bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risperidone Combination Therapy With Propentofylline for Treatment of Irritability in Autism Spectrum Disorders: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Behmanesh Helen , Moghaddam Hossein Sanjari , Mohammadi Mohammad-Reza , Akhondzadeh Shahin 
Published: November 2019

Objectives
Propentofylline is a xanthine phosphodiesterase inhibitor and adenosine reuptake blocker with neuroprotective effects linked to anti-inflammatory and antiexcitatory properties. This is a double-blind, placebo-controlled trial investigating the potential beneficial effects of propentofylline, as an adjunctive treatment with risperidone, on the severity and behavioral abnormalities of autism spectrum disorder (ASD).

Methods
A total of 48 children with ASD were randomly allocated into 2 groups of risperidone (initiating at 0.5 mg/d) plus propentofylline (initiating at 300 mg/d) and risperidone plus placebo. The Aberrant Behavior Checklist—Community (ABC-C) and Childhood Autism Rating Scale (CARS) were used for the evaluation of ASD severity and behavioral disruptions at baseline, week 4, and week 10. Primary outcome measure of the study was ABC-C irritability subscale score, whereas CARS score along with other 4 subscales of ABC-C (lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech subscales) were considered as secondary outcome measures.

Results
Results from the general linear model repeated measures analysis demonstrated significant time-treatment interaction on irritability subscale (F
1.55 = 3.45; P = 0.048) and CARS (F
1.41 = 4.08; P = 0.034) scores. Compared with the placebo group, children receiving propentofylline showed greater improvements in the CARS score (P = 0.037) from baseline to the study endpoint. Our results found no significant time-treatment effect on other subscales of ABC-C. Two trial groups were comparable based on the frequency of adverse effects.

Conclusions
Our findings demonstrated that adjunctive treatment with propentofylline is effective in alleviating disease severity and improving irritability in ASD patients. However, larger studies with longer durations are required to confirm these results.
Efficacy and Placebo Response of Multimodal Treatments for Primary Insomnia: A Network Meta-Analysis
Authors: Jiang Binghu , He Dongmei , Gao Zhanhui 
Published: November 2019

Background
Pharmacotherapy, psychotherapy, and complementary therapy have been used for primary insomnia. However, the efficacy and placebo response are not exactly clear because of limited clinical data. We therefore conducted a systematic review to examine the efficacy and placebo response of multimodal treatments.

Methods
We performed a comprehensive literature search for randomized placebo-controlled clinical trials evaluating the efficacy of multimodal treatments addressing primary insomnia. To pool effect size estimates (Hedges' g) of active and placebo conditions across studies for outcome measures, a meta-analysis was done according to the Cochrane guideline.

Results
The results of network meta-analysis for sleep efficiency showed that orexin receptor antagonists had the maximum effect size of 1.35 (95% confidence interval [CI], 0.88–1.82), followed by γ-aminobutyric acid agonists of 1.28 (95% CI, 0.85–1.71), cognitive behavioral therapy for insomnia of 1.07 (95% CI, 0.10–2.05), acupuncture of 0.64 (95% CI, −0.17 to 2.36), and repetitive transcranial magnetic stimulation of 0.61 (95% CI, −0.52 to 1.75), respectively. However, the placebo response was also significant and robust to improve insomnia symptoms, and 65.9% (95% CI, 49.3%–82.5%) of the effect size of multimodal treatments was actually produced by placebo conditions.

Conclusions
The pharmacotherapy seems the most effective in improving sleep efficiency. However, the optimal therapeutic regimen is still uncertain. In addition, the placebo response is significant and robust in treatments of primary insomnia.
Identification of suitable reference genes for qPCR expression analysis on the gonads of the invasive mussel Limnoperna fortunei
Authors: Americo Juliana Alves , Guerreiro Luana Tatiana Albuquerque , Gondim Tayssa Santos , da Cunha Yasmin Rodrigues , Wajsenzon Inês Julia Ribas , Afonso Luana Ferreira , Soares-Souza Giordano Bruno , de Freitas Rebelo Mauro 
Published: November 2019

