bluuebunny/crossref_metadata_2025_split huggingface dataset:
Slantwise Convection in the Irminger Sea
Authors: Le Bras I. A.‐A. , Callies J. , Straneo F. , Biló T. C. , Holte J. , Johnson H. L. 
Published: September 2022

AbstractThe subpolar North Atlantic is a site of significant carbon dioxide, oxygen, and heat exchange with the atmosphere. This exchange, which regulates transient climate change and prevents large‐scale hypoxia throughout the North Atlantic, is thought to be mediated by vertical mixing in the ocean's surface mixed layer. Here we present observational evidence that waters deeper than the conventionally defined mixed layer are affected directly by atmospheric forcing in this region. When northerly winds blow along the Irminger Sea's western boundary current, the Ekman response pushes denser water over lighter water, potentially triggering slantwise convection. We estimate that this down‐front wind forcing is four times stronger than air–sea heat flux buoyancy forcing and can mix waters to several times the conventionally defined mixed layer depth. Slantwise convection is not included in most large‐scale ocean models, which likely limits their ability to accurately represent subpolar water mass transformations and deep ocean ventilation.
Regulatory chromatin rewiring promotes metabolic switching during adaptation to oncogenic receptor tyrosine kinase inhibition
Authors: Ogden Samuel , Carys Kashmala , Ahmed Ibrahim , Bruce Jason , Sharrocks Andrew D. 
Published: September 2022

AbstractOesophageal adenocarcinoma (OAC) patients show poor survival rates and there are few targeted molecular therapies available. However, components of the receptor tyrosine kinase (RTK) driven pathways are commonly mutated in OAC, typified by high frequency amplifications of the RTK ERBB2. ERBB2 can be therapeutically targeted, but this has limited clinical benefit due to the acquisition of drug resistance. Here we examined how OAC cells adapt to ERBB2 inhibition as they transition to a drug resistant state. ERBB2 inhibition triggers widespread remodelling of the accessible chromatin landscape and the underlying gene regulatory networks. The transcriptional regulators HNF4A and PPARGC1A play a key role in this network rewiring. Initially, inhibition of cell cycle associated gene expression programmes is observed, with compensatory increases in the programmes driving changes in metabolic activity. Both PPARGC1A and HNF4A are required for the acquisition of resistance to ERBB2 inhibition and PPARGC1A is instrumental in promoting a switch to dependency on oxidative phosphorylation. Our work therefore reveals the molecular pathways that support the acquisition of a resistant state and points to potential new therapeutic strategies to combat cellular adaptation and ensuing drug resistance.
Histocompatibility Minor 13 (HM13), targeted by miR-760, exerts oncogenic role in breast cancer by suppressing autophagy and activating PI3K-AKT-mTOR pathway
Authors: Yang Haiyan , Li Zhi , Wang Zhangwei , Zhang Xu , Dai Xinyuan , Zhou Guoren , Ding Qiang 
Published: September 2022

AbstractHistocompatibility Minor 13 (HM13) is reported to participate in regulating multiple cancers. In the present study, we uncovered that HM13 was highly expressed in breast cancer and correlated with worse prognosis. Downregulation of HM13 could suppress breast cancer cell proliferation and metastasis abilities. Tumorigenicity mediated by HM13 was also observed in the xenograft model. Knockdown of HM13 could activate autophagy by inducing endoplasmic reticulum (ER) stress. Moreover, further experiments demonstrated that downregulated HM13 could inhibit PI3K-AKT-mTOR pathway. We then verified that HM13 was a direct target of miR-760 functioned as a tumor -suppressor in breast cancer. And the tumor suppressive effects of miR-760 could be partially reversed by HM13. Taken together, these findings elucidated that HM13, targeted by miR-760, could play an oncogenic role in breast cancer by inducing autophagic inhibition and facilitating PI3K-AKT-mTOR pathway. Our findings suggested HM13 could act as a novel therapeutic target candidate for breast cancer and supported the idea that autophagy inducers might represent a new approach to treat breast cancer.
Interplays of glucose metabolism and KRAS mutation in pancreatic ductal adenocarcinoma
Authors: Liu Yu-Huei , Hu Chun-Mei , Hsu Yuan-Sheng , Lee Wen-Hwa 
Published: September 2022

