bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of pharmacogenomic variants in 100 pharmacogenes among Southeast Asian populations under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm)
Authors: Runcharoen Chakkaphan , Fukunaga Koya , Sensorn Insee , Iemwimangsa Nareenart , Klumsathian Sommon , Tong Hang , Vo Nam Sy , Le Ly , Hlaing Tin Maung , Thant Myo , Zain Shamsul Mohd , Mohamed Zahurin , Pung Yuh-Fen , Capule Francis , Nevado Jose , Silao Catherine Lynn , Al-Mahayri Zeina N. , Ali Bassam R. , Yuliwulandari Rika , Prayuni Kinasih , Zahroh Hilyatuz , Noor Dzul Azri Mohamed , Xangsayarath Phonepadith , Xayavong Dalouny , Kounnavong Sengchanh , Sayasone Somphou , Kordou Zoe , Liopetas Ioannis , Tsikrika Athina , Tsermpini Evangelia-Eirini , Koromina Maria , Mitropoulou Christina , Patrinos George P. , Kesornsit Aumpika , Charoenyingwattana Angkana , Wattanapokayakit Sukanya , Mahasirimongkol Surakameth , Mushiroda Taisei , Chantratita Wasun 
Published: February 2021

AbstractPharmacogenomics can enhance the outcome of treatment by adopting pharmacogenomic testing to maximize drug efficacy and lower the risk of serious adverse events. Next-generation sequencing (NGS) is a cost-effective technology for genotyping several pharmacogenomic loci at once, thereby increasing publicly available data. A panel of 100 pharmacogenes among Southeast Asian (SEA) populations was resequenced using the NGS platform under the collaboration of the Southeast Asian Pharmacogenomics Research Network (SEAPharm). Here, we present the frequencies of pharmacogenomic variants and the comparison of these pharmacogenomic variants among different SEA populations and other populations used as controls. We investigated the different types of pharmacogenomic variants, especially those that may have a functional impact. Our results provide substantial genetic variations at 100 pharmacogenomic loci among SEA populations that may contribute to interpopulation variability in drug response phenotypes. Correspondingly, this study provides basic information for further pharmacogenomic investigations in SEA populations.
Filopodia-based contact stimulation of cell migration drives tissue morphogenesis
Authors: Bischoff Maik C. , Lieb Sebastian , Renkawitz-Pohl Renate , Bogdan Sven 
Published: February 2021

AbstractCells migrate collectively to form tissues and organs during morphogenesis. Contact inhibition of locomotion (CIL) drives collective migration by inhibiting lamellipodial protrusions at cell–cell contacts and promoting polarization at the leading edge. Here, we report a CIL-related collective cell behavior of myotubes that lack lamellipodial protrusions, but instead use filopodia to move as a cohesive cluster in a formin-dependent manner. We perform genetic, pharmacological and mechanical perturbation analyses to reveal the essential roles of Rac2, Cdc42 and Rho1 in myotube migration. These factors differentially control protrusion dynamics and cell–matrix adhesion formation. We also show that active Rho1 GTPase localizes at retracting free edge filopodia and that Rok-dependent actomyosin contractility does not mediate a contraction of protrusions at cell–cell contacts, but likely plays an important role in the constriction of supracellular actin cables. Based on these findings, we propose that contact-dependent asymmetry of cell–matrix adhesion drives directional movement, whereas contractile actin cables contribute to the integrity of the migrating cell cluster.
Mechanism of pore opening in the calcium-activated chloride channel TMEM16A
Authors: Lam Andy K. M. , Dutzler Raimund 
Published: February 2021

AbstractThe anion channel TMEM16A is activated by intracellular Ca2+ in a highly cooperative process. By combining electrophysiology and autocorrelation analysis, we investigated the mechanism of channel activation and the concurrent rearrangement of the gate in the narrow part of the pore. Features in the fluctuation characteristics of steady-state current indicate the sampling of intermediate conformations that are successively occupied during gating. The initial step is related to conformational changes induced by Ca2+ binding, which is ensued by rearrangements that open the pore. Mutations in the gate shift the equilibrium of transitions in a manner consistent with a progressive destabilization of this region during pore opening. We come up with a mechanism of channel activation where the binding of Ca2+ induces conformational changes in the protein that, in a sequential manner, propagate from the binding site and couple to the gate in the narrow pore to allow ion permeation.
Recognition of non-CpG repeats in Alu and ribosomal RNAs by the Z-RNA binding domain of ADAR1 induces A-Z junctions
Authors: Nichols Parker J. , Bevers Shaun , Henen Morkos , Kieft Jeffrey S. , Vicens Quentin , Vögeli Beat 
Published: February 2021