AbstractLimnoperna fortunei — popularly known as the Golden mussel — is an aggressive invasive species that has been causing environmental damage and adversely affecting economic sectors dependent on freshwater ecosystems in South America. As a non-model species, knowledge about its biology is very limited, especially molecular mechanisms that contribute to its invasiveness, such as its high reproduction rate. Quantitative PCR (qPCR) is considered the gold standard technique to determine gene expression levels and its accuracy relies on the use of stably expressed reference genes for data normalization and to minimize technical variability. Our goal was to identify reliable reference genes to perform gene expression analysis on the gonads of L. fortunei. The stability of five candidate genes (RPS3, EF1a, HS6ST3B, NAPA and UBE2F) in the gonads of male and female mussels was evaluated by using two algorithms, Bestkeeper and Genorm. Results show that NAPA, UBE2F and RPS3 genes are stable enough to compose a reliable normalization factor for gene expression analyses comparing both sexes. HS6ST3B and NAPA were found to be more stable in female gonads; thus, their application as a normalization factor is preferable for studies limited to female processes only.
Neuronal identity is maintained in the adult brain through KAT3-dependent enhancer acetylation
Authors: Lipinski Michal , Muñoz-Viana Rafael , del Blanco Beatriz , Medrano-Relinque Juan , Marquez-Galera Angel , Carames Jose M. , Szczepankiewicz Andrzej A. , Fernandez-Albert Jordi , Navarrón Carmen M. , Olivares Roman , Wilczynski Grzegorz M. , Canals Santiago , Lopez-Atalaya Jose P. , Barco Angel 
Published: November 2019

ABSTRACTVery little is known about the mechanisms responsible for maintaining cell identity in mature tissues. The paralogous type 3 lysine acetyltransferases (KAT3) CBP and p300 are both essential during development, but their specific functions in nondividing differentiated cells remains unclear. Here, we show that when both proteins are simultaneously knocked-out in excitatory neurons of the adult brain, the mice express a rapidly progressing neurological phenotype associated with reduced dendritic complexity and electrical activity, the transcriptional shutdown of neuronal genes, and a dramatic loss of H3K27 acetylation and pro-neural transcription factor binding at neuronal enhancers. The neurons lacking both KAT3 rapidly acquire a molecularly undefined fate with no sign of dedifferentiation, transdifferentiation or death. Restoring CBP expression or lysine acetylation reestablished neuronal-specific transcription. Our experiments demonstrate that KAT3 proteins act as fate-keepers in excitatory neurons and other cell types by jointly safeguarding chromatin acetylation levels at cell type-specific enhancers throughout life.
Antithetic integral feedback for the robust control of monostable and oscillatory biomolecular circuits
Authors: Olsman Noah , Forni Fulvio 
Published: November 2019

AbstractBiomolecular feedback systems are now a central application area of interest within control theory. While classical control techniques provide valuable insight into the function and design of both natural and synthetic biomolecular systems, there are certain aspects of biological control that have proven difficult to analyze with traditional methods. To this end, we describe here how the recently developed tools of dominance analysis can be used to gain insight into the nonlinear behavior of the antithetic integral feedback circuit, a recently discovered control architecture which implements integral control of arbitrary biomolecular processes using a simple feedback mechanism. We show that dominance theory can predict both monostability and periodic oscillations in the circuit, depending on the corresponding parameters and architecture. We then use the theory to characterize the robustness of the asymptotic behavior of this circuit in a nonlinear setting.
Hippocampal ensembles represent sequential relationships among discrete nonspatial events
Authors: Shahbaba Babak , Li Lingge , Agostinelli Forest , Saraf Mansi , Elias Gabriel A. , Baldi Pierre , Fortin Norbert J. 
Published: November 2019

