bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contributions of aerosol‐cloud interactions to mid‐Piacenzian seasonally sea ice‐free Arctic Ocean
Authors: Feng Ran , Otto‐Bliesner Bette L. , Xu Yangyang , Brady Esther , Fletcher Tamara , Ballantyne Ashley 
Published: July 2019

AbstractForcings and feedbacks controlling the seasonally sea ice‐free Arctic Ocean during the mid‐Piacenzian Warm period (3.264–3.025 Ma, MPWP), a period when CO2 level, geography, and topography were similar to present day, remain unclear given that many complex Earth System Models with comparatively higher skills at simulating twentieth century Arctic sea ice tend to produce perennial Arctic sea ice for this period. We demonstrate that explicitly simulating aerosol‐cloud interactions and the exclusion of industrial pollutants from model forcing conditions is key to simulating seasonally sea ice‐free Arctic Ocean of MPWP. The absence of industrial pollutants leads to fewer and larger cloud droplets over the high‐latitude Northern Europe and North Pacific, which allows greater absorption of solar radiation at the surface during the early summer. This enhanced absorption triggers the seasonally runaway sea ice surface albedo feedback that gives rise to September sea ice‐free Arctic Ocean and strongly amplified northern high‐latitude surface warmth.
Beyond the Minisolar Maximum of Solar Cycle 24: Declining Solar Magnetic Fields and the Response of the Terrestrial Magnetosphere
Authors: Ingale M. , Janardhan P. , Bisoi S. K. 
Published: July 2019

AbstractThe present study examines the response of the terrestrial magnetosphere to the long‐term steady declining trends observed in solar magnetic fields and solar wind microturbulence levels since mid‐1990s that has been continuing beyond the minisolar maximum of cycle 24. A detailed analysis of the response of the terrestrial magnetosphere has been carried out by studying the extent and shape of the Earth's magnetopause and bow shock over the past four solar cycles. We estimate subsolar stand‐off distance of the magnetopause and bow shock and the shape of the magnetopause, using numerical as well as empirical models. The computed magnetopause and bow shock stand‐off distances have been found to be increasing steadily since around mid‐1990s, consistent with the steady declining trend seen in solar magnetic fields and solar wind microturbulence levels. Similarly, we find an expansion in the shape of the magnetopause since 1996. The implications of the increasing trend seen in the magnetopause and bow shock stand‐off distances are discussed and a forecast of the shape of the magnetopause in 2020, the minimum of cycle 24, has been made. Importantly, we also find two instances between 1968 and 1991 when the magnetopause stand‐off distance dropped to values close to 6.6 Earth radii, the geostationary orbit, for duration ranging from 9–11 hr and one event in 2005, post 1995 when the decline in photospheric fields began. Though there have been no such events since 2005, it represents a clear and present danger to our satellite systems.
Surface Water Body Detection in Polarimetric SAR Data Using Contextual Complex Wishart Classification
Authors: Goumehei E. , Tolpekin V. , Stein A. , Yan W. 
Published: July 2019

AbstractDetection of surface water from satellite images is important for water management purposes like for mapping flood extents, inundation dynamics, and water resources distributions. In this research, we introduce a supervised contextual classification model to detect surface water bodies from polarimetric Synthetic Aperture Radar (SAR) data. A complex Wishart Markov Random Field (WMRF) combines Markov Random Fields with the complex Wishart distribution. It is applied on Single Look Complex Sentinel 1 data. Using Markov Random Fields, we utilize the geometry of surface water to remove speckle from SAR images. Results were compared with the Wishart Maximum Likelihood Classification (WMLC), the Gaussian Maximum Likelihood Classification, and a median filter followed by thresholding. Experiments demonstrate that the statistical representation of data using the Wishart distribution improves the F‐score to 0.95 for WMRF, while it is 0.67, 0.88, and 0.91 for Gaussian Maximum Likelihood Classification, WMLC, and thresholding, respectively. The main improvement in the precision increases from 0.80 and 0.86 for WMLC and thresholding to 0.96 for WMRF. The WMRF model accurately distinguishes classes that have a similar backscatter, like water and bare soil. Hence, the high accuracy of the proposed WMRF model is a result of its robustness for water detection from Single Look Complex data. We conclude that the proposed model is a great improvement on existing methods for the detection of calm surface water bodies.
Real-time decoding of question-and-answer speech dialogue using human cortical activity
Authors: Moses David A. , Leonard Matthew K. , Makin Joseph G. , Chang Edward F. 
Published: July 2019

