bluuebunny/crossref_metadata_2025_split huggingface dataset:
APOEε4 potentiates the relationship between amyloid-β and tau pathologies
Authors: Therriault Joseph , Benedet Andrea L. , Pascoal Tharick A. , Mathotaarachchi Sulantha , Savard Melissa , Chamoun Mira , Thomas Emilie , Kang Min Su , Lussier Firoza , Tissot Cecile , Soucy Jean-Paul , Massarweh Gassan , Rej Soham , Saha-Chaudhuri Paramita , Poirier Judes , Gauthier Serge , Rosa-Neto Pedro ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: March 2020

AbstractAPOEε4 is the most well-established genetic risk factor for sporadic Alzheimer’s disease and is associated with cerebral amyloid-β. However, the association between APOEε4 and tau pathology, the other major proteinopathy of Alzheimer’s disease, has been controversial. Here, we sought to determine whether the relationship between APOEε4 and tau pathology is determined by local interactions with amyloid-β. We examined three independent samples of cognitively unimpaired, mild cognitive impairment and Alzheimer’s disease subjects: (1) 211 participants who underwent tau-PET with [18F]MK6240 and amyloid-PET with [18F]AZD4694, (2) 264 individuals who underwent tau-PET with [18F]Flortaucipir and amyloid-PET with [18F]Florbetapir and (3) 487 individuals who underwent lumbar puncture and amyloid-PET with [18F]Florbetapir. Using a novel analytical framework, we applied voxel-wise regression models to assess the interactive effect of APOEε4 and amyloid-β on tau load, independently of age and clinical diagnosis. We found that the interaction effect between APOEε4 and amyloid-β, rather than the sum of their independent effects, was related to increased tau load in Alzheimer’s disease-vulnerable regions. The interaction between one APOEε4 allele and amyloid-β was related to increased tau load, while the interaction between amyloid-β and two APOEε4 alleles was related to a more widespread pattern of tau aggregation. Our results contribute to an emerging framework in which the elevated risk of developing dementia conferred by APOEε4 genotype involves mechanisms associated with both amyloid-β and tau aggregation. These results may have implications for future disease-modifying therapeutic trials targeting amyloid or tau pathologies.
CDK4/6 inhibition blocks cancer metastasis through a USP51-ZEB1-dependent deubiquitination mechanism
Authors: Zhang Zhen , Li Jianjun , Ou Yang , Yang Guang , Deng Kaiyuan , Wang Qiong , Wang Zhaoyang , Wang Wenhao , Zhang Quansheng , Wang Hang , Sun Wei , Sun Peiqing , Yang Shuang 
Published: March 2020

AbstractTumor metastasis is the most common cause of cancer-related deaths, yet it remains poorly understood. The transcription factor zinc-finger E-box binding homeobox 1 (ZEB1) is involved in the epithelial-to-mesenchymal transition (EMT) and plays a pivotal role in tumor metastasis. However, the underlying mechanisms of the posttranslational modification of ZEB1 remain largely unknown. Herein, we demonstrated that specific inhibition of CDK4/6 was able to block tumor metastasis of breast cancer by destabilizing the ZEB1 protein in vitro and in vivo. Mechanistically, we determined that the deubiquitinase USP51 is a bona fide target of CDK4/6. The phosphorylation and activation of USP51 by CDK4/6 is necessary to deubiquitinate and stabilize ZEB1. Moreover, we found a strong positive correlation between the expression of p-RB (an indicator of CDK4/6 activity), p-USP51 and ZEB1 in metastatic human breast cancer samples. Notably, the high expression of p-RB, p-USP51, and ZEB1 was significantly correlated with a poor clinical outcome. Taken together, our results provide evidence that the CDK4/6-USP51-ZEB1 axis plays a key role in breast cancer metastasis and could be a viable therapeutic target for the treatment of advanced human cancers.
Non-inferiority randomised phase 3 trial comparing two radiation schedules (single vs. five fractions) in malignant spinal cord compression
Authors: Thirion Pierre G. , Dunne Mary T. , Kelly Paul J. , Flavin Aileen , O’Sullivan Joe M. , Hacking Dayle , Sasiadek Wojciech , Small Cormac , Pomeroy Maeve M. , Martin Joseph , McArdle Orla , Parker Imelda , O’Sullivan Lydia S. , Shannon Aoife M. , Clayton-Lea Angela , Collins Conor D. , Stevenson Michael R. , Alvarez-Iglesias Alberto , Armstrong John G. , Moriarty Michael 
Published: March 2020

