bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recapitulating kidney development in vitro by priming and differentiating mouse embryonic stem cells in monolayers
Authors: Chow Theresa , Wong Frances T. M. , Monetti Claudio , Nagy Andras , Cox Brian , Rogers Ian M. 
Published: April 2020

AbstractIn order to harness the potential of pluripotent stem cells, we need to understand how to differentiate them to our target cell types. Here, we developed a protocol to differentiate mouse embryonic stem cells (ESCs) to renal progenitors in a step-wise manner. Microarrays were used to track the transcriptional changes at each stage of differentiation and we observed that genes associated with metanephros, ureteric bud, and blood vessel development were significantly upregulated as the cells differentiated towards renal progenitors. Priming the ESCs and optimizing seeding cell density and growth factor concentrations helped improve differentiation efficiency. Organoids were used to determine the developmental potential of the renal progenitor cells. Aggregated renal progenitors gave rise to organoids consisting of LTL+/E-cadherin+ proximal tubules, cytokeratin+ ureteric bud-derived tubules, and extracellular matrix proteins secreted by the cells themselves. Over-expression of key kidney developmental genes, Pax2, Six1, Eya1, and Hox11 paralogs, during differentiation did not improve differentiation efficiency. Altogether, we developed a protocol to differentiate mouse ESCs in a manner that recapitulates embryonic kidney development and showed that precise gene regulation is essential for proper differentiation to occur.
Including water quality monitoring in rural water services: why safe water requires challenging the quantity versus quality dichotomy
Authors: Nowicki Saskia , Koehler Johanna , Charles Katrina J. 
Published: April 2020

AbstractThe need to increase drinking water quality monitoring in rural sub-Saharan Africa is widely recognised. Rural water service providers (RWSPs) may be positioned to include water quality monitoring in their activities; however, it is important that water safety activities do not compromise cooperation between the RWSP, bureaucracy, and communities. Using dilemma analysis, drawing on an institutional experiment engaging 76 stakeholders, we find that conceptualising water quality versus quantity as a dichotomy delays progress on safe water. This false dichotomy makes it more difficult to deliver water safety improvements due to contrasting assumptions about the importance of quality; risks associated with not being able to act; and unclear divisions of responsibility. Monitoring water quality can be a threat to stakeholders and stakeholder cooperation; however, this may be mitigated by including supported water safety planning in the technical and institutional design of rural water projects at their conception.
Pharmacological and genetic targeting of 5-lipoxygenase interrupts c-Myc oncogenic signaling and kills enzalutamide-resistant prostate cancer cells via apoptosis
Authors: Monga Jitender , Subramani Dhatchayini , Bharathan Ajay , Ghosh Jagadananda 
Published: April 2020

AbstractMuch of the morbidity and mortality due to prostate cancer happen because of castration-resistant prostate cancer (CRPC) which invariably develops after anti-androgenic therapy. FDA-approved enzalutamide is commonly prescribed for CRPC which works by blocking androgen receptor function. However, even after initial good response, enzalutamide-resistant prostate cancer (ERPC) develops which eventually leads to widespread metastasis. Management of ERPC is extremely difficult because available therapeutic regimen cannot effectively kill and eliminate ERPC cells. Though the mechanism behind enzalutamide-resistance is not properly understood, over-activation of c-Myc has been found to be a common event which plays an important role in the maintenance and progression of ERPC phenotype. However, direct-targeting of c-Myc poses special problem because of its non-enzymatic nature and certain amount of c-Myc activity is needed by non-cancer cells as well. Thus, c-Myc has emerged as an elusive target which needs to be managed by novel agents and strategies in a cancer-specific way. We investigated the effects of pharmacological and genetic inhibition of 5-lipoxygenase (5-Lox) on cell proliferation, apoptosis and invasive potential of enzalutamide-resistant prostate cancer cells. Transcriptional activity of c-Myc was analyzed by DNA-binding, luciferase-assays, and expression of c-Myc-target genes. We found that 5-Lox regulates c-Myc signaling in enzalutamide-resistant prostate cancer cells and inhibition of 5-Lox by Quiflapon/MK591 or shRNA interrupts oncogenic c-Myc signaling and kills ERPC cells by triggering caspase-mediated apoptosis. Interestingly, MK591 does not affect normal, non-cancer cells in the same experimental conditions. Our findings indicate that inhibition of 5-Lox may emerge as a promising new approach to effectively kill ERPC cells sparing normal cells and suggest that development of a long-term curative therapy of prostate cancer may be possible by killing and eliminating ERPC cells with suitable 5-Lox-inhibitors.
Heavy reliance on plants for Romanian cave bears evidenced by amino acid nitrogen isotope analysis
Authors: Naito Yuichi I. , Meleg Ioana N. , Robu Marius , Vlaicu Marius , Drucker Dorothée G. , Wißing Christoph , Hofreiter Michael , Barlow Axel , Bocherens Hervé 
Published: April 2020

