bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Barbarians Are at the Gate!
Authors: Hatemi Pete 
Published: May 2020

AbstractNicholas Martin’s contribution to science is well known. This article reviews one small part of his pioneering work that integrated political and social attitudes with behavior genetics. Nick Martin, in part, led to a paradigm shift in the social sciences, and in political science in particular. These fields were previously wed to behavioralist approaches and now routinely include genetic influences in both theoretical and empirical study. This article also celebrates a part of Nick’s contribution that many do not know. Nick Martin does not just build science, he builds scientists. There are many who would not be academics or scholars without Nick’s guidance, mentorship and friendship. This review was written to express the deepest appreciation for what he has done and continues to do for science and the scientist.
Contributions of Nicholas Martin to Gambling Disorder Research
Authors: Slutske Wendy S. , Lind Penelope A. 
Published: May 2020

AbstractProfessor Nicholas G. Martin, from QIMR Berghofer Medical Research Institute in Brisbane, Australia, is a world leader in the effort to understand the genetic architecture underlying disordered gambling. This article pays tribute to Nick and his almost two decades of gambling research, highlighting his many strengths, ranging from the use of ingenious recruitment approaches, twin study methods, genomewide association studies, to facilitating international collaborations.
The Surge of the Hispar Glacier, Central Karakoram: SAR 3‐D Flow Velocity Time Series and Thickness Changes
Authors: Guo Lei , Li Jia , Li Zhi‐wei , Wu Li‐xin , Li Xin , Hu Jun , Li Hui‐lin , Li Hong‐yi , Miao Ze‐lang , Li Zhong‐qin 
Published: May 2020

AbstractThe Hispar Glacier is a useful site for studying surge mechanisms. Prior to this study, only two‐dimensional (2‐D) flow velocities having low temporal resolution were available for this glacier, providing inadequate information about its surge evolution. In this study, 139 synthetic aperture radar (SAR) images from Sentinel‐1A were used to obtain 3‐D flow velocity time series for the Hispar Glacier during the recent surge (2014–2016). The 3‐D flow velocities were sampled at an interval of 11 days, which is much greater than in previous studies. Besides, the Shuttle Radar Topography Mission (SRTM) digital elevation model (DEM) and two TanDEM‐X images were used to determine glacier thickness changes prior to and following the recent surge. Combining the results and geomorphologic features, we deduced that the recent surge was because of saturated basal water pressure in the Yutmaru tributary. The mass from the Yutmaru tributary squeezed into the trunk and rapidly flowed downslope along the northern margin, generating strong normal pressure to the trunk mass. Pushed by the Yutmaru tributary, the trunk began to surge in September 2014. The flow velocity reached a first peak in May 2015 and then decreased in October 2015, as part of the basal meltwater ran off. However, basal meltwater accumulated again during the following 4 months, and correspondingly, the trunk accelerated again after October 2015. Finally, as kinetic energy was released and resisting force increased, the trunk became almost stagnant in August 2016. The surge mass was blocked downstream in the trunk by the mass transferred from the Kunyang tributary, and consequently, the glacier did not advance.
Seasonal and Coseismic Velocity Variation in the Region of L'Aquila From Single Station Measurements and Implications for Crustal Rheology
Authors: Poli Piero , Marguin Valentin , Wang Qingyu , D'Agostino Nicola , Johnson Paul 
Published: May 2020

AbstractWe performed measurements of velocity variations for variable coda waves time lapse using empirical Green's functions reconstructed by autocorrelation of seismic noise recorded during a period of 17 years in the region of L'Aquila, Italy. The time lapse approach permitted us to evaluate the spatial (depth) dependence of velocity variation (dv/v). By quantitatively comparing the 17 years of dv/v time series with independent data (e.g., strain induced by earthquakes and hydrological loading), we unravel a group of physical processes inducing velocity variations in the crust over multiple time and spatial scales. We find that rapid shaking due to three magnitude 6+ earthquakes mainly induced near surface velocity variations. On the other hand, slow strain perturbation (period 5 years, in the preseismic period) associated with hydrological cycles, induced velocity changes primarily in the middle crust. The observed behavior suggests the existence of a large volume of fluid‐filled cracks exist deep in the crust. Our study highlights the possibility of using seasonal and multiyear perturbations to probe the physical properties of seismogenic fault volumes and shed new light into the depth‐dependent rheology of crustal rocks in the region or L'Aquila.
Source Regions of Infragravity Waves Recorded at the Bottom of the Equatorial Atlantic Ocean, Using OBS of the PI‐LAB Experiment
Authors: Bogiatzis P. , Karamitrou A. , Ward Neale J. , Harmon N. , Rychert C. A. , Srokosz M. 
Published: May 2020

