bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acarbose Protects From Central and Peripheral Metabolic Imbalance Induced by Benzene Exposure
Authors: Debarba LK. , Mulka A. , Lima J.B.M. , Didyuk O. , Fakhoury P. , Koshko L. , Awada AA. , Zhang K. , Klueh U. , Sadagurski M. 
Published: March 2020

AbstractBenzene is a well-known human carcinogen that is one of the major components of air pollution. Sources of benzene in ambient air include cigarette smoke, e-cigarettes vaping and evaporation of benzene containing petrol processes. While carcinogenic effects of benzene exposure have been well studied, less is known about metabolic effects of benzene exposure. We show that chronic exposure to benzene at low levels induces severe metabolic imbalance in a sex-specific manner, which is associated with hypothalamic inflammation and endoplasmic reticulum (ER) stress. Benzene exposure rapidly activates hypothalamic ER stress and neuroinflammatory responses in male mice, while pharmacological inhibition of ER stress response by inhibiting IRE1α-XBP1 pathway significantly alleviates benzene-induced glial inflammatory responses. Additionally, feeding mice with Acarbose, a clinically available anti-diabetes drug, protected against benzene induced central and peripheral metabolic imbalance. Acarbose imitates the slowing of dietary carbohydrate digestion, suggesting that choosing a diet with a low glycemic index might be a potential strategy for reducing the negative metabolic effect of chronic exposure to benzene for smokers or for people living/working in urban environments with high concentrations of exposure to automobile exhausts.
Excessive E2F transcription in single cancer cells precludes transient cell cycle exit after DNA damage
Authors: Segeren Hendrika A. , van Rijnberk Lotte M. , Moreno Eva , Riemers Frank M. , Yuan Ruixue , Wubbolts Richard , de Bruin Alain , Westendorp Bart 
Published: March 2020

AbstractE2F transcription factors control the expression of cell cycle genes. Cancers often demonstrate enhanced E2F target gene expression, which can be explained by increased percentages of replicating cells. However, we now demonstrate in human cancer biopsies that individual neoplastic cells display abnormally high levels of E2F-dependent transcription. To mimic this situation, we deleted the atypical E2F repressors (E2F7/8) in untransformed cells. Individual cells with elevated E2F-activity during S/G2-phase failed to exit the cell cycle after DNA damage and underwent mitosis. In contrast, wild type cells completed S-phase and then exit the cell cycle by activating the APC/CCdh1via repression of the E2F-target Emi1. Strikingly, many arrested wildtype cells could eventually inactivate APC/CCdh1to execute a second round of DNA replication and mitosis, thereby becoming tetraploid. Cells with elevated E2F-transcription fail to exit the cell cycle after DNA damage which potentially causes genomic instability, promotes malignant progression and reduces drug sensitivity.
Lamin A redistribution mediated by nuclear deformation determines dynamic localization of YAP
Authors: Koushki Newsha , Ghagre Ajinkya , Srivastava Luv Kishore , Sitaras Chris , Yoshie Haruka , Molter Clayton , Ehrlicher Allen J. 
Published: March 2020

SummaryYAP is a key mechanotransduction protein with essential roles in diverse physiological processes. Dysregulation in YAP activity is associated with multiple diseases such as atherosclerosis, fibrosis, and cancer progression. Here we examine the physical stimuli that regulate dynamic YAP translocation to the nucleus. Through a combination of biophysical studies, we demonstrate that YAP localization is insensitive to cell substrate stiffness, but strongly determined by cellular contractile work, which in turn deforms the nucleus. We show that nuclear deformation from LINC-mediated cytoskeletal contractility or extracellular osmotic forces triggers YAP nuclear localization. By modulating the expression of lamin A and nuclear stiffness, we illustrate that nuclear rigidity modulates deformation-mediated YAP nuclear localization. Finally, we show that nuclear deformation causes relocalization of lamin A from the nuclear membrane to the nucleoplasm, and this is essential in allowing YAP to enter the nucleus. These results reveal key physical nuclear deformation mechanics that drive YAP nuclear import.
Blunted Diurnal Firing in Lateral Habenula Projections to Dorsal Raphe Nucleus and Delayed Photoentrainment in Stress-Susceptible Mice
Authors: Liu He , Rastogi Ashutosh , Sabanovic Merima , Alhammadi Aisha Darwish , Xu Qing , Guo Lihua , Cao Jun-Li , Zhang Hongxing , Narain Priyam , Aqel Hala , Mlambo Vongai , Rezgui Rachid , Radwan Basma , Chaudhury Dipesh 
Published: March 2020

