bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromatin remodeling factor ARID2 suppresses hepatocellular carcinoma metastasis via DNMT1-Snail axis
Authors: Jiang Hao , Cao Hui-Jun , Ma Ning , Bao Wen-Dai , Wang Jing-Jing , Chen Tian-Wei , Zhang Er-Bin , Yuan Yan-Mei , Ni Qian-Zhi , Zhang Feng-Kun , Ding Xu-Fen , Zheng Qian-Wen , Wang Yi-Kang , Zhu Min , Wang Xiang , Feng Jing , Zhang Xue-Li , Cheng Shu-Qun , Ma Dan-Jun , Qiu Lin , Li Jing-Jing , Xie Dong 
Published: February 2020

Significance
In this study, we find that ARID2 expression is negatively correlated with HCC metastasis and positively associated with prognosis of HCC patients. We demonstrate that ARID2 inhibits metastasis of HCC cells by recruiting DNMT1 to the promoter of Snail, which elevates DNA methylation and suppresses Snail transcription. Notably, we discover a C2H2 truncated mutation (3817C > T) in metastatic HCC tissue. We further reveal that C2H2 domain is required for ARID2–DNMT1 interaction and find loss-of-function ARID2 mutants with disrupted C2H2 domain are positively associated with HCC metastasis and poor survival of HCC patients. Taken together, our study not only expands comprehensive understanding of ARID2 and its mutations in HCC, but also provides indication for treatment of ARID2-deficient HCC.
Proteins containing ubiquitin-like (Ubl) domains not only bind to 26S proteasomes but also induce their activation
Authors: Collins Galen A. , Goldberg Alfred L. 
Published: February 2020

Significance
Most protein degradation in eukaryotic cells is catalyzed by the 26S proteasome, which digests proteins marked for destruction by a chain of ubiquitin molecules. Typically, 26S proteasomes are present in cells as inactive particles that can become active when a ubiquitylated substrate binds. Proteasomes are usually viewed as containing a characteristic set of subunits, but, in cells, many important proteins associate transiently with proteasomes to deliver substrates or provide additional activities. Here, we show that a major class of proteasome-binding proteins that contain a ubiquitin-like (Ubl) domain can also enhance the 26S proteasome’s multiple enzymatic activities that are critical for protein degradation. Thus Ubl-containing proteins, in addition to their other functions, have this unexpected regulatory role.
Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke
Authors: Naito Masanori Gomi , Xu Daichao , Amin Palak , Lee Jinwoo , Wang Huibing , Li Wanjin , Kelliher Michelle , Pasparakis Manolis , Yuan Junying 
Published: February 2020

Significance
Necroptosis has been defined as a regulated cell death mechanism that can be activated under apoptosis deficient conditions. Here we show that necroptosis can be activated under brain ischemic conditions without inhibition of apoptosis. Furthermore, neuronal necroptosis can be followed by delayed apoptosis after the reduction of TAK1 under ischemic conditions. Our study demonstrates the complex interaction of apoptosis and necroptosis after ischemic brain insult and suggests the therapeutic targeting of RIPK1 kinase for the treatment of stroke.
Tyrosine phosphorylation of the AMPA receptor subunit GluA2 gates homeostatic synaptic plasticity
Authors: Yong Adeline J. H. , Tan Han L. , Zhu Qianwen , Bygrave Alexei M. , Johnson Richard C. , Huganir Richard L. 
Published: February 2020

Significance
Throughout an organism’s life span, neural circuits mediate sensory and cognitive processing via synaptic plasticity, which involves synapse-specific Hebbian plasticity and network-level homeostatic plasticity. Synaptic strengthening and weakening are finely tuned by changes in postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) -type glutamate receptors (AMPARs). We have elucidated a biochemical regulation of AMPARs that is specific to homeostatic synaptic plasticity while sparing Hebbian plasticity mechanisms. Specifically, phosphorylation of the AMPAR subunit, GluA2, at tyrosine-876 is required for homeostatic synaptic strengthening by dictating GluA2 binding to glutamate receptor interacting protein 1 (GRIP1), a scaffolding protein crucial for synaptic upscaling. This finding elucidates a mechanism through which neurons can maintain a range of synaptic signaling while not compromising their responsiveness to subsequent synaptic activity.
Metalinguistic discourses on translanguaging and
multimodality
Authors: Makoni Busi 
Published: February 2020