AbstractHeavy reliance on plants is rare in Carnivora and mostly limited to relatively small species in subtropical settings. The feeding behaviors of extinct cave bears living during Pleistocene cold periods at middle latitudes have been intensely studied using various approaches including isotopic analyses of fossil collagen. In contrast to cave bears from all other regions in Europe, some individuals from Romania show exceptionally high δ15N values that might be indicative of meat consumption. Herbivory on plants with high δ15N values cannot be ruled out based on this method, however. Here we apply an approach using the δ15N values of individual amino acids from collagen that offsets the baseline δ15N variation among environments. The analysis yielded strong signals of reliance on plants for Romanian cave bears based on the δ15N values of glutamate and phenylalanine. These results could suggest that the high variability in bulk collagen δ15N values observed among cave bears in Romania reflects niche partitioning but in a general trophic context of herbivory.
Stochastic growth pattern of untreated human glioblastomas predicts the survival time for patients
Authors: Ma Ziwei , Niu Ben , Phan Tuan Anh , Stensjøen Anne Line , Ene Chibawanye , Woodiwiss Timothy , Wang Tonghui , Maini Philip K. , Holland Eric C. , Tian Jianjun Paul 
Published: April 2020

AbstractGlioblastomas are highly malignant brain tumors. Knowledge of growth rates and growth patterns is useful for understanding tumor biology and planning treatment logistics. Based on untreated human glioblastoma data collected in Trondheim, Norway, we first fit the average growth to a Gompertz curve, then find a best fitted white noise term for the growth rate variance. Combining these two fits, we obtain a new type of Gompertz diffusion dynamics, which is a stochastic differential equation (SDE). Newly collected untreated human glioblastoma data in Seattle, US, re-verify our model. Instead of growth curves predicted by deterministic models, our SDE model predicts a band with a center curve as the tumor size average and its width as the tumor size variance over time. Given the glioblastoma size in a patient, our model can predict the patient survival time with a prescribed probability. The survival time is approximately a normal random variable with simple formulas for its mean and variance in terms of tumor sizes. Our model can be applied to studies of tumor treatments. As a demonstration, we numerically investigate different protocols of surgical resection using our model and provide possible theoretical strategies.
Accounting for detection unveils the intricacy of wild boar and rabbit co-occurrence patterns in a Mediterranean landscape
Authors: Barros Ana Luísa , Curveira-Santos Gonçalo , Marques Tiago André , Santos-Reis Margarida 
Published: April 2020

AbstractThe patterns of species co-occurrence have long served as a primary approach to explore concepts of interspecific interaction. However, the interpretation of such patterns is difficult as they can result from several complex ecological processes, in a scale-dependent manner. Here, we aim to investigate the co-occurrence pattern between European rabbit and wild boar in an estate in Central Portugal, using two-species occupancy modelling. With this framework, we tested species interaction for occupancy and detection, but also the interdependencies between both parameters. According to our results, the wild boar and European rabbit occurred independently in the study area. However, model averaging of the detection parameters revealed a potential positive effect of wild boar’s presence on rabbit’s detection probability. Upon further analysis of the parameter interdependencies, our results suggested that failing to account for a positive effect on rabbit’s detection could lead to potentially biased interpretations of the co-occurrence pattern. Our study, in spite of preliminary, highlights the need to understand these different pathways of species interaction to avoid erroneous inferences.
Spatially-resolved quantification of proteins in triple negative breast cancers reveals differences in the immune microenvironment associated with prognosis
Authors: Stewart Rachel L. , Matynia Anna P. , Factor Rachel E. , Varley Katherine E. 
Published: April 2020