AbstractAdenosine-to-inosine (A-to-I) editing of eukaryotic cellular RNAs is essential for protection against auto-immune disorders. Editing is carried out by ADAR1, whose innate immune response-specific cytoplasmic isoform possesses a Z-DNA binding domain (Zα) of unknown function. Zα also binds to CpG repeats in RNA, which are a hallmark of Z-RNA formation. Unexpectedly, Zα has been predicted — and in some cases even shown — to bind to specific regions within mRNA and rRNA devoid of such repeats. Here, we use NMR, circular dichroism, and other biophysical approaches to demonstrate and characterize the binding of Zα to mRNA and rRNA fragments. Our results reveal a broad range of RNA sequences that bind to Zα and adopt Z-RNA conformations. Binding is accompanied by destabilization of neighboring A-form regions which is similar in character to what has been observed for B-Z-DNA junctions. The binding of Zα to non-CpG sequences is specific, cooperative and occurs with an affinity in the low micromolar range. This work allows us to propose a model for how Zα could influence the RNA binding specificity of ADAR1.
Probiotics as a treatment for prenatal maternal anxiety and depression: a double-blind randomized pilot trial
Authors: Browne Pamela D. , Bolte Antoinette C. , Besseling-van der Vaart Isolde , Claassen Eric , de Weerth Carolina 
Published: February 2021

AbstractProbiotic use may be an efficacious treatment option to effectively manage symptoms of prenatal maternal anxiety and depression. Our primary aim was to test feasibility and acceptability for a probiotic randomized controlled trial (RCT) in pregnant women with pre-existing symptoms. This double-blind pilot RCT included 40 pregnant women with low-risk pregnancies and elevated depressive symptoms and/or anxiety. Once daily, participants orally consumed a probiotic (Ecologic Barrier) or a placebo, from 26 to 30 weeks gestation until delivery. A priori key progression criteria for primary outcomes were determined to decide whether or not a full RCT was feasible and acceptable. Secondary outcomes included depressive symptoms, anxiety, stress, and maternal bonding to offspring. In 19 months, 1573 women were screened; following screening, 155 women (10%) were invited for participation, of whom 135 (87%) received study information, and 40 women (30%) were included. Four out of six a priori determined criteria for success on feasibility and acceptability were met. After 8 weeks of intervention, there was no significant difference between the probiotic and placebo groups for secondary outcomes. The pilot trial was feasible and acceptable, but hampered by recruitment method and study design. Secondary endpoints did not reveal differences between the groups for improving maternal mood.
Surface slicks are pelagic nurseries for diverse ocean fauna
Authors: Whitney Jonathan L. , Gove Jamison M. , McManus Margaret A. , Smith Katharine A. , Lecky Joey , Neubauer Philipp , Phipps Jana E. , Contreras Emily A. , Kobayashi Donald R. , Asner Gregory P. 
Published: February 2021

AbstractMost marine animals have a pelagic larval phase that develops in the coastal or open ocean. The fate of larvae has profound effects on replenishment of marine populations that are critical for human and ecosystem health. Larval ecology is expected to be tightly coupled to oceanic features, but for most taxa we know little about the interactions between larvae and the pelagic environment. Here, we provide evidence that surface slicks, a common coastal convergence feature, provide nursery habitat for diverse marine larvae, including > 100 species of commercially and ecologically important fishes. The vast majority of invertebrate and larval fish taxa sampled had mean densities 2–110 times higher in slicks than in ambient water. Combining in-situ surveys with remote sensing, we estimate that slicks contain 39% of neustonic larval fishes, 26% of surface-dwelling zooplankton (prey), and 75% of floating organic debris (shelter) in our 1000 km2 study area in Hawai‘i. Results indicate late-larval fishes actively select slick habitats to capitalize on concentrations of diverse prey and shelter. By providing these survival advantages, surface slicks enhance larval supply and replenishment of adult populations from coral reef, epipelagic, and deep-water ecosystems. Our findings suggest that slicks play a critically important role in enhancing productivity in tropical marine ecosystems.
Impact of domestic travel restrictions on transmission of COVID-19 infection using public transportation network approach
Authors: Murano Yayoi , Ueno Ryo , Shi Shoi , Kawashima Takayuki , Tanoue Yuta , Tanaka Shiori , Nomura Shuhei , Shoji Hiromichi , Shimizu Toshiaki , Nguyen Huy , Miyata Hiroaki , Gilmour Stuart , Yoneoka Daisuke 
Published: February 2021

