bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal DNA Electron Transfer Catalysts Switched by a Chaotropic Ion
Authors: Hoog Tanner G. , Pawlak Matthew R. , Aufdembrink Lauren M. , Bachan Benjamin R. , Galles Matthew B. , Bense Nicholas B. , Adamala Katarzyna P. , Engelhart Aaron E. 
Published: October 2019

AbstractHere we demonstrate that a DNA nanodevice can perform switchable electron transfer. The nanodevice is comprised of two strands, one of which can be selectively switched between a G-quadruplex and duplex or single-stranded conformations. In the G-quadruplex state, it binds the cofactor hemin, enabling peroxidase activity. This switching ability arises from our discovery that perchlorate, a chaotropic Hofmeister ion, selectively destabilizes duplex over G-quadruplex DNA. By varying perchlorate concentration, we show that the device can be switched between states that do and do not catalyze electron transfer catalysis. State switching can be achieved in three ways: thermally, by dilution, or by concentration. In each case, when operated in the presence of the cofactor hemin, the device catalyzes electron transfer in only the G-quadruplex state.
MTHFR gene A1298C polymorphism and Alzheimer’s disease susceptibility
Authors: Rai Vandana 
Published: October 2019

AbstractMethylenetetrahydrofolate reductase (MTHFR) is a crucial enzyme involved in homocysteine/methionone metabolism. It catalyzes the conversion of 5,10methlenetetrahydrofolate in to 5methyltetrahydrofolate. A number of studies have examined the association of MTHFR A1298C polymorphism as risk factor for Alzheimer’s disease (AD), but the results were contradictory. To clarify the influence of MTHFR A1298C polymorphism on Alzheimer’s disease (AD), a meta-analysis of ten case-control studies was carried out. Four electronic databases were searched up to August, 2019 for suitable articles. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were used to evaluate the association. All statistical analyses were performed by MetaAnalyst program.The results of meta-analysis suggested that except allele contrast model, A1298C polymorphism is not risk for Alzheimer’s disease using overall comparisons in three genetic models (C vs. A: OR= 1.26, 95%CI= 0.912-1.76, p= 0.04; CC+AC vs. AA: OR= 1.43; 95%CI= 0.85-2.44; p=0.05; CC vs. AA: OR= 1.16, 95%CI= .88-1.55, p= 0.51; AC vs. AA: 1.55; 95%CI= 0.81-2.93,p=0.07). Publication bias was absent in all five genetic models. In conclusion, results of present meta-analysis showed no significant association between MTHFR A1298C polymorphism and AD risk.
Mechanisms of tissue-specific genetic regulation revealed by latent factors across eQTLs
Authors: He Yuan , Chhetri Surya B. , Arvanitis Marios , Srinivasan Kaushik , Aguet François , Ardlie Kristin G. , Barbeira Alvaro N. , Bonazzola Rodrigo , Im Hae Kyung ,   GTEx Consortium, Brown Christopher D. , Battle Alexis 
Published: October 2019

AbstractBackgroundGenetic regulation of gene expression, revealed by expression quantitative trait loci (eQTLs), varies across tissues in complex patterns ranging from highly tissue-specific effects to effects shared across many or all tissues. Improved characterization of these patterns may allow us to better understand the biological mechanisms that underlie tissue-specific gene regulation and disease etiology.ResultsWe develop a constrained matrix factorization model to learn patterns of tissue sharing and tissue specificity of eQTLs across 49 human tissues from the Genotype-Tissue Expression (GTEx) project. The learned factors include patterns reflecting tissues with known biological similarity or shared cell types, in addition to a dense factor representing a universal genetic effect across all tissues. To explore the regulatory mechanisms that generate tissue-specific patterns of expression, we evaluate chromatin state enrichment and identify specific transcription factors with binding sites enriched for eQTLs from each factor.ConclusionsOur results demonstrate that matrix factorization can be applied to learn the tissue specificity pattern of eQTLs and that it exhibits better biological interpretability than heuristic methods. We present a framework to characterize the tissue specificity of eQTLs, and we identify examples of tissue-specific eQTLs that may be driven by tissue-specific transcription factor (TF) binding, with relevance to interpretation of disease association.
Longitudinal study of persistence in professional development outcomes of early career biology faculty
Authors: Emery Nathan C , Maher Jessica Middlemis , Ebert-May Diane 
Published: October 2019