AbstractBackgroundThe optimal EBRT schedule for MSCC is undetermined. Our aim was to determine whether a single fraction (SF) was non-inferior to five daily fractions (5Fx), for functional motor outcome.MethodsPatients not proceeding with surgical decompression in this multicentre non-inferiority, Phase 3 trial were randomised to 10 Gy/SF or 20 Gy/5Fx. A change in mobility from baseline to 5 weeks for each patient, was evaluated by a Modified Tomita score: 1 = ‘Walk unaided’, 2 = ‘With walking aid’ and 3 = ‘Bed-bound’. The margin used to establish non-inferiority was a detrimental change of −0.4 in the mean difference between arms.ResultsOne-hundred and twelve eligible patients were enrolled. Seventy-three patients aged 30–87 were evaluated for the primary analysis. The 95% CI for the difference in the mean change in mobility scores between arms was −0.12 to 0.6. Since −0.4 is not included in the interval, there is evidence that 10 Gy/SF is non-inferior to 20 Gy/5Fx. One grade 3 AE was reported in the 5Fx arm. Twelve (26%) patients in the 5Fx arm had a Grade 2–3 AE compared with six (11%) patients in the SF arm (p = 0.093).ConclusionFor mobility preservation, one 10-Gy fraction is non-inferior to 20 Gy in five fractions, in patients with MSCC not proceeding with surgical decompression.Clinical Trial RegistrationCancer Trials Ireland ICORG 05-03; NCT00968643; EU-20952.
An integrated analysis of lymphocytic reaction, tumour molecular characteristics and patient survival in colorectal cancer
Authors: Haruki Koichiro , Kosumi Keisuke , Li Peilong , Arima Kota , Väyrynen Juha P. , Lau Mai Chan , Twombly Tyler S. , Hamada Tsuyoshi , Glickman Jonathan N. , Fujiyoshi Kenji , Chen Yang , Du Chunxia , Guo Chunguang , Väyrynen Sara A. , Dias Costa Andressa , Song Mingyang , Chan Andrew T. , Meyerhardt Jeffrey A. , Nishihara Reiko , Fuchs Charles S. , Liu Li , Zhang Xuehong , Wu Kana , Giannakis Marios , Nowak Jonathan A. , Ogino Shuji 
Published: March 2020

Abstract
Background
Histological lymphocytic reaction is regarded as an independent prognostic marker in colorectal cancer. Considering the lack of adequate statistical power, adjustment for selection bias and comprehensive tumour molecular data in most previous studies, we investigated the strengths of the prognostic associations of lymphocytic reaction in colorectal carcinoma by utilising an integrative database of two prospective cohort studies.

Methods
We examined Crohn’s-like reaction, intratumoural periglandular reaction, peritumoural reaction and tumour-infiltrating lymphocytes in 1465 colorectal carcinoma cases. Using covariate data of 4420 colorectal cancer cases in total, inverse probability-weighted Cox proportional hazard regression model was used to control for selection bias (due to tissue availability) and potential confounders, including stage, MSI status, LINE-1 methylation, PTGS2 and CTNNB1 expression, KRAS, BRAF and PIK3CA mutations, and tumour neoantigen load.

Results
Higher levels of each lymphocytic reaction component were associated with better colorectal cancer-specific survival (Ptrend < 0.002). Compared with cases with negative/low intratumoural periglandular reaction, multivariable-adjusted HRs were 0.55 (95% CI, 0.42–0.71) in cases with intermediate reaction and 0.20 (95% CI, 0.12–0.35) in cases with high reaction. These relationships were consistent in strata of MSI status or neoantigen loads (Pinteraction > 0.2).

Conclusions
The four lymphocytic reaction components are prognostic biomarkers in colorectal carcinoma.
UBB pseudogene 4 encodes functional ubiquitin variants
Authors: Dubois Marie-Line , Meller Anna , Samandi Sondos , Brunelle Mylène , Frion Julie , Brunet Marie A. , Toupin Amanda , Beaudoin Maxime C. , Jacques Jean-François , Lévesque Dominique , Scott Michelle S. , Lavigne Pierre , Roucou Xavier , Boisvert François-Michel 
Published: March 2020