AbstractThe international spread of COVID-19 infection has attracted global attention, but the impact of local or domestic travel restriction on public transportation network remains unclear. Passenger volume data for the domestic public transportation network in Japan and the time at which the first confirmed COVID-19 case was observed in each prefecture were extracted from public data sources. A survival approach in which a hazard was modeled as a function of the closeness centrality on the network was utilized to estimate the risk of importation of COVID-19 in each prefecture. A total of 46 prefectures with imported cases were identified. Hypothetical scenario analyses indicated that both strategies of locking down the metropolitan areas and restricting domestic airline travel would be equally effective in reducing the risk of importation of COVID-19. While caution is necessary that the data were limited to June 2020 when the pandemic was in its initial stage and that no other virus spreading routes have been considered, domestic travel restrictions were effective to prevent the spread of COVID-19 on public transportation network in Japan. Instead of lockdown that might seriously damage the economy, milder travel restrictions could have the similar impact on controlling the domestic transmission of COVID-19.
Discovery of novel chemical reactions by deep generative recurrent neural network
Authors: Bort William , Baskin Igor I. , Gimadiev Timur , Mukanov Artem , Nugmanov Ramil , Sidorov Pavel , Marcou Gilles , Horvath Dragos , Klimchuk Olga , Madzhidov Timur , Varnek Alexandre 
Published: February 2021

AbstractThe “creativity” of Artificial Intelligence (AI) in terms of generating de novo molecular structures opened a novel paradigm in compound design, weaknesses (stability & feasibility issues of such structures) notwithstanding. Here we show that “creative” AI may be as successfully taught to enumerate novel chemical reactions that are stoichiometrically coherent. Furthermore, when coupled to reaction space cartography, de novo reaction design may be focused on the desired reaction class. A sequence-to-sequence autoencoder with bidirectional Long Short-Term Memory layers was trained on on-purpose developed “SMILES/CGR” strings, encoding reactions of the USPTO database. The autoencoder latent space was visualized on a generative topographic map. Novel latent space points were sampled around a map area populated by Suzuki reactions and decoded to corresponding reactions. These can be critically analyzed by the expert, cleaned of irrelevant functional groups and eventually experimentally attempted, herewith enlarging the synthetic purpose of popular synthetic pathways.
A longitudinal, randomized experimental pilot study to investigate the effects of airborne infrasound on human mental health, cognition, and brain structure
Authors: Ascone L. , Kling C. , Wieczorek J. , Koch C. , Kühn S. 
Published: February 2021

AbstractAirborne infrasound (IS; emitted by e.g., large machinery, wind farms) is ubiquitous in technologized environments. Health hazards are controversially discussed at present. This study investigated long-term effects of IS on brain (regional grey matter volume; rGMV) and behavior in humans. Specifically engineered infrasonic (6 Hz, 80–90 dB) vs. sham devices were installed in participants’ (N = 38) bedrooms and active for 28 nights. Somatic and psychiatric symptoms, sound-sensitivity, sleep quality, cognitive performance, and structural MRI were assessed pre-post. Null findings emerged for all behavioral variables. Exploratory analyses revealed a trend (p = .083) with individuals exposed to IS reporting more physical weakness at post-test (d = 0.38). Voxel-based morphometry (VBM) revealed no rGMV increases, but there were decreases within clusters in the cerebellum VIIIa (bilateral) and left angular gyrus (BA39) in verum. In conclusion, IS does not affect healthy individuals on a global scale. However, future trials should consider more fine-grained specific effects, combining self-report with physiological assessments, particularly directed at bodily sensations and perception. As no brain-behavior-links could be established, the identified grey matter decline cannot be interpreted in terms of potential harmfulness vs. improvement through IS-exposure. Parameters that may best reflect brain changes as established in the present study include motor function, sensory processing/ bodily- and motor-perceptions, working memory, and higher auditory processing (i.e., language-related tasks), which are hence potential target variables for further research.
Preclinical assessment of a modified Occlutech left atrial appendage closure device in a porcine model
Authors: Reinthaler Markus , Grosshauser Johannes , Schmidt Tanja , Unger Juliane , Morgan Ross , Zimmermann Friederike , Hartung Johannes , Seppelt Claudio , Meteva Denitsa , Haider Wolfram , Landmesser Ulf , Skurk Carsten 
Published: February 2021