AbstractNatural communication often occurs in dialogue, differentially engaging auditory and sensorimotor brain regions during listening and speaking. However, previous attempts to decode speech directly from the human brain typically consider listening or speaking tasks in isolation. Here, human participants listened to questions and responded aloud with answers while we used high-density electrocorticography (ECoG) recordings to detect when they heard or said an utterance and to then decode the utterance’s identity. Because certain answers were only plausible responses to certain questions, we could dynamically update the prior probabilities of each answer using the decoded question likelihoods as context. We decode produced and perceived utterances with accuracy rates as high as 61% and 76%, respectively (chance is 7% and 20%). Contextual integration of decoded question likelihoods significantly improves answer decoding. These results demonstrate real-time decoding of speech in an interactive, conversational setting, which has important implications for patients who are unable to communicate.
m6A modification of a 3′ UTR site reduces RME1 mRNA levels to promote meiosis
Authors: Bushkin G. Guy , Pincus David , Morgan Jeffrey T. , Richardson Kris , Lewis Caroline , Chan Sze Ham , Bartel David P. , Fink Gerald R. 
Published: July 2019

AbstractDespite the vast number of modification sites mapped within mRNAs, known examples of consequential mRNA modifications remain rare. Here, we provide multiple lines of evidence to show that Ime4p, an N6-methyladenosine (m6A) methyltransferase required for meiosis in yeast, acts by methylating a site in the 3′ UTR of the mRNA encoding Rme1p, a transcriptional repressor of meiosis. Consistent with this mechanism, genetic analyses reveal that IME4 functions upstream of RME1. Transcriptome-wide, RME1 is the primary message that displays both increased methylation and reduced expression in an Ime4p-dependent manner. In yeast strains for which IME4 is dispensable for meiosis, a natural polymorphism in the RME1 promoter reduces RME1 transcription, obviating the requirement for methylation. Mutation of a single m6A site in the RME1 3′ UTR increases Rme1p repressor production and reduces meiotic efficiency. These results reveal the molecular and physiological consequences of a modification in the 3′ UTR of an mRNA.
Detailed modeling of positive selection improves detection of cancer driver genes
Authors: Zhao Siming , Liu Jun , Nanga Pranav , Liu Yuwen , Cicek A. Ercument , Knoblauch Nicholas , He Chuan , Stephens Matthew , He Xin 
Published: July 2019

AbstractIdentifying driver genes from somatic mutations is a central problem in cancer biology. Existing methods, however, either lack explicit statistical models, or use models based on simplistic assumptions. Here, we present driverMAPS (Model-based Analysis of Positive Selection), a model-based approach to driver gene identification. This method explicitly models positive selection at the single-base level, as well as highly heterogeneous background mutational processes. In particular, the selection model captures elevated mutation rates in functionally important sites using multiple external annotations, and spatial clustering of mutations. Simulations under realistic evolutionary models demonstrate the increased power of driverMAPS over current approaches. Applying driverMAPS to TCGA data of 20 tumor types, we identified 159 new potential driver genes, including the mRNA methyltransferase METTL3-METTL14. We experimentally validated METTL3 as a tumor suppressor gene in bladder cancer, providing support to the important role mRNA modification plays in tumorigenesis.
Disentangling molecular alterations from water-content changes in the aging human brain using quantitative MRI
Authors: Filo Shir , Shtangel Oshrat , Salamon Noga , Kol Adi , Weisinger Batsheva , Shifman Sagiv , Mezer Aviv A. 
Published: July 2019

AbstractIt is an open question whether aging-related changes throughout the brain are driven by a common factor or result from several distinct molecular mechanisms. Quantitative magnetic resonance imaging (qMRI) provides biophysical parametric measurements allowing for non-invasive mapping of the aging human brain. However, qMRI measurements change in response to both molecular composition and water content. Here, we present a tissue relaxivity approach that disentangles these two tissue components and decodes molecular information from the MRI signal. Our approach enables us to reveal the molecular composition of lipid samples and predict lipidomics measurements of the brain. It produces unique molecular signatures across the brain, which are correlated with specific gene-expression profiles. We uncover region-specific molecular changes associated with brain aging. These changes are independent from other MRI aging markers. Our approach opens the door to a quantitative characterization of the biological sources for aging, that until now was possible only post-mortem.
Clostridium perfringens epsilon toxin vaccine candidate lacking toxicity to cells expressing myelin and lymphocyte protein
Authors: Morcrette Helen , Bokori-Brown Monika , Ong Stephanie , Bennett Leo , Wren Brendan W. , Lewis Nick , Titball Richard W. 
Published: July 2019