AbstractInfragravity waves are generated along coasts, and some small fraction of their energy escapes to the open oceans and propagates with little attenuation. Due to the scarcity of deep‐ocean observations of these waves, the mechanism and the extent of the infragravity waves energy leakage from the coasts remains poorly understood. Understanding the generation and pathways of infragravity wave energy is important among others for understanding the breakup of ice‐shelves and the contamination of high‐resolution satellite radar altimetry measurements of sea level. We examine data from 37 differential pressure gauges of Ocean Bottom Seismometers (OBS) near the equatorial mid‐Atlantic ridge, deployed during the Passive Imaging of the Lithosphere‐Asthenosphere Boundary (PI‐LAB) experiment. We use the beamforming technique to investigate the incoming directions of infragravity waves. Next, we develop a graph‐theory‐based global back‐projection method of noise cross‐correlation function envelopes, which minimizes the effects of array geometry using an adaptive weighting scheme. This approach allows us to locate the sources of the infragravity energy. We assess our observations by comparing to a global model of infragravity wave heights. Our results reveal strong coherent energy from sources and/or reflected phases at the west coast of Africa and some sources from South America. These energy sources are in good agreement with the global infragravity wave model. In addition, we also observe infragravity waves arriving from North America during specific events that mostly occur during October–February 2016. Finally, we find indications of waves that propagate with little attenuation, long distances through sea ice, reflecting off Antarctica.
The Acceleration of Lunar Ions by Magnetic Forces in the Terrestrial Magnetotail Lobes
Authors: Cao Xin , Halekas Jasper , Poppe Andrew , Chu Feng , Glassmeier Karl‐Heinz 
Published: May 2020

AbstractIn order to study the acceleration of ions originating from the tenuous exosphere and surface of the Moon, we analyzed data from the ElectroStatic Analyzer (ESA) and Flux Gate Magnetometer (FGM) carried by the Acceleration, Reconnection, Turbulence, and Electrodynamics of Moon's Interaction with the Sun (ARTEMIS) spacecraft. Previous investigations have modeled the acceleration of lunar ions by the motional electric field of the surrounding plasma. However, in the terrestrial magnetotail, where the lunar ion density can equal or even exceed the ambient plasma density, other forces may play an important role in the tenuous plasma environment. Determining what forces govern lunar ion motion is important in understanding their interaction with the ambient plasma in the unique environment of the magnetotail. Based on a detailed analysis of two individual ARTEMIS observations, we find that magnetic pressure and magnetic tension forces may play an important role in accelerating the lunar ions.
Surface charge of Merkel cell polyomavirus small T antigen determines cell transformation through allosteric FBW7 WD40 domain targeting
Authors: Nwogu Nnenna , Ortiz Luz E. , Kwun Hyun Jin 
Published: May 2020

AbstractMerkel cell polyomavirus (MCV) small T (sT) is the main oncoprotein in Merkel cell carcinoma (MCC) development. A unique domain of sT, LT stabilization domain (LSD), has been reported to bind and inactivate multiple SCF (Skp1-Cullin-F-box) E3 ligases. These interactions impede the turnover of MCV large T (LT) antigen and cellular oncoproteins such as c-Myc and cyclin E, thereby promoting viral replication and cell transformation. However, it is currently unclear how this LSD region contributes to multiple transforming activities of sT. Structural docking simulation of sT and F-box and WD repeat domain-containing 7 (FBW7) revealed a novel allosteric interaction between sT and FBW7 WD40 domain. This model is supported by experimental evidence confirming that charge engineering in the LSD alters sT-WD40 binding. Specifically, loss of net positive charge in the LSD prevents sT-FBW7 binding by abrogating the electrostatic interaction, thus impeding inhibition of FBW7 by sT. Furthermore, positively charged mutations in the LSD significantly restored the sT function and its ability to transform rodent fibroblast cells. We infer that the surface charge of sT is a major determinant for targeting E3 ligases, which leads to sT-induced cell transformation, an observation that could be used to develop targeted therapeutics for MCC.
Drp1-dependent remodeling of mitochondrial morphology triggered by EBV-LMP1 increases cisplatin resistance
Authors: Xie Longlong , Shi Feng , Li Yueshuo , Li We , Yu Xinfang , Zhao Lin , Zhou Min , Hu Jianmin , Luo Xiangjian , Tang Min , Fan Jia , Zhou Jian , Gao Qiang , Wu Weizhong , Zhang Xin , Liao Weihua , Bode Ann M. , Cao Ya 
Published: May 2020

