bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole Transcriptome Analysis of Renal Intercalated Cells Predicts Lipopolysaccharide Mediated Inhibition of Retinoid X Receptor alpha Function
Authors: Saxena Vijay , Fitch James , Ketz John , White Peter , Wetzel Amy , Chanley Melinda A. , Spencer John D. , Becknell Brian , Pierce Keith R. , Arregui Sam W. , Nelson Raoul D. , Schwartz George J. , Velazquez Victoria , Walker Logan A. , Chen Xi , Yan Pearlly , Hains David S. , Schwaderer Andrew L. 
Published: January 2019

AbstractThe renal collecting duct consists of intercalated cells (ICs) and principal cells (PCs). We have previously demonstrated that collecting ducts have a role in the innate immune defense of the kidney. Transcriptomics is an important tool used to enhance systems-level understanding of cell biology. However, transcriptomics performed on whole kidneys provides limited insight of collecting duct cell gene expression, because these cells comprise a small fraction of total kidney cells. Recently we generated reporter mouse models to enrich collecting duct specific PC and ICs and reported targeted gene expression of anti-microbial peptide genes. Here we report transcriptomics on enriched ICs and PCs and performed a pilot study sequencing four single ICs. We identified 3,645 genes with increased relative expression in ICs compared to non-ICs. In comparison to non-PCs, 2,088 genes had higher relative expression in PCs. IC associated genes included the innate interleukin 1 receptor, type 1 and the antimicrobial peptide (AMP) adrenomedullin. The top predicted canonical pathway for enriched ICs was lipopolysaccharide/Interleukin 1 mediated inhibition of Retinoid X Receptor alpha function and decreased Retinoid X Receptor expression was confirmed to occur 1-hour post experimental murine UTI in ICs but not in non-ICs.
Assessing robustness of radiomic features by image perturbation
Authors: Zwanenburg Alex , Leger Stefan , Agolli Linda , Pilz Karoline , Troost Esther G. C. , Richter Christian , Löck Steffen 
Published: January 2019

AbstractImage features need to be robust against differences in positioning, acquisition and segmentation to ensure reproducibility. Radiomic models that only include robust features can be used to analyse new images, whereas models with non-robust features may fail to predict the outcome of interest accurately. Test-retest imaging is recommended to assess robustness, but may not be available for the phenotype of interest. We therefore investigated 18 combinations of image perturbations to determine feature robustness, based on noise addition (N), translation (T), rotation (R), volume growth/shrinkage (V) and supervoxel-based contour randomisation (C). Test-retest and perturbation robustness were compared for combined total of 4032 morphological, statistical and texture features that were computed from the gross tumour volume in two cohorts with computed tomography imaging: I) 31 non-small-cell lung cancer (NSCLC) patients; II): 19 head-and-neck squamous cell carcinoma (HNSCC) patients. Robustness was determined using the 95% confidence interval (CI) of the intraclass correlation coefficient (1, 1). Features with CI ≥ 0:90 were considered robust. The NTCV, TCV, RNCV and RCV perturbation chain produced similar results and identified the fewest false positive robust features (NSCLC: 0.2–0.9%; HNSCC: 1.7–1.9%). Thus, these perturbation chains may be used as an alternative to test-retest imaging to assess feature robustness.
Scanning the genomes of parents for imprinted loci acting in their un-genotyped progeny
Authors: Blunk Inga , Mayer Manfred , Hamann Henning , Reinsch Norbert 
Published: January 2019

AbstractDepending on their parental origin, alleles at imprinted loci are fully or partially inactivated through epigenetic mechanisms. Their effects contribute to the broader class of parent-of-origin effects. Standard methodology for mapping imprinted quantitative trait loci in association studies requires phenotypes and parental origin of marker alleles (ordered genotypes) to be simultaneously known for each individual. As such, many phenotypes are known from un-genotyped offspring in ongoing breeding programmes (e.g. meat animals), while their parents have known genotypes but no phenotypes. By theoretical considerations and simulations, we showed that the limitations of standard methodology can be overcome in such situations. This is achieved by first estimating parent-of-origin effects, which then serve as dependent variables in association analyses, in which only imprinted loci give a signal. As a theoretical foundation, the regression of parent-of-origin effects on the number of B-alleles at a biallelic locus — representing the un-ordered genotype — equals the imprinting effect. The applicability to real data was demonstrated for about 1800 genotyped Brown Swiss bulls and their un-genotyped fattening progeny. Thus, this approach unlocks vast data resources in various species for imprinting analyses and offers valuable clues as to what extent imprinted loci contribute to genetic variability.
HPLC analysis of CSF hypocretin-1 in type 1 and 2 narcolepsy
Authors: Sakai Noriaki , Matsumura Mari , Lin Ling , Mignot Emmanuel , Nishino Seiji 
Published: January 2019