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadliest cancer worldwide. The primary reasons for this are the lack of early detection methods and targeted therapy. Emerging evidence highlights the metabolic addiction of cancer cells as a potential target to combat PDAC. Oncogenic mutations ofKRASare the most common triggers that drive glucose uptake and utilization via metabolic reprogramming to support PDAC growth. Conversely, high glucose levels in the pancreatic microenvironment trigger genome instability andde novomutations, includingKRASG12D, in pancreatic cells through metabolic reprogramming. Here, we review convergent and diverse metabolic networks related to oncogenicKRASmutations between PDAC initiation and progression, emphasizing the interplay among oncogenic mutations, glucose metabolic reprogramming, and the tumor microenvironment. Recognizing cancer-related glucose metabolism will provide a better strategy to prevent and treat the high risk PDAC population.
RNF4~RGMb~BMP6 axis required for osteogenic differentiation and cancer cell survival
Authors: Novak Rostislav , Ahmad Yamen Abu , Timaner Michael , Bitman-Lotan Eliya , Oknin-Vaisman Avital , Horwitz Roi , Hartmann Oliver , Reissland Michaela , Buck Viktoria , Rosenfeldt Mathias , Nikomarov David , Diefenbacher Markus Elmar , Shaked Yuval , Orian Amir 
Published: September 2022

AbstractMolecular understanding of osteogenic differentiation (OD) of human bone marrow-derived mesenchymal stem cells (hBMSCs) is important for regenerative medicine and has direct implications for cancer. We report that the RNF4 ubiquitin ligase is essential for OD of hBMSCs, and that RNF4-deficient hBMSCs remain as stalled progenitors. Remarkably, incubation of RNF4-deficient hBMSCs in conditioned media of differentiating hBMSCs restored OD. Transcriptional analysis of RNF4-dependent gene signatures identified two secreted factors that act downstream of RNF4 promoting OD: (1) BMP6 and (2) the BMP6 co-receptor, RGMb (Dragon). Indeed, knockdown of either RGMb or BMP6 in hBMSCs halted OD, while only the combined co-addition of purified RGMb and BMP6 proteins to RNF4-deficient hBMSCs fully restored OD. Moreover, we found that the RNF4-RGMb-BMP6 axis is essential for survival and tumorigenicity of osteosarcoma and therapy-resistant melanoma cells. Importantly, patient-derived sarcomas such as osteosarcoma, Ewing sarcoma, liposarcomas, and leiomyosarcomas exhibit high levels of RNF4 and BMP6, which are associated with reduced patient survival. Overall, we discovered that the RNF4~BMP6~RGMb axis is required for both OD and tumorigenesis.
Pathological variants in genes associated with disorders of sex development and central causes of hypogonadism in a whole-genome reference panel of 8380 Japanese individuals
Authors: Shiga Naomi , Yamaguchi-Kabata Yumi , Igeta Saori , Yasuda Jun , Tadaka Shu , Minato Takamichi , Watanabe Zen , Kanno Junko , Tamiya Gen , Fuse Nobuo , Kinoshita Kengo , Kure Shigeo , Kondo Akiko , Tachibana Masahito , Yamamoto Masayuki , Yaegashi Nobuo , Sugawara Junichi 
Published: September 2022

AbstractDisorders of sex development (DSD) comprises a congenital condition in which chromosomal, gonadal, or anatomical sex development is atypical. In this study, we screened for pathogenic variants in 32 genes associated with DSDs and central causes of hypogonadism (CHG) in a whole-genome reference panel including 8380 Japanese individuals constructed by Tohoku Medical Megabank Organization. Candidate pathogenic (P) or likely pathogenic (LP) variants were extracted from the ClinVar, InterVar, and Human Gene Mutation databases. Ninety-one candidate pathological variants were found in 25 genes; 28 novel candidate variants were identified. Nearly 1 in 40 (either ClinVar or InterVar P or LP) to 157 (both ClinVar and InterVar P or LP) individuals were found to be carriers of recessive DSD and CHG alleles. In these data, genes implicated in gonadal dysfunction did not show loss-of-function variants, with a relatively high tendency of intolerance for haploinsufficiency based on pLI and Episcore, both of which can be used for estimating haploinsufficiency. We report the types and frequencies of causative variants for DSD and CHG in the general Japanese population. This study furthers our understanding of the genetic causes and helps to refine genetic counseling of DSD and CHG.
A wind environment and Lorentz factors of tens explain gamma-ray bursts X-ray plateau
Authors: Dereli-Bégué Hüsne , Pe’er Asaf , Ryde Felix , Oates Samantha R. , Zhang Bing , Dainotti Maria G. 
Published: September 2022