ABSTRACTThe hippocampus is critical to the temporal organization of our experiences, including the ability to remember past event sequences and predict future ones. Although this fundamental capacity is conserved across modalities and species, its underlying neuronal mechanisms remain poorly understood. Here we recorded hippocampal ensemble activity as rats remembered a sequence of nonspatial events (5 odor presentations unfolding over several seconds), using a task with established parallels in humans. Using novel statistical methods and deep learning techniques, we then identified new forms of sequential organization in hippocampal activity linked with task performance. We discovered that sequential firing fields (“time cells”) provided temporal information within and across events in the sequence, and that distinct types of task-critical information (stimulus identity, temporal order, and trial outcome) were also sequentially differentiated within event presentations. Finally, as previously only observed with spatial information, we report that the representations of past, present and future events were sequentially activated within individual event presentations, and that these sequential representations could be compressed within an individual theta cycle. These findings strongly suggest that a fundamental function of the hippocampal network is to encode and preserve the sequential order of experiences, and use these representations to generate predictions to inform decision-making.
Whole Genome Sequencing and Assembly of the Asian Honey BeeApis dorsata
Authors: Oppenheim Sara , Cao Xiaolong , Rueppel Olav , Chantawannakul Panuwan , Krongdang Sasiprapa , Phokasem Patcharin , DeSalle Rob , Goodwin Sara , Xing Jinchuan , Rosenfeld Jeffrey 
Published: November 2019

AbstractThe Asian honey bee (Apis dorsata)is distinct from its more widely distributed cousinA. melliferaby a few key characteristics. Most prominently,A. dorsata, nest in the open by forming a colony clustered around the honeycomb, whileA. melliferanest in concealed cavities. Additionally, the worker and reproductive castes are all of the same size inA. dorsata. In order to investigate these differences, we performed whole genome sequencing ofA. dorsatausing a hybrid Oxford Nanopore and Illumina approach. The 223MB genome has an N50 of 35kb with the largest scaffold of 302kb. We have found that there are many genes in thedorsatagenome that are distinct from other hymenoptera and also large amounts of transposable elements, and we suggest some candidate genes forA. dorsata’s exceptional level of defensive aggression.
SOLQC : Synthetic Oligo Library Quality Control Tool
Authors: Sabary Omer , Orlev Yoav , Shafir Roy , Anavy Leon , Yaakobi Eitan , Yakhini Zohar 
Published: November 2019

AbstractMotivationRecent years have seen a growing number and a broadening scope of studies using synthetic oligo libraries for a range of applications in synthetic biology. As experiments are growing by numbers and complexity, analysis tools can facilitate quality control and help in assessment and inference.ResultsWe present a novel analysis tool, called SOLQC, which enables fast and comprehensive analysis of synthetic oligo libraries, based on NGS analysis performed by the user. SOLQC provides statistical information such as the distribution of variant representation, different error rates and their dependence on sequence or library properties. SOLQC produces graphical descriptions of the analysis results. The results are reported in a flexible report format. We demonstrate SOLQC by analyzing literature libraries. We also discuss the potential benefits and relevance of the different components of the analysis.Availabilityhttps://app.gitbook.com/@yoav-orlev/s/solqc/
Optimal reproductive phenology under size-dependent cannibalism
Authors: Takashina Nao , Fiksen Øyvind 
Published: November 2019

AbstractIntra-cohort cannibalism is an example of a size-mediated priority effect. If early life stages cannibalize slightly smaller individuals, then parents face a trade-off between breeding at the best time for larval growth or development and predation risk from offspring born earlier. This game-theoretic situation among parents may drive adaptive reproductive phenology towards earlier breeding. However, it is not straightforward to quantify how cannibalism affects seasonal egg fitness or to distinguish emergent breeding phenology from alternative adaptive drivers. Here, we devise an age-structured game-theoretic mathematical model to find evolutionary stable breeding phenologies. We predict how size-dependent cannibalism acting on eggs, larvae, or both change emergent breeding phenology, and find that breeding under inter-cohort cannibalism occurs earlier than the optimal match to environmental conditions. We show that emergent breeding phenology patterns at the level of the population are sensitive to the ontogeny of cannibalism, i.e. which life stage is subject to cannibalism. This suggests that the nature of cannibalism among early life stages is a potential driver of the diversity of reproductive phenologies seen across taxa, and may be a contributing factor in situations where breeding occurs earlier than expected from environmental conditions.
Mediator subunit Med15 dictates the conserved “fuzzy” binding mechanism of yeast transcription activators Gal4 and Gcn4
Authors: Tuttle Lisa M. , Pacheco Derek , Warfield Linda , Hahn Steven , Klevit Rachel E. 
Published: November 2019

