bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutation-specific non-canonical pathway of PTEN as a distinct therapeutic target for glioblastoma
Authors: Choi Seung Won , Lee Yeri , Shin Kayoung , Koo Harim , Kim Donggeon , Sa Jason K. , Cho Hee Jin , Shin Hye-mi , Lee Se Jeong , Kim Hyunho , Chung Seok , Shin Jihye , Lee Cheolju , Nam Do-Hyun 
Published: April 2021

AbstractPTEN is one of the most frequently altered tumor suppressor genes in malignant tumors. The dominant-negative effect of PTEN alteration suggests that the aberrant function of PTEN mutation might be more disastrous than deletion, the most frequent genomic event in glioblastoma (GBM). This study aimed to understand the functional properties of various PTEN missense mutations and to investigate their clinical relevance. The genomic landscape of PTEN alteration was analyzed using the Samsung Medical Center GBM cohort and validated via The Cancer Genome Atlas dataset. Several hotspot mutations were identified, and their subcellular distributions and phenotypes were evaluated. We established a library of cancer cell lines that overexpress these mutant proteins using the U87MG and patient-derived cell models lacking functional PTEN. PTEN mutations were categorized into two major subsets: missense mutations in the phosphatase domain and truncal mutations in the C2 domain. We determined the subcellular compartmentalization of four mutant proteins (H93Y, C124S, R130Q, and R173C) from the former group and found that they had distinct localizations; those associated with invasive phenotypes (‘edge mutations’) localized to the cell periphery, while the R173C mutant localized to the nucleus. Invasive phenotypes derived from edge substitutions were unaffected by an anti-PI3K/Akt agent but were disrupted by microtubule inhibitors. PTEN mutations exhibit distinct functional properties regarding their subcellular localization. Further, some missense mutations (‘edge mutations’) in the phosphatase domain caused enhanced invasiveness associated with dysfunctional cytoskeletal assembly, thus suggesting it to be a potent therapeutic target.
Hypoxic glioma-derived exosomes promote M2-like macrophage polarization by enhancing autophagy induction
Authors: Xu Jianye , Zhang Jian , Zhang Zongpu , Gao Zijie , Qi Yanhua , Qiu Wei , Pan Ziwen , Guo Qindong , Li Boyan , Zhao Shulin , Guo Xiaofan , Qian Mingyu , Chen Zihang , Wang Shaobo , Gao Xiao , Zhang Shouji , Wang Huizhi , Guo Xing , Zhang Ping , Zhao Rongrong , Xue Hao , Li Gang 
Published: April 2021

AbstractExosomes participate in intercellular communication and glioma microenvironment modulation, but the exact mechanisms by which glioma-derived exosomes (GDEs) promote the generation of the immunosuppressive microenvironment are still unclear. Here, we investigated the effects of GDEs on autophagy, the polarization of tumor-associated macrophages (TAMs), and glioma progression. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) markedly facilitated autophagy and M2-like macrophage polarization, which subsequently promoted glioma proliferation and migration in vitro and in vivo. Western blot and qRT-PCR analyses indicated that interleukin 6 (IL-6) and miR-155-3p were highly expressed in H-GDEs. Further experiments showed that IL-6 and miR-155-3p induced M2-like macrophage polarization via the IL-6-pSTAT3-miR-155-3p-autophagy-pSTAT3 positive feedback loop, which promotes glioma progression. Our study clarifies a mechanism by which hypoxia and glioma influence autophagy and M2-like macrophage polarization via exosomes, which could advance the formation of the immunosuppressive microenvironment. Our findings suggest that IL-6 and miR-155-3p may be novel biomarkers for diagnosing glioma and that treatments targeting autophagy and the STAT3 pathway may contribute to antitumor immunotherapy.
A novel defined pyroptosis-related gene signature for predicting the prognosis of ovarian cancer
Authors: Ye Ying , Dai Qinjin , Qi Hongbo 
Published: April 2021