AbstractLatent membrane protein 1 (LMP1) is a major Epstein–Barr virus (EBV)-encoded oncoprotein involved in latency infection that regulates mitochondrial functions to facilitate cell survival. Recently, mitochondrial fission has been demonstrated as a crucial mechanism in oncovirus-mediated carcinogenesis. Mitochondrial dynamin-related protein 1 (Drp1)-mediated mitochondrial fission has an impact on the chemoresistance of cancers. However, the mechanism by which oncogenic stress promotes mitochondrial fission, potentially contributing to tumorigenesis, is not entirely understood. The role of Drp1 in the oncogenesis and prognosis of EBV-LMP1-positive nasopharyngeal carcinoma (NPC) was determined in our study. We show that EBV-LMP1 exhibits a new function in remodeling mitochondrial morphology by activating Drp1. A high level of p-Drp1 (Ser616) or a low level of p-Drp1 (Ser637) correlates with poor overall survival and disease-free survival. Furthermore, the protein level of p-Drp1 (Ser616) is related to the clinical stage (TNM stage) of NPC. Targeting Drp1 impairs mitochondrial function and induces cell death in LMP1-positive NPC cells. In addition, EBV-LMP1 regulates Drp1 through two oncogenic signaling axes, AMPK and cyclin B1/Cdk1, which promote cell survival and cisplatin resistance in NPC. Our findings provide novel insight into the role of EBV-LMP1-driven mitochondrial fission in regulating Drp1 phosphorylation at serine 616 and serine 637. Disruption of Drp1 could be a promising therapeutic strategy for LMP1-positive NPC.
Do AKT1, COMT and FAAH influence reports of acute cannabis intoxication experiences in patients with first episode psychosis, controls and young adult cannabis users?
Authors: Hindocha Chandni , Quattrone Diego , Freeman Tom P. , Murray Robin M. , Mondelli Valeria , Breen Gerome , Curtis Charles , Morgan Celia J. A. , Valerie Curran H. , Di Forti Marta 
Published: May 2020

AbstractEpidemiological and biological evidence support the association between heavy cannabis use and psychosis. However, it is unclear which cannabis users are susceptible to its psychotogenic effect. Therefore, understanding genetic factors contributing to this relationship might prove an important strategy to identify the mechanisms underlying cannabis-associated psychotic experiences. We aimed to determine how variation in AKT1, COMT and FAAH genotypes, and their interaction with three different groups (first episode psychosis (FEP) patients (n = 143), controls (n = 92) and young adult (YA) cannabis usersn = 485)) influenced cannabis experiences, in those who had used cannabis at least once. We investigated the role of AKT1 (rs2494732), COMT Val158Met (rs4680) and FAAH (rs324420) on cannabis experiences by combining data from a large case-control study of FEP patients, with a naturalistic study of YA cannabis users (n = 720). Outcome measures were cannabis-induced psychotic-like experiences (cPLEs) and euphoric experiences (cEEs). We used linear mixed effects models to assess the effects of each genotype and their interaction with group, adjusting for age, sex, ethnicity, age of first cannabis use, years of use and frequency. cPLEs were more frequent in FEP patients than controls and YA cannabis users. cEEs were more prevalent in YA cannabis users than FEP patients or controls. Variation in AKT1, COMT or FAAH was not associated with cPLEs/cEEs. There was no interaction between genotype and group (FEP cases, controls and YA cannabis users) on cPLEs/cEEs. In conclusion, AKT1, COMT or FAAH did not modulate specific psychotomimetic response to cannabis and did not interact with group, contrary to previous research.
Quantitative genetics of wing morphology in the parasitoid wasp Nasonia vitripennis: hosts increase sibling similarity
Authors: Xia Shuwen , Pannebakker Bart A. , Groenen Martien A. M. , Zwaan Bas J. , Bijma Piter 
Published: May 2020

