bluuebunny/crossref_metadata_2025_split huggingface dataset:
A longitudinal study of gene expression in first-episode schizophrenia; exploring relapse mechanisms by co-expression analysis in peripheral blood
Authors: Gassó P. , Rodríguez N. , Martínez-Pinteño A. , Mezquida G. , Ribeiro M. , González-Peñas J. , Zorrilla I. , Martínez-Sadurni L. , Rodriguez-Jimenez R. , Corripio I. , Sarró S. , Ibáñez A. , Usall J. , Lobo A. , Moren C. , Cuesta M. J. , Parellada M. , González-Pinto A. , Berrocoso E. , Bernardo M. , Mas S. ,   2EPs Group, Bioque M. , Amoretti S. , Andreu-Bernabeu A. , Gurriarán X. , Alonso-Solís A. , Grasa E. , López P. , Garcia E. , Bergé D. , Trabsa A. , Sànchez-Pastor L. , Jiménez-Rodríguez O. , Pomarol-Clotet E. , Feria-Raposo I. , Butjosa A. , Pardo M. , Moreno-Izco L. , Sánchez-Torres A. M. , Saiz-Ruiz J. , León-Quismondo L. , Nacher J. , Contreras F. , De-la-Cámara C. , Gutiérrez M. , Sáiz P. A. 
Published: October 2021

AbstractLittle is known about the pathophysiological mechanisms of relapse in first-episode schizophrenia, which limits the study of potential biomarkers. To explore relapse mechanisms and identify potential biomarkers for relapse prediction, we analyzed gene expression in peripheral blood in a cohort of first-episode schizophrenia patients with less than 5 years of evolution who had been evaluated over a 3-year follow-up period. A total of 91 participants of the 2EPs project formed the sample for baseline gene expression analysis. Of these, 67 provided biological samples at follow-up (36 after 3 years and 31 at relapse). Gene expression was assessed using the Clariom S Human Array. Weighted gene co-expression network analysis was applied to identify modules of co-expressed genes and to analyze their preservation after 3 years of follow-up or at relapse. Among the 25 modules identified, one module was semi-conserved at relapse (DarkTurquoise) and was enriched with risk genes for schizophrenia, showing a dysregulation of the TCF4 gene network in the module. Two modules were semi-conserved both at relapse and after 3 years of follow-up (DarkRed and DarkGrey) and were found to be biologically associated with protein modification and protein location processes. Higher expression of DarkRed genes was associated with higher risk of suffering a relapse and early appearance of relapse (p = 0.045). Our findings suggest that a dysregulation of the TCF4 network could be an important step in the biological process that leads to relapse and suggest that genes related to the ubiquitin proteosome system could be potential biomarkers of relapse.
Molecular and genomic characterisation of a panel of human anal cancer cell lines
Authors: Guerra Glen R. , Kong Joseph C. , Millen Rosemary M. , Read Matthew , Liu David S. , Roth Sara , Sampurno Shienny , Sia Joseph , Bernardi Maria-Pia , Chittleborough Timothy J. , Behrenbruch Corina C. , Teh Jiasian , Xu Huiling , Haynes Nicole M. , Yu Jiaan , Lupat Richard , Hawkes David , Di Costanzo Natasha , Tothill Richard W. , Mitchell Catherine , Ngan Samuel Y. , Heriot Alexander G. , Ramsay Robert G. , Phillips Wayne A. 
Published: October 2021

