bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene expression imputation identifies candidate genes and susceptibility loci associated with cutaneous squamous cell carcinoma
Authors: Ioannidis Nilah M. , Wang Wei , Furlotte Nicholas A. , Hinds David A. ,   23andMe Research Team, Agee Michelle , Alipanahi Babak , Auton Adam , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Huber Karen E. , Kleinman Aaron , Litterman Nadia K. , McCreight Jennifer C. , McIntyre Matthew H. , Mountain Joanna L. , Noblin Elizabeth S. , Northover Carrie A. M. , Pitts Steven J. , Sathirapongsasuti J. Fah , Sazonova Olga V. , Shelton Janie F. , Shringarpure Suyash , Tian Chao , Tung Joyce Y. , Vacic Vladimir , Wilson Catherine H. , Bustamante Carlos D. , Jorgenson Eric , Asgari Maryam M. , Whittemore Alice S. 
Published: October 2018

AbstractCutaneous squamous cell carcinoma (cSCC) is a common skin cancer with genetic susceptibility loci identified in recent genome-wide association studies (GWAS). Transcriptome-wide association studies (TWAS) using imputed gene expression levels can identify additional gene-level associations. Here we impute gene expression levels in 6891 cSCC cases and 54,566 controls in the Kaiser Permanente Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort and 25,558 self-reported cSCC cases and 673,788 controls from 23andMe. In a discovery-validation study, we identify 19 loci containing 33 genes whose imputed expression levels are associated with cSCC at false discovery rate < 10% in the GERA cohort and validate 15 of these candidate genes at Bonferroni significance in the 23andMe dataset, including eight genes in five novel susceptibility loci and seven genes in four previously associated loci. These results suggest genetic mechanisms contributing to cSCC risk and illustrate advantages and disadvantages of TWAS as a supplement to traditional GWAS analyses.
The fungal peptide toxin Candidalysin activates the NLRP3 inflammasome and causes cytolysis in mononuclear phagocytes
Authors: Kasper Lydia , König Annika , Koenig Paul-Albert , Gresnigt Mark S. , Westman Johannes , Drummond Rebecca A. , Lionakis Michail S. , Groß Olaf , Ruland Jürgen , Naglik Julian R. , Hube Bernhard 
Published: October 2018

AbstractClearance of invading microbes requires phagocytes of the innate immune system. However, successful pathogens have evolved sophisticated strategies to evade immune killing. The opportunistic human fungal pathogen Candida albicans is efficiently phagocytosed by macrophages, but causes inflammasome activation, host cytolysis, and escapes after hypha formation. Previous studies suggest that macrophage lysis by C. albicans results from early inflammasome-dependent cell death (pyroptosis), late damage due to glucose depletion and membrane piercing by growing hyphae. Here we show that Candidalysin, a cytolytic peptide toxin encoded by the hypha-associated gene ECE1, is both a central trigger for NLRP3 inflammasome-dependent caspase-1 activation via potassium efflux and a key driver of inflammasome-independent cytolysis of macrophages and dendritic cells upon infection with C. albicans. This suggests that Candidalysin-induced cell damage is a third mechanism of C. albicans-mediated mononuclear phagocyte cell death in addition to damage caused by pyroptosis and the growth of glucose-consuming hyphae.
Pregnancy duration and breast cancer risk
Authors: Husby Anders , Wohlfahrt Jan , Øyen Nina , Melbye Mads 
Published: October 2018

AbstractFull-term pregnancies reduce a woman’s long-term breast cancer risk, while abortions have been shown to have no effect. The precise minimal duration of pregnancy necessary to lower a woman’s breast cancer risk is, however, unknown. Here we provide evidence which point to the protective effect of pregnancy on breast cancer risk arising precisely at the 34th pregnancy week. Using a cohort of 2.3 million Danish women, we found the reduction in breast cancer risk was not observed for pregnancies lasting 33 weeks or less, but restricted to those pregnancies lasting 34 weeks or longer. We further found that parity, socioeconomic status, and vital status of the child at birth did not explain the association, and also replicated our finding in data from 1.6 million women in Norway. We suggest that a distinct biological effect introduced around week 34 of pregnancy holds the key to understand pregnancy-associated breast cancer protection.
Skin-touch-actuated textile-based triboelectric nanogenerator with black phosphorus for durable biomechanical energy harvesting
Authors: Xiong Jiaqing , Cui Peng , Chen Xiaoliang , Wang Jiangxin , Parida Kaushik , Lin Meng-Fang , Lee Pooi See 
Published: October 2018