Abstract
This article explores metalinguistic discourses of black African
immigrants (BAIs) in Johannesburg on how they mobilize multilingual and
multimodal resources in their communicative practices to pass as South Africans
(SAs), concealing their identities as non-SAs to avert violent xenophobic
attacks. Drawing data from semi-structured interviews and group discussions with
BAIs, the article investigates how BAIs report on creatively, strategically
using translanguaging and multimodality in performance of ingroup membership as
local black SAs, blurring the boundaries between “outsiders” and “insiders.”
BAIs use passing as a social identity management strategy, to negotiate their
putative identity and resist ascription of the foreigner-outsider categorization
and attendant social meanings. Besides language(s), BAIs use modes of corporeal
practice (embodiment, clothing semiosis, skin-bleaching) as legitimating markers
of belonging. The article argues that using passing unsettles the distinction
between local/insider/citizen and migrant/outsider/non-citizen – concepts framed
around a nation-state – revealing tensions, contradictions, and complexities in
the politics of identity in Johannesburg.
Unsupervised identification of topological phase transitions using predictive models
Authors: Greplova Eliska , Valenti Agnes , Boschung Gregor , Schäfer Frank , Lörch Niels , Huber Sebastian D 
Published: February 2020

Abstract
Machine-learning driven models have proven to be powerful tools for the identification of phases of matter. In particular, unsupervised methods hold the promise to help discover new phases of matter without the need for any prior theoretical knowledge. While for phases characterized by a broken symmetry, the use of unsupervised methods has proven to be successful, topological phases without a local order parameter seem to be much harder to identify without supervision. Here, we use an unsupervised approach to identify boundaries of the topological phases. We train artificial neural nets to relate configurational data or measurement outcomes to quantities like temperature or tuning parameters in the Hamiltonian. The accuracy of these predictive models can then serve as an indicator for phase transitions. We successfully illustrate this approach on both the classical Ising gauge theory as well as on the quantum ground state of a generalized toric code.
Sentinel-1 observation frequency significantly increases burnt area detectability in tropical SE Asia
Authors: Carreiras Joao M B , Quegan Shaun , Tansey Kevin , Page Susan 
Published: February 2020

Abstract
Frequent cloud cover in the tropics significantly affects the observation of the surface by satellites. This has enormous implications for current approaches that estimate greenhouse gas (GHG) emissions from fires or map fire scars. These mainly employ data acquired in the visible to middle infrared bands to map fire scars or thermal data to estimate fire radiative power and consequently derive emissions. The analysis here instead explores the use of microwave data from the operational Sentinel-1A (S-1A) in dual-polarisation mode (VV and VH) acquired over Central Kalimantan during the 2015 fire season. Burnt areas were mapped in three consecutive periods between August and October 2015 using the random forests machine learning algorithm. In each mapping period, the omission and commission errors of the unburnt class were always below 3%, while the omission and commission errors of the burnt class were below 20% and 5% respectively. Summing the detections from the three periods gave a total burnt area of ∼1.6 million ha, but this dropped to ∼1.2 million ha if using only a pair of pre- and post-fire season S-1A images. Hence the ability of Sentinel-1 to make frequent observations significantly increases fire scar detection. Comparison with burnt area estimates from the Moderate Resolution Imaging Spectroradiometer (MODIS) burnt area product at 5 km scale showed poor agreement, with consistently much lower estimates produced by the MODIS data-on average 14%–51% of those obtained in this study. The method presented in this study offers a way to reduce the substantial errors likely to occur in optical-based estimates of GHG emissions from fires in tropical areas affected by substantial cloud cover.
The Combination of Non-dipper Heart Rate and High Brain Natriuretic Peptide Predicts Cardiovascular Events: The Japan Morning Surge-Home Blood Pressure (J-HOP) Study
Authors: Ogoyama Yukako , Kabutoya Tomoyuki , Hoshide Satoshi , Kario Kazuomi 
Published: February 2020

Abstract

BACKGROUND
We hypothesized that the association between the dipping heart rate (HR) pattern and cardiovascular (CV) events differs according to the brain natriuretic peptide (BNP) level.

METHODS
We examined a subgroup of 1,369 patients from the Japan Morning Surge Home Blood Pressure study; these were patients who had CV risk factors and had undergone ambulatory blood pressure (BP) monitoring. HR non-dipping status was defined as (awake HR − sleep HR)/awake HR &lt;0.1, and high BNP was defined as ≥35 pg/ml. We divided the patients into four groups according to their HR dipper status (dipping or non-dipping) and BNP level (normal or high).