SUMMARYThe acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in both transcription repression and activation through sequence-dependent binding to Gal80 repressor and sequence-independent binding to Mediator subunit Med15. The activation function of Gal4 arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds the Mediator subunit Med15 using a “fuzzy” protein interface. Remarkably, comparison of chemical shift perturbations shows that Gal4 and Gcn4, two ADs of different sequence, interact nearly identically with Med15. The findings that two ADs of different sequence use an identical fuzzy binding mechanism shows a common sequence-independent mechanism for AD-Mediator binding, similar to interactions within a hydrophobic cloud. In contrast, the same region of Gal4 AD interacts with Gal80 via a tight structured complex, implying that the structured binding partner of an intrinsically disordered protein dictates the type of protein interaction.
BDKANN - Biological Domain Knowledge-based Artificial Neural Network for drug response prediction
Authors: Snow Oliver , Sharifi-Noghabi Hossein , Lu Jialin , Zolotareva Olga , Lee Mark , Ester Martin 
Published: November 2019

AbstractMotivationOne of the main goals of precision oncology is to predict the response of a patient to a given cancer treatment based on their genomic profile. Although current models for drug response prediction are becoming more accurate, they are also ‘black boxes’ and cannot explain their predictions, which is of particular importance in cancer treatment. Many models also do not leverage prior biological knowledge, such as the hierarchical information on how proteins form complexes and act together in pathways.ResultsIn this work, we use this prior biological knowledge to form the architecture of a deep neural network to predict cancer drug response from cell line gene expression data. We find that our approach not only has a low prediction error compared to baseline models but also allows meaningful interpretation of the network. These interpretations can both explain predictions made and discover novel connections in the biological knowledge that may lead to new hypotheses about mechanisms of drug action.AvailabilityCode at https://github.com/osnow/BDKANNSupplementary informationIncluded with submission
SpecificgyrAgene mutations correlate with high prevalence of discordant levofloxacin resistance inMycobacterium tuberculosisisolates from Beijing, China
Authors: Huo Fengmin , Ma Yifeng , Li Shanshan , Xue Yi , Shang Yuanyuan , Dong Lingling , Li Yunxu , Pang Yu 
Published: November 2019

ABSTRACTAlthough molecular diagnostics are highly sensitive in the diagnosis of fluroquinolone (FQ)-resistant tuberculosis (TB), the discordant results with the sequential phenotypic drug susceptibility testing (DST) invariably occur. To investigate the prevalence and the cause of discordant results between molecular and phenotypic DST for levofloxacin (LFX), the cases who were determined to be LFX-susceptible using the phenotypic DST but LFX-resistant using the MeltPro assay were retrospectively reviewed in Beijing, China. We measured LFX minimal inhibitory concentrations (MICs) using Middlebrook 7H9 broth. Sanger sequencing was used to determine genotypic characteristics of discordant isolates. Between January and December 2018, 126 (22.1%) out of 571 smear-positive TB patients were identified as LFX-resistant TB by MeltPro assay. Among the 126 LFX-resistant TB, there were 34 isolates identified as LFX-susceptible TB by phenotypical DST. This result demonstrated a discordance prevalence of 27.0%. LFX MICs were majorly centered around the critical concentration, and 7 (21.2%) and 13 (39.4%) had MICs of 2.0 mg/l and 4.0 mg/l, respectively. The most prevalent mutations conferring discordant LFX resistance were the amino acid substitutions of Ser to Leu in 90 codon (13, 39.4%) and Asp to Ala in 94 codon ofgyrA(11, 33.3mg/l belonged to Ala90Val and Asp94Ala group. In conclusion, our data demonstrate that more than one quarter of LFX-resistant isolates by molecular method are susceptible to LFX using the phenotypic DST. The high prevalence of discordant LFX resistance is majorly due to the isolates with specific mutations withingyrAgene conferring proximity of MICs to the critical concentration.
Integrating genome-wide association mapping of additive and dominance genetic effects to improve genomic prediction accuracy inEucalyptus
Authors: Tan Biyue , Ingvarsson Pär K. 
Published: November 2019