AbstractTextiles that are capable of harvesting biomechanical energy via triboelectric effects are of interest for self-powered wearable electronics. Fabrication of conformable and durable textiles with high triboelectric outputs remains challenging. Here we propose a washable skin-touch-actuated textile-based triboelectric nanogenerator for harvesting mechanical energy from both voluntary and involuntary body motions. Black phosphorus encapsulated with hydrophobic cellulose oleoyl ester nanoparticles serves as a synergetic electron-trapping coating, rendering a textile nanogenerator with long-term reliability and high triboelectricity regardless of various extreme deformations, severe washing, and extended environmental exposure. Considerably high output (~250–880 V, ~0.48–1.1 µA cm−2) can be attained upon touching by hand with a small force (~5 N) and low frequency (~4 Hz), which can power light-emitting diodes and a digital watch. This conformable all-textile-nanogenerator is incorporable onto cloths/skin to capture the low output of 60 V from subtle involuntary friction with skin, well suited for users’ motion or daily operations.
BRCA1/2-negative, high-risk breast cancers (BRCAX) for Asian women: genetic susceptibility loci and their potential impacts
Authors: Lee Joo-Yeon , Kim Jisun , Kim Sung-Won , Park Sue K. , Ahn Sei Hyun , Lee Min Hyuk , Suh Young Jin , Noh Dong-Young , Son Byung Ho , Cho Young Up , Lee Sae Byul , Lee Jong Won , Hopper John L. , Sung Joohon 
Published: October 2018

Abstract“BRCAX” refers breast cancers occurring in women with a family history predictive of being a BRCA1/2 mutation carrier, but BRCA1/2 genetic screening has failed to find causal mutations. In this study, we report the findings of the genetic architecture of BRCAX with novel and redefined candidate loci and their potential impacts on preventive strategy. We performed a genome-wide association study involving 1,469 BRCAX cases from the Korean Hereditary Breast Cancer study, and high-risk breast cancer cases (1,482 Asians and 9,902 Europeans) from the Breast Cancer Association Consortium. We also evaluated the previously reported susceptibility loci for their roles in the high-risk breast cancers. We have identified three novel loci (PDE7B, UBL3, and a new independent marker in CDKN2B-AS1) associated with BRCAX, and replicated previously reported SNPs (24 of 92) and moderate/high-penetrance (seven of 23) genes for Korean BRCAX. For the novel candidate loci, evidence supported their roles in regulatory function. We estimated that the common low-penetrance loci might explain a substantial part of high-risk breast cancer (39.4% for Koreans and 24.0% for Europeans). Our study findings suggest that common genetic markers with lower penetrance constitute a part of susceptibility to high-risk breast cancers, with potential implications for a more comprehensive genetic screening test.
Multiple dimensions of biodiversity drive human interest in tide pool communities
Authors: Fairchild Tom P. , Fowler Mike S. , Pahl Sabine , Griffin John N. 
Published: October 2018

AbstractActivities involving observation of wild organisms (e.g. wildlife watching, tidepooling) can provide recreational and learning opportunities, with biologically diverse animal assemblages expected to be more stimulating to humans. In turn, more diverse communities may enhance human interest and facilitate provisioning of cultural services. However, no experimental tests of this biodiversity-interest hypothesis exist to date. We therefore investigated the effects of different dimensions of animal biodiversity (species richness, phyletic richness and functional diversity) on self-reported interest using tide pools as a model system. We performed two experiments by manipulating: (1) the richness of lower (species) and higher taxonomic levels (phyla) in an image based, online survey, and (2) the richness of the higher taxonomic level (phyla) in live public exhibits. In both experiments, we further quantified functional diversity, which varied freely, and within the online experiment we also included the hue diversity and colourfulness arising from the combination of organisms and the background scenes. Interest was increased by phyletic richness (both studies), animal species richness (online study) and functional diversity (online study). A structural equation model revealed that functional diversity and colourfulness (of the whole scene) also partially mediated the effects of phyletic richness on interest in the online study. In both studies, the presence of three of four phyla additively increased interest, supporting the importance of multiple, diverse phyla rather than a single particularly interesting phylum. These results provide novel experimental evidence that multiple dimensions of biodiversity enhance human interest and suggest that conservation initiatives that maintain or restore biodiversity will help stimulate interest in ecosystems, facilitating educational and recreational benefits.
Irisin inhibits pancreatic cancer cell growth via the AMPK-mTOR pathway
Authors: Liu Jiayu , Song Nannan , Huang Yibing , Chen Yuxin 
Published: October 2018