RESULTS
The mean follow-up period was 60 ± 30 months. The primary endpoints were fatal/nonfatal CV events (myocardial infarction, angina pectoris, stroke, hospitalization for heart failure, and aortic dissection). During the follow-up period, 23 patients (2.8%) in the dipper HR with normal BNP group, 8 patients (4.4%) in the non-dipper HR with normal BNP group, 24 patients (9.5%) in the dipper HR with high-BNP group, and 25 patients (21.0%) in the non-dipper HR with high-BNP group suffered primary endpoints (log rank 78.8, P &lt; 0.001). Non-dipper HR was revealed as an independent predictor of CV events (hazard ratio, 2.13; 95% confidence interval, 1.35–3.36; P = 0.001) after adjusting for age, gender and smoking, dyslipidemia, diabetes mellitus, chronic kidney disease, BNP, non-dipper BP, 24-h HR, and 24-h systolic blood pressure.

CONCLUSIONS
The combination of non-dipper HR and higher BNP was associated with a higher incidence of CV events.
Proline: an efficient and user-friendly software suite for large-scale proteomics
Authors: Bouyssié David , Hesse Anne-Marie , Mouton-Barbosa Emmanuelle , Rompais Magali , Macron Charlotte , Carapito Christine , Gonzalez de Peredo Anne , Couté Yohann , Dupierris Véronique , Burel Alexandre , Menetrey Jean-Philippe , Kalaitzakis Andrea , Poisat Julie , Romdhani Aymen , Burlet-Schiltz Odile , Cianférani Sarah , Garin Jerome , Bruley Christophe 
Published: February 2020

Abstract

Motivation
The proteomics field requires the production and publication of reliable mass spectrometry-based identification and quantification results. Although many tools or algorithms exist, very few consider the importance of combining, in a unique software environment, efficient processing algorithms and a data management system to process and curate hundreds of datasets associated with a single proteomics study.

Results
Here, we present Proline, a robust software suite for analysis of MS-based proteomics data, which collects, processes and allows visualization and publication of proteomics datasets. We illustrate its ease of use for various steps in the validation and quantification workflow, its data curation capabilities and its computational efficiency. The DDA label-free quantification workflow efficiency was assessed by comparing results obtained with Proline to those obtained with a widely used software using a spiked-in sample. This assessment demonstrated Proline’s ability to provide high quantification accuracy in a user-friendly interface for datasets of any size.

Availability and implementation
Proline is available for Windows and Linux under CECILL open-source license. It can be deployed in client–server mode or in standalone mode at http://proline.profiproteomics.fr/#downloads.

Supplementary information
Supplementary data are available at Bioinformatics online.
A probabilistic graphical model for system-wide analysis of gene regulatory networks
Authors: Kotiang Stephen , Eslami Ali 
Published: February 2020

Abstract

Motivation
The inference of gene regulatory networks (GRNs) from DNA microarray measurements forms a core element of systems biology-based phenotyping. In the recent past, numerous computational methodologies have been formalized to enable the deduction of reliable and testable predictions in today’s biology. However, little focus has been aimed at quantifying how well existing state-of-the-art GRNs correspond to measured gene-expression profiles.

Results
Here, we present a computational framework that combines the formulation of probabilistic graphical modeling, standard statistical estimation, and integration of high-throughput biological data to explore the global behavior of biological systems and the global consistency between experimentally verified GRNs and corresponding large microarray compendium data. The model is represented as a probabilistic bipartite graph, which can handle highly complex network systems and accommodates partial measurements of diverse biological entities, e.g. messengerRNAs, proteins, metabolites and various stimulators participating in regulatory networks. This method was tested on microarray expression data from the M3D database, corresponding to sub-networks on one of the best researched model organisms, Escherichia coli. Results show a surprisingly high correlation between the observed states and the inferred system’s behavior under various experimental conditions.

Availability and implementation
Processed data and software implementation using Matlab are freely available at https://github.com/kotiang54/PgmGRNs. Full dataset available from the M3D database.
Phage protein receptors have multiple interaction partners and high expressions
Authors: Zhang Zheng , Yu Fen , Zou Yuanqiang , Qiu Ye , Wu Aiping , Jiang Taijiao , Peng Yousong 
Published: February 2020

Abstract

Motivation
Receptors on host cells play a critical role in viral infection. How phages select receptors is still unknown.