AbstractA variant form of Clostridium perfringens epsilon toxin (Y30A-Y196A) with mutations, which shows reduced binding to Madin–Darby canine kidney (MDCK) cells and reduced toxicity in mice, has been proposed as the next-generation enterotoxaemia vaccine. Here we show that, unexpectedly, the Y30A-Y196A variant does not show a reduction in toxicity towards Chinese hamster ovary (CHO) cells engineered to express the putative receptor for the toxin (myelin and lymphocyte protein; MAL). The further addition of mutations to residues in a second putative receptor binding site of the Y30A-Y196A variant further reduces toxicity, and we selected Y30A-Y196A-A168F for further study. Compared to Y30A-Y196A, Y30A-Y196A-A168F showed more than a 3-fold reduction in toxicity towards MDCK cells, more than a 4-fold reduction in toxicity towards mice and at least 200-fold reduction in toxicity towards CHO cells expressing sheep MAL. The immunisation of rabbits or sheep with Y30A-Y196A-A168F induced high levels of neutralising antibodies against epsilon toxin, which persisted for at least 1 year. Y30A-Y196A-A168F is a candidate for development as a next-generation enterotoxaemia vaccine.
Opportunistic complexes of E. coli L-asparaginases with citrate anions
Authors: Lubkowski Jacek , Chan Waikin , Wlodawer Alexander 
Published: July 2019

AbstractActive sites of enzymes are highly optimized for interactions with specific substrates, thus binding of opportunistic ligands is usually observed only in the absence of native substrates or products. However, during growth of crystals required for structure determination enzymes are often exposed to conditions significantly divergent from the native ones, leading to binding of unexpected ligands to active sites even in the presence of substrates. Failing to recognize this possibility may lead to incorrect interpretation of experimental results and to faulty conclusions. Here, we present several examples of binding of a citrate anion to the active sites of E. coli L-asparaginases I and II, even in the presence of the native substrate, L-Asn. A part of this report focuses on a comprehensive re-interpretation of structural results published previously for complexes of type I L-asparaginase (EcAI) from E. coli. In two re-refined structures a citrate anion forms an acyl-enzyme reaction intermediate with the catalytic threonine. These results emphasize the importance of careful and critical analysis during interpretation of crystallographic data.
Endogenous IQGAP1 and IQGAP3 do not functionally interact with Ras
Authors: Morgan Chase J. , Hedman Andrew C. , Li Zhigang , Sacks David B. 
Published: July 2019

AbstractThe Ras family of small GTPases modulates numerous essential processes. Activating Ras mutations result in hyper-activation of selected signaling cascades, which leads to human diseases. The high frequency of Ras mutations in human malignant neoplasms has led to Ras being a desirable chemotherapeutic target. The IQGAP family of scaffold proteins binds to and regulates multiple signaling molecules, including the Rho family GTPases Rac1 and Cdc42. There are conflicting data in the published literature regarding interactions between IQGAP and Ras proteins. Initial reports showed no binding, but subsequent studies claim associations of IQGAP1 and IQGAP3 with K-Ras and H-Ras, respectively. Therefore, we set out to resolve this controversy. Here we demonstrate that neither endogenous IQGAP1 nor endogenous IQGAP3 binds to the major Ras isoforms, namely H-, K-, and N-Ras. Importantly, Ras activation by epidermal growth factor is not altered when IQGAP1 or IQGAP3 proteins are depleted from cells. These data strongly suggest that IQGAP proteins are not functional interactors of H-, K-, or N-Ras and challenge the rationale for targeting the interaction of Ras with IQGAP for the development of therapeutic agents.
The relationship between pubertal timing and markers of vascular and cardiac structure and function in men and women aged 60–64 years
Authors: Hardy Rebecca , Maddock Jane , Ghosh Arjun K. , Hughes Alun D. , Kuh Diana 
Published: July 2019