AbstractOvarian cancer (OC) is a highly malignant gynaecological tumour that has a very poor prognosis. Pyroptosis has been demonstrated in recent years to be an inflammatory form of programmed cell death. However, the expression of pyroptosis-related genes in OC and their correlations with prognosis remain unclear. In this study, we identified 31 pyroptosis regulators that were differentially expressed between OC and normal ovarian tissues. Based on these differentially expressed genes (DEGs), all OC cases could be divided into two subtypes. The prognostic value of each pyroptosis-related gene for survival was evaluated to construct a multigene signature using The Cancer Genome Atlas (TCGA) cohort. By applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, a 7-gene signature was built and classified all OC patients in the TCGA cohort into a low- or high-risk group. OC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001). Utilizing the median risk score from the TCGA cohort, OC patients from a Gene Expression Omnibus (GEO) cohort were divided into two risk subgroups, and the low-risk group had increased overall survival (OS) time (P = 0.014). Combined with the clinical characteristics, the risk score was found to be an independent factor for predicting the OS of OC patients. Gene ontology (GO) and Kyoto Encylopedia of Genes and Genomes (KEGG) analyses indicated that immune-related genes were enriched and that the immune status was decreased in the high-risk group. In conclusion, pyroptosis-related genes play important roles in tumour immunity and can be used to predict the prognosis of OCs.
Genetic substructure and complex demographic history of South African Bantu speakers
Authors: Sengupta Dhriti , Choudhury Ananyo , Fortes-Lima Cesar , Aron Shaun , Whitelaw Gavin , Bostoen Koen , Gunnink Hilde , Chousou-Polydouri Natalia , Delius Peter , Tollman Stephen , Gómez-Olivé F. Xavier , Norris Shane , Mashinya Felistas , Alberts Marianne ,   AWI-Gen Study,   H3Africa Consortium, Hazelhurst Scott , Schlebusch Carina M. , Ramsay Michèle 
Published: April 2021

AbstractSouth Eastern Bantu-speaking (SEB) groups constitute more than 80% of the population in South Africa. Despite clear linguistic and geographic diversity, the genetic differences between these groups have not been systematically investigated. Based on genome-wide data of over 5000 individuals, representing eight major SEB groups, we provide strong evidence for fine-scale population structure that broadly aligns with geographic distribution and is also congruent with linguistic phylogeny (separation of Nguni, Sotho-Tswana and Tsonga speakers). Although differential Khoe-San admixture plays a key role, the structure persists after Khoe-San ancestry-masking. The timing of admixture, levels of sex-biased gene flow and population size dynamics also highlight differences in the demographic histories of individual groups. The comparisons with five Iron Age farmer genomes further support genetic continuity over ~400 years in certain regions of the country. Simulated trait genome-wide association studies further show that the observed population structure could have major implications for biomedical genomics research in South Africa.
Skilful predictions of the Asian summer monsoon one year ahead
Authors: Takaya Yuhei , Kosaka Yu , Watanabe Masahiro , Maeda Shuhei 
Published: April 2021

AbstractThe interannual variability of the Asian summer monsoon has significant impacts on Asian society. Advances in climate modelling have enabled us to make useful predictions of the seasonal Asian summer monsoon up to approximately half a year ahead, but long-range predictions remain challenging. Here, using a 52-member large ensemble hindcast experiment spanning 1980–2016, we show that a state-of-the-art climate model can predict the Asian summer monsoon and associated summer tropical cyclone activity more than one year ahead. The key to this long-range prediction is successfully simulating El Niño-Southern Oscillation evolution and realistically representing the subsequent atmosphere–ocean response in the Indian Ocean–western North Pacific in the second boreal summer of the prediction. A large ensemble size is also important for achieving a useful prediction skill, with a margin for further improvement by an even larger ensemble.
Integrating science to address food and health within Global Agenda 2030
Authors: McBean Gordon A. 
Published: April 2021