AbstractIrisin, a recently identified myokine that is released from skeletal muscle following exercise, regulates body weight and influences various metabolic diseases such as obesity and diabetes. In this study, human recombinant nonglycosylated P-irisin (expressed in Escherichia coli prokaryote cell system) or glycosylated E-irisin (expressed in Pichia pastoris eukaryote cell system) were compared to examine the role of recombinant irisin against pancreatic cancer (PC) cells lines, MIA PaCa-2 and Panc03.27. MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-di phenyltetrazolium bromide] and cell colony formation assays revealed that irisin significantly inhibited the growth of MIA PaCa-2 and Panc03.27 in a dose-dependent manner. Irisin also induced G1 arrest in both cell lines. Scratch wound healing and transwell assays revealed that irisin also inhibited the migration of PC cells. Irisin reversed the activity of epithelial–mesenchymal transition (EMT) while increasing E-cadherin expression and reducing vimentin expression. Irisin activated the adenosine monophosphate-activated protein kinase (AMPK) pathway and suppressed the mammalian target of rapamycin (mTOR) signaling. Besides, our results suggest that irisin receptors exist on the surface of human MIA PaCa-2 and Panc03.27 cells. Our results clearly demonstrate that irisin suppressed PC cell growth via the activation of AMPK, thereby downregulating the mTOR pathway and inhibiting EMT of PC cells.
Hearing impairment and the risk of neurodegenerative dementia: A longitudinal follow-up study using a national sample cohort
Authors: Kim So Young , Lim Jae-Sung , Kong Il Gyu , Choi Hyo Geun 
Published: October 2018

AbstractThis study aimed to explore the risk of dementia in a middle- and older-aged population with severe or profound hearing impairments. Data were collected for the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013. Participants aged 40 or older were selected. The 4,432 severely hearing-impaired participants were matched 1:4 with 17,728 controls, and the 958 profoundly hearing-impaired participants were matched 1:4 with 3,832 controls who had not reported any hearing impairment. Age, sex, income, region of residence, hypertension, diabetes mellitus, and dyslipidemia histories were matched between hearing-impaired and control groups. The crude (simple) and adjusted (age, sex, income, region of residence, dementia, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, cerebrovascular disease, and depression) hazard ratios (HRs) of hearing impairment on dementia were analyzed using Cox-proportional hazard models. The severe hearing impairment group showed an increased risk of dementia (adjusted HR = 1.17, 95% confidence interval [CI] = 1.04–1.31, P = 0.010). The profound hearing impairment group also showed an increased risk of dementia (adjusted HR = 1.51, 95% CI = 1.14–2.00, P = 0.004). Both severe and profound hearing impairments were associated with elevated the risk of dementia in middle- and older-aged individuals.
Finite-resource teleportation stretching for continuous-variable systems
Authors: Laurenza Riccardo , Braunstein Samuel L. , Pirandola Stefano 
Published: October 2018

AbstractWe show how adaptive protocols of quantum and private communication through bosonic Gaussian channels can be simplifed into much easier block versions that involve resource states with finite energy. This is achieved by combining an adaptive-to-block reduction technique devised earlier, based on teleportation stretching and relative entropy of entanglement, with a recent finite-resource simulation of Gaussian channels. In this way, we derive weak converse upper bounds for the secret-key capacity of phase-insensitive Gaussian channels which approximate the optimal limit for infinite energy. Our results apply to both point-to-point and repeater-assisted private communications.
Caring for infants is associated with increased reproductive success for male mountain gorillas
Authors: Rosenbaum Stacy , Vigilant Linda , Kuzawa Christopher W. , Stoinski Tara S. 
Published: October 2018