Results
Here, we manually curated a high-quality database named phageReceptor, including 427 pairs of phage–host receptor interactions, 341 unique viral species or sub-species and 69 bacterial species. Sugars and proteins were most widely used by phages as receptors. The receptor usage of phages in Gram-positive bacteria was different from that in Gram-negative bacteria. Most protein receptors were located on the outer membrane. The phage protein receptors (PPRs) were highly diverse in their structures, and had little sequence identity and no common protein domain with mammalian virus receptors. Further functional characterization of PPRs in Escherichia coli showed that they had larger node degrees and betweennesses in the protein–protein interaction network, and higher expression levels, than other outer membrane proteins, plasma membrane proteins or other intracellular proteins. These findings were consistent with what observed for mammalian virus receptors reported in previous studies, suggesting that viral protein receptors tend to have multiple interaction partners and high expressions. The study deepens our understanding of virus–host interactions.

Availability and implementation
phageReceptor is publicly available from: http://www.computationalbiology.cn/phageReceptor/index.html.

Supplementary information
Supplementary data are available at Bioinformatics online.
Sweet Thermal Taste: Perceptual Characteristics in Water and Dependence on TAS1R2/TAS1R3
Authors: Nachtigal Danielle , Green Barry G 
Published: February 2020

Abstract
The initial objective of this study was to determine if activation of the sweet taste receptor TAS1R2/TAS1R3 is necessary for perception of sweet thermal taste (swTT). Our approach was to inhibit the receptor with the inverse agonist lactisole using a temperature-controlled flow gustometer. Because all prior studies of thermal taste (TT) used metal thermodes to heat the tongue tip, we first investigated whether it could be generated in heated water. Experiment 1 showed that sweetness could be evoked when deionized water was heated from 20 to 35 °C, and testing with static temperatures between 20 and 35 °C demonstrated the importance of heating from a cool temperature. As in previous studies, thermal sweetness was reported by only a subset of participants, and replicate measurements found variability in reports of sweetness across trials and between sessions. Experiment 2 then showed that exposure to 8 mM lactisole blocked perception of swTT. Confirmation of the involvement of TAS1R2/TAS1R3 led to an investigation of possible sensory and cognitive interactions between thermal and chemical sweetness. Using sucrose as a sweet stimulus and quinine as a nonsweet control, we found that dynamic heating capable of producing thermal sweetness did not increase the sweetness of sucrose compared with static heating at 35 °C. However, swTT was disrupted if trials containing sucrose (but not quinine) were interspersed among heating-only trials. These findings provide new information relevant to understanding the perceptual processes and receptor mechanisms of swTT, as well as the heat sensitivity of sweet taste in general.
The Natural History of Anal High-grade Squamous Intraepithelial Lesions in Gay and Bisexual Men
Authors: Poynten I Mary , Jin Fengyi , Roberts Jennifer M , Templeton David J , Law Carmella , Cornall Alyssa M , Molano Monica , Machalek Dorothy A , Carr Andrew , Farnsworth Annabelle , Tabrizi Sepehr , Phillips Samuel , Fairley Christopher K , Garland Suzanne M , Hillman Richard J , Grulich Andrew E 
Published: February 2020

Abstract

Background
Gay and bisexual men (GBM) are disproportionately affected by anal cancer. Prevention is hindered by incomplete understanding of the natural history of its precursor, anal high-grade squamous intraepithelial lesions (HSIL).

Methods
The Study of the Prevention of Anal Cancer, conducted between 2010 and 2018, enrolled human immunodeficiency virus (HIV)-positive and HIV-negative GBM aged ≥35 years. Anal cytology and high-resolution anoscopy (HRA) were performed at baseline and 3 annual visits. A composite HSIL diagnosis (cytology ± histology cHSIL) was used. Cytological high-grade squamous intraepithelial lesions (cHSIL) incidence and clearance rates were calculated with 95% confidence intervals (CIs). Predictors were calculated using Cox regression with hazard ratios (HRs) and 95% CIs.

Results
Among 617 men, 220 (35.7%) were HIV-positive, median age 49 years. And 124 incident cHSIL cases occurred over 1097.3 person-years (PY) follow-up (11.3, 95% CI 9.5–13.5 per 100 PY). Significant bivariate predictors of higher incidence included age &lt;45 years (HR 1.64, 95% CI 1.11–2.41), HIV positivity (HR 1.43, 95% CI .99–2.06), prior SIL diagnosis (P-trend &lt; .001) and human papillomavirus (HPV)16 (HR 3.39, 2.38–4.84). Over 695.3 PY follow-up, 153 cHSIL cleared (clearance 22.0, 95% CI 18.8–25.8 per 100 PY). Predictors were age &lt; 45 years (HR 1.52, 1.08–2.16), anal intraepithelial neoplasia (AIN)2 rather than AIN3 (HR 1.79, 1.29–2.49), smaller lesions (HR 1.62, 1.11–2.36) and no persistent HPV16 (HR 1.72, 1.23–2.41). There was 1 progression to cancer (incidence 0.224, 95% CI .006–1.25 per 100 PY).