AbstractWhen recovering from the pandemic, it is important for Planet Earth to address the Global Agenda 2030, including food and water crises, and to bounce forward sustainably. The World Economic Forum’s Global Risk Report and Global Agenda 2030 provide a framework for action and an integrated global science agenda response, involving food and health, is essential. The UN 2021 Summit on Food Systems provides an opportunity for the global science community to come together to address the Summit’s Action Tracks, including building resilience to vulnerabilities, shocks and stresses. There would be major global benefits to have an international scientific network working with the UN to address the mandates of the UN Food Summit and Global Agenda 2030.
The structure, function and evolution of a complete human chromosome 8
Authors: Logsdon Glennis A. , Vollger Mitchell R. , Hsieh PingHsun , Mao Yafei , Liskovykh Mikhail A. , Koren Sergey , Nurk Sergey , Mercuri Ludovica , Dishuck Philip C. , Rhie Arang , de Lima Leonardo G. , Dvorkina Tatiana , Porubsky David , Harvey William T. , Mikheenko Alla , Bzikadze Andrey V. , Kremitzki Milinn , Graves-Lindsay Tina A. , Jain Chirag , Hoekzema Kendra , Murali Shwetha C. , Munson Katherine M. , Baker Carl , Sorensen Melanie , Lewis Alexandra M. , Surti Urvashi , Gerton Jennifer L. , Larionov Vladimir , Ventura Mario , Miga Karen H. , Phillippy Adam M. , Eichler Evan E. 
Published: April 2021

AbstractThe complete assembly of each human chromosome is essential for understanding human biology and evolution1,2. Here we use complementary long-read sequencing technologies to complete the linear assembly of human chromosome 8. Our assembly resolves the sequence of five previously long-standing gaps, including a 2.08-Mb centromeric α-satellite array, a 644-kb copy number polymorphism in the β-defensin gene cluster that is important for disease risk, and an 863-kb variable number tandem repeat at chromosome 8q21.2 that can function as a neocentromere. We show that the centromeric α-satellite array is generally methylated except for a 73-kb hypomethylated region of diverse higher-order α-satellites enriched with CENP-A nucleosomes, consistent with the location of the kinetochore. In addition, we confirm the overall organization and methylation pattern of the centromere in a diploid human genome. Using a dual long-read sequencing approach, we complete high-quality draft assemblies of the orthologous centromere from chromosome 8 in chimpanzee, orangutan and macaque to reconstruct its evolutionary history. Comparative and phylogenetic analyses show that the higher-order α-satellite structure evolved in the great ape ancestor with a layered symmetry, in which more ancient higher-order repeats locate peripherally to monomeric α-satellites. We estimate that the mutation rate of centromeric satellite DNA is accelerated by more than 2.2-fold compared to the unique portions of the genome, and this acceleration extends into the flanking sequence.
A biosensor for the direct visualization of auxin
Authors: Herud-Sikimić Ole , Stiel Andre C. , Kolb Martina , Shanmugaratnam Sooruban , Berendzen Kenneth W. , Feldhaus Christian , Höcker Birte , Jürgens Gerd 
Published: April 2021

AbstractOne of the most important regulatory small molecules in plants is indole-3-acetic acid, also known as auxin. Its dynamic redistribution has an essential role in almost every aspect of plant life, ranging from cell shape and division to organogenesis and responses to light and gravity1,2. So far, it has not been possible to directly determine the spatial and temporal distribution of auxin at a cellular resolution. Instead it is inferred from the visualization of irreversible processes that involve the endogenous auxin-response machinery3–7; however, such a system cannot detect transient changes. Here we report a genetically encoded biosensor for the quantitative in vivo visualization of auxin distribution. The sensor is based on the Escherichia coli tryptophan repressor8, the binding pocket of which is engineered to be specific to auxin. Coupling of the auxin-binding moiety with selected fluorescent proteins enables the use of a fluorescence resonance energy transfer signal as a readout. Unlike previous systems, this sensor enables direct monitoring of the rapid uptake and clearance of auxin by individual cells and within cell compartments in planta. By responding to the graded spatial distribution along the root axis and its perturbation by transport inhibitors—as well as the rapid and reversible redistribution of endogenous auxin in response to changes in gravity vectors—our sensor enables real-time monitoring of auxin concentrations at a (sub)cellular resolution and their spatial and temporal changes during the lifespan of a plant.
Sensitive protein alignments at tree-of-life scale using DIAMOND
Authors: Buchfink Benjamin , Reuter Klaus , Drost Hajk-Georg 
Published: April 2021