AbstractSocioecological theory predicts that male parenting among mammals should be rare due to the large payoffs of prioritizing mating effort over parenting. Although these predictions are generally met, in some promiscuous primate species males overcome this by identifying their offspring, and providing benefits such as protection and resource access. Mountain gorillas, which often organize into multi-male groups, are an intriguing exception. Males frequently affiliate with infants despite not discriminating their own from other males’ offspring, raising questions about the function of this behavior. Here we demonstrate that, independent of multiple controls for rank, age, and siring opportunities, male gorillas who affiliated more with all infants, not only their own, sired more offspring than males who affiliated less with young. Predictive margins indicate males in the top affiliation tertile can expect to sire approximately five times more infants than males in the bottom tertile, across the course of their reproductive careers. These findings establish a link between males’ fitness and their associations with infants in the absence of kin discrimination or high paternity certainty, and suggest a strategy by which selection could generate more involved male parenting among non-monogamous species.
Photo-catalytic Killing of HeLa Cancer Cells Using Facile Synthesized Pure and Ag Loaded WO3 Nanoparticles
Authors: AbuMousa Rasha A. , Baig Umair , Gondal Mohammed A. , AlSalhi Mohamad S. , Alqahtani Fulwah Yahya , Akhtar Sultan , Aleanizy Fadilah Sfouq , Dastageer Mohamed A. 
Published: October 2018

AbstractChemotherapy, the most commonly used therapeutic method for cancer, has the inherent constraint of low bioavailability. A number of physical cancer therapeutic treatments like radiation, ultrasound, photo-acoustic/photo thermal, microwave therapies are based on locating the afflicted sites with the help of imaging, but the serious drawbacks of these treatment options are that they damage the neighboring normal tissues and/or induce undesired cancer metastasis. In addition, these methods of treatment are very expensive and not in the reach of a common man especially in the developing countries. Therefore, innovative, less invasive and cost effective treatment methods with the help of less toxic drugs have been sought for treating cancer. In this work, photo-catalytic method of killing cancer cells, using the nanostructured silver loaded tungsten oxide (Ag/WO3) as photo-catalysts, in conjunction with broadband UV radiation is presented. Ag/WO3with two different mass ratios of Ag and WO3 (1% Ag/WO3 and 3% Ag/WO3) were synthesized, characterized and these nanostructured materials served as photo-catalysts in the process of killing cancer cells by photo-catalytic method. The advantage of loading Ag in WO3 is quite evident from the observed increase in the photo-catalytic killing of the HeLa cells. This photo-catalytic enhancement was effectively caused by the development of Schottky junction between Ag in WO3, which led to a substantial inhibition of photo-generated charge recombination and also by the stimulation of surface plasmon resonance in silver nanoparticles, which led to the enhanced visible light absorption by the material.
Seasonal difference in temporal transferability of an ecological model: near-term predictions of lemming outbreak abundances
Authors: Kleiven Eivind Flittie , Henden John-André , Ims Rolf Anker , Yoccoz Nigel Gilles 
Published: October 2018

AbstractEcological models have been criticized for a lack of validation of their temporal transferability. Here we answer this call by investigating the temporal transferability of a dynamic state-space model developed to estimate season-dependent biotic and climatic predictors of spatial variability in outbreak abundance of the Norwegian lemming. Modelled summer and winter dynamics parametrized by spatial trapping data from one cyclic outbreak were validated with data from a subsequent outbreak. There was a distinct difference in model transferability between seasons. Summer dynamics had good temporal transferability, displaying ecological models’ potential to be temporally transferable. However, the winter dynamics transferred poorly. This discrepancy is likely due to a temporal inconsistency in the ability of the climate predictor (i.e. elevation) to reflect the winter conditions affecting lemmings both directly and indirectly. We conclude that there is an urgent need for data and models that yield better predictions of winter processes, in particular in face of the expected rapid climate change in the Arctic.
Lrig1 marks a population of gastric epithelial cells capable of long-term tissue maintenance and growth in vitro
Authors: Schweiger Pawel J. , Clement Ditte L. , Page Mahalia E. , Schepeler Troels , Zou Xiangang , Sirokmány Gabor , Watt Fiona M. , Jensen Kim B. 
Published: October 2018