AbstractThe central aim of evolutionary biology is to understand patterns of genetic variation between species and within populations. To quantify the genetic variation underlying intraspecific differences, estimating quantitative genetic parameters of traits is essential. In Pterygota, wing morphology is an important trait affecting flight ability. Moreover, gregarious parasitoids such as Nasonia vitripennis oviposit multiple eggs in the same host, and siblings thus share a common environment during their development. Here we estimate the genetic parameters of wing morphology in the outbred HVRx population of N. vitripennis, using a sire-dam model adapted to haplodiploids and disentangled additive genetic and host effects. The results show that the wing-size traits have low heritability (h2 ~ 0.1), while most wing-shape traits have roughly twice the heritability compared with wing-size traits. However, the estimates increased to h2 ~ 0.6 for wing-size traits when omitting the host effect from the statistical model, while no meaningful increases were observed for wing-shape traits. Overall, host effects contributed to ~50% of the variation in wing-size traits. This indicates that hosts have a large effect on wing-size traits, about fivefold more than genetics. Moreover, bivariate analyses were conducted to derive the genetic relationships among traits. Overall, we demonstrate the evolutionary potential for morphological traits in the N. vitripennis HVRx-outbred population, and report the host effects on wing morphology. Our findings can contribute to a further dissection of the genetics underlying wing morphology in N. vitripennis, with relevance for gregarious parasitoids and possibly other insects as well.
Somatic SF3B1 hotspot mutation in prolactinomas
Authors: Li Chuzhong , Xie Weiyan , Rosenblum Jared S. , Zhou Jianyu , Guo Jing , Miao Yazhou , Shen Yutao , Wang Hongyun , Gong Lei , Li Mingxuan , Zhao Sida , Cheng Sen , Zhu Haibo , Jiang Tao , Ling Shiying , Wang Fei , Zhang Hongwei , Zhang Mingshan , Qu Yanming , Zhang Qi , Li Guilin , Wang Junmei , Ma Jun , Zhuang Zhengping , Zhang Yazhuo 
Published: May 2020

AbstractThe genetic basis and corresponding clinical relevance of prolactinomas remain poorly understood. Here, we perform whole genome sequencing (WGS) on 21 patients with prolactinomas to detect somatic mutations and then validate the mutations with digital polymerase chain reaction (PCR) analysis of tissue samples from 227 prolactinomas. We identify the same hotspot somatic mutation in splicing factor 3 subunit B1 (SF3B1R625H) in 19.8% of prolactinomas. These patients with mutant prolactinomas display higher prolactin (PRL) levels (p = 0.02) and shorter progression-free survival (PFS) (p = 0.02) compared to patients without the mutation. Moreover, we identify that the SF3B1R625H mutation causes aberrant splicing of estrogen related receptor gamma (ESRRG), which results in stronger binding of pituitary-specific positive transcription factor 1 (Pit-1), leading to excessive PRL secretion. Thus our study validates an important mutation and elucidates a potential mechanism underlying the pathogenesis of prolactinomas that may lead to the development of targeted therapeutics.
2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer
Authors: Blomme Arnaud , Ford Catriona A. , Mui Ernest , Patel Rachana , Ntala Chara , Jamieson Lauren E. , Planque Mélanie , McGregor Grace H. , Peixoto Paul , Hervouet Eric , Nixon Colin , Salji Mark , Gaughan Luke , Markert Elke , Repiscak Peter , Sumpton David , Blanco Giovanny Rodriguez , Lilla Sergio , Kamphorst Jurre J. , Graham Duncan , Faulds Karen , MacKay Gillian M. , Fendt Sarah-Maria , Zanivan Sara , Leung Hing Y. 
Published: May 2020

AbstractDespite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased characterisation of LNCaP cells chronically exposed to multiple AR inhibitors (ARI). Combined proteomics and metabolomics analyses implicate an acquired metabolic phenotype common in ARI-resistant cells and associated with perturbed glucose and lipid metabolism. To exploit this phenotype, we delineate a subset of proteins consistently associated with ARI resistance and highlight mitochondrial 2,4-dienoyl-CoA reductase (DECR1), an auxiliary enzyme of beta-oxidation, as a clinically relevant biomarker for CRPC. Mechanistically, DECR1 participates in redox homeostasis by controlling the balance between saturated and unsaturated phospholipids. DECR1 knockout induces ER stress and sensitises CRPC cells to ferroptosis. In vivo, DECR1 deletion impairs lipid metabolism and reduces CRPC tumour growth, emphasizing the importance of DECR1 in the development of treatment resistance.
Social-media and newspaper reports reveal large-scale meteorological drivers of floods on Sumatra
Authors: Baranowski Dariusz B. , Flatau Maria K. , Flatau Piotr J. , Karnawati Dwikorita , Barabasz Katarzyna , Labuz Michal , Latos Beata , Schmidt Jerome M. , Paski Jaka A. I. , Marzuki  
Published: May 2020

