bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influenza A virus endoribonuclease PA-X usurps host mRNA processing machinery to limit host gene expression
Authors: Gaucherand Lea , Porter Brittany K. , Schmaling Summer K. , Rycroft Christopher Harley , Kevorkian Yuzo , McCormick Craig , Khaperskyy Denys A. , Gaglia Marta Maria 
Published: October 2018

SUMMARYMany viruses globally shut off host gene expression to inhibit activation of cell-intrinsic antiviral responses. However, host shutoff is not indiscriminate, since viral proteins and host proteins required for viral replication are still synthesized during shutoff. The molecular determinants of target selectivity in host shutoff remain incompletely understood. Here, we report that the influenza A virus shutoff factor PA-X usurps RNA splicing to selectively target host RNAs for destruction. PA-X preferentially degrades spliced mRNAs, both transcriptome-wide and in reporter assays. Moreover, proximity-labeling proteomics revealed that PA-X interacts with cellular proteins involved in RNA splicing. The interaction with splicing contributes to target discrimination and is unique among viral host shutoff nucleases. This novel mechanism sheds light on the specificity of viral control of host gene expression and may provide opportunities for development of new host-targeted antivirals.
Hippocampal State Transitions at the Boundaries between Trial Epochs
Authors: Bulkin David A. , Sinclair David G. , Law L. Matthew , Smith David M. 
Published: October 2018

AbstractThe hippocampus encodes distinct environmental and behavioral contexts with unique patterns of activity. Representational shifts with changes in the context, referred to as remapping, have been extensively studied. However, less is known about the nature of transitions between representations. In this study, we leverage a large dataset of 2056 neurons recorded while rats performed an olfactory memory task with a predictable temporal structure involving trials and inter-trial intervals, separated by salient boundaries at the trial start and trial end. We found that trial epochs were associated with stable hippocampal population representations, despite moment to moment variability in stimuli and behavior. Representations of trial and inter-trial interval epochs were far more distinct than spatial factors would predict and the transitions between the two were abrupt, with a sharp boundary suggestive of a dynamic shift in the representational state. This boundary was associated with a large spike in multi-unit activity, with many individual cells specifically active at the start or end of each trial. Both epochs and boundaries were encoded by hippocampal populations, and these representations carried information on orthogonal axes readily identified using principal component analysis. We suggest that the activity spike at trial boundaries might serve to drive hippocampal activity from one stable state to another, and may play a role in segmenting continuous experience into discrete episodic memories.
A flexible and generalizable model of online latent-state learning
Authors: Cochran Amy L , Cisler Josh M 
Published: October 2018

AbstractMany models of classical conditioning fail to describe important phenomena, notably the rapid return of fear after extinction. To address this shortfall, evidence converged on the idea that learning agents rely on latent-state inferences, i.e. an ability to index disparate associations from cues to rewards (or penalties) and infer which index (i.e. latent state) is presently active. Our goal was to develop a model of latent-state inferences that uses latent states to predict rewards from cues efficiently and that can describe behavior in a diverse set of experiments. The resulting model combines a Rescorla-Wagner rule, for which updates to associations are proportional to prediction error, with an approximate Bayesian rule, for which beliefs in latent states are proportional to prior beliefs and an approximate likelihood based on current associations. In simulation, we demonstrate the model’s ability to reproduce learning effects both famously explained and not explained by the Rescorla-Wagner model, including rapid return of fear after extinction, the Hall-Pearce effect, partial reinforcement extinction effect, backwards blocking, and memory modification. Lastly, we derive our model as an online algorithm to maximum likelihood estimation, demonstrating it is an efficient approach to outcome prediction. Establishing such a framework is a key step towards quantifying normative and pathological ranges of latent-state inferences in various contexts.Author summaryComputational researchers are increasingly interested in a structured form of learning known as latent-state inferences. Latent-state inferences is a type of learning that involves categorizing, generalizing, and recalling disparate associations between observations in one’s environment and is used in situations when the correct association is latent or unknown. This type of learning has been used to explain overgeneralization of a fear memory and the cognitive role of certain brain regions important to cognitive neuroscience and psychiatry. Accordingly, latent-state inferences are an important area of inquiry. Through simulation and theory, we establish a new model of latent-state inferences. Moving forward, we aim to use this framework to measure latent-state inferences in healthy and psychiatric populations.
A role for long-range, through-lattice coupling in microtubule catastrophe
Authors: Kim Tae , Rice Luke M. 
Published: October 2018