AbstractPseudogenes are mutated copies of protein-coding genes that cannot be translated into proteins, but a small subset of pseudogenes has been detected at the protein level. Although ubiquitin pseudogenes represent one of the most abundant pseudogene families in many organisms, little is known about their expression and signaling potential. By re-analyzing public RNA-sequencing and proteomics datasets, we here provide evidence for the expression of several ubiquitin pseudogenes including UBB pseudogene 4 (UBBP4), which encodes UbKEKS (Q2K, K33E, Q49K, N60S). The functional consequences of UbKEKS conjugation appear to differ from canonical ubiquitylation. Quantitative proteomics shows that UbKEKS modifies specific proteins including lamins. Knockout of UBBP4 results in slower cell division, and accumulation of lamin A within the nucleolus. Our work suggests that a subset of proteins reported as ubiquitin targets may instead be modified by ubiquitin variants that are the products of wrongly annotated pseudogenes and induce different functional effects.
An open data infrastructure for the study of anthropogenic hazards linked to georesource exploitation
Authors: Orlecka-Sikora Beata , Lasocki Stanisław , Kocot Joanna , Szepieniec Tomasz , Grasso Jean Robert , Garcia-Aristizabal Alexander , Schaming Marc , Urban Paweł , Jones Glenda , Stimpson Ian , Dineva Savka , Sałek Piotr , Leptokaropoulos Konstantinos , Lizurek Grzegorz , Olszewska Dorota , Schmittbuhl Jean , Kwiatek Grzegorz , Blanke Aglaja , Saccorotti Gilberto , Chodzińska Karolina , Rudziński Łukasz , Dobrzycka Izabela , Mutke Grzegorz , Barański Adam , Pierzyna Aleksandra , Kozlovskaya Elena , Nevalainen Jouni , Kinscher Jannes , Sileny Jan , Sterzel Mariusz , Cielesta Szymon , Fischer Tomas 
Published: March 2020

AbstractMining, water-reservoir impoundment, underground gas storage, geothermal energy exploitation and hydrocarbon extraction have the potential to cause rock deformation and earthquakes, which may be hazardous for people, infrastructure and the environment. Restricted access to data constitutes a barrier to assessing and mitigating the associated hazards. Thematic Core Service Anthropogenic Hazards (TCS AH) of the European Plate Observing System (EPOS) provides a novel e-research infrastructure. The core of this infrastructure, the IS-EPOS Platform (tcs.ah-epos.eu) connected to international data storage nodes offers open access to large grouped datasets (here termed episodes), comprising geoscientific and associated data from industrial activity along with a large set of embedded applications for their efficient data processing, analysis and visualization. The novel team-working features of the IS-EPOS Platform facilitate collaborative and interdisciplinary scientific research, public understanding of science, citizen science applications, knowledge dissemination, data-informed policy-making and the teaching of anthropogenic hazards related to georesource exploitation. TCS AH is one of 10 thematic core services forming EPOS, a solid earth science European Research Infrastructure Consortium (ERIC) (www.epos-ip.org).
Inner Mongolian Cashmere Goat Secondary Follicle Development Regulation Research Based on mRNA-miRNA Co-analysis
Authors: Han Wenjing , Yang Feng , Wu Zhihong , Guo Fuqiang , Zhang Junjie , Hai Erhan , Shang Fangzheng , Su Rui , Wang Ruijun , Wang Zhiying , Liu Zhihong , Zhao Yanhong , Wang Zhixin , Zhang Yanjun , Li Jinquan 
Published: March 2020

AbstractInner Mongolia cashmere goats, as an important part of animal husbandry production, play an important role in animal fiber industry. In recent years, scientific research has made a lot of explorations on the molecular regulation mechanism of hair follicle cycle growth, but few studies have been reported on the development of cashmere hair in fetal period. This study was based on the completion of 21 skin samples of mRNA and miRNA sequencing in 7 fetal periods (45 days, 55 days,65 days,75 days,95 days,115 days and 135 days) of the Inner Mongolia Cashmere goat. The target genes of miRNA associated with the development of secondary hair follicles in the cashmere goats were selected through the combination analysis of mRNA and miRNA data. Then the overexpression vector was constructed and the interaction between the miRNA and the target gene was identified by Dual-Luciferase Reporter Gene System. The function and interaction relationship of chi-miR-199a-5p and TGF-β2 were verified by RT-qPCR and western blot at the level of the fibroblasts in Inner Mongolia Cashmere goat. It provides a theoretical basis for further study of miRNA and its target genes regulating the occurrence and development of skin hair follicles. As the result shows, the expression trends of 7 genes (BAMBI, SMAD1, LTBP1, PPP2R1B, ID4, BMP8B and PITX2) and 7 miRNA (chi-miR-17-5p, chi-miR-125b-3p, chi-miR-21-5p, chi-miR-143-5p and chi-miR-106b-5p) in the skin samples for the seven stages of the fetus were shown to be consistent with the sequencing results. the results of sequencing are reliable. The correlation coefficient of TGF-β2 and chi-miR-199a-5p in fetal 45d-135d expression is −0.84, showing a strong negative correlation, The target relationship was preliminarily judged. The results of double luciferase vector report showed that chi-miR-199a-5p significantly decreased the expression of luciferase in TGF-β2 3′UTR, It is determined that there is a reciprocal relationship between them at a specific time. We transfected chi-miR199a-5p-FAM mimics into fibroblasts cultured in vitro from Inner Mongolia cashmere goats. After transfection, the cells were harvested to extract total RNA and protein. The mRNA and protein expression levels of TGF-β2 in fibroblasts were detected by RT-qPCR and western blot. It was verified that chi-miR-199a-5p inhibited TGF-β2 expression at both mRNA and protein translation levels in fibroblasts. At the same time, it was again proved that the TGF-β2 gene is a target gene of chi-miR199a-5p.
Graphene-enhanced Raman scattering on single layer and bilayers of pristine and hydrogenated graphene
Authors: Valeš Václav , Drogowska-Horná Karolina , Guerra Valentino L. P. , Kalbáč Martin 
Published: March 2020