AbstractThe processes involved in renewal of the epithelium that lines the mouse stomach remain unclear. Apart from the cells in the isthmus, several other populations located deeper in the gastric glands have been suggested to contribute to the maintenance of the gastric epithelium. Here, we reveal that Lrig1 is expressed in the basal layer of the forestomach and the lower part of glands in the corpus and pylorus. In the glandular epithelium of the stomach, Lrig1 marks a heterogeneous population comprising mainly non-proliferative cells. Yet, fate-mapping experiments using a knock-in mouse line expressing Cre specifically in Lrig1+ cells demonstrate that these cells are able to contribute to the long-term maintenance of the gastric epithelium. Moreover, when cultured in vitro, cells expressing high level of Lrig1 have much higher organoid forming potential than the corresponding cellular populations expressing lower levels of Lrig1. Taken together, these observations show that Lrig1 is expressed primarily by differentiated cells, but that these cells can be recruited to contribute to the maintenance of the gastric epithelium. This confirms previous observations that cells located in the lower segments of gastric glands can participate in tissue replenishment.
NTnC-like genetically encoded calcium indicator with a positive and enhanced response and fast kinetics
Authors: Barykina Natalia V. , Doronin Danila A. , Subach Oksana M. , Sotskov Vladimir P. , Plusnin Viktor V. , Ivleva Olga A. , Gruzdeva Anna M. , Kunitsyna Tatiana A. , Ivashkina Olga I. , Lazutkin Alexander A. , Malyshev Aleksey Y. , Smirnov Ivan V. , Varizhuk Anna M. , Pozmogova Galina E. , Piatkevich Kiryl D. , Anokhin Konstantin V. , Enikolopov Grigori , Subach Fedor V. 
Published: October 2018

AbstractThe NTnC genetically encoded calcium indicator has an advantageous design because of its smaller size, GFP-like N- and C-terminal ends and two-fold reduced number of calcium binding sites compared with widely used indicators from the GCaMP family. However, NTnC has an inverted and modest calcium response and a low temporal resolution. By replacing the mNeonGreen fluorescent part in NTnC with EYFP, we engineered an NTnC-like indicator, referred to as YTnC, that had a positive and substantially improved calcium response and faster kinetics. YTnC had a 3-fold higher calcium response and 13.6-fold lower brightness than NTnC in vitro. According to stopped-flow experiments performed in vitro, YTnC had 4-fold faster calcium-dissociation kinetics than NTnC. In HeLa cells, YTnC exhibited a 3.3-fold lower brightness and 4.9-fold increased response to calcium transients than NTnC. The spontaneous activity of neuronal cultures induced a 3.6-fold larger ΔF/F response of YTnC than previously shown for NTnC. On patched neurons, YTnC had a 2.6-fold lower ΔF/F than GCaMP6s. YTnC successfully visualized calcium transients in neurons in the cortex of anesthetized mice and the hippocampus of awake mice using single- and two-photon microscopy. Moreover, YTnC outperformed GCaMP6s in the mitochondria and endoplasmic reticulum of cultured HeLa and neuronal cells.
Small heterodimer partner negatively regulates C-X-C motif chemokine ligand 2 in hepatocytes during liver inflammation
Authors: Noh Jung-Ran , Kim Yong-Hoon , Kim Don-Kyu , Hwang Jung Hwan , Kim Kyoung-Shim , Choi Dong-Hee , Lee Seon-Jin , Lee Hee Gu , Lee Tae Geol , Weng Hong-Lei , Dooley Steven , Choi Hueng-Sik , Lee Chul-Ho 
Published: October 2018

AbstractRecently, we reported that orphan nuclear receptor small heterodimer partner (SHP) is involved in neutrophil recruitment through the regulation of C-X-C motif chemokine ligand 2 (CXCL2) expression in a concanavalin A (ConA)-induced hepatitis model. In the present study, we examined the mechanisms underlying CXCL2 regulation by SHP and the cell types involved in liver inflammation. To this end, eitherShpknockout (KO) or wild-type (WT) bone marrow cells were transferred into sublethally-irradiated WT (KO → WT or WT → WT) orShpKO (KO → KO or WT → KO) recipients, followed by intravenous injection of ConA (20–30 mg/kg) 8 weeks later. The KO recipient groups showed higher ConA-induced lethality than the WT recipient groups. Accordingly, plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, and inflammatory cytokine expressions were significantly higher in the KO recipients than in the WT recipients regardless of donor genotype. Massively increased hepatocyte death in KO recipients, as determined by H&E and TUNEL staining, was observed after ConA challenge. Bone marrow chimera experiments andin vitrochemotaxis assay also showed that SHP-deficient hepatocytes have an enhanced ability to recruit neutrophils to the injured liver.In vitropromoter assays showed that SHP is a negative regulator ofCxcl2transcription by interfering with c-Jun binding to the AP-1 site within theCxcl2promoter. Collectively, SHP regulatesCxcl2transcription in hepatocytes, playing a pivotal role in the recruitment of neutrophils. SHP-targeting strategies may represent alternative approaches to control fulminant hepatitis.