bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancing the interpretability of transcription factor binding site prediction using attention mechanism
Authors: Park Sungjoon , Koh Yookyung , Jeon Hwisang , Kim Hyunjae , Yeo Yoonsun , Kang Jaewoo 
Published: August 2020

AbstractTranscription factors (TFs) regulate the gene expression of their target genes by binding to the regulatory sequences of target genes (e.g., promoters and enhancers). To fully understand gene regulatory mechanisms, it is crucial to decipher the relationships between TFs and DNA sequences. Moreover, studies such as GWAS and eQTL have verified that most disease-related variants exist in non-coding regions, and highlighted the necessity to identify such variants that cause diseases by interrupting TF binding mechanisms. To do this, it is necessary to build a prediction model that precisely predicts the binding relationships between TFs and DNA sequences. Recently, deep learning based models have been proposed and have shown competitive results on a transcription factor binding site prediction task. However, it is difficult to interpret the prediction results obtained from the previous models. In addition, the previous models assumed all the sequence regions in the input DNA sequence have the same importance for predicting TF-binding, although sequence regions containing TF-binding-associated signals such as TF-binding motifs should be captured more than other regions. To address these challenges, we propose TBiNet, an attention based interpretable deep neural network for predicting transcription factor binding sites. Using the attention mechanism, our method is able to assign more importance on the actual TF binding sites in the input DNA sequence. TBiNet outperforms the current state-of-the-art methods (DeepSea and DanQ) quantitatively in the TF-DNA binding prediction task. Moreover, TBiNet is more effective than the previous models in discovering known TF-binding motifs.
A single unified model for fitting simple to complex receptor response data
Authors: Buchwald Peter 
Published: August 2020

AbstractThe fitting of complex receptor-response data where fractional response and occupancy do not match is challenging. They encompass important cases including (a) the presence of “receptor reserve” and/or partial agonism, (b) multiple responses assessed at different vantage points along a pathway, (c) responses that are different along diverging downstream pathways (biased agonism), and (d) constitutive activity. For these, simple models such as the well-known Clark or Hill equations cannot be used. Those that can, such as the operational (Black&Leff) model, do not provide a unified approach, have multiple nonintuitive parameters that are challenging to fit in well-defined manner, have difficulties incorporating binding data, and cannot be reduced or connected to simpler forms. We have recently introduced a quantitative receptor model (SABRE) that includes parameters for Signal Amplification (γ), Binding affinity (Kd), Receptor activation Efficacy (ε), and constitutive activity (εR0). It provides a single equation to fit complex cases within a full two-state framework with the possibility of incorporating receptor occupancy data (i.e., experimental Kds). Simpler cases can be fit by using consecutively reduced forms obtained by constraining parameters to specific values, e.g., εR0 = 0: no constitutive activity, γ = 1: no amplification (Emax-type fitting), and ε = 1: no partial agonism (Clark equation). Here, a Hill-type extension is introduced (n ≠ 1), and simulated and experimental receptor-response data from simple to increasingly complex cases are fitted within the unified framework of SABRE with differently constrained parameters.
Update analysis on the association between Methionine synthase rs1805087 A/G variant and risk of prostate cancer
Authors: Zhang Wei , Zhang Ze , Wu Hao , Xu Kai , Yuan Wei , Mi Yuan-Yuan , Shi Li , Zuo Li , Shi Yun-Feng 
Published: August 2020