AbstractEarlier age at menarche has been associated with higher risk of coronary heart disease, but the mechanisms underlying the association remain unclear. We assessed the relationship of pubertal timing, in both men (n = 672) and women (n = 713), with vascular (carotid intima-media thickness (cIMT), pulse wave velocity (PWV)) and cardiac (left ventricular (LV) structure and function) measures recorded at age 60–64 yrs in a British birth cohort study. Regression models found that earlier menarche was associated with higher (more adverse) LV mass, LV end diastolic volume and left atrial volume, but not with other cardiac measures, cIMT or PWV. Associations were attenuated after adjustment for either adult or childhood BMI (e.g. mean difference in LV mass per year later menarche: −4.2 g (95% CI:−7.0,−1.4) reducing to −2.2 g (95% CI:−4.7,0.4) after adjustment for adult BMI). There were no associations among men, despite those fully mature at 15 yrs having higher blood pressure than the least mature group by 10.21 mmHg (95% CI:19.45,0.98). Any effect of pubertal timing on vascular and cardiac structure and function is likely to be small and primarily confounded by pre-pubertal BMI and/or mediated through adult adiposity.
Healthy ageing trajectories and lifestyle behaviour: the Mexican Health and Aging Study
Authors: Daskalopoulou Christina , Koukounari Artemis , Wu Yu-Tzu , Terrera Graciela Muniz , Caballero Francisco Félix , de la Fuente Javier , Tyrovolas Stefanos , Panagiotakos Demosthenes B. , Prince Martin , Prina Matthew 
Published: July 2019

AbstractProjections show that the number of people above 60 years old will triple by 2050 in Mexico. Nevertheless, ageing is characterised by great variability in the health status. In this study, we aimed to identify trajectories of health and their associations with lifestyle factors in a national representative cohort study of older Mexicans. We used secondary data of 14,143 adults from the Mexican Health and Aging Study (MHAS). A metric of health, based on the conceptual framework of functional ability, was mapped onto four waves (2001, 2003, 2012, 2015) and created by applying Bayesian multilevel Item Response Theory (IRT). Conditional Growth Mixture Modelling (GMM) was used to identify latent classes of individuals with similar trajectories and examine the impact of physical activity, smoking and alcohol on those. Conditional on sociodemographic and lifestyle behaviour four latent classes were suggested: high-stable, moderate-stable, low-stable and decliners. Participants who did not engage in physical activity, were current or previous smokers and did not consume alcohol at baseline were more likely to be in the trajectory with the highest deterioration (i.e. decliners). This study confirms ageing heterogeneity and the positive influence of a healthy lifestyle. These results provide the ground for new policies.
Travel linearity and speed of human foragers and chimpanzees during their daily search for food in tropical rainforests
Authors: Jang Haneul , Boesch Christophe , Mundry Roger , Ban Simone D. , Janmaat Karline R. L. 
Published: July 2019

AbstractTo understand the evolutionary roots of human spatial cognition, researchers have compared spatial abilities of humans and one of our closest living relatives, the chimpanzee (Pan troglodytes). However, how humans and chimpanzees compare in solving spatial tasks during real-world foraging is unclear to date, as measuring such spatial abilities in natural habitats is challenging. Here we compared spatial movement patterns of the Mbendjele BaYaka people and the Taï chimpanzees during their daily search for food in rainforests. We measured linearity and speed during off-trail travels toward out-of-sight locations as proxies for spatial knowledge. We found similarly high levels of linearity in individuals of Mbendjele foragers and Taï chimpanzees. However, human foragers and chimpanzees clearly differed in their reactions to group size and familiarity with the foraging areas. Mbendjele foragers increased travel linearity with increasing familiarity and group size, without obvious changes in speed. This pattern was reversed in Taï chimpanzees. We suggest that these differences between Mbendjele foragers and Taï chimpanzees reflect their different ranging styles, such as life-time range size and trail use. This result highlights the impact of socio-ecological settings on comparing spatial movement patterns. Our study provides a first step toward comparing long-range spatial movement patterns of two closely-related species in their natural environments.
Application of a Limit-Cycle Oscillator Model for Prediction of Circadian Phase in Rotating Night Shift Workers
Authors: Stone Julia E. , Aubert Xavier L. , Maass Henning , Phillips Andrew J. K. , Magee Michelle , Howard Mark E. , Lockley Steven W. , Rajaratnam Shantha M. W. , Sletten Tracey L. 
Published: July 2019