AbstractTriple negative breast cancer (TNBC) is an aggressive breast cancer subtype. Recent studies have shown that MHC class II (MHCII) expression and tumor infiltrating lymphocytes are important prognostic factors in patients with TNBC, although the relative importance of lymphocyte subsets and associated protein expression is incompletely understood. NanoString Digital Spatial Profiling (DSP) allows for spatially resolved, highly multiplexed quantification of proteins in clinical samples. In this study, we sought to determine if DSP could be used to characterize expression of MHCII and other immune related proteins in tumor epithelial versus stromal compartments of patient-derived TNBCs (N = 10) using a panel of 39 markers. We confirmed that a subset of TNBCs have elevated expression of HLA-DR in tumor epithelial cells; HLA-DR expression was also significantly higher in the tumors of patients with long-term disease-free survival when compared to patients that relapsed. HLA-DR expression in the epithelial compartment was correlated with high expression of CD4 and ICOS in the stromal compartment of the same tumors. We also identified candidate protein biomarkers with significant differential expression between patients that relapsed versus those that did not. In conclusion, DSP is a powerful method that allows for quantification of proteins in the immune microenvironment of TNBCs.
Nutrient availability affects the polar lipidome of Halimione portulacoides leaves cultured in hydroponics
Authors: Custódio Marco , Maciel Elisabete , Domingues Maria Rosário , Lillebø Ana Isabel , Calado Ricardo 
Published: April 2020

AbstractHalophytes are increasingly regarded as suitable extractive species and co-products for coastal Integrated Multi-Trophic Aquaculture (IMTA) and studying their lipidome is a valid means towards their economic valorization. Halimione portulacoides (L.) Aellen edible leaves are rich in functional lipids with nutraceutical and pharmaceutical relevance and the present study aimed to investigate the extent to which its lipidome remains unchanged under a range of dissolved inorganic nitrogen (N) and phosphorus (P) concentrations typical of aquaculture effluents. Lipidomics analysis, done by hydrophilic interaction liquid chromatography coupled to high resolution mass spectrometry, identified 175 lipid species in the lipid extract of leaves: 140 phospholipids (PLs) and 35 glycolipids (GLs). Plants irrigated with a saline solution with 20–100 mg DIN-N L−1 and 3–15.5 mg DIP-P L−1 under a 1-week hydraulic retention time displayed a relatively stable lipidome. At lower concentrations (6 mg DIN-N L−1 and 0.8 mg DIP-P L−1), plants exhibited less PLs and GLs per unit of leaves dry weight and the GLs fraction of the lipidome changed significantly. This study reveals the importance of analyzing the lipidomic profile of halophytes under different nutritional regimens in order to establish nutrient-limitation thresholds and assure production conditions that deliver a final product with a consistent lipid profile.
Evaluation of a five-year predicted survival model for cystic fibrosis in later time periods
Authors: Liou Theodore G. , Kartsonaki Christiana , Keogh Ruth H. , Adler Frederick R. 
Published: April 2020

AbstractWe evaluated a multivariable logistic regression model predicting 5-year survival derived from a 1993–1997 cohort from the United States Cystic Fibrosis (CF) Foundation Patient Registry to assess whether therapies introduced since 1993 have altered applicability in cohorts, non-overlapping in time, from 1993–1998, 1999–2004, 2005–2010 and 2011–2016. We applied Kaplan-Meier statistics to assess unadjusted survival. We tested logistic regression model discrimination using the C-index and calibration using Hosmer-Lemeshow tests to examine original model performance and guide updating as needed. Kaplan-Meier age-adjusted 5-year probability of death in the CF population decreased substantially during 1993–2016. Patients in successive cohorts were generally healthier at entry, with higher average age, weight and lung function and fewer pulmonary exacerbations annually. CF-related diabetes prevalence, however, steadily increased. Newly derived multivariable logistic regression models for 5-year survival in new cohorts had similar estimated coefficients to the originals. The original model exhibited excellent calibration and discrimination when applied to later cohorts despite improved survival and remains useful for predicting 5-year survival. All models may be used to stratify patients for new studies, and the original coefficients may be useful as a baseline to search for additional but rare events that affect survival in CF.
Intraventricular Medium B Treatment Benefits an Ischemic Stroke Rodent Model via Enhancement of Neurogenesis and Anti-apoptosis
Authors: Chen Yun-An , Tsai Yi-Chieh , Chen Yi-Dao , Liu Der-Zen , Young Tai-Horng , Tsai Li-Kai 
Published: April 2020