AbstractPrevious studies have investigated the association of the rs1805087 A/G variant ofMethionine synthasegene with the susceptibility to prostate cancer (PCa). Nevertheless, the conclusions remain divergent. We performed a systemic analysis with odds ratios (ORs) and 95% confidence intervals (95% CIs) to assessMethionine synthasers1805087 A/G variant and PCa risk. Furthermore, we utilized in silico analysis to investigate the relationship betweenMethionine synthaseexpression and the overall survival (OS) time. Totally, 10,666 PCa patients and 40,750 controls were included. We observed thatMethionine synthasers1805087 A/G variant is associated with an elevated risk of PCa (G-allele vs. A-allele: OR = 1.06, 95% CI = 1.01–1.11,P = 0.013; heterozygous model: OR = 1.08, 95% CI = 1.02–1.14,P = 0.009; dominant model: OR = 1.08, 95% CI = 1.02–1.14,P = 0.007). During stratified analysis, similar results were obtained in Asian populations, hospital-based, high quality studies and that with large sample size. Moreover, in silico analysis indicated theMethionine synthaseexpression is down-regulated in both young and old PCa subjects (P < 0.05). Compared with the normal subjects, the down-regulated expression ofMethionine synthasewas found in PCa cases with Gleason score 6 to 9. Our study showed thatMethionine synthasers1805087 A/G variant may be associated with susceptibility of PCa, especially in Asian populations, hospital-based studies and that with high quality and large sample size. Furthermore,Methionine synthasers1805087 A/G variant may be related to the prognosis of PCa.
An ambient temperature collection and stabilization strategy for canine microbiota studies
Authors: Lin Ching-Yen , Cross Tzu-Wen L. , Doukhanine Evgueni , Swanson Kelly S. 
Published: August 2020

AbstractSimilar to humans, the fecal microbiome of dogs may be useful in diagnosing diseases or assessing dietary interventions. The accuracy and reproducibility of microbiome data depend on sample integrity, which can be affected by storage methods. Here, we evaluated the ability of a stabilization device to preserve canine fecal samples under various storage conditions simulating shipping in hot or cold climates. Microbiota data from unstabilized samples stored at room temperature (RT) and samples placed in PERFORMAbiome·GUT collection devices (PB-200) (DNA Genotek, Inc. Ottawa, Canada) and stored at RT, 37 °C, 50 °C, or undergoing repeated freeze–thaw cycles, were compared with freshly extracted samples. Alpha- and beta diversity indices were not affected in stabilized samples, regardless of storage temperature. Unstabilized samples stored at RT, however, had higher alpha diversity. Moreover, the relative abundance of dominant bacterial phyla (Firmicutes, Fusobacteria, Bacteriodetes, and Actinobacteria) and 24 genera were altered in unstabilized samples stored at RT, while microbiota abundance was not significantly changed in stabilized samples stored at RT. Our results suggest that storage method is important in microbiota studies and that the stabilization device may be useful in maintaining microbial profile integrity, especially for samples collected off-site and/or those undergoing temperature changes during shipment or storage.
Early-life stress affects drug abuse susceptibility in adolescent rat model independently of depression vulnerability
Authors: Alves Renata L. , Oliveira Pedro , Lopes Igor M. , Portugal Camila C. , Alves Cecília J. , Barbosa Fernando , Summavielle Teresa , Magalhães Ana 
Published: August 2020

AbstractThe development of substance abuse problems occurs due to a diverse combination of risk factors. Among these risks, studies have reported depression and early-life stress as of importance. These two factors often occur simultaneously, however, there is a lack of understanding of how their combined effect may impact vulnerability to drug abuse in adolescence. The present study used rats with different vulnerability to depression (Wistar and Wistar-Kyoto) to investigate the impact of maternal separation (MS) on emotional state and drug addiction vulnerability during the adolescence period. Mothers and their litters were subjected to MS (180 min/day) from postnatal day 2 to 14. The offspring emotional state was assessed by observing their exploratory behavior. Drug abuse vulnerability was assessed through conditioning to cocaine. MS impacted the emotional state in both strains. Wistar responded with increased exploration, while Wistar-Kyoto increased anxiety-like behaviours. Despite the different coping strategies displayed by the two strains when challenged with the behavioural tests, drug conditioning was equally impacted by MS in both strains. Early-life stress appears to affect drug abuse vulnerability in adolescence independently of a depression background, suggesting emotional state as the main driving risk factor.
Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems
Authors: Naseem Muhammad , Othman Eman M. , Fathy Moustafa , Iqbal Jibran , Howari Fares M. , AlRemeithi Fatima A. , Kodandaraman Geema , Stopper Helga , Bencurova Elena , Vlachakis Dimitrios , Dandekar Thomas 
Published: August 2020