AbstractThe diversity of teaching professional development (PD) programs that occurred over the last few decades merits our collective attention to assess the impact of these programs over time. In general, the goal of PD programs is that participants continue to practice what they learn in the long term. However, we do not know the degree to which the outcomes of these programs were achieved and ultimately persist. We tracked postdoc participants from the Faculty Institutes for Reformed Science Teaching (FIRST) IV program into their current position as early-career faculty at institutions across the United States. We assessed their teaching approaches, practices, and student perceptions of the learning environment over 6-10 years. Additionally, the FIRST IV faculty were paired with colleagues of similar status in the same departments. We found that professional development outcomes from the FIRST IV program persisted over time and across a significant career transition, from postdoc to faculty. These participants not only maintained their student-centered practices, but were significantly more student-focused than their peers. Lastly, we found that faculty approaches to teaching were correlated with observed teaching practices in the classroom for both groups of faculty. These results provide compelling evidence for the success of the FIRST IV program and the long-term persistence of professional development outcomes.
Pitfalls in estimating the global carbon removal via forest expansion – a comment on Bastin et al. (2019)
Authors: Krause Andreas , Arneth Almut , Bayer Anita , Buras Allan , Knoke Thomas , Zang Christian , Rammig Anja 
Published: October 2019

AbstractWe believe the carbon removal potential of 205 Gt C reported by Bastin et al. (2019) to be overestimated. The authors did not consider the carbon already stored on the land with identified tree restoration potential. For instance, grasslands and degraded forests have similar soil carbon stocks as old-growth forests. Accounting for these inconsistencies in the calculation, we estimate a carbon removal potential of 81 Gt C, i.e. only 39% of the Bastin et al. estimate. In addition, some of the assumptions about potential restoration area seem questionable and an essential question remains unanswered: why do areas identified as suitable for tree growth currently lack tree cover?
Hormonal and modality specific effects on males’ emotion recognition ability
Authors: Lausen Adi , Broering Christina , Penke Lars , Schacht Annekathrin 
Published: October 2019

AbstractSuccessful emotion recognition is a key component of our socio-emotional communication skills. However, little is known about the factors impacting males’ accuracy in emotion recognition tasks. This pre-registered study examined potential candidates, focusing on the modality of stimulus presentation, emotion category, and individual hormone levels. We obtained accuracy and reaction time scores from 312 males who categorized voice, face and voice-face stimuli for nonverbal emotional content. Results showed that recognition accuracy was significantly higher in the audio-visual than in the auditory or visual modality. While no significant association was found for testosterone and cortisol alone, the effect of the interaction with recognition accuracy and reaction time was significant, but small. Our results establish that audio-visual congruent stimuli enhance recognition accuracy and provide novel empirical support by showing that the interaction of testosterone and cortisol modulate to some extent males’ accuracy and response times in emotion recognition tasks.
Nonsense suppression position effect implicates poly(A)-binding protein in the regulation of translation termination
Authors: Wu Chan , Roy Bijoyita , He Feng , Jacobson Allan 
Published: October 2019

SUMMARYReadthrough of translation termination codons, also known as nonsense suppression, is a relatively inefficient process mediated by ribosomal A site recognition and insertion of near-cognate tRNAs. Multiple factors influence readthrough efficiency, including nonsense codon specificity and context. To determine whether nonsense codon position in a gene influences the extent of readthrough, we generated a series ofLUCnonsense alleles and quantitated both readthrough and termination efficiencies at each nonsense codon in yeast cells lacking nonsense-mediated mRNA decay (NMD) activity. Readthrough efficiency for premature termination codons (PTCs) manifested a marked dependence on PTC proximity to the mRNA 3’-end, decreasing progressively across theLUCORF but increasing with 3’-UTR lengthening. These effects were eliminated, and translation termination efficiency decreased considerably, in cells harboringpab1mutations. Our results support a critical role for poly(A)-binding protein in the regulation of translation termination and suggest that inefficient termination is the trigger for NMD.
Isolation and comparative genomic analysis of reuterin-producingLactobacillus reuterifrom poultry gastrointestinal tract
Authors: Greppi Anna , Asare Paul Tetteh , Schwab Clarissa , Zemp Niklaus , Stephan Roger , Lacroix Christophe 
Published: October 2019