Conclusion
These data strongly suggest that not all anal HSIL detected in screening requires treatment. Men with persistent HPV16 were less likely to clear HSIL and are more likely to benefit from effective HSIL treatments.

Clinical Trials Registration
Australia New Zealand Clinical Trials Registry (ANZCTR365383).
The choice of targets and ligands for site-specific delivery of nanomedicine to atherosclerosis
Authors: Zia Adil , Wu Yuao , Nguyen Tuan , Wang Xiaowei , Peter Karlheinz , Ta Hang T 
Published: February 2020

Abstract
As nanotechnologies advance into clinical medicine, novel methods for applying nanomedicine to cardiovascular diseases are emerging. Extensive research has been undertaken to unlock the complex pathogenesis of atherosclerosis. However, this complexity presents challenges to develop effective imaging and therapeutic modalities for early diagnosis and acute intervention. The choice of ligand-receptor system vastly influences the effectiveness of nanomedicine. This review collates current ligand-receptor systems used in targeting functionalized nanoparticles for diagnosis and treatment of atherosclerosis. Our focus is on the binding affinity and selectivity of ligand-receptor systems, as well as the relative abundance of targets throughout the development and progression of atherosclerosis. Antibody-based targeting systems are currently the most commonly researched due to their high binding affinities when compared with other ligands, such as antibody fragments, peptides, and other small molecules. However, antibodies tend to be immunogenic due to their size. Engineering antibody fragments can address this issue but will compromise their binding affinity. Peptides are promising ligands due to their synthetic flexibility and low production costs. Alongside the aforementioned binding affinity of ligands, the choice of target and its abundance throughout distinct stages of atherosclerosis and thrombosis is relevant to the intended purpose of the nanomedicine. Further studies to investigate the components of atherosclerotic plaques are required as their cellular and molecular profile shifts over time.
Is Therapeutic Drug Monitoring for Anti-tumour Necrosis Factor Agents in Adults With Inflammatory Bowel Disease Ready for Standard of Care? A Systematic Review and Meta-analysis
Authors: Shah Raj , Hoffman Gila R , El-Dallal Mohammed , Goldowsky Alexander M , Chen Ye , Feuerstein Joseph D 
Published: February 2020

Abstract

Introduction
Using therapeutic drug monitoring [TDM] in adult patients with inflammatory bowel disease [IBD] remains controversial. We conducted a systematic review and meta-analysis to answer four clinical PICO [Population, Intervention, Comparator, Outcome] questions.

Methods
We searched MEDLINE, Embase, Web of Science, and Cochrane Central from inception to June 30, 2019. Remission was defined by the manuscripts’ definitions of clinical remission. Data were analysed using RevMan 5.3. Quality of evidence was assessed with GRADE methodology.

Results
We identified and screened 3365 abstracts and 11 articles. PICO 1 Reactive vs No TDM: six studies pooled showed 57.1% [257/450] failed to achieve remission following reactive TDM vs 44.7% [268/600] in the no TDM group (risk ratio [RR]: 1.14; 95% confidence interval [CI] 0.88–1.47). PICO 2 Proactive vs no TDM: five studies pooled showed 19.5% [75/384] failed to maintain remission in the proactive TDM group vs 33.4% [248/742] in the no TDM group [RR: 0.60; 95% CI 0.35–1.04]. PICO 3 Proactive vs Reactive TDM: two retrospective studies pooled showed 14.2% [26/183] failure to maintain remission in the proactive TDM group and 64.7% [119/184] in the reactive TDM group [RR: 0.22; 95% CI 0.15–0.32]. PICO 4 TDM [proactive/reactive] vs No TDM: we pooled 10 studies showing 39.7% [332/837] failed to achieve remission in the TDM [proactive/reactive] cohort vs 40.3% [428/1063] in the no TDM cohort [RR: 0.94; 95% CI 0.77–1.14]. Overall, the quality of evidence in each PICO was very low when using GRADE.

Conclusions
This meta-analysis shows that data supporting use of TDM in adults are limited and of very low quality. Further well-designed randomized controlled trials are needed to determine the place of TDM in clinical practice.