AbstractLeft atrial appendage (LAA) closure is being developed as an alternative for stroke prevention in patients with atrial fibrillation that cannot tolerate long-term oral anticoagulation. To assess the feasibility, safety, and performance of a novel modified Occlutech LAA closure device in a preclinical porcine model, the modified Occlutech modified Occlutech Plus LAA closure device was implanted in 12 female pigs (25–39 kg body weight) under fluoroscopic and transesophageal echocardiography (TEE) guidance. Procedural and technical success, as well as safety of LAA closure, were evaluated peri-procedurally and after 4, 8, and 12 weeks. Moreover, after 4, 8 and, 12 weeks animals were sacrificed for pathological analysis (e.g., thrombus formation, device ingrowth, endothelialization, and inflammation). All LAA closure devices were successfully implanted. On follow-up, no serious adverse events such as device-associated thrombus or translocalization/embolization were observed. A clinically non-significant pericarditis was observed in 4 animals at the time of autopsy. Endothelialization of the device was visible after 4 weeks, advanced after 8 weeks and completed after 12 weeks. Immunohistochemistry showed low amounts of inflammatory infiltration on the edges of the device. The results of this study indicate that implantation of a modified Occlutech LAA closure device is feasible with rapid endothelialization and low inflammatory infiltration in a porcine model. Human data are needed to further characterize safety and efficacy.
Spatial asymmetry of the paternity success in nests of a fish with alternative reproductive tactics
Authors: Poli F. , Marino I. A. M. , Santon M. , Bozzetta E. , Pellizzato G. , Zane L. , Rasotto M. B. 
Published: February 2021

AbstractGuard-sneaker tactics are widespread among fish, where territorial males defend a nest and provide parental care while sneakers try to steal fertilizations. Territorials and sneakers adopt diverse pre- and post-mating strategies, adjusting their ejaculate investment and/or behavioural responses to the presence of competitors. The relative distance of competitors from the spawning female plays a major role in influencing male mating strategies and the resulting paternity share. However, territorial male quality and sneaking intensity do not fully account for the variability in the relative siring success occurring among species. An often neglected factor potentially affecting sneakers proximity to females is the nest structure. We conducted a field experiment using the black goby, whose nests show two openings of different size. We found that territorial males defend more and sneaking pressure is higher at the front, larger access of the nest than at the back, smaller one. Moreover, microsatellite paternity analysis shows that territorials sire more offspring at the back of their nest. Such a predictable spatial distribution of the paternity share suggests that nest structure might work as an indirect cue of male relative siring success, potentially influencing the territorial male investment in parental care and/or the female egg deposition strategy.
Reaction mechanism of the farnesyl pyrophosphate C-methyltransferase towards the biosynthesis of pre-sodorifen pyrophosphate by Serratia plymuthica 4Rx13
Authors: Lemfack Marie Chantal , Brandt Wolfgang , Krüger Katja , Gurowietz Alexandra , Djifack Jacky , Jung Jan-Philip , Hopf Marius , Noack Heiko , Junker Björn , von Reuß Stephan , Piechulla Birgit 
Published: February 2021

