bluuebunny/crossref_metadata_2025_split huggingface dataset:
SERRATE interacts with the nuclear exosome targeting (NEXT) complex to degrade primary miRNA precursors in Arabidopsis
Authors: Bajczyk Mateusz , Lange Heike , Bielewicz Dawid , Szewc Lukasz , Bhat Susheel Sagar , Dolata Jakub , Kuhn Lauriane , Szweykowska-Kulinska Zofia , Gagliardi Dominique , Jarmolowski Artur 
Published: April 2020

AbstractSERRATE/ARS2 is a conserved RNA effector protein involved in transcription, processing and export of different types of RNAs. In Arabidopsis, the best-studied function of SERRATE (SE) is to promote miRNA processing. Here, we report that SE interacts with the Nuclear Exosome Targeting (NEXT) complex, comprising the RNA helicase HEN2, the RNA binding protein RBM7 and one of the two zinc-knuckle proteins ZCCHC8A/ZCCHC8B. The identification of common targets of SE and HEN2 by RNA-seq supports the idea that SE cooperates with NEXT for RNA surveillance by the nuclear exosome. Among the RNA targets accumulating in absence of SE or NEXT are miRNA precursors. Loss of NEXT components results in the accumulation of pri-miRNAs without affecting levels of miRNAs, indicating that NEXT is, unlike SE, not required for miRNA processing. As compared tose-2,se-2 hen2-2double mutants showed increased accumulation of pri-miRNAs, but partially restored levels of mature miRNAs and attenuated developmental defects. We propose that the slow degradation of pri-miRNAs caused by loss of HEN2 compensates for the poor miRNA processing efficiency inse-2mutants, and that SE regulates miRNA biogenesis through its double contribution in promoting miRNA processing but also pri-miRNA degradation through the recruitment of the NEXT complex.
MicroHapDB: a portable and extensible database of all published microhaplotype marker and frequency data
Authors: Standage Daniel , Mitchell Rebecca 
Published: April 2020

ABSTRACTMicrohaplotypes are the subject of significant interest in the forensics community as a promising multi-purpose forensic DNA marker for human identification. Microhaplotype markers are composed of multiple SNPs in close proximity, such that a single NGS read can simultaneously genotype the individual SNPs and phase them in aggregate to determine the associated donor haplotype. Abundant throughout the human genome, numerous recent studies have sought to discover and rank microhaplotype markers according to allelic diversity within and among populations. Microhaplotypes provide an appealing alternative to STR markers for human identification and mixture deconvolution, but can also be optimized for ancestry inference or combined with phenotype SNPs for prediction of externally visible characteristics in a multiplex NGS assay. Designing and evaluating panels of microhaplotypes is complicated by the lack of a convenient database of all published data, as well as the lack of population allele frequency data spanning disparate marker collections. We present MicroHapDB, a comprehensive database of published microhaplotype marker and frequency data, as a tool to advance the development of microhaplotype-based human forensics capabilities. We also present population allele frequencies derived from 26 global population samples for all microhaplotype markers published to date, facilitating the design and interpretation of custom multi-source panels. We submit MicroHapDB as a resource for community members engaged in marker discovery, population studies, assay development, and panel and kit design.
Estrogen receptor alpha mutations in breast cancer cells cause gene expression changes through constant activity and secondary effects
Authors: Arnesen Spencer , Blanchard Zannel , Williams Michelle M , Berrett Kristofer C , Li Zheqi , Oesterreich Steffi , Richer Jennifer K , Gertz Jason 
Published: April 2020

