in several diseases including cancer, ischemic vascular disease, and Alzheimer’s disease. High throughput screening of endothelial tube formation provides a robust approach for identifying drugs that impact microvascular network formation and morphology. However, the analysis of resulting imaging datasets has been limited to a few phenotypic features such as the total tube length or the number of branching points. Here we developed a high content analysis framework for detailed quantification of various aspects of network morphology including network complexity, symmetry and topology. By applying our approach to a high content screen of 1,280 drugs, we found that many drugs that result in a similar phenotype share the same mechanism of action or common downstream signalling pathways. Our multiparametric analysis revealed a group of drugs, that target glutamate receptors, results in enhanced branching and network connectivity. Using an integrative meta-analysis approach, we validated the link between these receptors and angiogenesis. We further found that the expression of these genes correlates with the prognosis of Alzheimer’s patients. In conclusion, our work shows that detailed image analysis of complex endothelial phenotypes can reveal new insights into biological mechanisms modulating the morphogenesis of endothelial networks and identify potential therapeutics for angiogenesis-related diseases.
A Novel Chloroplast Super-Complex Consisting of the ATP Synthase and Photosystem I Reaction Center
Authors: Bhaduri Satarupa , Singh Sandeep K , Cohn Whitaker , Saif Hasan S. , Whitelegge Julian P. , Cramer William A. 
Published: December 2019

AbstractSeveral ‘super-complexes’ of individual hetero-oligomeric membrane protein complexes, whose function is to facilitate intra-membrane electron and proton transfer and harvesting of light energy, have been previously characterized in the mitochondrial cristae and chloroplast thylakoid membranes. The latter membrane is reported here to also be the location of an intra-membrane super-complex which is dominated by the ATP-synthase and photosystem I (PSI) reaction-center complexes, defined by mass spectrometry, clear-native PAGE and Western Blot analyses. This is the first documented presence of ATP synthase in a super-complex with the PSI reaction-center located in the non-appressed stromal domain of the thylakoid membrane.
Exploring the Conformational Transition Between the Fully Folded and Locally Unfolded Substates of theEscherichia colithiol peroxidase
Authors: Vazquez Diego S. , Zeida Ari , Agudelo William A. , Montes Mónica , Ferrer-Sueta Gerardo , Santos Javier 
Published: December 2019

AbstractThiol peroxidase fromEscherichia coli(EcTPx) is a peroxiredoxin that catalyzes the reduction of different hydroperoxides. During the catalytic cycle ofEcTPx, the peroxidatic cysteine (CP) is oxidized to a sulfenic acid by peroxide, then the resolving cysteine (CR) condenses with the sulfenic acid of CPto form a disulfide bond, which is finally reduced by thioredoxin. PurifiedEcTPx as dithiol and disulfide behaves as a monomer in close to physiological conditions. Although secondary structure rearrangements are present when comparing different redox states of the enzyme, no significant differences in unfolding free energies are observed under reducing and oxidizing conditions. A conformational change denominatedfully folded (FF) to locally unfolded (LU) transition, involving a partial unfolding of αH2 and αH3 helices, must occur to enable the formation of the disulfide bond since the catalytic cysteines are 12 Å apart in the FF conformation ofEcTPx. To explore this crucial process, the mechanism of the FF→LU and the LU→FF transitions were studied using long time scale conventional molecular dynamic simulations and an enhanced conformational sampling technique for different oxidation and protonation states of CPand/or CR. Our results suggest that the FF→LU transition has a higher associated energy barrier than the refolding LU→FF process in agreement with the relatively slow experimental turnover number ofEcTPx. Furthermore,in silicodesigned single-point mutants of the αH3 enhanced locally unfolding events, suggesting that the native FF interactions in the active site are not evolutionary optimized to fully speed-up the conformational transition of wild-typeEcTPx.
Opponent regulation of action performance and timing by striatonigral and striatopallidal pathways
Authors: Bakhurin Konstantin I. , Li Xiaoran , Friedman Alexander D. , Lusk Nicholas A. , Watson Glenn D.R. , Kim Namsoo , Yin Henry H. 
Published: December 2019

AbstractThe basal ganglia have been implicated in action selection and timing, but the relative contributions of the striatonigral (direct) and striatopallidal (indirect) pathways to these functions remain unclear. We investigated the effects of optogenetic stimulation of D1+ (direct) and A2A+ (indirect) neurons in the ventrolateral striatum in head-fixed mice on a fixed time reinforcement schedule. Direct pathway stimulation initiates licking, whereas indirect pathway stimulation suppresses licking and results in rebound licking after stimulation. Moreover, direct and indirect pathways also play distinct roles in timing. Direct pathway stimulation produced a resetting of the internal timing process, whereas indirect pathway stimulation transiently paused timing, and proportionally delayed the next bout of licking. Our results provide evidence for the continuous and opposing contributions of the direct and indirect pathways in the production and timing of reward-guided behavior.