AbstractMicrotubules are cylindrical polymers of αβ-tubulin that play critical roles in fundamental processes like chromosome segregation and vesicular transport. Microtubules display dynamic instability, switching stochastically between growing and rapid shrinking as a consequence of GTPase activity in the lattice. The molecular mechanisms behind microtubule catastrophe, the switch from growing to rapid shrinking, remain poorly defined. Indeed, two-state stochastic models that seek to describe microtubule dynamics purely in terms of the biochemical properties of GTP- and GDP-bound αβ-tubulin incorrectly predict the concentration-dependence of microtubule catastrophe. Recent studies provided evidence for three distinct conformations of αβ-tubulin in the lattice that likely correspond to GTP, GDP.Pi, and GDP. The incommensurate lattices observed for these different conformations raises the possibility that in a mixed nucleotide state lattice, neighboring tubulin dimers might modulate each other’s conformations and hence their biochemistry. We explored whether incorporating a GDP.Pistate or the likely effects of conformational accommodation can improve predictions of catastrophe. Adding a GDP.Piintermediate did not improve the model. In contrast, adding neighbor-dependent modulation of tubulin biochemistry improved predictions of catastrophe. Conformational accommodation should propagate beyond nearest-neighbor contacts, and consequently our modeling demonstrates that long-range, through-lattice effects are important determinants of microtubule catastrophe.
Endovascular stroke treatment does not preclude high thrombolysis rates
Authors: Feda S. , Nikoubashman O. , Schürmann K. , Matz O. , Tauber S. C. , Wiesmann M. , Schulz J. B. , Reich A. 
Published: October 2018

Background and purposeIn 1995 intravenous recombinant tissue plasminogen activator (IVRTPA) was the first reperfusion therapy to be approved in patients with acute ischaemic stroke (AIS). The significance and impact of IVRTPA in times of modern endovascular stroke treatment (EST) were analysed in a German academic stroke centre.MethodsA retrospective observational cohort analysis of 1034 patients with suspected AIS presenting at the emergency department in 2014 was performed. Patients were evaluated for baseline characteristics, reperfusion procedures, IVRTPA eligibility, clinical outcome, symptomatic intracranial haemorrhage (sICH) and mortality. Data acquisition was part of an investigator‐initiated, prospective and blinded end‐point registry.ResultsIn 718 (69%) patients the diagnosis of symptomatic AIS was confirmed. 419 (58%) patients presented within 4.5 h of symptom onset and of those 260 (62%) received reperfusion therapy (IVRTPA alone, n = 183; combination or bridging therapy, n = 60; EST alone, n = 17). Subtracting cases with absolute contraindications for IVRTPA resulted in an effective thrombolysis rate of 82%. sICH occurred in two patients treated with IVRTPA alone (1.1%). The median door‐to‐needle interval was 30 min. Fifty (17%) non‐EST eligible AIS patients presenting within 4.5 h without absolute contraindications did not receive IVRTPA mainly due to mild or regressive symptoms. Most of these untreated IVRTPA eligible patients (82%) were discharged with a good clinical outcome (modified Rankin Scale ≤ 2).ConclusionsIntravenous recombinant tissue plasminogen activator remains the most frequently applied reperfusion therapy in AIS patients presenting within 4.5 h of onset in a tertiary stroke centre. An effective thrombolysis rate of over 80% can be achieved without increased rates of sICH.
Effectiveness of complementary irrigation routines in debriding pulp tissue from root canals instrumented with a single reciprocating file
Authors: Varela P. , Souza E. , de Deus G. , Duran‐Sindreu F. , Mercadé M. 
Published: October 2018