AbstractWhile breast cancer patients with tumors that express estrogen receptor α (ER) generally respond well to hormone therapies that block ER activity, a significant number of patients relapse. Approximately 30% of these recurrences harbor activating mutations in the ligand binding domain (LBD) of ER, which have been shown to confer ligand-independent function. However, much is still unclear regarding the effect of mutant ER beyond its estrogen independence. To investigate the molecular effects of mutant ER, we developed multiple isogenic ER mutant cell lines for the most common LBD mutations, Y537S and D538G. These mutations induced differential expression of thousands of genes, the majority of which were mutant allele-specific and were not observed upon estrogen treatment of wildtype cells. These mutant-specific genes showed consistent differential expression across ER mutant lines developed in other laboratories. Wildtype cells with long-term estrogen exposure only exhibited some of these transcriptional changes, suggesting that mutant ER causes novel regulatory effects that are not simply due to constant activity. While ER mutations exhibited minor effects on ER genomic binding, with the exception of ligand independence, ER mutations conferred substantial differences in chromatin accessibility. Mutant ER was bound to approximately a quarter of mutant-enriched accessible regions that were enriched for other DNA binding factors including FOXA1, CTCF, and OCT1. Overall, our findings indicate that mutant ER causes several consistent effects on gene expression, both indirectly and through constant activity.
The Series of a Four-node Motif and Coherent Type-1 Feed-forward Loop can Provide Sensitive Detection over Arbitrary Range of Input Signal, thereby Explain Weber’s Law in Higher-Order Sensory Processes, and Compute Logarithm
Authors: Wadhwa Dinkar 
Published: April 2020

AbstractWeber’s law states that the ratio of the smallest perceptual change in an input signal and the background signal is constant. The law is observed across the perception of weight, light intensity, and sound intensity and pitch. Conventionally, two models of perception have been proposed to explain Weber’s law, namely the logarithmic and the linear model. Later, another formulation of Weber’s law was proposed which links it with exact adaptation. This paper argues in favour of the linear model, which requires the sensory system to generate linear input-output relationship over several orders of magnitude. To this end, a four-node motif (FNM) is constructed from first principles whose series provides almost linear relationship between input signal and output over arbitrary range of input signal. Mathematical analysis into the origin of this quasi-linear relationship shows that the series of coherent type-1 feed-forward loop (C1-FFL) is able to provide perfectly linear input-output relationship over arbitrary range of input signal. FNM also reproduces the neuronal data of numerosity detection study on monkey. The series of FNM also provides a mechanism for sensitive detection over arbitrary range of input signal when the output has an upper limit. Further, the series of FNM provides a general basis for a class of bow-tie architecture where the number of receptors is much lower than the range of input signal and the “decoded output”. Besides (quasi-)linear input-output relationship, another example of this class of bow-tie architecture that the series of FNM is able to produce is absorption spectra of cone opsins of humans. Further, the series of FNM and C1-FFL, respectively, can compute logarithm over arbitrary range of input signal.
Climate, crypsis and Gloger’s rule in a large family of tropical passerine birds (Furnariidae)
Authors: Marcondes Rafael S. , Nations Jonathan A. , Seeholzer Glenn F. , Brumfield Robb T. 
Published: April 2020

AbstractGloger’s rule predicts endothermic animals should have darker colors under warm and rainy climates, but empirical studies have typically found that animals tend to be darker under cool and rainy climates. Moreover, Gloger’s rule has rarely been tested jointly with the prediction that animals occupying dark habitats should have darker colors to enhance crypsis. We aimed to disentangle the effects of climate and light environments (habitat type) as correlates of plumage brightness in a large Neotropical passerine family. We found that cooler and rainier climates are associated with darker plumage, even after accounting for habitat types, and that darker habitats are associated with darker plumage, even after accounting climate. There was an important interaction between precipitation and temperature, whereby the negative effect of temperature on brightness becomes stronger under cooler temperatures. Climate and light environments have separate but complementary effects in driving macroevolutionary patterns of plumage color variation in birds.
Thyroglobulin Interactome Profiling Uncovers Molecular Mechanisms of Thyroid Dyshormonogenesis
Authors: Wright Madison T. , Kouba Logan , Plate Lars 
Published: April 2020