ABSTRACTDaily rhythms are disrupted in patients suffering from mood disorders. The lateral habenula (LHb) and dorsal raphe nucleus (DRN) contribute to circadian timekeeping and regulate mood. Thus, pathophysiology in these nuclei may be responsible for aberrations in daily rhythms during mood disorders. Using the chronic social defeat stress (CSDS) paradigm andin-vitroslice electrophysiology we measured the effects of stress on diurnal rhythms in firing of LHb cells projecting to the DRN (cellsLHb→DRN) and DRN cells alone. We also performed optogenetic experiments to investigate if increased firing in cellsLHb→DRNduring exposure to subthreshold social defeat stress (SSDS), induces stress-susceptibility. Last we investigated whether exposure to CSDS affected the ability of mice to phototentrain to a new LD cycle. The cellsLHb→DRNand DRN cells alone of stress-susceptible mice express greater blunted diurnal firing compared to stress-naive (control) and stress-resilient mice. Day-time optogenetic activation of cellsLHb→DRNduring SSDS induces stress-susceptibility which shows the direct correlation between increased activity in this circuit and putative mood disorders. Finally, we found that stress-susceptible mice are slower, while stress-resilient mice are faster, at photoentraining to a new LD cycle. Our findings suggest that CSDS induces blunted daily rhythms in firing in cellsLHb→DRNand slow rate of photoentrainment in susceptible-mice. In contrast, resilientmice may undergo homeostatic adaptations that maintain daily rhythms in firing in cellsLHb→DRNand also show rapid photoentrainment to a new LD-cycle.
An Experimental Validation of the Computer Fluid Dynamics of Normal Human Nasal Airflow Using a Precise 3-D Printing Model
Authors: Fu Xiaoli , Cheng Yin , Liu Huanhai , Liao Jianchun , Kou Mingqing , Shen Chao , Ge Qinghua , Yan Shenglin , Peng Hu 
Published: March 2020

AbstractComputer Fluid Dynamics(CFD) is a popular method for studying airflow of nasal cavities. However, the data of CFD studies has rarely been validated through experiments. To test the accuracy of CFD computation, we studied the consistency of the air pressure of nasal cavities in the CFD and the experiment. A proportional resin model of a normal human subject’s nasal cavities was created by a 3-d printer with a precision value of 0.1mm. The pressure of 63 check points in the nasal cavities in different breathing states was measured. The experimental data was compared with the data obtained by CFD simulation. At the flow rates of 180 ml s-1and 560 ml s-1, the pressure in all check points remained highly consistent with the CFD data. At 1100 ml s-1flow rate, there was a significant deviation in the posterior segment of the nasal cavity during exhalation. The method used in this study to measure the pressure in the nasal cavities can be used in experimental validation of CFD data. The computational methods and the boundary conditions used in this study resulted in a high agreement between the results of the CFD simulation and the experiment.Author SummaryIn the contemporary era, Computer fluid dynamics (CFD) is the mainstream method for studying air flow. Due to the complex anatomical structure of the nasal cavity, the CFD results of the nasal flow have rarely been experimentally verified. This study provides a method to verify the methods and results of nasal CFD. We printed an accurate model of a normal person’s nasal cavity with a high-precision 3D printer. In this nasal cavity model, we set 63 small holes to detect the air pressure of the places we concerned. Three different nasal flow quantity are used to represent different breathing conditions: high (1100 ml s-1), medium (560 ml s-1), and low (180 ml s-1). In medium and low nasal flow quantities, our CFD results are in good agreement with the experimental pressure values. On this basis, we analyzed the characteristics of nasal airflow in normal people. The method used in this study to measure the pressure in the nasal cavities can be used in experimental measurements of the partial resistance of the nasal cavity. With proper modification, it can be applied to the clinical practice for nasal resistance, giving more help for the design of the operation plan.
Assessing the statistical reporting quality in high-impact factor urology journals
Authors: Dai Shuangyang , Xu Hong , Li Beibei , Zhang Jingao , Zhou Xiaobin 
Published: March 2020