AbstractWe are at the beginning of a genomic revolution in which all known species are planned to be sequenced. Accessing such data for comparative analyses is crucial in this new age of data-driven biology. Here, we introduce an improved version of DIAMOND that greatly exceeds previous search performances and harnesses supercomputing to perform tree-of-life scale protein alignments in hours, while matching the sensitivity of the gold standard BLASTP.
Differences between children with Down syndrome and typically developing children in adaptive behaviour, executive functions and visual acuity
Authors: de Weger Christine , Boonstra F. Nienke , Goossens Jeroen 
Published: April 2021

AbstractIn children with Down syndrome (DS) development of visual, motor and cognitive functions is atypical. It is unknown whether the visual impairments in children with DS aggravate their lag in cognitive development. Visual impairment and developmental lags in adaptive behaviour and executive functions were assessed in 104 children with DS, 2–16 years, by comparing their adaptive behaviour, executive functions and visual acuity (distant and near) scores against published age-matched norm scores of typically developing children. Associations between these lags were explored. Mean (± SEM) differences to age-matched norms indicated reduced performance in DS: Vineland Screener questionnaire, − 63 ± 3.8 months; task-based Minnesota Executive Function Scale (MEFS), − 46.09 ± 2.07 points; BRIEF-P questionnaire, 25.29 ± 4.66 points; BRIEF parents’ and teachers’ questionnaire, 17.89 ± 3.92 points and 40.10 ± 3.81 points; distant and near visual acuity, 0.51 ± 0.03 LogMAR and 0.63 ± 0.03 LogMAR (near − 0.11 ± 0.04 LogMAR poorer than distant). Adaptive behaviour (Vineland-S) correlated with the severity of visual impairment (r = − 0.396). Children with DS are severely impaired in adaptive behaviour, executive functions and visual acuities (near visual acuity more severely impaired than distant visual acuity). Larger impairment in adaptive behaviour is found in children with larger visual impairment. This supports the idea that visual acuity plays a role in adaptive development.
Heuristic assessment of choices for risk network control
Authors: Brissette Christopher , Niu Xiang , Jiang Chunheng , Gao Jianxi , Korniss Gyorgy , Szymanski Boleslaw K. 
Published: April 2021

AbstractData-driven risk networks describe many complex system dynamics arising in fields such as epidemiology and ecology. They lack explicit dynamics and have multiple sources of cost, both of which are beyond the current scope of traditional control theory. We construct the global economy risk network by combining the consensus of experts from the World Economic Forum with risk activation data to define its topology and interactions. Many of these risks, including extreme weather and drastic inflation, pose significant economic costs when active. We introduce a method for converting network interaction data into continuous dynamics to which we apply optimal control. We contribute the first method for constructing and controlling risk network dynamics based on empirically collected data. We simulate applying this method to control the spread of COVID-19 and show that the choice of risks through which the network is controlled has significant influence on both the cost of control and the total cost of keeping network stable. We additionally describe a heuristic for choosing the risks trough which the network is controlled, given a general risk network.
Magnetoinductive waves in attenuating media
Authors: Chu Son , Luloff Mark S. , Yan Jiaruo , Petrov Pavel , Stevens Christopher J. , Shamonina Ekaterina 
Published: April 2021

AbstractThe capability of magnetic induction to transmit signals in attenuating environments has recently gained significant research interest. The wave aspect—magnetoinductive (MI) waves—has been proposed for numerous applications in RF-challenging environments, such as underground/underwater wireless networks, body area networks, and in-vivo medical diagnosis and treatment applications, to name but a few, where conventional electromagnetic waves have a number of limitations, most notably losses. To date, the effects of eddy currents inside the dissipative medium have not been characterised analytically. Here we propose a comprehensive circuit model of coupled resonators in a homogeneous dissipative medium, that takes into account all the electromagnetic effects of eddy currents, and, thereby, derive a general dispersion equation for the MI waves. We also report laboratory experiments to confirm our findings. Our work will serve as a fundamental model for design and analysis of every system employing MI waves or more generally, magnetically-coupled circuits in attenuating media.
The impact of late-career job loss and genetic risk on body mass index: Evidence from variance polygenic scores
Authors: Schmitz Lauren L. , Goodwin Julia , Miao Jiacheng , Lu Qiongshi , Conley Dalton 
Published: April 2021