AbstractAnal cancer is a rare disease that has doubled in incidence over the last four decades. Current treatment and survival of patients with this disease has not changed substantially over this period of time, due, in part, to a paucity of preclinical models to assess new therapeutic options. To address this hiatus, we set-out to establish, validate and characterise a panel of human anal squamous cell carcinoma (ASCC) cell lines by employing an explant technique using fresh human ASCC tumour tissue. The panel of five human ASCC cell lines were validated to confirm their origin, squamous features and tumourigenicity, followed by molecular and genomic (whole-exome sequencing) characterisation. This panel recapitulates the genetic and molecular characteristics previously described in ASCC including phosphoinositide-3-kinase (PI3K) mutations in three of the human papillomavirus (HPV) positive lines and TP53 mutations in the HPV negative line. The cell lines demonstrate the ability to form tumouroids and retain their tumourigenic potential upon xenotransplantation, with varied inducible expression of major histocompatibility complex class I (MHC class I) and Programmed cell death ligand 1 (PD-L1). We observed differential responses to standard chemotherapy, radiotherapy and a PI3K specific molecular targeted agent in vitro, which correlated with the clinical response of the patient tumours from which they were derived. We anticipate this novel panel of human ASCC cell lines will form a valuable resource for future studies into the biology and therapeutics of this rare disease.
Downregulation of PHLPP induced by endoplasmic reticulum stress promotes eIF2α phosphorylation and chemoresistance in colon cancer
Authors: Guo Bianqin , Xiong Xiaopeng , Hasani Sumati , Wen Yang-An , Li Austin T. , Martinez Rebecca , Skaggs Ashley T. , Gao Tianyan 
Published: October 2021

AbstractAberrant activation of endoplasmic reticulum (ER) stress by extrinsic and intrinsic factors contributes to tumorigenesis and resistance to chemotherapies in various cancer types. Our previous studies have shown that the downregulation of PHLPP, a novel family of Ser/Thr protein phosphatases, promotes tumor initiation, and progression. Here we investigated the functional interaction between the ER stress and PHLPP expression in colon cancer. We found that induction of ER stress significantly decreased the expression of PHLPP proteins through a proteasome-dependent mechanism. Knockdown of PHLPP increased the phosphorylation of eIF2α as well as the expression of autophagy-associated genes downstream of the eIF2α/ATF4 signaling pathway. In addition, results from immunoprecipitation experiments showed that PHLPP interacted with eIF2α and this interaction was enhanced by ER stress. Functionally, knockdown of PHLPP improved cell survival under ER stress conditions, whereas overexpression of a degradation-resistant mutant PHLPP1 had the opposite effect. Taken together, our studies identified ER stress as a novel mechanism that triggers PHLPP downregulation; and PHLPP-loss promotes chemoresistance by upregulating the eIF2α/ATF4 signaling axis in colon cancer cells.
Genomic health data generation in the UK: a 360 view
Authors: Ormondroyd Elizabeth , Border Peter , Hayward Judith , Papanikitas Andrew 
Published: October 2021

AbstractIn the UK, genomic health data is being generated in three major contexts: the healthcare system (based on clinical indication), in large scale research programmes, and for purchasers of direct-to-consumer genetic tests. The recently delivered hybrid clinical/research programme, 100,000 Genomes Project set the scene for a new Genomic Medicine Service, through which the National Health Service aims to deliver consistent and equitable care informed by genomics, while providing data to inform academic and industry research and development. In parallel, a large scale research study, Our Future Health, has UK Government and Industry investment and aims to recruit 5 million volunteers to support research intended to improve early detection, risk stratification, and early intervention for chronic diseases. To explore how current models of genomic health data generation intersect, and to understand clinical, ethical, legal, policy and social issues arising from this intersection, we conducted a series of five multidisciplinary panel discussions attended by 28 invited stakeholders. Meetings were recorded and transcribed. We present a summary of issues identified: genomic test attributes; reasons for generating genomic health data; individuals’ motivation to seek genomic data; health service impacts; role of genetic counseling; equity; data uses and security; consent; governance and regulation. We conclude with some suggestions for policy consideration.
Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis
Authors: Pradhan Saurabh J. , Reddy Puli Chandramouli , Smutny Michael , Sharma Ankita , Sako Keisuke , Oak Meghana S. , Shah Rini , Pal Mrinmoy , Deshpande Ojas , Dsilva Greg , Tang Yin , Mishra Rakesh , Deshpande Girish , Giraldez Antonio J. , Sonawane Mahendra , Heisenberg Carl-Philipp , Galande Sanjeev 
Published: October 2021

AbstractZygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.
Reaching silicon-based NEMS performances with 3D printed nanomechanical resonators
Authors: Stassi Stefano , Cooperstein Ido , Tortello Mauro , Pirri Candido Fabrizio , Magdassi Shlomo , Ricciardi Carlo 
Published: October 2021

AbstractThe extreme miniaturization in NEMS resonators offers the possibility to reach an unprecedented resolution in high-performance mass sensing. These very low limits of detection are related to the combination of two factors: a small resonator mass and a high quality factor. The main drawback of NEMS is represented by the highly complex, multi-steps, and expensive fabrication processes. Several alternatives fabrication processes have been exploited, but they are still limited to MEMS range and very low-quality factor. Here we report the fabrication of rigid NEMS resonators with high-quality factors by a 3D printing approach. After a thermal step, we reach complex geometry printed devices composed of ceramic structures with high Young’s modulus and low damping showing performances in line with silicon-based NEMS resonators ones. We demonstrate the possibility of rapid fabrication of NEMS devices that present an effective alternative to semiconducting resonators as highly sensitive mass and force sensors.
Structural basis of soluble membrane attack complex packaging for clearance
Authors: Menny Anaïs , Lukassen Marie V. , Couves Emma C. , Franc Vojtech , Heck Albert J. R. , Bubeck Doryen 
Published: October 2021

AbstractUnregulated complement activation causes inflammatory and immunological pathologies with consequences for human disease. To prevent bystander damage during an immune response, extracellular chaperones (clusterin and vitronectin) capture and clear soluble precursors to the membrane attack complex (sMAC). However, how these chaperones block further polymerization of MAC and prevent the complex from binding target membranes remains unclear. Here, we address that question by combining cryo electron microscopy (cryoEM) and cross-linking mass spectrometry (XL-MS) to solve the structure of sMAC. Together our data reveal how clusterin recognizes and inhibits polymerizing complement proteins by binding a negatively charged surface of sMAC. Furthermore, we show that the pore-forming C9 protein is trapped in an intermediate conformation whereby only one of its two transmembrane β-hairpins has unfurled. This structure provides molecular details for immune pore formation and helps explain a complement control mechanism that has potential implications for how cell clearance pathways mediate immune homeostasis.
Two-billion-year-old volcanism on the Moon from Chang’e-5 basalts
Authors: Li Qiu-Li , Zhou Qin , Liu Yu , Xiao Zhiyong , Lin Yangting , Li Jin-Hua , Ma Hong-Xia , Tang Guo-Qiang , Guo Shun , Tang Xu , Yuan Jiang-Yan , Li Jiao , Wu Fu-Yuan , Ouyang Ziyuan , Li Chunlai , Li Xian-Hua 
Published: October 2021

AbstractThe Moon has a magmatic and thermal history that is distinct from that of the terrestrial planets1. Radioisotope dating of lunar samples suggests that most lunar basaltic magmatism ceased by around 2.9–2.8 billion years ago (Ga)2,3, although younger basalts between 3 Ga and 1 Ga have been suggested by crater-counting chronology, which has large uncertainties owing to the lack of returned samples for calibration4,5. Here we report a precise lead–lead age of 2,030 ± 4 million years ago for basalt clasts returned by the Chang’e-5 mission, and a 238U/204Pb ratio (µ value)6 of about 680 for a source that evolved through two stages of differentiation. This is the youngest crystallization age reported so far for lunar basalts by radiometric dating, extending the duration of lunar volcanism by approximately 800–900 million years. The µ value of the Chang’e-5 basalt mantle source is within the range of low-titanium and high-titanium basalts from Apollo sites (µ value of about 300–1,000), but notably lower than those of potassium, rare-earth elements and phosphorus (KREEP) and high-aluminium basalts7 (µ value of about 2,600–3,700), indicating that the Chang’e-5 basalts were produced by melting of a KREEP-poor source. This age provides a pivotal calibration point for crater-counting chronology in the inner Solar System and provides insight on the volcanic and thermal history of the Moon.
Automated CUT&Tag profiling of chromatin heterogeneity in mixed-lineage leukemia
Authors: Janssens Derek H. , Meers Michael P. , Wu Steven J. , Babaeva Ekaterina , Meshinchi Soheil , Sarthy Jay F. , Ahmad Kami , Henikoff Steven 
Published: October 2021