AbstractLactobacillus reuteriis a natural inhabitant of selected animal and human gastrointestinal tract (GIT). Certain strains have the capacity to transform glycerol to 3-hydroxypropionaldehyde (3-HPA), further excreted to form reuterin, a potent antimicrobial system. Reuterin-producing strains may be applied as a natural antimicrobial in feed to prevent pathogen colonization of animals, such as in poultry, and replace added antimicrobials. To date, only sevenL. reuteristrains isolated from poultry have been characterized which limits phylogenetic studies and host-microbes interactions characterization. This study aimed to isolateL. reuteristrains from poultry GIT and to characterize their reuterin production and antimicrobial resistance (AMR) profiles using phenotypic and genetic methods. Seventy reuterin-producing strains were isolated from poultry crop, faeces and caeca and twenty-five selected for further characterization. Draft genomes were generated for the new 25 isolates and integrated in a phylogenetic tree of 40 strains from different hosts. Phylogenetic analysis based on gene content as well as on core genomes showed grouping of the selected 25L. reuteripoultry isolates within the poultry/human lineage VI. Strains harbouringpdu-cob-cbi-hemgenes (23/25) produced between 156 mM ± 11 and 330 mM ± 14 3-HPA, from 600 mM of glycerol, in the conditions of the test. All 25 poultry strains were sensitive to cefotaxime (MIC between 0.016 and 1 μg/mL) and penicillin (MIC between 0.02 and 4 μg/mL). Akin to the reference strains DSM20016 and SD2112, the novel isolates were resistant to penicillin, possibly associated with identified point mutations inponA,pbpX,pbpFandpbpB. All strains resistant to erythromycin (4/27) carried the ermB gene, and it was only present in poultry strains. All strains resistant to tetracycline (5/27) harbored tetW gene. This study confirms the evolutionary history of poultry/human lineage VI and identifiespdu-cob-cbi-hemas a frequent trait but not always present in this lineage.L. reuteripoultry strains producing high 3-HPA yield may have potential to prevent enteropathogen colonization of poultry.
Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings
Authors: Silote Gabriela P. , de Oliveira Sabrina F.S. , Ribeiro Deidiane E. , Machado Mayara S. , Andreatini Roberto , Joca Sâmia R. L. , Beijamini Vanessa 
Published: October 2019

AbstractKetamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies. Regarding ketamine effects on anxiety, there is a widespread discordance among pre-clinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species. Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.HighlightsKetamine induces mixed effects in animal anxiety testsFew studies investigated the individual effects of S-ketamine in anxiety/fear testsNone study evaluated the effects of R-Ketamine on anxiety/fear-related behaviorsSystemic ketamine does not affect panic-like behaviors in the elevated T-maze
Spontaneous variability in gamma dynamics described by a linear harmonic oscillator driven by noise
Authors: Spyropoulos Georgios , Dowdall Jarrod Robert , Schölvinck Marieke Louise , Bosman Conrado Arturo , Lima Bruss , Peter Alina , Onorato Irene , Klon-Lipok Johanna , Roese Rasmus , Neuenschwander Sergio , Singer Wolf , Vinck Martin , Fries Pascal 
Published: October 2019

SUMMARYCircuits of excitatory and inhibitory neurons can generate rhythmic activity in the gamma frequency-range (30-80Hz). Individual gamma-cycles show spontaneous variability in amplitude and duration. The mechanisms underlying this variability are not fully understood. We recorded local-field-potentials (LFPs) and spikes from awake macaque V1, and developed a noise-robust method to detect gamma-cycle amplitudes and durations. Amplitudes and durations showed a weak but positive correlation. This correlation, and the joint amplitude-duration distribution, is well reproduced by a dampened harmonic oscillator driven by stochastic noise. We show that this model accurately fits LFP power spectra and is equivalent to a linear PING (Pyramidal Interneuron Network Gamma) circuit. The model recapitulates two additional features of V1 gamma: (1) Amplitude-duration correlations decrease with oscillation strength; (2) Amplitudes and durations exhibit strong and weak autocorrelations, respectively, depending on oscillation strength. Finally, longer gamma-cycles are associated with stronger spike-synchrony, but lower spike-rates in both (putative) excitatory and inhibitory neurons. In sum, V1 gamma-dynamics are well described by the simplest possible model of gamma: A linear harmonic oscillator driven by noise.
SKIPHOS: non-kinase specific phosphorylation site prediction with random forests and amino acid skip-gram embeddings
Authors: Dang Thanh Hai , Trac Quang Thinh , Phan Huy Kinh , Nguyen Manh Cuong , Pham Thi Quynh Trang 
Published: October 2019