AbstractClassical terpenoid biosynthesis involves the cyclization of the linear prenyl pyrophosphate precursors geranyl-, farnesyl-, or geranylgeranyl pyrophosphate (GPP, FPP, GGPP) and their isomers, to produce a huge number of natural compounds. Recently, it was shown for the first time that the biosynthesis of the unique homo-sesquiterpene sodorifen by Serratia plymuthica 4Rx13 involves a methylated and cyclized intermediate as the substrate of the sodorifen synthase. To further support the proposed biosynthetic pathway, we now identified the cyclic prenyl pyrophosphate intermediate pre-sodorifen pyrophosphate (PSPP). Its absolute configuration (6R,7S,9S) was determined by comparison of calculated and experimental CD-spectra of its hydrolysis product and matches with those predicted by semi-empirical quantum calculations of the reaction mechanism. In silico modeling of the reaction mechanism of the FPP C-methyltransferase (FPPMT) revealed a SN2 mechanism for the methyl transfer followed by a cyclization cascade. The cyclization of FPP to PSPP is guided by a catalytic dyad of H191 and Y39 and involves an unprecedented cyclopropyl intermediate. W46, W306, F56, and L239 form the hydrophobic binding pocket and E42 and H45 complex a magnesium cation that interacts with the diphosphate moiety of FPP. Six additional amino acids turned out to be essential for product formation and the importance of these amino acids was subsequently confirmed by site-directed mutagenesis. Our results reveal the reaction mechanism involved in methyltransferase-catalyzed cyclization and demonstrate that this coupling of C-methylation and cyclization of FPP by the FPPMT represents an alternative route of terpene biosynthesis that could increase the terpenoid diversity and structural space.
Credal decision tree based novel ensemble models for spatial assessment of gully erosion and sustainable management
Authors: Arabameri Alireza , Sadhasivam Nitheshnirmal , Turabieh Hamza , Mafarja Majdi , Rezaie Fatemeh , Pal Subodh Chandra , Santosh M. 
Published: February 2021

AbstractWe introduce novel hybrid ensemble models in gully erosion susceptibility mapping (GESM) through a case study in the Bastam sedimentary plain of Northern Iran. Four new ensemble models including credal decision tree-bagging (CDT-BA), credal decision tree-dagging (CDT-DA), credal decision tree-rotation forest (CDT-RF), and credal decision tree-alternative decision tree (CDT-ADTree) are employed for mapping the gully erosion susceptibility (GES) with the help of 14 predictor factors and 293 gully locations. The relative significance of GECFs in modelling GES is assessed by random forest algorithm. Two cut-off-independent (area under success rate curve and area under predictor rate curve) and six cut-off-dependent metrics (accuracy, sensitivity, specificity, F-score, odd ratio and Cohen Kappa) were utilized based on both calibration as well as testing dataset. Drainage density, distance to road, rainfall and NDVI were found to be the most influencing predictor variables for GESM. The CDT-RF (AUSRC = 0.942, AUPRC = 0.945, accuracy = 0.869, specificity = 0.875, sensitivity = 0.864, RMSE = 0.488, F-score = 0.869 and Cohen’s Kappa = 0.305) was found to be the most robust model which showcased outstanding predictive accuracy in mapping GES. Our study shows that the GESM can be utilized for conserving soil resources and for controlling future gully erosion.
Alterations in glutathione redox homeostasis among adolescents with obesity and anemia
Authors: Alkazemi Dalal , Rahman Abdur , Habra Banan 
Published: February 2021

AbstractThe reduced (GSH)-to-oxidized (GSSG) glutathione ratio represents a dynamic balance between oxidants and antioxidants. However, redox status in adolescents with obesity and anemia has not been investigated. This study investigated the association of erythrocyte GSH redox status (GSH, GSH:GSSG ratio, and glutathione peroxidase [GPx] activity) with anemia and adiposity in adolescents. This case–control study nested in a cross-sectional study enrolled 524 adolescents (268 boys; 256 girls). The prevalence of anemia in overweight and obesity (OWOB) was 5.2% in boys and 11.7% in girls. The GSH:GSSG ratio and GPx activity were significantly higher in girls than in boys (p < 0.001), in anemic than in non-anemic subjects (p < 0.001), and in OWOB than in normal-weight subjects (p < 0.001). Similarly, significantly higher GSH: GSSG level (p < 0.001) and GPx activity (p < 0.001) were found in subjects with 90th percentile waist circumference than in those with < 90th percentile. GPx and GSH:GSSG were positively associated with anemia after adjusting for age, sex, and body mass index (adjusted odds ratio, adjOR [95% confidence interval, CI] 2.18 [1.44–3.29]) or tertiles (adjOR [95% CI], T3 = 2.49 [1.03–6.01]). A similar association was noted for GSH and GPx. A compensatory increased redox defense mechanism exists in anemia and obesity among adolescents without metabolic disturbances.