AbstractUnemployment shocks from the COVID-19 pandemic have reignited concerns over the long-term effects of job loss on population health. Past research has highlighted the corrosive effects of unemployment on health and health behaviors. This study examines whether the effects of job loss on changes in body mass index (BMI) are moderated by genetic predisposition using data from the U.S. Health and Retirement Study (HRS). To improve detection of gene-by-environment (G × E) interplay, we interacted layoffs from business closures—a plausibly exogenous environmental exposure—with whole-genome polygenic scores (PGSs) that capture genetic contributions to both the population mean (mPGS) and variance (vPGS) of BMI. Results show evidence of genetic moderation using a vPGS (as opposed to an mPGS) and indicate genome-wide summary measures of phenotypic plasticity may further our understanding of how environmental stimuli modify the distribution of complex traits in a population.
Climate change and anthropogenic food manipulation interact in shifting the distribution of a large herbivore at its altitudinal range limit
Authors: Bright Ross Julius G. , Peters Wibke , Ossi Federico , Moorcroft Paul R. , Cordano Emanuele , Eccel Emanuele , Bianchini Filippo , Ramanzin Maurizio , Cagnacci Francesca 
Published: April 2021

AbstractUngulates in alpine ecosystems are constrained by winter harshness through resource limitation and direct mortality from weather extremes. However, little empirical evidence has definitively established how current climate change and other anthropogenic modifications of resource availability affect ungulate winter distribution, especially at their range limits. Here, we used a combination of historical (1997–2002) and contemporary (2012–2015) Eurasian roe deer (Capreolus capreolus) relocation datasets that span changes in snowpack characteristics and two levels of supplemental feeding to compare and forecast probability of space use at the species’ altitudinal range limit. Scarcer snow cover in the contemporary period interacted with the augmented feeding site distribution to increase the elevation of winter range limits, and we predict this trend will continue under climate change. Moreover, roe deer have shifted from historically using feeding sites primarily under deep snow conditions to contemporarily using them under a wider range of snow conditions as their availability has increased. Combined with scarcer snow cover during December, January, and April, this trend has reduced inter-annual variability in space use patterns in these months. These spatial responses to climate- and artificial resource-provisioning shifts evidence the importance of these changing factors in shaping large herbivore spatial distribution and, consequently, ecosystem dynamics.
Method of lines for analysis of plane wave scattering by periodic arrays of magnetically-biased graphene strips
Authors: Ziaee Bideskan Mehri , Forooraghi Keyvan , Atlasbaf Zahra 
Published: April 2021

AbstractIn this paper, efficient analysis of the plane wave scattering by periodic arrays of magnetically-biased graphene strips (PAMGS) is performed using the semi-numerical, semi-analytical method of lines (MoL). In MoL, all but one independent variable is discretized to reduce a system of partial differential equations to a system of ordinary differential equations. Since the solution in one coordinate direction is obtained analytically, this method is time effective with a fast convergence rate. In the case of a multi-layered PAMGS, the governing equations of the problem are discretized concerning periodic boundary conditions (PBCs) in the transverse direction. The reflection coefficient transformation approach is then used to obtain an analytical solution in the longitudinal direction. Here, magnetically-biased graphene strips are modeled as conductive strips with a tensor surface conductivity which is electromagnetically characterized with tensor graphene boundary condition (TGBC). The reflectance and transmittance of different multi-layered PAMGS are carefully obtained and compared with those of other methods reported in the literature. Very good accordance between the results is observed which confirms the accuracy and efficiency of the proposed method.