AbstractMetabolism and signaling of cytokinins was first established in plants, followed by cytokinin discoveries in all kingdoms of life. However, understanding of their role in mammalian cells is still scarce. Kinetin is a cytokinin that mitigates the effects of oxidative stress in mammalian cells. The effective concentrations of exogenously applied kinetin in invoking various cellular responses are not well standardized. Likewise, the metabolism of kinetin and its cellular targets within the mammalian cells are still not well studied. Applying vitality tests as well as comet assays under normal and hyper-oxidative states, our analysis suggests that kinetin concentrations of 500 nM and above cause cytotoxicity as well as genotoxicity in various cell types. However, concentrations below 100 nM do not cause any toxicity, rather in this range kinetin counteracts oxidative burst and cytotoxicity. We focus here on these effects. To get insights into the cellular targets of kinetin mediating these pro-survival functions and protective effects we applied structural and computational approaches on two previously testified targets for these effects. Our analysis deciphers vital residues in adenine phosphoribosyltransferase (APRT) and adenosine receptor (A2A-R) that facilitate the binding of kinetin to these two important human cellular proteins. We finally discuss how the therapeutic potential of kinetin against oxidative stress helps in various pathophysiological conditions.
A versatile bulk electrotransfection protocol for murine embryonic fibroblasts and iPS cells
Authors: Eghbalsaied Shahin , Hyder Iqbal , Kues Wilfried A. 
Published: August 2020

AbstractAlthough electroporation has been widely accepted as the main gene transfer tool, there is still considerable scope to improve the electroporation efficiency of exogenous DNAs into primary cells. Here, we developed a square-wave pulsing protocol using OptiMEM-GlutaMAX for highly efficient transfection of murine embryonic fibroblasts (MEF) and induced pluripotency stem (iPS) cells using reporter genes as well as gRNA/Cas9-encoding plasmids. An electrotransfection efficiency of > 95% was achieved for both MEF and iPS cells using reporter-encoding plasmids. The protocol was efficient for plasmid sizes ranging from 6.2 to 13.5 kb. Inducing the error prone non-homologous end joining repair by gRNA/Cas9 plasmid transfection, a high rate of targeted gene knockouts of up to 98% was produced in transgenic cells carrying a single-copy of Venus reporter. Targeted deletions in the Venus transgene were efficiently (up to 67% deletion rate) performed by co-electroporation of two gRNA-encoding plasmids. We introduced a plasmid electrotransfection protocol which is straight-forward, cost-effective, and efficient for CRISPRing murine primary cells. This protocol is promising to make targeted genetic engineering using the CRISPR/Cas9 plasmid system.
liputils: a Python module to manage individual fatty acid moieties from complex lipids
Authors: Manzini Stefano , Busnelli Marco , Colombo Alice , Kiamehr Mostafa , Chiesa Giulia 
Published: August 2020

AbstractLipidomic analyses address the problem of characterizing the lipid components of given cells, tissues and organisms by means of chromatographic separations coupled to high-resolution, tandem mass spectrometry analyses. A number of software tools have been developed to help in the daunting task of mass spectrometry signal processing and cleaning, peak analysis and compound identification, and a typical finished lipidomic dataset contains hundreds to thousands of individual molecular lipid species. To provide researchers without a specific technical expertise in mass spectrometry the possibility of broadening the exploration of lipidomic datasets, we have developed liputils, a Python module that specializes in the extraction of fatty acid moieties from individual molecular lipids. There is no prerequisite data format, as liputils extracts residues from RefMet-compliant textual identifiers and from annotations of other commercially available services. We provide three examples of real-world data processing with liputils, as well as a detailed protocol on how to readily process an existing dataset that can be followed with basic informatics skills.
A randomized, double-blind water taste test to evaluate the equivalence of taste between tap water and filtered water in the Taipei metropolis
Authors: Jhuang Jing-Rong , Lee Wen-Chung , Chan Chang-Chuan 
Published: August 2020