ABSTRACTThyroglobulin (Tg) is a secreted iodoglycoprotein serving as the precursor for T3 and T4 hormones. Many characterized Tg gene mutations produce secretion-defective variants resulting in congenital hypothyroidism (CH). Tg processing and secretion is controlled by extensive interactions with chaperone, trafficking, and degradation factors comprising the secretory proteostasis network. While dependencies on individual proteostasis network components are known, the integration of proteostasis pathways mediating Tg protein quality control and the molecular basis of mutant Tg misprocessing remain poorly understood. We employ a multiplexed quantitative affinity purification–mass spectrometry approach to define the Tg proteostasis interactome and changes between WT and several CH-variants. Mutant Tg processing is associated with common imbalances in proteostasis engagement including increased chaperoning, oxidative folding, and routing towards ER-associated degradation components, yet variants are inefficiently degraded. Furthermore, we reveal mutation-specific changes in engagement with N-glycosylation components, suggesting distinct requirements for one Tg variant on dual engagement of both oligosaccharyltransferase complex isoforms for degradation. Modulating dysregulated proteostasis components and pathways may serve as a therapeutic strategy to restore Tg secretion and thyroid hormone biosynthesis.
An approach for normalization and quality control for NanoString RNA expression data
Authors: Bhattacharya Arjun , Hamilton Alina M. , Furberg Helena , Pietzak Eugene , Purdue Mark P. , Troester Melissa A. , Hoadley Katherine A. , Love Michael I. 
Published: April 2020

ABSTRACTThe NanoString RNA counting assay for formalin-fixed paraffin embedded samples is unique in its sensitivity, technical reproducibility, and robustness for analysis of clinical and archival samples. While commercial normalization methods are provided by NanoString, they are not optimal for all settings, particularly when samples exhibit strong technical or biological variation or where housekeeping genes have variable performance across the cohort. Here, we develop and evaluate a more comprehensive normalization procedure for NanoString data with steps for quality control, selection of housekeeping targets, normalization, and iterative data visualization and biological validation. The approach was evaluated using a large cohort (N = 1,649) from the Carolina Breast Cancer Study, two cohorts of moderate sample size (N = 359 and 130), and a small published dataset (N = 12). The iterative process developed here eliminates technical variation (e.g. from different study phases or sites) more reliably than the three other methods, including NanoString’s commercial package, without diminishing biological variation, especially in long-term longitudinal multi-phase or multi-site cohorts. We also find that probe sets validated for nCounter, such as the PAM50 gene signature, are impervious to batch issues. This work emphasizes that systematic quality control, normalization, and visualization of NanoString nCounter data is an imperative component of study design that influences results in downstream analyses.
Activity dependent translation in astrocytes dynamically alters the proteome of the perisynaptic astrocyte process
Authors: Sapkota D. , Kater M.S.J. , Sakers K. , Nygaard K.R. , Liu Y. , Lake A.M. , Khazanchi R. , Khankan R.R. , Smit A.B. , Maloney S.E. , Verheijen M.H.G. , Zhang Y. , Dougherty J.D. 
Published: April 2020

AbstractGene expression requires two steps – transcription and translation – which can be regulated independently to allow nuanced, localized, and rapid responses to cellular stimuli. Neurons are known to respond transcriptionally and translationally to bursts of brain activity, and a transcriptional response to this activation has also been recently characterized in astrocytes. However, the extent to which astrocytes respond translationally is unknown. We tested the hypothesis that astrocytes also have a programmed translational response by characterizing the change in transcript ribosome occupancy in astrocytes using Translating Ribosome Affinity Purification(TRAP) subsequent to a robust induction of neuronal activityin vivovia acute seizure. We identified a change in transcripts on astrocyte ribosomes, highlighted by a rapid decrease in transcripts coding for ribosomal and mitochondrial components, and a rapid increase in transcripts related to cytoskeletal dynamics, motor activity, ion transport, and cell communication. This indicates a set of dynamic responses, some of which might be secondary to activation of Receptor Tyrosine Kinase(TRK) signaling. Using acute slices, we quantified the extent to which individual cues and sequela of neuronal activity can activate translation acutely in astrocytes. We identified both BDNF and ion concentration changes as contributors to translation induction, with potassium using both action-potential sensitive and insensitive components. We showed this translational response requires the presence of neurons, indicating the response is non-cell autonomous. We also show that this induction of new translation extends into peripheral astrocyte processes (PAPs). Accordingly, proteomics following fear conditioning in mice, showed that new translation influences peri-synaptic astrocyte protein compositionin vivounder physiological conditions. Regulation of translation in astrocytes by neuronal activity suggests an additional mechanism by which astrocytes may dynamically modulate nervous system functioning.Main PointsAstrocytes have a programmed, transcript-specific translational response to neuronal activity.Both BDNF and K+, cues of neuronal activity, trigger this response.This response requires the presence of neurons.This response alters the astrocytic protein composition at the synapse.
Whole transcriptomein-silicoscreening implicates cardiovascular and infectious disease in the mechanism of action underlying atypical antipsychotic side-effects
Authors: Malekizadeh Yasaman , Williams Gareth , Kelson Mark , Whitfield David , Mill Jonathan , Collier David A , Ballard Clive , Jeffries Aaron R , Creese Byron 
Published: April 2020