AbstractPractical alternatives to gold-standard measures of circadian timing in shift workers are needed. We assessed the feasibility of applying a limit-cycle oscillator model of the human circadian pacemaker to estimate circadian phase in 25 nursing and medical staff in a field setting during a transition from day/evening shifts (diurnal schedule) to 3–5 consecutive night shifts (night schedule). Ambulatory measurements of light and activity recorded with wrist actigraphs were used as inputs into the model. Model estimations were compared to urinary 6-sulphatoxymelatonin (aMT6s) acrophase measured on the diurnal schedule and last consecutive night shift. The model predicted aMT6s acrophase with an absolute mean error of 0.69 h on the diurnal schedule (SD = 0.94 h, 80% within ±1 hour), and 0.95 h on the night schedule (SD = 1.24 h, 68% within ±1 hour). The aMT6s phase shift from diurnal to night schedule was predicted to within ±1 hour in 56% of individuals. Our findings indicate the model can be generalized to a shift work setting, although prediction of inter-individual variability in circadian phase shift during night shifts was limited. This study provides the basis for further adaptation and validation of models for predicting circadian phase in rotating shift workers.
Correlation between Jejunal Microbial Diversity and Muscle Fatty Acids Deposition in Broilers Reared at Different Ambient Temperatures
Authors: Li Xing , Cao Zhenhui , Yang Yuting , Chen Liang , Liu Jianping , Lin Qiuye , Qiao Yingying , Zhao Zhiyong , An Qingcong , Zhang Chunyong , Li Qihua , Ji Qiaoping , Zhang Hongfu , Pan Hongbin 
Published: July 2019

AbstractTemperature, which is an important environmental factor in broiler farming, can significantly influence the deposition of fatty acids in muscle. 300 one-day-old broiler chicks were randomly divided into three groups and reared at high, medium and low temperatures (HJ, MJ and LJ), respectively. Breast muscle and jejunal chyme samples were collected and subjected to analyses of fatty acid composition and 16S rRNA gene sequencing. Through spearman’s rank correlation coefficient, the data were used to characterize the correlation between jejunal microbial diversity and muscle fatty acid deposition in the broilers. The results showed that Achromobacter, Stenotrophomonas, Pandoraea, Brevundimonas, Petrobacter and Variovorax were significantly enriched in the MJ group, and all of them were positively correlated with the fatty acid profiling of muscle and multiple lipid metabolism signaling pathways. Lactobacillus was significantly enriched in the HJ group and exhibited a positive correlation with fatty acid deposition. Pyramidobacter, Dialister, Bacteroides and Selenomonas were significantly enriched in the LJ group and displayed negative correlation with fatty acid deposition. Taken together, this study demonstrated that the jejunal microflora manifested considerable changes at high and low ambient temperatures and that jejunal microbiota changes were correlated with fatty acid deposition of muscle in broilers.
Serum anti-EIF3A autoantibody as a potential diagnostic marker for hepatocellular carcinoma
Authors: Heo Chang-Kyu , Hwang Hai-Min , Lee Hye-Jung , Kwak Sang-Seob , Yoo Jong-Shin , Yu Dae-Yeul , Lim Kook-Jin , Lee Soojin , Cho Eun-Wie 
Published: July 2019

AbstractTumor-associated autoantibodies are promising diagnostic biomarkers for early detection of tumors. We have screened a novel tumor-associated autoantibody in hepatocellular carcinoma (HCC) model mice. Its target antigen was identified as eukaryotic translation initiation factor 3 subunit A (EIF3A) by proteomic analysis, and the elevated expression of EIF3A in HCC tissues of tumor model mice as well as human patients was shown. Also, its existence in tumor-derived exosomes was revealed, which seem to be the cause of tumor-associated autoantibody production. To use serum anti-EIF3A autoantibody as biomarker, ELISA detecting anti-EIF3A autoantibody in human serum was performed using autoantibody-specific epitope. For the sensitive detection of serum autoantibodies its specific conformational epitopes were screened from the random cyclic peptide library, and a streptavidin antigen displaying anti-EIF3A autoantibody-specific epitope, XC90p2(-CPVRSGFPC-), was used as capture antigen. It distinguished patients with HCC (n = 102) from healthy controls (n = 0285) with a sensitivity of 79.4% and specificity of 83.5% (AUC = 0.87). Also, by simultaneously detecting with other HCC biomarkers, including alpha-fetoprotein, HCC diagnostic sensitivity improved from 79.4% to 85%. Collectively, we suggest that serum anti-EIF3A autoantibody is a useful biomarker for the diagnosis of HCC and the combinational detection of related biomarkers can enhance the accuracy of the cancer diagnosis.