AbstractHigh water quality and sufficient water availability are the main concerns of water users. Promoting the efficient use of tap water can contribute to sustainable drinking water management and progress towards Sustainable Development Goals. In many metropolises, water suppliers treat municipal water with appropriate treatment processes and well-maintained distribution infrastructure. Under this circumstance, it is acceptable that municipal water can be a source of drinking water. The presence of residual chlorine in tap water, connected to municipal water supply, inactivates pathogenic microorganisms and prevents recontamination. However, adding chlorine to tap water may affect the organoleptic properties of drinking water. On the other hand, the use of point-of-use (POU) water dispensers, which provides an additional treatment step on tap water, is not energy-efficient. A randomized, double-blind water taste test was conducted in the Taipei metropolis to assess whether tap water from public drinking fountains and filtered water from POU water dispensers have similar organoleptic properties. An odds ratio (OR) and the area under the receiver operating characteristic curve (AUC) were used to measure the participants’ ability to distinguish between the two water varieties. A five-region hypothesis test was conducted to test the OR, and a 95% bootstrap confidence interval of the AUC was calculated. The results of the study showed that the 95% five-region confidence interval of OR equal to (0.5, 1.49), and the 95% bootstrap confidence interval of AUC equal to (0.42, 0.56). These results implied that people in the Taipei metropolis could not distinguish between tap water and filtered water. It is recommended that more drinking fountains be installed and maintained fully functional and clean to achieve excellence in tap water access.
Marine heatwaves and the collapse of marginal North Atlantic kelp forests
Authors: Filbee-Dexter K. , Wernberg T. , Grace S. P. , Thormar J. , Fredriksen S. , Narvaez C. N. , Feehan C. J. , Norderhaug K. M. 
Published: August 2020

AbstractExtreme climatic events including marine heatwaves (MHWs) are becoming more frequent and severe in the Anthropocene. However, our understanding of how these events affect population dynamics of ecologically important species is limited, in part because extreme events are rare and difficult to predict. Here, we quantified the occurrence and severity of MHWs over 60 years in warm range edge kelp forests on both sides of the North Atlantic. The cumulative annual intensity of MHWs increased two- to four-fold during this period, coinciding with the disappearance of kelps. We experimentally demonstrated a relationship between strong and severe 2018 heatwaves and high kelp mortality in both regions. Patterns of kelp mortality were strongly linked to maximum temperature anomalies, which crossed lethal thresholds in both regions. Translocation and tagging experiments revealed similar kelp mortality rates on reefs dominated by healthy kelp forests and degraded sediment-laden algal ‘turfs’, indicating equal vulnerability to extreme events. These results suggest a mechanistic link between MHWs and broad-scale kelp loss, and highlight how warming can make ecosystem boundaries unstable, forcing shifts to undesirable ecosystem states under episodically extreme climatic conditions.
NOTCH2 participates in Jagged1-induced osteogenic differentiation in human periodontal ligament cells
Authors: Manokawinchoke Jeeranan , Sumrejkanchanakij Piyamas , Boonprakong Lawan , Pavasant Prasit , Egusa Hiroshi , Osathanon Thanaphum 
Published: August 2020

AbstractJagged1 activates Notch signaling and subsequently promotes osteogenic differentiation in human periodontal ligament cells (hPDLs). The present study investigated the participation of the Notch receptor, NOTCH2, in the Jagged1-induced osteogenic differentiation in hPDLs. NOTCH2 and NOTCH4 mRNA expression levels increased during hPDL osteogenic differentiation. However, the endogenous NOTCH2 expression levels were markedly higher compared with NOTCH4. NOTCH2 expression knockdown using shRNA in hPDLs did not dramatically alter their proliferation or osteogenic differentiation compared with the shRNA control. After seeding on Jagged1-immobilized surfaces and maintaining the hPDLs in osteogenic medium, HES1 and HEY1 mRNA levels were markedly reduced in the shNOTCH2-transduced cells compared with the shControl group. Further, shNOTCH2-transduced cells exhibited less alkaline phosphatase enzymatic activity and in vitro mineralization than the shControl cells when exposed to Jagged1. MSX2 and COL1A1 mRNA expression after Jagged1 activation were reduced in shNOTCH2-transduced cells. Endogenous Notch signaling inhibition using a γ-secretase inhibitor (DAPT) attenuated mineralization in hPDLs. DAPT treatment significantly promoted TWIST1, but decreased ALP, mRNA expression, compared with the control. In conclusion, Notch signaling is involved in hPDL osteogenic differentiation. Moreover, NOTCH2 participates in the mechanism by which Jagged1 induced osteogenic differentiation in hPDLs.
Glass shape influences drinking behaviours in three laboratory experiments
Authors: Langfield Tess , Pechey Rachel , Gilchrist Philippe T. , Pilling Mark , Marteau Theresa M. 
Published: August 2020