AbstractMotivationPhosphorylation, which is catalyzed by kinase proteins, is in the top two most common and widely studied types of known essential post-translation protein modification (PTM). Phosphorylation is known to regulate most cellular processes such as protein synthesis, cell division, signal transduction, cell growth, development and aging. Various phosphorylation site prediction models have been developed, which can be broadly categorized as being kinase-specific or non-kinase specific (general). Unlike the latter, the former requires a large enough number of experimentally known phosphorylation sites annotated with a given kinase for training the model, which is not the case in reality: less than 3% of the phosphorylation sites known to date have been annotated with a responsible kinase. To date, there are a few non-kinase specific phosphorylation site prediction models proposed.ResultsThis paper proposes SKIPHOS, a non-kinase specific phosphorylation site prediction model based on random forests on top of a continuous distributed representation of amino acids. Experimental results on the benchmark dataset and the independent test set demonstrate that SKIPHOS compares favorably to recent state-of-the-art related methods for three phosphorylation residues. Although being trained on phosphorylation sites in mamals, SKIPHOS can yield predictions for Y residues better than PHOSFER, a recently proposed plants-specific phosphorylation prediction model.Availability and ImplementationSKIPHOS Web Server is freely available for non-commercial use athttp://fit.uet.vnu.edu.vn/SKIPHOSorhttp://112.137.130.46:5000.Contacthai.dang@vnu.edu.vnSupplementary informationSupplementary data are available atBioinformaticsonline.
Control of brain state transitions with light
Authors: Barbero-Castillo Almudena , Riefolo Fabio , Matera Carlo , Caldas-Martínez Sara , Mateos-Aparicio Pedro , Weinert Julia F. , Claro Enrique , Sánchez-Vives Maria Victoria , Gorostiza Pau 
Published: October 2019

ABSTRACTBehavior is driven by specific neuronal activity and can be directly associated with characteristic brain states. The oscillatory activity of neurons contains information about the mental state of an individual, and the transition between physiological brain states is largely controlled by neuromodulators. Manipulating neural activity, brain rhythms or synchronization is of significant therapeutic interest in several neurological disorders and can be achieved by different means such as transcranial current and magnetic stimulation techniques, and by light through optogenetics, although the clinical translation of the latter is hampered by the need of gene therapy. Here, we directly modulate brain rhythms with light using a novel photoswitchable muscarinic agonist. Synchronous slow wave activity is transformed into a higher frequency pattern in the cerebral cortex both in slices in vitro and in anesthetized mice. These results open the way to the study of the neuromodulation and control of spatiotemporal patterns of activity and pharmacology of brain states, their transitions, and their links to cognition and behavior, in different organisms without requiring any genetic manipulation.
B-cell enforced expression of the mouse ortholog of MYD88L265P is responsible for Waldenström-like B-cell lymphoma
Authors: Ouk Catherine , Roland Lilian , Saintamand Alexis , Gachard Nathalie , Thomas Morgane , Devéza Mélanie , Faumont Nathalie , Feuillard Jean , Vincent-Fabert Christelle 
Published: October 2019

AbstractHere, we created a conditional transgenic mouse model with insertion of a sequence coding for both MYD88L252P and the Yellow Fluorescent Protein (YFP) into the rosa26-locus. B-cell specific induction of the transgene constantly led to spleen enlargement with expansion of YFP positive B-cells in 8-12 month-old mice, with a moderate B-cell proliferation increase. Being clonal or oligoclonal, these B-cells exhibited a marked morphological and immunophenotypic lymphoplasmocytic aspect with a plasma cell transcriptomic signature and a serum immunoglobulin M peak. Therefore, continuous activation of MYD88 in mice can lead on its own to a lymphoma close to Waldenström Macroglobulinemia.Key pointB-cell specific enforced expression of MYD88L252P leads to a clonal indolent lymphoplasmocytic B-cell lymphoma with a serum IgM peak.
Structural effects and functional implications of phalloidin and jasplakinolide binding to actin filaments
Authors: Pospich Sabrina , Merino Felipe , Raunser Stefan 
Published: October 2019

SummaryActin undergoes structural transitions during polymerization, ATP hydrolysis and subsequent release of inorganic phosphate. Several actin binding proteins sense specific states during this transition and can thus target different regions of the actin filament. Here we show in atomic detail that phalloidin, a mushroom toxin that is routinely used to stabilize and label actin filaments, suspends the structural changes in actin, likely influencing its interaction with actin binding proteins. Furthermore, high-resolution cryo-EM structures reveal structural rearrangements in F-actin upon inorganic phosphate release in phalloidin-stabilized filaments. We find that the effect of the sponge toxin jasplakinolide differs from the one of phalloidin, despite their overlapping binding site and similar interactions with the actin filament. Analysis of structural conformations of F-actin suggests that stabilizing agents trap states within the natural conformational space of actin.Abstract FigureHighlightsFive high-resolution cryo-EM structures of stabilized filamentous actinPhalloidin traps different structural states depending on when it is addedThe effect of phalloidin and jasplakinolide on filamentous actin is not identicalBoth toxins likely interfere with the binding of proteins sensing F-actin’s nucleotide state