AbstractEnhancement of endogenous neurogenesis after ischemic stroke may improve functional recovery. We previously demonstrated that medium B, which is a combination with epidermal growth factor (EGF) and fibronectin, can promote neural stem/progenitor cell (NSPC) proliferation and migration. Here, we showed that medium B promoted proliferation and migration of cultured NSPCs onto various 3-dimentional structures. When rat cortical neurons with oxygen glucose deprivation (OGD) were co-cultured with NSPCs, medium B treatment increased neuronal viability and reduced cell apoptosis. In a rat model with transient middle cerebral artery occlusion (MCAO), post-insult intraventricular medium B treatment enhanced proliferation, migration, and neuronal differentiation of NSPCs and diminished cell apoptosis in the infarct brain. In cultured post-OGD neuronal cells and the infarct brain from MCAO rats, medium B treatment increased protein levels of Bcl-xL, Bcl-2, phospho-Akt, phospho-GSK-3β, and β-catenin and decreased the cleaved caspase-3 level, which may be associated with the effects of anti-apoptosis. Notably, intraventricular medium B treatment increased neuronal density, improved motor function and reduced infarct size in MCAO rats. In summary, medium B treatment results in less neuronal death and better functional outcome in both cellular and rodent models of ischemic stroke, probably via promotion of neurogenesis and reduction of apoptosis.
Controlling Nutritional Status (CONUT) score is a prognostic factor in patients with resected breast cancer
Authors: Li Wen , Li Min , Wang Ting , Ma Guangzhi , Deng Yunfu , Pu Dan , Liu Zhenkun , Wu Qiang , Liu Xuejuan , Zhou Qinghua 
Published: April 2020

AbstractThe present study aimed to determine the correlation between controlling nutritional status (CONUT) and prognosis in resected breast cancer patients. Totally, 861 breast cancer patients with surgical resection in West China Hospital of Sichuan University between 2007 and 2010 were included. The relationship between CONUT and various clinicopathological factors as well as prognosis was evaluated. The results showed that the optimal cutoff value for CONUT to predict the 5-year survival was 3 and CONUT had a higher area under the ROC curve (AUC) for 5-year disease free survival (DFS) and overall survival (OS) prediction compared with the neutrophil lymphocyte ratio (NLR) and prognostic nutritional index (PNI). High CONUT was significantly correlated with older age, lymph node involvement, advanced T-stage, and surgery type. In the multivariate analysis, CONUT-high patients had worse DFS and OS, when compared with CONUT-low patients. In conclusion, preoperative CONUT is a useful marker for predicting long term outcomes in breast cancer patients after curative resection.
Identifying threshold responses of Australian dryland rivers to future hydroclimatic change
Authors: Larkin Z. T. , Ralph T. J. , Tooth S. , Fryirs K. A. , Carthey A. J. R. 
Published: April 2020

AbstractRivers provide crucial ecosystem services in water-stressed drylands. Australian dryland rivers are geomorphologically diverse, ranging from through-going, single channels to discontinuous, multi-channelled systems, yet we have limited understanding of their sensitivity to future hydroclimatic changes. Here, we characterise for the first time the geomorphology of 29 dryland rivers with catchments across a humid to arid gradient covering >1,800,000 km2 of continental eastern and central Australia. Statistical separation of five specific dominantly alluvial river types and quantification of their present-day catchment hydroclimates enables identification of potential thresholds of change. Projected aridity increases across eastern Australia by 2070 (RCP4.5) will result in ~80% of the dryland rivers crossing a threshold from one type to another, manifesting in major geomorphological changes. Dramatic cases will see currently through-going rivers (e.g. Murrumbidgee, Macintyre) experience step changes towards greater discontinuity, characterised by pronounced downstream declines in channel size and local termination. Expanding our approach to include other river styles (e.g. mixed bedrock-alluvial) would allow similar analyses of dryland rivers globally where hydroclimate is an important driver of change. Early identification of dryland river responses to future hydroclimatic change has far-reaching implications for the ~2 billion people that live in drylands and rely on riverine ecosystem services.
The TIPE Molecular Pilot That Directs Lymphocyte Migration in Health and Inflammation
Authors: Sun Honghong , Lin Mei , Zamani Ali , Goldsmith Jason R. , Boggs Amanda E. , Li Mingyue , Lee Chin-Nien , Chen Xu , Li Xinyuan , Li Ting , Dorrity Brigid L. , Li Ning , Lou Yunwei , Shi Songlin , Wang Wei , Chen Youhai H. 
Published: April 2020