AbstractReducing consumption of drinks which contain high levels of sugar and/or alcohol may improve population health. There is increasing interest in health behaviour change approaches which work by changing cues in physical environments (“nudges”). Glassware represents a modifiable cue in the drinking environment that may influence how much we drink. Here, we report three laboratory experiments measuring consumption of soft drinks served in different glasses (straight-sided vs. outward-sloped), using distinct paradigms to measure drinking. In Study 1 (N = 200), though total drinking time was equivalent, participants consumed a soft drink with a more ‘decelerated’ trajectory from outward-sloped tumblers, characterised by a greater amount consumed in the first half of the drinking episode. In Study 2 (N = 72), during a bogus taste test, participants consumed less from straight-sided wine flutes than outward-sloped martini coupes. In Study 3 (N = 40), using facial electromyography to explore a potential mechanism for decreased consumption, straight-sided glasses elicited more ‘pursed’ lip embouchures, which may partly explain reduced consumption from these glasses. Using a combination of methods, including objective measures of volume drunk and physiological measures, these findings suggest that switching to straight-sided glasses may be one intervention contributing to the many needed to reduce consumption of health-harming drinks.
Spectral photon-counting CT imaging of colorectal peritoneal metastases: initial experience in rats
Authors: Thivolet Arnaud , Si-Mohamed Salim , Bonnot Pierre-Emmanuel , Blanchet Christophe , Képénékian Vahan , Boussel Loïc , Douek Philippe , Rousset Pascal 
Published: August 2020

AbstractComputed tomography imaging plays a major role in the preoperative assessment of tumor burden by providing an accurate mapping of the distribution of peritoneal metastases (PM). Spectral Photon Counting Computed Tomography (SPCCT) is an innovative imaging modality that could overcome the current limitations of conventional CT, offering not only better spatial resolution but also better contrast resolution by allowing the discrimination of multiple contrast agents. Based on this capability, we tested the feasibility of SPCCT in the detection of PM at different time of tumor growth in 16 rats inoculated with CC531 cells using dual-contrast injection protocols in two compartments (i.e. intravenous iodine and intraperitoneal gadolinium or the reverse protocol), compared to surgery. For all peritoneal regions and for both protocols, sensitivity was 69%, specificity was 100% and accuracy was 80%, and the correlation with surgical exploration was strong (p = 0.97; p = 0.0001). No significant difference was found in terms of diagnostic performance, quality of peritoneal opacification or diagnostic quality between the 2 injection protocols. We also showed poor vascularization of peritoneal metastases by measuring low concentrations of contrast agent in the largest lesions using SPCCT, which was confirmed by immunohistochemical analyses. In conclusion, SPCCT using dual-contrast agent injection protocols in 2 compartments is a promising imaging modality to assess the extent of PM in a rat model.
Thermal niche helps to explain the ability of dung beetles to exploit disturbed habitats
Authors: Giménez Gómez Victoria C. , Verdú José R. , Zurita Gustavo A. 
Published: August 2020

AbstractIn terrestrial ecosystems, insects face a wide range of temperatures among habitats and time; consequently, the thermal niche is one of the main determinants of habitat selection and temporal patterns of activity. The replacement of native forests changes micro-climatic conditions and reduces the diversity of dung beetles; however, the physiological mechanisms behind these changes are not clear. We explore the role of the thermal niche in dung beetles to explain the ability of native species to exploit human-created habitats. Using infrared thermography, we measured variables associated with the thermal niche in 17 native species and used linear mixed-effects model and ANOVAs to compare disturbed habitats and the native forest. Endothermy and body mass explained the ability of dung beetles to exploit human-created open habitats. Small and diurnal species with very low endothermy were able to exploit deforested open habitats; evening/nocturnal/crepuscular species showed similar body mass and high endothermy in all habitats. Regarding thermoregulation mechanisms, none of the species (except one) showed defined or efficient mechanisms of physiological thermoregulation. In view of the accelerated process of forest replacement and climate change, a more profound understanding of the physiological requirements of species is essential to predict and mitigate future extinctions.