AbstractGraphene-enhanced Raman scattering (GERS) on isotopically labelled bilayer and a single layer of pristine and partially hydrogenated graphene has been studied. The hydrogenated graphene sample showed a change in relative intensities of Raman bands of Rhodamine 6 G (R6G) with different vibrational energies deposited on a single layer and bilayer graphene. The change corresponds qualitatively to different doping of graphene in both areas. Pristine graphene sample exhibited no difference in doping nor relative intensities of R6G Raman peaks in the single layer and bilayer areas. Therefore, it was concluded that strain and strain inhomogeneities do not affect the GERS. Because of analyzing relative intensities of selected peaks of the R6G probe molecules, it is possible to obtain these results without determining the enhancement factor and without assuming homogeneous coverage of the molecules. Furthermore, we tested the approach on copper phtalocyanine molecules.
Synechocystis sp. PCC 6803 overexpressing genes involved in CBB cycle and free fatty acid cycling enhances the significant levels of intracellular lipids and secreted free fatty acids
Authors: Eungrasamee Kamonchanock , Incharoensakdi Aran , Lindblad Peter , Jantaro Saowarath 
Published: March 2020

AbstractThe integrative aspect on carbon fixation and lipid production is firstly implemented in cyanobacterium Synechocystis sp. PCC 6803 using metabolic engineering approach. Genes related to Calvin–Benson–Bassham (CBB) cycle including rbcLXS and glpD and free fatty acid recycling including aas encoding acyl-ACP synthetase were practically manipulated in single, double and triple overexpressions via single homologous recombination. The significantly increased growth rate and intracellular pigment contents were evident in glpD-overexpressing (OG) strain among all strains studied under normal growth condition. The triple aas_glpD_rbcLXS-overexpressing (OAGR) strain notably gave the highest contents of both intracellular lipids and extracellular free fatty acids (FFAs) of about 35.9 and 9.6% w/DCW, respectively, when compared to other strains at day 5 of cultivation. However, the highest intracellular lipid titer and production rate were observed in OA strain at day 5 (228.7 mg/L and 45.7 mg/L/day, respectively) and OG strain at day 10 (358.3 mg/L and 35.8 mg/L/day, respectively) due to their higher growth. For fatty acid (FA) compositions, the main saturated fatty acid of palmitic acid (C16:0) was dominantly found in both intracellular lipid and secreted FFAs fractions. Notably, intracellular FA proportion of myristic acid (C14:0) was induced in all engineered strains whereas the increase of stearic acid (C18:0) composition was found in extracellular FFAs fraction. Altogether, these overexpressing strains efficiently produced higher lipid production via homeostasis balance on both its lipid synthesis and FFAs secretion.
Diagnostic accuracy of intraoperative CT-imaging in complex articular fractures – a cadaveric study
Authors: Luxenhofer M. , Beisemann N. , Schnetzke M. , Vetter S. Y. , Grützner P. A. , Franke J. , Keil H. 
Published: March 2020