AbstractGamma-ray bursts (GRBs) are known to have the most relativistic jets, with initial Lorentz factors in the order of a few hundreds. Many GRBs display an early X-ray light-curve plateau, which was not theoretically expected and therefore puzzled the community for many years. Here, we show that this observed signal is naturally obtained within the classical GRB fireball model, provided that the initial Lorentz factor is rather a few tens, and the expansion occurs into a medium-low density wind. The range of Lorentz factors in GRB jets is thus much wider than previously thought and bridges an observational gap between mildly relativistic jets inferred in active galactic nuclei, to highly relativistic jets deduced in few extreme GRBs. Furthermore, long GRB progenitors are either not Wolf-Rayet stars, or the wind properties during the final stellar evolution phase are different than at earlier times. Our model has predictions that can be tested to verify or reject it in the future, such as lack of GeV emission, lack of strong thermal component and long (few seconds) variability during the prompt phase characterizing plateau bursts.
Genomic and biological study of fusion genes as resistance mechanisms to EGFR inhibitors
Authors: Kobayashi Yoshihisa , Oxnard Geoffrey R. , Cohen Elizabeth F. , Mahadevan Navin R. , Alessi Joao V. , Hung Yin P. , Bertram Arrien A. , Heppner David E. , Ribeiro Mauricio F. , Sacardo Karina P. , Saddi Rodrigo , Macedo Mariana P. , Blasco Rafael B. , Li Jiaqi , Kurppa Kari J. , Nguyen Tom , Voligny Emma , Ananda Guruprasad , Chiarle Roberto , Katz Artur , Tolstorukov Michael Y. , Sholl Lynette M. , Jänne Pasi A. 
Published: September 2022

AbstractThe clinical significance of gene fusions detected by DNA-based next generation sequencing remains unclear as resistance mechanisms to EGFR tyrosine kinase inhibitors in EGFR mutant non-small cell lung cancer. By studying EGFR inhibitor-resistant patients treated with a combination of an EGFR inhibitor and a drug targeting the putative resistance-causing fusion oncogene, we identify patients who benefit and those who do not from this treatment approach. Through evaluation including RNA-seq of potential drug resistance-imparting fusion oncogenes in 504 patients with EGFR mutant lung cancer, we identify only a minority of them as functional, potentially capable of imparting EGFR inhibitor resistance. We further functionally validate fusion oncogenes in vitro using CRISPR-based editing of EGFR mutant cell lines and use these models to identify known and unknown drug resistance mechanisms to combination therapies. Collectively, our results partially reveal the complex nature of fusion oncogenes as potential drug resistance mechanisms and highlight approaches that can be undertaken to determine their functional significance.
Square-root higher-order Weyl semimetals
Authors: Song Lingling , Yang Huanhuan , Cao Yunshan , Yan Peng 
Published: September 2022

AbstractThe mathematical foundation of quantum mechanics is built on linear algebra, while the application of nonlinear operators can lead to outstanding discoveries under some circumstances, such as the prediction of positron, a direct outcome of the Dirac equation which stems from the square-root of the Klein-Gordon equation. In this article, we propose a model of square-root higher-order Weyl semimetal (SHOWS) by inheriting features from its parent Hamiltonians. It is found that the SHOWS hosts both “Fermi-arc” surface and hinge states that respectively connect the projection of the Weyl points on the side surface and arris. We theoretically construct and experimentally observe the exotic SHOWS state in three-dimensional (3D) stacked electric circuits with honeycomb-kagome hybridizations and double-helix interlayer couplings. Our results open the door for realizing the square-root topology in 3D solid-state platforms.
Field-induced orientational switching produces vertically aligned Ti3C2Tx MXene nanosheets
Authors: Lee Changjae , Park Soon Mo , Kim Soobin , Choi Yun-Seok , Park Geonhyeong , Kang Yun Chan , Koo Chong Min , Kim Seon Joon , Yoon Dong Ki 
Published: September 2022