AbstractBackgroundsObservational studies plays an important role in urology studies, But few studies have paid attention to the statistical reporting quality of observational studies. The purpose of this study was to investigate the frequency and evaluate the reporting quality of statistical methods of the published observational studies in urology.MethodsThe five urology journals were selected according to the 5-year impact factor. A systematic literature search was performed in PubMed for relevant articles. The quality of statistical reporting was assessed according to assessment criteria.ResultsA total of 193 articles were included in this study. The mean statistical reporting score of included articles was 0.42 (SD=0.15), accounting for 42% of total score. The items that must be reported with a reporting rate more than 50% were: alpha level (n=122, 65.2%), confidence intervals (n=134, 69.4%), name of statistical package (n=158, 84.5%) and exactP-values (n=161, 86.1%). The items with a reporting rate less than 50% were: outliers (n=2, 1.0%) and sample size (n=13, 6.7%). For multivariable regression models (liner, logistic and Cox), variables coding (n=27, 40.7%), validation analysis of assumptions (n=58, 40.3%), interaction test (n=43, 30.0%), collinearity diagnostics (n=5, 3.5%) and goodness of fit test (n=6, 5.9%) were reported. Number of authors more than 7(OR=2.06, 95%CI=1.04-4.08) and participation of statistician or epidemiologist (OR=1.73, 95%CI=1.18-3.39) were associated with the superior reporting quality.ConclusionThe statistical reporting quality of published observational studies in 5 high-impact factor urological journals was alarming. We encourage researchers to collaborate with statistician or epidemiologist. The authors, reviewers and editors should increase their knowledge of statistical methods, especially new and complex methods.
The dominance hierarchy of the female Yunnan snub-nosed monkeys (Rhinopithecus bieti)
Authors: Huang Kai , Xia Wancai , Fu Yi , Wan Yaqiong , Feng Hao , Krzton Ali , Li Jiaqi , Li Dayong 
Published: March 2020

AbstractDominance hierarchies are common in social mammals, especially primates. The formation of social hierarchies is conducive to solving the problem of the allocation of scarce resources among individuals. From August 2015 to July 2016, we observed a wild, provisioned Yunnan snub-nosed monkey (Rhinopithecus bieti) group at Xiangguqing in Baimaxueshan National Nature Reserve, Yunnan Province, China. Aggressive and submissive behaviors were used to investigate dominance hierarchies between female individuals in the same one-male unit (OMU), and the grooming reciprocity index was used to detect reciprocal relationships between these females within the OMU. The results showed that loose social hierarchies exist among the females in each OMU, and more dominant individuals have higher grooming incomes. These results are consistent with the aggressive-submissive hypothesis and the resource control hypothesis.
The effects of Hurricane Otto on the soil ecosystems of three forest types in the Northern Zone of Costa Rica
Authors: Eaton William D. , McGee Katie M. , Alderfer Kiley , Jimenez Angie Ramirez , Hajibabaei Mehrdad 
Published: March 2020