AbstractAimTo compare histologically the debridement efficacy of four irrigation techniques in root canals instrumented with a reciprocating single file.MethodologyFrom recently extracted premolars with vital pulp, 68 were selected and classified as having round canals (mesiodistal diameter similar to buccolingual) or oval‐shaped canals (mesiodistal diameter 2.5 times larger than buccolingual) (n = 32, each) by means of bidirectional radiographs. Four additional uninstrumented samples served as histological controls. The root canals of the specimens were accessed and then instrumented with Reciproc R25® and further assigned to one of four experimental groups according to the complementary irrigation technique: Group I, conventional syringe; Group II, passive ultrasonic irrigation; Group III, manual dynamic activation (MDA); and Group IV, EndoActivator®. Roots were then demineralized and the apical 3 mm was multi‐sliced and processed for histologic examination. The percentage of residual pulp tissue was calculated at each cross section. Kruskal–Wallis and Mann–Whitney tests were used to evaluate the effects of irrigation technique, root canal shape and level of cross section on the percentage of residual pulp tissue (P < 0.05).ResultsIrrigation technique and root canal shape significantly influenced the percentage of residual pulp tissue (P < 0.05) of canals instrumented with the R25 instrument. Percentage of residual pulp tissue was significantly less using ultrasonic irrigation (P < 0.05), but there was no difference between other irrigation techniques (P > 0.05). Round canals retained significantly less percentage of residual pulp tissue compared to oval‐shaped canals (P = 0.001). At 3 mm, there was less pulp tissue compared to levels 2 and 1 mm (P < 0.05).ConclusionsIn canals instrumented with R25 files, ultrasonic irrigation was more effective in removing pulp tissue in the apical level, especially for the debridement of oval‐shaped canals.
Novel four‐session treatment intervention for anxiety and high‐functioning autism: A single case report for Externalizing Metaphors Therapy
Authors: McGuinty Everett F. , Bird Brian M. , Nelson John , McGuinty Jazlyn L. , Cashin Andrew 
Published: October 2018

AbstractTopicThe Brief Services psychotherapy paradigm has evolved to produce cost‐effective and clinically significant outcomes in children's mental health. Though its clinical evaluation is still in its infancy, it has been utilized to a much lesser degree with autism spectrum disorders, which typically require a longer‐term approach to psychotherapy treatment.PurposeThe current paper introduces a novel, four‐session intervention that aims to decrease anxiety experienced by clients presenting with high‐functioning autism. Externalizing Metaphors Therapy is based upon the externalization of problems, transformation of metaphoric imagery, shifting of maladaptive emotional schemas, and the generalization of problems. A case study is utilized to visually aid in the understanding of this new treatment intervention.SourceA composite literature review was conducted with regards to significant works in Narrative Therapy, treatment interventions for anxiety and high functioning autism, evidence‐based treatments for anxiety, and practice based approaches in psychotherapy. Works were selected based on their relevance to the research filed of anxiety and autism.ConclusionsThis clinical research challenges the children's mental health field in addressing anxiety and high‐functioning autism from a brief framework. Further clinical research is needed to clinically evaluate the current model.
Long‐term efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis: subgroup analyses of an open‐label, phase 3 study (UNCOVER‐J)
Authors: Okubo Y. , Mabuchi T. , Iwatsuki K. , Elmaraghy H. , Torisu‐Itakura H. , Morisaki Y. , Nakajo K. 
Published: October 2018

AbstractBackgroundErythrodermic and generalized pustular psoriasis are rare, difficult to treat forms of psoriasis. In previous reports, we documented 24‐ and 52‐week findings of an open‐label, phase 3 trial (UNCOVER‐J) of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis; most patients responded to treatment and maintained response through 52 weeks.ObjectiveTo assess the long‐term (>3 years) efficacy and safety of ixekizumab in Japanese patients with erythrodermic or generalized pustular psoriasis.MethodsThese subgroup analyses were of a partial population of patients from UNCOVER‐J (NCT01624233; Sponsored by Eli Lilly and Company), specifically those with erythrodermic psoriasis (N = 8) or generalized pustular psoriasis (N = 5). These patients received 160 mg ixekizumab at Week 0, ixekizumab 80 mg every 2 weeks through Week 12, and ixekizumab 80 mg every 4 weeks thereafter up to Week 244. This regimen is consistent with the regimen approved in Japan for plaque, erythrodermic, and generalized pustular psoriasis and psoriatic arthritis. Efficacy assessments included Global Improvement Score (GIS), Psoriasis Area and Severity Index (PASI), dermal symptoms (for patients with generalized pustular psoriasis), Dermatology Life Quality Index (DLQI) and Itch Numeric Rating Scale (NRS). Safety assessments included treatment‐emergent adverse events and adverse events of special interest.ResultsMost patients had a GIS of resolved or improved from Week 12 onwards, and all patients had early and sustained improvement in PASI and dermal symptom (generalized pustular psoriasis only) scores. Mean improvements in DLQI and Itch NRS at Week 12 were sustained through Week 244. Ixekizumab was well tolerated over 3 years of treatment in patients with erythrodermic psoriasis or generalized pustular psoriasis, and no new safety concerns were identified.ConclusionThese findings suggest that ixekizumab can be an effective long‐term treatment option for erythrodermic or generalized pustular psoriasis.
Intra‐cortical myelin mediates personality differences
Authors: Toschi Nicola , Passamonti Luca 
Published: October 2018