AbstractControlling the orientation of two-dimensional materials is essential to optimize or tune their functional properties. In particular, aligning MXene, a two-dimensional carbide and/or nitride material, has recently received much attention due to its high conductivity and high-density surface functional group properties that can easily vary based on its arranged directions. However, erecting 2D materials vertically can be challenging, given their thinness of few nanometres. Here, vertical alignment of Ti3C2Tx MXene sheets is achieved by applying an in-plane electric field, which is directly observed using polarised optical microscopy and scanning electron microscopy. The electric field-induced vertical alignment parallel to the applied alternating-current field is demonstrated to be reversible in the absence of a field, back to a random orientation distribution. Interdigitated electrodes with uniaxially aligned MXene nanosheets are demonstrated. These can be further modulated to achieve various patterns using diversified electrode substrates. Anisotropic electrical conductivity is also observed in the uniaxially aligned MXene nanosheet film, which is quite different from the randomly oriented ones. The proposed orientation-controlling technique demonstrates potential for many applications including sensors, membranes, polarisers, and general energy applications.
Vacancy driven surface disorder catalyzes anisotropic evaporation of ZnO (0001) polar surface
Authors: Wang Zhen , Byun Jinho , Lee Subin , Seo Jinsol , Park Bumsu , Kim Jong Chan , Jeong Hu Young , Bang Junhyeok , Lee Jaekwang , Oh Sang Ho 
Published: September 2022

AbstractThe evaporation and crystal growth rates of ZnO are highly anisotropic and are fastest on the Zn-terminated ZnO (0001) polar surface. Herein, we study this behavior by direct atomic-scale observations and simulations of the dynamic processes of the ZnO (0001) polar surface during evaporation. The evaporation of the (0001) polar surface is accelerated dramatically at around 300 °C with the spontaneous formation of a few nanometer-thick quasi-liquid layer. This structurally disordered and chemically Zn-deficient quasi-liquid is derived from the formation and inward diffusion of Zn vacancies that stabilize the (0001) polar surface. The quasi-liquid controls the dissociative evaporation of ZnO with establishing steady state reactions with Zn and O2 vapors and the underlying ZnO crystal; while the quasi-liquid catalyzes the disordering of ZnO lattice by injecting Zn vacancies, it facilitates the desorption of O2 molecules. This study reveals that the polarity-driven surface disorder is the key structural feature driving the fast anisotropic evaporation and crystal growth of ZnO nanostructures along the [0001] direction.
A miniaturized bionic ocean-battery mimicking the structure of marine microbial ecosystems
Authors: Zhu Huawei , Xu Liru , Luan Guodong , Zhan Tao , Kang Zepeng , Li Chunli , Lu Xuefeng , Zhang Xueli , Zhu Zhiguang , Zhang Yanping , Li Yin 
Published: September 2022

AbstractMarine microbial ecosystems can be viewed as a huge ocean-battery charged by solar energy. It provides a model for fabricating bio-solar cell, a bioelectrochemical system that converts light into electricity. Here, we fabricate a bio-solar cell consisting of a four-species microbial community by mimicking the ecological structure of marine microbial ecosystems. We demonstrate such ecological structure consisting of primary producer, primary degrader, and ultimate consumers is essential for achieving high power density and stability. Furthermore, the four-species microbial community is assembled into a spatial-temporally compacted cell using conductive hydrogel as a sediment-like anaerobic matrix, forming a miniaturized bionic ocean-battery. This battery directly converts light into electricity with a maximum power of 380 μW and stably operates for over one month. Reproducing the photoelectric conversion function of marine microbial ecosystems in this bionic battery overcomes the sluggish and network-like electron transfer, showing the biotechnological potential of synthetic microbial ecology.
Oscillating light engine realized by photothermal solvent evaporation
Authors: Li Jingjing , Mou Linlin , Liu Zunfeng , Zhou Xiang , Chen Yongsheng 
Published: September 2022

AbstractContinuous mechanical work output can be generated by using combustion engines and electric motors, as well as actuators, through on/off control via external stimuli. Solar energy has been used to generate electricity and heat in human daily life; however, the direct conversion of solar energy to continuous mechanical work has not been realized. In this work, a solar engine is developed using an oscillating actuator, which is realized through an alternating volume decrease of each side of a polypropylene/carbon black polymer film induced by photothermal-derived solvent evaporation. The anisotropic solvent evaporation and fast gradient diffusion in the polymer film sustains oscillating bending actuation under the illumination of divergent light. This light-driven oscillator shows excellent oscillation performance, excellent loading capability, and high energy conversion efficiency, and it can never stop with solvent supply. The oscillator can cyclically lift up a load and output work, exhibiting a maximum specific work of 30.9 × 10−5 J g−1 and a maximum specific power of 15.4 × 10−5 W g−1 under infrared light. This work can inspire the development of autonomous devices and provide a design strategy for solar engines.
DNA methylation signatures of Alzheimer’s disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types
Authors: Shireby Gemma , Dempster Emma L. , Policicchio Stefania , Smith Rebecca G. , Pishva Ehsan , Chioza Barry , Davies Jonathan P. , Burrage Joe , Lunnon Katie , Seiler Vellame Dorothea , Love Seth , Thomas Alan , Brookes Keeley , Morgan Kevin , Francis Paul , Hannon Eilis , Mill Jonathan 
Published: September 2022

AbstractAlzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the progressive accumulation of amyloid-beta and neurofibrillary tangles of tau in the neocortex. We profiled DNA methylation in two regions of the cortex from 631 donors, performing an epigenome-wide association study of multiple measures of AD neuropathology. We meta-analyzed our results with those from previous studies of DNA methylation in AD cortex (totaln = 2013 donors), identifying 334 cortical differentially methylated positions (DMPs) associated with AD pathology including methylomic variation at loci not previously implicated in dementia. We subsequently profiled DNA methylation in NeuN+ (neuronal-enriched), SOX10+ (oligodendrocyte-enriched) and NeuN–/SOX10– (microglia- and astrocyte-enriched) nuclei, finding that the majority of DMPs identified in ‘bulk’ cortex tissue reflect DNA methylation differences occurring in non-neuronal cells. Our study highlights the power of utilizing multiple measures of neuropathology to identify epigenetic signatures of AD and the importance of characterizing disease-associated variation in purified cell-types.
In-depth insights into cervicovaginal microbial communities and hrHPV infections using high-resolution microbiome profiling
Authors: Molina Mariano A. , Andralojc Karolina M. , Huynen Martijn A. , Leenders William P. J. , Melchers Willem J. G. 
Published: September 2022

AbstractThe cervicovaginal microbiome (CVM) correlates with women’s cervical health, and variations in its composition are associated with high-risk human papillomavirus (hrHPV) infection outcomes. Cervicovaginal microbes have been grouped into five community state types (CSTs) based on microbial community composition and abundance. However, studying the impact of CSTs in health and disease is challenging because the current sequencing technologies have limited confident discrimination between closely related and yet functionally different bacterial species. Circular probe-based RNA sequencing (ciRNAseq) achieves high-resolution microbiome profiling and therefore provides in-depth and unambiguous knowledge about the composition of the CVM. Based on ciRNAseq profiling of a large cohort of cervical smears (n = 541), we here define subgroups of CSTs I, III, and IV based on intra-CST differences with respect to abundances of Lactobacillus acidophilus (CSTs I-A vs. I-B and CSTs III-A vs. III-B), Lactobacillus iners (CSTs I-A vs. I-B and CSTs III-A vs. III-B), and Megasphaera genomosp type 1 (CSTs IV-A vs. IV-B). Our results further support the existence of subgroups of CST IV-C that are dominant for non-Lactobacillus species and have intermediate microbial diversity. We also show that CST V is associated with uninfected conditions, and CST IV-A associates with hrHPV-induced cervical disease. In conclusion, we characterized new subdivisions of cervicovaginal CSTs, which may further advance our understanding of women’s cervical health and hrHPV-related progression to disease.
Predicting solid state material platforms for quantum technologies
Authors: Hebnes Oliver Lerstøl , Bathen Marianne Etzelmüller , Schøyen Øyvind Sigmundson , Winther-Larsen Sebastian G. , Vines Lasse , Hjorth-Jensen Morten 
Published: September 2022

AbstractSemiconductor materials provide a compelling platform for quantum technologies (QT). However, identifying promising material hosts among the plethora of candidates is a major challenge. Therefore, we have developed a framework for the automated discovery of semiconductor platforms for QT using material informatics and machine learning methods. Different approaches were implemented to label data for training the supervised machine learning (ML) algorithms logistic regression, decision trees, random forests and gradient boosting. We find that an empirical approach relying exclusively on findings from the literature yields a clear separation between predicted suitable and unsuitable candidates. In contrast to expectations from the literature focusing on band gap and ionic character as important properties for QT compatibility, the ML methods highlight features related to symmetry and crystal structure, including bond length, orientation and radial distribution, as influential when predicting a material as suitable for QT.