AbstractHurricanes rapidly deposit large amounts of canopy material onto tropical forest floors, stimulating metabolic processes involved in the decomposition of these materials and production of N and C resources into the food web. However, little is known about the effects that hurricanes have on specific soil microbial taxa or functional groups involved in these processes. The objectives of this study were to determine how Hurricane Otto influenced three different tropical forest soil ecosystems within the first 8 months after causing damage to a tropical forest by assessing the soil C and N factors and how the soil bacterial and fungal community compositions differed before and after the hurricane. Soil samples were collected from five 2000 m2permanent plots in Lowland, Upland and Riparian forest systems within the same area in the Northern Zone of Costa Rica. Standard methods were used to measure the amounts Total N, NO3-, NH4+, Total organic C, and Biomass C, while Illumina MiSeq methods were used to generate bacterial and fungal sequences. All data were analyzed using univariate and multivariate statistical methods. Using this “before and after” study design, it was found that the levels of the inorganic N and Biomass C were greater in the Post-Hurricane soil samples. The mean proportion of DNA sequences of complex C degrading/lignin degrading, NH4+-producing, and ammonium oxidizing bacteria, and the complex C degrading/wood rot/lignin degrading and ectomycorrhizal fungi also were greater in the Post-Hurricane soils. We also provide evidence that the excessive amounts of canopy leaf litter and woody debris deposited on the forest floor during Hurricane Otto appears to be selecting for genera that become more dominant Post-Hurricane, perhaps because they may be better able to rapidly process the newly deposited C and N-rich canopy material. This is a rare “before and after” a natural hurricane design that warrants further monitoring.
Single cell derived mRNA signals across human kidney tumors
Authors: Young Matthew D , Mitchell Thomas J , Custers Lars , Margaritis Thanasis , Morales Francisco , Kwakwa Kwasi , Khabirova Eleonora , Kildisiute Gerda , Oliver Thomas RW , de Krijger Ronald R. , van den Heuvel-Eibrink Marry M. , Comitani Federico , Piapi Alice , Bugallo-Blanco Eva , Thevanesan Christine , Burke Christina , Prigmore Elena , Ambridge Kirsty , Roberts Kenny , Vieira Braga Felipe A , Coorens Tim HH , Del Valle Ignacio , Wilbrey-Clark Anna , Mamanova Lira , Stewart Grant D , Gnanapragasam Vincent J , Rampling Dyanne , Sebire Neil , Coleman Nicholas , Hook Liz , Warren Anne , Haniffa Muzlifah , Kool Marcel , Pfister Stefan M , Achermann John C , He Xiaoling , Barker Roger A , Shlien Adam , Bayraktar Omer A , Teichmann Sarah , Holstege Frank C. , Meyer Kerstin B , Drost Jarno , Straathof Karin , Behjati Sam 
Published: March 2020

AbstractThe cellular transcriptome may provide clues into the differentiation state and origin of human cancer, as tumor cells may retain patterns of gene expression similar to the cell they derive from. Here, we studied the differentiation state and cellular origin of human kidney tumors, by assessing mRNA signals in 1,300 childhood and adult renal tumors, spanning seven different tumor types. Using single cell mRNA reference maps of normal tissues generated by theHuman Cell Atlasproject, we measured the abundance of reference “cellular signals” in each tumor. Quantifying global differentiation states, we found that, irrespective of tumor type, childhood tumors exhibited fetal cellular signals, thus replacing the long-held presumption of “fetalness” with a precise, quantitative readout of immaturity. By contrast, in adult cancers our assessment refuted the suggestion of dedifferentiation towards a fetal state in the overwhelming majority of cases, with the exception of lethal variants of clear cell renal cell carcinoma. Examining the specific cellular phenotype of each tumor type revealed an intimate connection between the different mesenchymal populations of the developing kidney and childhood renal tumors, whereas adult tumors mostly represented specific mature tubular cell types. RNA signals of each tumor type were remarkably uniform and specific, indicating a possible therapeutic and diagnostic utility. We demonstrated this utility with a case study of a cryptic renal tumor. Whilst not classifiable by clinical pathological work-up, mRNA signals revealed the diagnosis. Our findings provide a cellular definition of human renal tumors through an approach that is broadly applicable to human cancer.
Maintenance of epithelial traits and resistance to mesenchymal reprogramming promote proliferation in metastatic breast cancer
Authors: Eichelberger Laura , Saini Massimo , Moreno Helena Domínguez , Klein Corinna , Bartsch Johanna M. , Falcone Mattia , Reitberger Manuel , Espinet Elisa , Vogel Vanessa , Graf Elisabeth , Schwarzmayr Thomas , Strom Tim-Matthias , Lehmann Mareike , Königshoff Melanie , Pfarr Nicole , Würth Roberto , Donato Elisa , Haas Simon , Spaich Saskia , Sütterlin Marc , Schneeweiss Andreas , Weichert Wilko , Schotta Gunnar , Trumpp Andreas , Sprick Martin R. , Scheel Christina H. 
Published: March 2020