AbstractFloods are a major contributor to natural disasters in Sumatra. However, atmospheric conditions leading to floods are not well understood due, among other factors, to the lack of a complete record of floods. Here, the 5 year flood record for Sumatra derived from governmental reports, as well as from crowd-sourcing data, based on Twitter messages and local newspapers’ reports, is created and used to analyze atmospheric phenomena responsible for floods. It is shown, that for the majority of analyzed floods, convectively coupled Kelvin waves, large scale precipitation systems propagating at ∼12 m/s along the equator, play the critical role. While seasonal and intraseasonal variability can also create conditions favorable for flooding, the enhanced precipitation related to Kelvin waves was found in over 90% of flood events. In 30% of these events precipitation anomalies were attributed to Kelvin waves only. These results indicate the potential for increased predictability of flood risk.
nNOS-expressing neurons in the vmPFC transform pPVT-derived chronic pain signals into anxiety behaviors
Authors: Liang Hai-Ying , Chen Zhi-Jin , Xiao Hui , Lin Yu-Hui , Hu Ying-Yi , Chang Lei , Wu Hai-Yin , Wang Peng , Lu Wei , Zhu Dong-Ya , Luo Chun-Xia 
Published: May 2020

AbstractAnxiety is common in patients suffering from chronic pain. Here, we report anxiety-like behaviors in mouse models of chronic pain and reveal that nNOS-expressing neurons in ventromedial prefrontal cortex (vmPFC) are essential for pain-induced anxiety but not algesia, using optogenetic and chemogenetic strategies. Additionally, we determined that excitatory projections from the posterior subregion of paraventricular thalamic nucleus (pPVT) provide a neuronal input that drives the activation of vmPFC nNOS-expressing neurons in our chronic pain models. Our results suggest that the pain signal becomes an anxiety signal after activation of vmPFC nNOS-expressing neurons, which causes subsequent release of nitric oxide (NO). Finally, we show that the downstream molecular mechanisms of NO likely involve enhanced glutamate transmission in vmPFC CaMKIIα-expressing neurons through S-nitrosylation-induced AMPAR trafficking. Overall, our data suggest that pPVT excitatory neurons drive chronic pain-induced anxiety through activation of vmPFC nNOS-expressing neurons, resulting in NO-mediated AMPAR trafficking in vmPFC pyramidal neurons.
Dissecting the cellular specificity of smoking effects and reconstructing lineages in the human airway epithelium
Authors: Goldfarbmuren Katherine C. , Jackson Nathan D. , Sajuthi Satria P. , Dyjack Nathan , Li Katie S. , Rios Cydney L. , Plender Elizabeth G. , Montgomery Michael T. , Everman Jamie L. , Bratcher Preston E. , Vladar Eszter K. , Seibold Max A. 
Published: May 2020

AbstractCigarette smoke first interacts with the lung through the cellularly diverse airway epithelium and goes on to drive development of most chronic lung diseases. Here, through single cell RNA-sequencing analysis of the tracheal epithelium from smokers and non-smokers, we generate a comprehensive atlas of epithelial cell types and states, connect these into lineages, and define cell-specific responses to smoking. Our analysis infers multi-state lineages that develop into surface mucus secretory and ciliated cells and then contrasts these to the unique specification of submucosal gland (SMG) cells. Accompanying knockout studies reveal that tuft-like cells are the likely progenitor of both pulmonary neuroendocrine cells and CFTR-rich ionocytes. Our smoking analysis finds that all cell types, including protected stem and SMG populations, are affected by smoking through both pan-epithelial smoking response networks and hundreds of cell-specific response genes, redefining the penetrance and cellular specificity of smoking effects on the human airway epithelium.
DALRD3 encodes a protein mutated in epileptic encephalopathy that targets arginine tRNAs for 3-methylcytosine modification
Authors: Lentini Jenna M. , Alsaif Hessa S. , Faqeih Eissa , Alkuraya Fowzan S. , Fu Dragony 
Published: May 2020

AbstractIn mammals, a subset of arginine tRNA isoacceptors are methylated in the anticodon loop by the METTL2 methyltransferase to form the 3-methylcytosine (m3C) modification. However, the mechanism by which METTL2 identifies specific tRNA arginine species for m3C formation as well as the biological role of m3C in mammals is unknown. Here, we show that human METTL2 forms a complex with DALR anticodon binding domain containing 3 (DALRD3) protein to recognize particular arginine tRNAs destined for m3C modification. DALRD3-deficient human cells exhibit nearly complete loss of the m3C modification in tRNA-Arg species. Notably, we identify a homozygous nonsense mutation in the DALRD3 gene that impairs m3C formation in human patients exhibiting developmental delay and early-onset epileptic encephalopathy. These findings uncover an unexpected function for the DALRD3 protein in the targeting of distinct arginine tRNAs for m3C modification and suggest a crucial biological role for DALRD3-dependent tRNA modification in proper neurological development.