AbstractINTRODUCTIONStroke/thromboembolic events, infections and death are all significantly increased by antipsychotics in dementia but little is known about why they can be harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify potential mechanisms underlying adverse events.METHODWhole transcriptome signatures were generated for SH-SY5Y cells treated with amisulpride, risperidone and volinanserin using RNA-sequencing. Bioinformatic analysis was performed which scored the association between antipsychotic signatures and expression data from 415,252 samples in the NCBI GEO repository.RESULTSAtherosclerosis, venous thromboembolism and influenza NCBI GEO-derived samples scored positively against antipsychotic signatures. Pathways enriched in antipsychotic signatures were linked to the cardiovascular and immune systems (e.g. BDNF, PDGFR-beta, TNF, TGF-beta, selenoamino acid metabolism and influenza infection).CONCLUSIONThese findings for the first time mechanistically link antipsychotics to specific cardiovascular and infectious diseases which are known side effects of their use in dementia, providing new information to explain related adverse events.
A novel method to protect bronze in atmospheric environment: the click-assembly of triazole film
Authors: Zhou Hao , Zhang Kai , Zhang Lin , Lu Jiamin , Li Jin , Zhang Daquan , Gao Lixin 
Published: April 2020

Purpose
The authors have prepared the triazole film on copper surface by click reaction and explored its inhibition mechanism.

Design/methodology/approach
The protective film is assembled by immersing bronze in solution containing p-toluenesulfonyl azide (TA) and propiolic acid (PA).

Findings
Fourier transform infrared spectroscopy (FT-IR) indicates that triazole (TTP) film was formed on bronze surface via click chemistry reaction between TA and PA. It shows TTP film has a good protection for bronze in the atmospheric environment simulation solution. Quantum chemical calculation (QC) and molecule dynamics simulation suggests TTP molecule adsorbs on bronze surface via N and O.

Originality/value
This is beneficial to develop the corrosion inhibitors for the corroded copper alloys.
Study of the corrosion protection efficiency of polypyrrole/metal oxide nanocomposites as additives in anticorrosion coating
Authors: Rajkumar R. , Vedhi C. 
Published: April 2020

PurposePolypyrrole (PPy) and PPy/metal oxide nanocomposites were synthesized by oxidative polymerization process, and its corrosion protection ability was studied by immersion test and electrochemical corrosion studies in 1 per cent HCl and 3.5 per cent NaCl solution.Design/methodology/approachThe prepared composites were loaded in acrylic resin and subsequently coated on a mild steel surface. The characterization of the polymer composites using FT-IR, UV-vis, XRD and FE-SEM with EDS analysis confirmed the interaction between PPy and metal oxide nanoparticles. The PPy nanoparticles were less protected on the mild steel, but the nanocomposite coating with metal oxide nanoparticles dramatically increased the corrosion resistance.FindingsAccording to the corrosion protection ability of the coating, it was demonstrated that the acrylic resin coating composed of PPy/metal oxide nanocomposites was highly efficient in protecting the mild steel compared to the PPy nanoparticles. The highest protection efficiency was obtained by PPy/TiO2 nanocomposites with acrylic resin coating.Originality/valueTo the best of the authors’ knowledge, this paper consists of original, unpublished work which is not under consideration for publication elsewhere and that all the co-authors have approved the contents of this manuscript and submission.
What is discussed about eldercare?
Authors: Zhao Dongxiang , Zhang Qiping , Ma Feicheng 
Published: April 2020