AbstractAnatomic reconstruction of articular fractures is one of the critical factors in later achieving good functional outcome. Intraoperative 3D imaging has been shown to offer better evaluation and therefore can significantly improve the results. The purpose of this study was to assess the difference between intraoperative three-dimensional fluoroscopy (3D) and intraoperative computed tomography (iCT) imaging regarding fracture reduction, implant placement and articular impressions in a distal humeral fracture model. AO type 13-B2 fracture pattern were created in upper extremity cadaver specimens. Articular step-offs, intra-articular screw placement and intraarticular impressions of different degrees of severity were created. All specimens had imaging performed. For each articular pattern 3D fluoroscopy in standard (3Ds) and high quality (3Dh) were performed (Arcadis Orbic, Siemens, Germany) as well as an intraoperative CT scan (iCT, Airo, Brainlab, Germany). Three observers evaluated all imaging studies regarding subjective and objective parameters. iCT is more precise than 3D fluoroscopic imaging for detection of articular impressions. Articular step-offs and intraarticular screw placement are similar for iCT and 3D. Subjective imaging quality is the highest for iCT and lowest for 3Ds. Intraoperative CT may be particularly useful in assessing articular impressions and providing a good subjective image quality for the surgeon.
NBEAL1 controls SREBP2 processing and cholesterol metabolism and is a susceptibility locus for coronary artery disease
Authors: Bindesbøll Christian , Aas Aleksander , Ogmundsdottir Margret Helga , Pankiv Serhiy , Reine Trine , Zoncu Roberto , Simonsen Anne 
Published: March 2020

AbstractDysregulated cholesterol homeostasis promotes the pathology of atherosclerosis, myocardial infarction and strokes. Cellular cholesterol is mainly regulated at the transcriptional level by SREBP2, but also through uptake of extracellular cholesterol from low density lipoproteins (LDL) via expression of LDL receptors (LDLR) at the cell surface. Identification of the mechanisms involved in regulation of these processes are thus key to understand the pathology of coronary artery disease. Here, we identify the large and poorly characterized BEACH domain protein Neurobeachin-like (NBEAL) 1 as a Golgi- associated protein required for regulation of cholesterol metabolism. NBEAL1 is most abundantly expressed in arteries. Genetic variants in NBEAL1 are associated with decreased expression of NBEAL1 in arteries and increased risk of coronary artery disease in humans. We show that NBEAL1 regulates cholesterol metabolism by modulating LDLR expression in a mechanism involving interaction with SCAP and PAQR3 and subsequent SREBP2-processing. Thus, low expression of NBEAL1 may lead to increased risk of coronary artery disease by downregulation of LDLR levels.
Compositional heterogeneity confers selective advantage to model protocellular membranes during the origins of cellular life
Authors: Sarkar Susovan , Dagar Shikha , Verma Ajay , Rajamani Sudha 
Published: March 2020

AbstractProtocellular membranes are thought to be composed of mixtures of single chain amphiphiles, such as fatty acids and their derivatives, moieties that would have been part of the complex prebiotic chemical landscape. The composition and physico-chemical properties of these prebiological membranes would have been significantly affected and regulated by their environment. In this study, pertinent properties were systematically characterized, under early Earth conditions. Two different fatty acids were mixed with their respective alcohol and/or glycerol monoester derivatives to generate combinations of binary and tertiary membrane systems. Their properties were then evaluated as a function of multiple factors including their stability under varying pH, varying Mg2+ ion concentrations, dilution regimes, and their permeability to calcein. Our results demonstrate how environmental constraints would have acted as important prebiotic selection pressures to shape the evolution of prebiological membranes. The study also illustrates that compositionally diverse membrane systems are more stable and robust to multiple selection pressures, thereby making them more suitable for supporting protocellular life.
The Impact of Microplastic Particles on Population Dynamics of Predator and Prey: Implication of the Lotka-Volterra Model
Authors: Huang Qi , Lin Yuyang , Zhong Qiyin , Ma Fei , Zhang Yixin 
Published: March 2020

AbstractMicroplastic particles are widely distributed in a variety of ecosystems and can be transferred to predators along a food chain after being ingested by prey. However, how microplastic particles affect prey and predator populations is not fully understood. In this study, using the Lotka-Volterra model, we theoretically investigated predator-prey population dynamics in terms of toxicological response intensity (strength to population growth rate) to microplastic particles, and examined the negative effects on prey feeding ability and predator performance due to microplastic particles. Results of numerical simulations indicate the critical properties of the predator-prey system in response to microplastic particles: (i) predators are more vulnerable than prey under exposure to microplastic particles; (ii) the effect of microplastic particles on prey and predator population growths can be negligible when toxicological response intensities of prey and predator are small; (iii) this system is prey dependent for predator functional response, whose stability highly relies on the density of prey; (iv) the reduced feeding capacity of prey and predator induced by microplastic particles does not significantly affect the population dynamics of the predator-prey system. Moreover, our analysis suggests that dynamic Lotka-Volterra models can play a vital role in predicting ecological impacts of microplastic particles on predator-prey population dynamics.