AbstractObjectiveDifferences in myelination in the cortical mantle are important neurobiological mediators of variability in cognitive, emotional, and behavioral functioning. Past studies have found that personality traits reflecting such variability are linked to neuroanatomical and functional changes in prefrontal and temporo‐parietal cortices. Whether these effects are partially mediated by the differences in intra‐cortical myelin remains to be established.MethodTo test this hypothesis, we employed vertex‐wise intra‐cortical myelin maps in n = 1,003 people from the Human Connectome Project. Multivariate regression analyses were used to test for the relationship between intra‐cortical myelin and each of the five‐factor model’s personality traits, while accounting for age, sex, intelligence quotient, total intracranial volume, and the remaining personality traits.ResultsNeuroticism negatively related to frontal‐pole myelin and positively to occipital cortex myelin. Extraversion positively related to superior parietal myelin. Openness negatively related to anterior cingulate myelin, while Agreeableness positively related to orbitofrontal myelin. Conscientiousness positively related to frontal‐pole myelin and negatively to myelin content in the dorsal anterior cingulate cortex.ConclusionsIntra‐cortical myelin levels in brain regions with prolonged myelination are positively associated with personality traits linked to favorable outcome measures. These findings improve our understanding of the neurobiological underpinnings of variability in common behavioral dispositions.
Adeylithon bosencei gen. et sp. nov. (Corallinales, Rhodophyta): a new reef‐building genus with anatomical affinities with the fossil Aethesolithon
Authors: Peña Viviana , Le Gall Line , Rösler Anja , Payri Claude E. , Braga Juan Carlos 
Published: October 2018

Adeylithon gen. nov. with one species, A. bosencei sp. nov., belonging to the subfamily Hydrolithoideae is described from Pacific coral reefs based on psbA sequences and morpho‐anatomy. In contrast with Hydrolithon, A. bosencei showed layers of large polygonal “cells,” which resulted from extensive lateral fusions of perithallial cells, interspersed among layers of vegetative cells. This anatomical feature is shared with the fossil Aethesolithon, but lacking DNA sequences from the fossils and the fragmentary nature of Aethesolithon type material, we cannot ascertain if Adeylithon and Aethesolithon are congeneric. Morpho‐anatomical features of A. bosencei were generally congruent with diagnostic features of the subfamily Hydrolithoideae: (i) outline of cell filaments entirely lost in large portions due to pervasive and extensive cell fusions, (ii) trichocytes not arranged in tightly packed horizontal fields, (iii) basal layer without palisade cells, and (iv) cells lining the canal pore oriented more or less perpendicular to roof surface and not protruding into the canal. However, it showed a predominant monomerous thallus organization and trichocytes were disposed in large pustulate, horizontal fields, although they were not tightly packed and did not become distinctly buried in the thallus. Only mature tetrasporangial conceptacles were observed, therefore the type of conceptacle roof formation remained undetermined. Adeylithon bosencei occurs on shallow coral reefs, in Australia, Papua New Guinea, and South Pacific islands (Fiji, Vanuatu). Fossil Aethesolithon is considered an important component of shallow coral reefs since the Miocene; fossil records showed a broad Indo‐Pacific distribution, but a long‐term process of range contraction in the last 2.6 million years, resulting in an overlap with the distribution of the extant Adeylithon. While the congeneric nature of extant and fossil taxa remained uncertain, similarities in morpho‐anatomy, habitat, and distribution may indicate that both taxa likely shared a common ancestor.
Plant‐mediated effects of soil phosphorus on the root‐associated fungal microbiota in Arabidopsis thaliana
Authors: Fabiańska Izabela , Gerlach Nina , Almario Juliana , Bucher Marcel 
Published: October 2018

Summary

Plants respond to phosphorus (P) limitation through an array of morphological, physiological and metabolic changes which are part of the phosphate (Pi) starvation response (PSR). This response influences the establishment of the arbuscular mycorrhizal (AM) symbiosis in most land plants. It is, however, unknown to what extent available P and the PSR redefine plant interactions with the fungal microbiota in soil.