AbstractDespite important advances in the treatment of breast cancer, the 5-year survival rate for patients with distant metastasis remains less than 30%. Metastasis is a complex, multi-step process beginning with local invasion and ending with the outgrowth of systemically disseminated cells into actively proliferating metastases that ultimately cause the destruction of vital organs. It is this last step that limits patient survival and, at the same time, remains the least understood mechanistically. Here, we focus on understanding determinants of metastatic outgrowth using metastatic effusion biopsies from stage IV breast cancer patients. By modelling metastatic outgrowth through xenograft transplantation, we show that tumour initiation potential of patient-derived metastatic breast cancer cells across breast cancer subtypes is strongly linked to high levels of EPCAM expression. Breast cancer cells with high EPCAM levels are highly plastic and, upon induction of epithelial-mesenchymal transition (EMT), readily adopt mesenchymal traits while maintaining epithelial identity. In contrast, low EPCAM levels are caused by the irreversible reprogramming to a mesenchymal state with concomitant suppression of metastatic outgrowth. The ability of breast cancer cells to retain epithelial traits is tied to a global epigenetic program that limits the actions of EMT-transcription factor ZEB1, a suppressor of epithelial genes. Our results provide direct evidence that maintenance of epithelial identity is required for metastatic outgrowth while concomitant expression of mesenchymal markers enables plasticity. In contrast, loss of epithelial traits is characteristic of an irreversible mesenchymal reprogramming associated to a deficiency for metastatic outgrowth. Collectively, our data provide a framework for the intricate intercalation of mesenchymal and epithelial traits in metastatic growth.
Clinal and seasonal change are correlated inDrosophila melanogasternatural populations
Authors: Rodrigues Murillo F. , Vibranovski Maria D. , Cogni Rodrigo 
Published: March 2020

AbstractSpatial and seasonal variation in the environment are ubiquitous. Environmental heterogeneity can affect natural populations and lead to covariation between environment and allele frequencies.Drosophila melanogasteris known to harbor polymorphisms that change both with latitude and seasons. Identifying the role of selection in driving these changes is not trivial, because non-adaptive processes can cause similar patterns. Given the environment changes in similar ways across seasons and along the latitudinal gradient, one promising approach may be to look for parallelism between clinal and seasonal change. Here, we test whether there is a genome-wide correlation between clinal and seasonal change, and whether the pattern is consistent with selection. Allele frequency estimates were obtained from pooled samples from seven different locations along the east coast of the US, and across seasons within Pennsylvania. We show that there is a genome-wide correlation between clinal and seasonal variation, which cannot be explained by linked selection alone. This pattern is stronger in genomic regions with higher functional content, consistent with natural selection. We derive a way to biologically interpret these correlations and show that around 3.7% of the common, autosomal variants could be under parallel seasonal and spatial selection. Our results highlight the contribution of natural selection in driving fluctuations in allele frequencies in natural fly populations and point to a shared genomic basis to climate adaptation which happens over space and time inD. melanogaster.
Recollection-related hippocampal fMRI effects predict longitudinal memory change in healthy older adults
Authors: Hou Mingzhu , de Chastelaine Marianne , Jayakumar Manasi , Donley Brian E. , Rugg Michael D. 
Published: March 2020

AbstractPrior fMRI studies have reported relationships between memory-related activity in the hippocampus and in-scanner memory performance, but whether such activity is predictive of longitudinal memory change remains unclear. Here, we administered a neuropsychological test battery to a sample of cognitively healthy older adults on three occasions, the second and third sessions occurring one month and three years after the first session. Structural and functional MRI data were acquired between the first two sessions. The fMRI data were derived from an associative recognition procedure and allowed estimation of hippocampal effects associated with both successful associative encoding and successful associative recognition (recollection). Baseline memory performance and memory change were evaluated using memory component scores derived from a principal components analysis of the neuropsychological test scores. Across participants, right hippocampal encoding effects correlated significantly with baseline memory performance after controlling for chronological age. Additionally, both left and right hippocampal associative recognition effects correlated significantly with longitudinal memory change after controlling for age, and the relationship with the left hippocampal effect remained after also controlling for left hippocampal volume. Thus, in cognitively healthy older adults, the magnitude of hippocampal recollection effects appears to be a robust predictor of future memory change.