AbstractAcute myeloid and lymphoid leukemias often harbor chromosomal translocations involving the KMT2A gene, encoding the KMT2A lysine methyltransferase (also known as mixed-lineage leukemia-1), and produce in-frame fusions of KMT2A to other chromatin-regulatory proteins. Here we map fusion-specific targets across the genome for diverse KMT2A oncofusion proteins in cell lines and patient samples. By modifying CUT&Tag chromatin profiling for full automation, we identify common and tumor-subtype-specific sites of aberrant chromatin regulation induced by KMT2A oncofusion proteins. A subset of KMT2A oncofusion-binding sites are marked by bivalent (H3K4me3 and H3K27me3) chromatin signatures, and single-cell CUT&Tag profiling reveals that these sites display cell-to-cell heterogeneity suggestive of lineage plasticity. In addition, we find that aberrant enrichment of H3K4me3 in gene bodies is sensitive to Menin inhibitors, demonstrating the utility of automated chromatin profiling for identifying therapeutic vulnerabilities. Thus, integration of automated and single-cell CUT&Tag can uncover epigenomic heterogeneity within patient samples and predict sensitivity to therapeutic agents.
Biocompatible artificial synapses based on a zein active layer obtained from maize for neuromorphic computing
Authors: Kim Youngjin , Park Chul Hyeon , An Jun Seop , Choi Seung-Hye , Kim Tae Whan 
Published: October 2021

AbstractArtificial synaptic devices based on natural organic materials are becoming the most desirable for extending their fields of applications to include wearable and implantable devices due to their biocompatibility, flexibility, lightweight, and scalability. Herein, we proposed a zein material, extracted from natural maize, as an active layer in an artificial synapse. The synaptic device exhibited notable digital-data storage and analog data processing capabilities. Remarkably, the zein-based synaptic device achieved recognition accuracy of up to 87% and exhibited clear digit-classification results on the learning and inference test. Moreover, the recognition accuracy of the zein-based artificial synapse was maintained within a difference of less than 2%, regardless of mechanically stressed conditions. We believe that this work will be an important asset toward the realization of wearable and implantable devices utilizing artificial synapses.
Dopant activation process in Mg-implanted GaN studied by monoenergetic positron beam
Authors: Uedono Akira , Tanaka Ryo , Takashima Shinya , Ueno Katsunori , Edo Masaharu , Shima Kohei , Kojima Kazunobu , Chichibu Shigefusa F. , Ishibashi Shoji 
Published: October 2021

AbstractA process for activating Mg and its relationship with vacancy-type defects in Mg-implanted GaN were studied by positron annihilation spectroscopy. Mg+ ions were implanted with an energy of 10 keV, and the Mg concentration in the subsurface region (≤ 50 nm) was on the order of 1019 cm−3. After the Mg-implantation, N+ ions were implanted to provide a 300-nm-deep box profile with a N concentration of 6 × 1018 cm−3. From capacitance–voltage measurements, the sequential implantation of N was found to enhance the activation of Mg. For N-implanted GaN before annealing, the major defect species were determined to Ga-vacancy related defects such as divacancy. After annealing below 1000 °C, the clustering of vacancies was observed. Above 1200 °C annealing, however, the size of the vacancies started to decrease, which was due to recombinations of vacancy clusters and excess N atoms in the damaged region. The suppression of vacancy clustering by sequential N-implantation in Mg-implanted GaN was attributed to the origin of the enhancement of the Mg activation.
Radiation effects on 3D rotating flow of Cu-water nanoliquid with viscous heating and prescribed heat flux using modified Buongiorno model
Authors: Owhaib Wahib , Basavarajappa Mahanthesh , Al-Kouz Wael 
Published: October 2021