Using amplicon sequencing of the fungal taxonomic marker ITS2, we examined the changes in root‐associated fungal communities in the AM nonhost species Arabidopsis thaliana in response to soil amendment with P and to genetic perturbations in the plant PSR.

We observed robust shifts in root‐associated fungal communities of P‐replete plants in comparison with their P‐deprived counterparts, while bulk soil communities remained unaltered. Moreover, plants carrying mutations in the phosphate signaling network genes, phr1, phl1 and pho2, exhibited similarly altered root fungal communities characterized by the depletion of the chytridiomycete taxon Olpidium brassicae specifically under P‐replete conditions.

This study highlights the nutritional status and the underlying nutrient signaling network of an AM nonhost plant as previously unrecognized factors influencing the assembly of the plant fungal microbiota in response to P in nonsterile soil.
Use of trichostatin A alters the expression of HDAC3 and KAT2 and improves in vitro development of bovine embryos cloned using less methylated mesenchymal stem cells
Authors: Silva Carolina Gonzales da , Martins Carlos Frederico , Bessler Heidi Christina , da Fonseca Neto Álvaro Moraes , Cardoso Tereza Cristina , Franco Maurício Machaim , Mendonça Anelise dos Santos , Leme Ligiane de Oliveira , Borges José Renato Junqueira , Malaquias Juaci Vitoria , Báo Sônia Nair 
Published: October 2018

ContentsThe aim of this work was to investigate the methylation and hydroxymethylation status of mesenchymal stem cells (MSC) from amniotic fluid (MSC‐AF), adipose tissue (MSC‐AT) and fibroblasts (FIB‐control) and to verify the effect of trichostatin A (TSA) on gene expression and development of cloned bovine embryos produced using these cells. Characterization of MSC from two animals (BOV1 and BOV2) was performed by flow cytometry, immunophenotyping and analysis of cellular differentiation genes expression. The cells were used in the nuclear transfer in the absence or presence of 50 nM TSA for 20 hr in embryo culture. Expression of HDAC1, HDAC3 and KAT2A genes was measured in embryos by qRT‐PCR. Methylation results showed difference between animals, with MSC from BOV2 demonstrating lower methylation rate than BOV1. Meanwhile, MSC‐AF were less hydroxymethylated for both animals. MSC‐AF from BOV2 produced 44.92 ± 8.88% of blastocysts when embryos were exposed to TSA and similar to embryo rate of MSC‐AT also treated with TSA (37.96 ± 15.80%). However, when methylation was lower in FIB compared to MSC, as found in BOV1, the use of TSA was not sufficient to increase embryo production. MSC‐AF embryos expressed less HDAC3 when treated with TSA, and expression of KAT2A was higher in embryos produced with all MSC and treated with TSA than embryos produced with FIB. The use of MSC less methylated and more hydroxymethylated in combination with embryo incubation with TSA can induce lower expression of HDAC3 and higher expression of KAT2A in the embryos and consequently improve bovine embryo production.
On the numerical investigations to the Cahn-Allen equation by using finite difference method
Authors: Yokus Asıf , Bulut Hasan 
Published: October 2018

In this study, by using the finite difference method (FDM for short) and operators, the discretized Cahn-Allen equation is obtained. New initial condition for the Cahn-Allen equation is introduced, considering the analytical solution given in Application of the modified exponential function method to the Cahn-Allen equation, AIP Conference Proceedings 1798, 020033 [1]. It is shown that the FDM is stable for the usage of the Fourier-Von Neumann technique. Accuracy of the method is analyzed in terms of the errors in and Furthermore, the FDM is treated in order to obtain the numerical results and to construct a table including numerical and exact solutions as well as absolute measuring error. A comparison between the numerical and the exact solutions is supported with two and three dimensional graphics via Wolfram Mathematica 11.