AbstractLymphocytes are some of the most motile cells of vertebrates, constantly navigating through various organ systems. Their specific positioning in the body is delicately controlled by site-specific directional cues such as chemokines. While it has long been suspected that an intrinsic molecular pilot, akin to a ship’s pilot, guides lymphocyte navigation, the nature of this pilot is unknown. Here we show that the TIPE (TNF-α-induced protein 8-like) family of proteins pilot lymphocytes by steering them toward chemokines. TIPE proteins are carriers of lipid second messengers. They mediate chemokine-induced local generation of phosphoinositide second messengers, but inhibit global activation of the small GTPase Rac. TIPE-deficient T lymphocytes are completely pilot-less: they are unable to migrate toward chemokines despite their normal ability to move randomly. As a consequence, TIPE-deficient mice have a marked defect in positioning their T lymphocytes to various tissues, both at the steady-state and during inflammation. Thus, TIPE proteins pilot lymphocytes during migration and may be targeted for the treatment of lymphocyte-related disorders.
Mesenchymal-endothelial transition-derived cells as a potential new regulatory target for cardiac hypertrophy
Authors: Dong Wenyan , Li Ruiqi , Yang Haili , Lu Yan , Zhou Longhai , Sun Lei , Wang Dianliang , Duan Jinzhu 
Published: April 2020

AbstractThe role of Mesenchymal-endothelial transition (MEndoT) in cardiac hypertrophy is unclear. To determine the difference between MEndoT-derived and coronary endothelial cells is essential for understanding the revascularizing strategy in cardiac repair. Using lineage tracing we demonstrated that MEndoT-derived cells exhibit highly heterogeneous which were characterized with highly expression of endothelial markers such as vascular endothelial cadherin(VECAD) and occludin but low expression of Tek receptor tyrosine kinase(Tek), isolectin B4, endothelial nitric oxide synthase(eNOS), von Willebrand factor(vWF), and CD31 after cardiac hypertrophy. RNA-sequencing showed altered expression of fibroblast lineage commitment genes in fibroblasts undergoing MEndoT. Compared with fibroblasts, the expression of p53 and most endothelial lineage commitment genes were upregulated in MEndoT-derived cells; however, the further analysis indicated that MEndoT-derived cells may represent an endothelial-like cell sub-population. Loss and gain function study demonstrated that MEndoT-derived cells are substantial sources of neovascularization, which can be manipulated to attenuate cardiac hypertrophy and preserve cardiac function by improving the expression of endothelial markers in MEndoT-derived cells. Moreover, fibroblasts undergoing MEndoT showed significantly upregulated anti-hypertrophic factors and downregulated pro-hypertrophic factors. Therefore MEndoT-derived cells are an endothelial-like cell population that can be regulated to treat cardiac hypertrophy by improving neovascularization and altering the paracrine effect of fibroblasts.
Normative data and associated factors of hand grip strength among elderly individuals: The Yilan Study, Taiwan
Authors: Pan Po-Jung , Lin Ching-Heng , Yang Nan-Ping , Chen Hsi-Chung , Tsao Hsuan-Ming , Chou Pesus , Hsu Nai-Wei 
Published: April 2020

AbstractWeak grip strength is associated with subsequent mortality in elderly populations. The normative data and associated factors of HGS in community-dwelling elderly Taiwanese populations require further evaluation. From February 2012 until the end of 2016, all residents of Yilan City, Taiwan aged 65 years or older were randomly selected for a population-based community health survey. A total of 2,470 older adults were enrolled in this study. The relationships between HGS and various anthropometric and sociodemographic correlates were examined. The results showed that HGS was higher in men than in women. The mean HGS exhibited a decreasing trend with advanced age in both men and women. HGS was significantly associated with height, weight, and exercise habits. The physical as well as the mental component summary measures of health-related quality of life (HRQoL) were positively associated with HGS. After HRQoL was integrated into the regression model, female sex, age, waist circumference, and diabetes mellitus were significantly negatively associated with HGS. In conclusion, HGS significantly decreased with advanced age. among community-dwelling Taiwanese elderly people, Various factors had different effects on HGS.