Purpose
The purpose of this paper is to investigate eldercare issues in China through exploring what was discussed about eldercare in a Chinese online community for older adults (OCOA).

Design/methodology/approach
Netnography was used to explore eldercare-related online discussion in a Chinese OCOA – LaoYouBang. After a two-month-long online observation, 275 microblogs and 594 comments were collected and analysed qualitatively and quantitatively.

Findings
The main findings include as follows: the users involved in an online discussion about eldercare were consist of four categories, namely, elderly user, non-elderly user, advertiser and community administrator. Non-elderly user include the elderly’s caregivers and families, young and middle-aged people concerning about eldercare. From 2012 to 2017, eldercare issues gradually became refined and differentiated in China and elderly users’ contribution proportion and activeness increased yearly. According to the results of thematic analysis, users’ information needs for eldercare included opinion, news, practice, emotion, knowledge and others. In China, some changes have taken place in the public’s conceptions of eldercare, embodied in the changes in the public’s attention, attitudes and cognition. Changes in user structure and communication patterns in OCOA have also been noted. OCOA plays an important role in eldercare information dissemination and social support exchange and helps to meet the eldercare challenges.

Originality/value
This study explored an online community for older adults. This is the first netnography study in the information field on Chinese OCOA. This paper provides new perspectives to explore eldercare issues and OCOA in other regions and cultures and it also provides some suggestions to improve OCOA.
A finite element model for estimating time-dependent reliability of a corroded pipeline elbow
Authors: Nahal Mourad , Khelif Rabia 
Published: April 2020

PurposeThe aim of this paper is to investigate the failure probability in an irregular area in pipeline (elbow) over its lifetime. The reliability analysis is performed by using of an enhanced first-order reliability method / second-order reliability method (FORM/SORM) and Monte Carlo simulation methods: a numerical model of a corroded pipeline elbow was developed by using finite element method; also, an empirical mechanical behavior model has been proposed. A numerical case with high, moderate and low corrosion rates was conducted to calculate the deferent reliability indexes. The found results can be used in an application case for managing an irregular area in pipeline lifetime. Hence, it is necessary to ensure a rigorous inspection for this part of a pipeline to avoid human and environmental disasters.Design/methodology/approachThe present paper deals a methodology for estimating time-dependent reliability of a corroded pipeline elbow. Firstly, a numerical model of corroded elbow is proposed by using the finite element method. A mechanical behavior under the corrosion defect in time is studied, and an empirical model was also developed.FindingsThe result of this paper can be summarized as: a mechanical characterization of the material was carried out experimentally. A numerical model of a corroded pipeline elbow was developed by using the finite element method. An empirical mechanical behavior model has been developed. The reliability of a corroding pipe elbow can be significantly affected by corrosion and residual stress. A proportional relationship has been found between probability of failure and corrosion rate. The yield stress and pressure service have an important sensitivity factor.Originality/valueAiming to help Algerian gas and oil companies' decision makers, the present paper illustrates a methodology for estimating time-dependent reliability of a corroded pipeline elbow over its lifetime using numerical models by applying the finite element method. Firstly, a numerical model of a corroded pipe elbow was developed and coupled with an empirical mechanical behavior model, which is also proposed. A probabilistic is then developed to provide realistic corrosion parameters and time modeling, leading to the real impact on the lifetime of an elbow zone in pipeline. The reliability indexes and probability of failure for various corrosion rates with and without issued residual stress are computed using Monte Carlo simulation and FORM.