SummaryGenome-wide association studies (GWAS) is a powerful and widely used approach to decipher the genetic control of complex traits. A major challenge for dissecting quantitative traits in forest trees is statistical power. In this study, we use a population consisting of 1123 samples from two successive generations that have been phenotyped for growth and wood property traits and genotyped using the EuChip60K chip, yielding 37,832 informative SNPs. We use multi-locus GWAS models to assess both additive and dominance effects to identify markers associated with growth and wood property traits in the eucalypt hybrids. Additive and dominance association models identified 78 and 82 significant SNPs across all traits, respectively, which captured between 39 and 86% of the genomic-based heritability. We also used SNPs identified from the GWAS and SNPs using less stringent significance thresholds to evaluate predictive abilities in a genomic selection framework. Genomic selection models based on the top 1% SNPs captured a substantially greater proportion of the genetic variance of traits compared to when all SNPs were used for model training. The prediction ability of estimated breeding values was significantly improved for all traits using either the top 1% SNPs or SNPs identified using a relaxedp-value threshold (p<10-3). This study highlights the added value of also considering dominance effects for identifying genomic regions controlling growth traits in trees. Moreover, integrating GWAS results into genomic selection method provides enhanced power relative to discrete associations for identifying genomic variation potentially useful in tree breeding.
Motor circuit function is stabilized during postembryonic growth by anterograde trans-synaptic Jelly Belly - Anaplastic Lymphoma Kinase signaling
Authors: Gärtig Phil-Alan , Ostrovsky Aaron , Manhart Linda , Giachello Carlo N. G. , Kovacevic Tatjana , Lustig Heidi , Chwalla Barbara , Cachero Sebastian , Baines Richard A. , Landgraf Matthias , Evers Jan Felix 
Published: November 2019

SummaryThe brain adapts to a changing environment or growing body size by structural growth and synaptic plasticity. Mechanisms studied to date promote synaptic growth between partner neurons, while negative counterparts that inhibit such interactions have so far remained elusive. Here, we investigate the role of Jeb-Alk signaling in coordinating motor circuit growth during larval stages of Drosophila. We quantify neuronal growth dynamics by intra-vital imaging, and synaptogenesis at nanometer resolution using endogenously labeled synaptic proteins, conditionally tagged with a fluorophore, and link changes in circuit anatomy with altered synaptic physiology and behavior. We find that loss of Jeb-Alk signaling leads to increased strengthening of synaptic excitation by developmental addition of additional postsynaptic but not pre-synaptic specializations. These changes ultimately lead to an epilepsy-like seizure behavior. We thus demonstrate that trans-synaptic anterograde Jeb-Alk signaling acts to stabilize developmental plasticity and circuit function, and that it does so specifically during postembryonic growth.
Sequencing-based quantitative mapping of the cellular small RNA landscape
Authors: Hu Jennifer F. , Yim Daniel , Huber Sabrina M. , Bacusmo Jo Marie , Ma Duanduan , DeMott Michael S. , Levine Stuart S. , de Crécy-Lagard Valerie , Dedon Peter C. , Cao Bo 
Published: November 2019

AbstractCurrent next-generation RNA sequencing methods cannot provide accurate quantification of the population of small RNAs within a sample due to strong sequence-dependent biases in capture, ligation, and amplification during library preparation. We report the development of an RNA sequencing method – AQRNA-seq – that minimizes biases and enables absolute quantification of all small RNA species in a sample mixture. Validation of AQRNA-seq library preparation and data mining algorithms using a 963-member microRNA reference library, RNA oligonucleotide standards of varying lengths, and northern blots demonstrated a direct, linear correlation between sequencing read count and RNA abundance. Application of AQRNA-seq to bacterial tRNA pools, a traditionally hard-to-sequence class of RNAs, revealed 80-fold variation in tRNA isoacceptor copy numbers, patterns of site-specific tRNA fragmentation caused by stress, and quantitative maps of ribonucleoside modifications, all in a single AQRNA-seq experiment. AQRNA-seq thus provides a means to quantitatively map the small RNA landscape in cells and tissues.