AbstractIn this article, the three-dimensional (3D) flow and heat transport of viscous dissipating Cu-H2O nanoliquid over an elongated plate in a rotating frame of reference is studied by considering the modified Buongiorno model. The mechanisms of haphazard motion and thermo-migration of nanoparticles along with effective nanoliquid properties are comprised in the modified Buongiorno model (MBM). The Rosseland radiative heat flux and prescribed heat flux at the boundary are accounted. The governing nonlinear problem subjected to Prandtl’s boundary layer approximation is solved numerically. The consequence of dimensionless parameters on the velocities, temperature, and nanoparticles volume fraction profiles is analyzed via graphical representations. The temperature of the base liquid is improved significantly owing to the existence of copper nanoparticles in it. The phenomenon of rotation improves the structure of the thermal boundary layer, while, the momentum layer thickness gets reduced. The thermal layer structure gets enhanced due to the Brownian movement and thermo-migration of nanoparticles. Moreover, it is shown that temperature enhances owing to the presence of thermal radiation. In addition, it is revealed that the haphazard motion of nanoparticles decays the nanoparticle volume fraction layer thickness. Also, the skin friction coefficients found to have a similar trend for larger values of rotation parameter. Furthermore, the results of the single-phase nanoliquid model are limiting the case of this study.
Proposal for an initial screening method for identifying microplastics in marine sediments
Authors: Hata Toshiro , Jiang Ningjun 
Published: October 2021

AbstractMarine debris, which is often called microplastics, is widespread in marine environments, particularly in sediments, and is recognized as an environmental hazard because it concentrates contaminants, forms biofilms, and sinks into marine sediments. In sediments, it may be ingested by benthos and have a negative impact on higher food chain levels. In this study, a new protocol was developed to identify microplastics in various sediment fractions. This protocol combined sieving and staining based on ordinal geotechnical/geological testing methods. The sieving process was derived from the conventional particle size distribution test, and nontoxic dyes were employed in the staining process. The protocol is safe and easy to perform as it merely involves the use of conventional geological/geotechnical testing equipment. The new protocol was successfully employed to stain and categorize different types and sizes of microplastic particles from contaminated sediments. This safe, easy-to-use, and efficient protocol can serve as the basis for a new alternative approach to study microplastics present in sediments, which can be performed using basic materials familiar to geotechnical/geological engineers.
Enriching laying hens eggs by feeding diets with different fatty acid composition and antioxidants
Authors: Vlaicu Petru Alexandru , Panaite Tatiana Dumitra , Turcu Raluca Paula 
Published: October 2021

AbstractThe current study was conducted to evaluate egg quality, egg yolk fatty acids, health-related indices and antioxidants from laying hens' eggs fed different combined vegetable by-products, rich in fatty acids and antioxidants. One hundred twenty 50 weeks-old Tetra SL laying hens were divided into three groups. They were given daily a standard diet (Control, C), a diet containing 9% rapeseed meal with 3% grapeseed meal (T1 diet), or a diet containing 9% flaxseed meal and 3% sea buckthorn meal (T2 diet). Hen production performances, egg quality, egg yolk fatty acids total polyphenols content and antioxidant capacity were determined. The T1 diet significantly reduced the egg yolk content of palmitic acid from 76.615 mg (C) to 46.843 mg (T1) and that of oleic acid from 788.13 mg (C) to 682.83 mg (T1). Feeding flaxseed and sea buckthorn meals significantly increased the egg yolk content of α-linolenic acid in T2 yolks (35.297 mg) compared with C yolks (4.752 mg) and that of docosahexaenoic acid (DHA) from 16.282 mg (C) to 74.918 mg (T2). The atherogenicity indices (AI) were not significantly affected, whereas the thrombogenicity indices (TI) decreased significantly (p < 0.0007) from 0.72 (C) to 0.60 (T1) and 0.66 (T2), respectively. Adding this combination of meals to the hens' diets, increased the total polyphenol content and antioxidant capacity in T1 and T2 eggs compared to C eggs. The significant enrichment of eggs with n-3 fatty acids and antioxidant capacity, as well on the health-related indices especially from T2 eggs, represents a potential functional feed ingredient in poultry feeding, to obtain eggs as functional food.