AbstractNarcolepsy is a chronic sleep disorder caused by a loss of hypocretin (hcrt) neurons in the hypothalamus. Cerebrospinal fluid (CSF) hcrt-1 measurement has been well established as a gold standard of narcolepsy diagnosis, although some portions of narcoleptic patients show normal hcrt-1 levels. We aimed to examine peptide degradation of hcrt-1 and its abnormality in the CSF of patients by using high performance liquid chromatography (HPLC) followed by radioimmunoassay (RIA). CSF was collected from healthy controls, narcoleptic patients of type 1 with hcrt-1 deficiency, type 1 with normal hcrt-1 level, and type 2 with normal hcrt-1 level. We found that the majority of hcrt-1 immunoreactivity in extracted CSF was derived from unauthentic hcrt-1 peaks, which are predicted to be inactive metabolites, and the intact hcrt-1 peptide was less than 10% of the gross amount, suggesting that the regular RIA for CSF hcrt-1 measures largely reflect the unauthentic hcrt-1-related metabolites rather than the intact one. As expected, all hcrt-1-related peaks were abolished in type 1 with hcrt-1 deficiency. Importantly, we also found that the sum of the authentic hcrt-1 peptide (peaks 3 and 4) significantly decreased in non-deficient type 1 and tended to decrease in type 2 narcoleptic patients although the levels with the regular RIA in non-extracted CSF was equivalent to healthy controls. Immunoreactivity with unauthentic hcrt-1 metabolites may masks the possible decline in authentic hcrt-1 level caused by the partial loss of hcrt neurons. Our findings may provide new insights into the degradation of the hcrt-1 peptide and the pathophysiology of narcolepsy.
Discovery of novel hit compounds with broad activity against visceral and cutaneous Leishmania species by comparative phenotypic screening
Authors: Lamotte S. , Aulner N. , Späth G. F. , Prina E. 
Published: January 2019

AbstractThe limited success of recent phenotypic anti-leishmanial drug screening campaigns calls for new screening strategies for the discovery of clinically relevant hits. Here we present such a novel strategy based on physiologically relevant, ex vivo biology. We established high content phenotypic assays that combine primary murine macrophages and lesion-derived, virulent L. donovani and L. amazonensis amastigotes, which we applied to validate previously identified, anti-leishmanial hit compounds referred to as ‘GSK Leish-Box’. Together with secondary screens using cultured promastigotes, our pipeline distinguished stage- and/or species-specific compounds, including 20 hits with broad activity at 10 µM against intracellular amastigotes of both viscerotropic and dermotropic Leishmania. Even though the GSK Leish-Box hits were identified by phenotypic screening using THP-1 macrophage-like cells hosting culture-derived L. donovani LdBob parasites, our ex vivo assays only validated anti-leishmanial activity at 10 µM on intra-macrophagic L. donovani for 23 out of the 188 GSK Leish-Box hits. In conclusion, our comparative approach allowed the identification of hits with broad anti-leishmanial activity that represent interesting novel candidates to be tested in animal models. Physiologically more relevant screening approaches such as described here may reduce the very high attrition rate observed during pre-clinical and clinical phases of the drug development process.
Effects of the long-term storage of human fecal microbiota samples collected in RNAlater
Authors: Tap Julien , Cools-Portier Stéphanie , Pavan Sonia , Druesne Anne , Öhman Lena , Törnblom Hans , Simren Magnus , Derrien Muriel 
Published: January 2019

AbstractThe adequate storage of fecal samples from clinical trials is crucial if analyses are to be performed later and in long-term studies. However, it is unknown whether the composition of the microbiota is preserved during long-term stool storage (>1 year). We therefore evaluated the influence of long-term storage on the microbiota composition of human stool samples collected in RNAlater and stored for approximately five years at −80 °C. We compared storage effects on stool samples from 24 subjects with the effects of technical variation due to different sequencing runs and biological variation (intra- and inter-subject), in another 101 subjects, based on alpha-diversity, beta-diversity and taxonomic composition. We also evaluated the impact of initial alpha-diversity and fecal microbiota composition on beta-diversity instability upon storage. Overall, long-term stool storage at −80 °C had only limited effects on the microbiota composition of human feces. The magnitude of changes in alpha- and beta- diversity and taxonomic composition after long-term storage was similar to inter-sequencing variation and smaller than biological variation (both intra- and inter-subject). The likelihood of fecal samples being affected by long-term storage correlated with the initial relative abundance of some genera and tend to be affected by initial taxonomic richness.
Detection of alpha particle emitters originating from nuclear fuel inside reactor building of Fukushima Daiichi Nuclear Power Plant
Authors: Morishita Yuki , Torii Tatsuo , Usami Hiroshi , Kikuchi Hiroyuki , Utsugi Wataru , Takahira Shiro 
Published: January 2019

AbstractWe measured alpha emitters obtained from a reactor building in the Fukushima Daiichi Nuclear Power Plant (FDNPP) by using an alpha particle imaging detector. For developing the detector, we used a very thin (0.05-mm-thick) a cerium-doped Gd3(Ga,Al)5O12 (Ce:GAGG) scintillator and silicon photomultiplier (SiPM) arrays as the photodetector. The floor of the reactor building in FDNPP was wiped off by using smear papers, and the radioactivity of these papers was measured by the alpha particle imaging detector. In addition, we measured a Plutonium (Pu) sample (mainly 5.5 MeV alpha particles from 238Pu) obtained from a nuclear fuel facility by using of the same detector for comparison with the smear papers. The alpha spectrum was in the energy range of 5–6 MeV, which corresponds to the alpha particle energy of 238Pu (5.5 MeV). The correlation coefficient of the alpha spectra of the smear papers and the Pu sample had a strong positive linear relation. Moreover, the peak of 241Am was identified by gamma spectrum measurement. Based on these results, we report actual findings of alpha emitters in the FDNPP reactor buildings originating from nuclear fuels. The surface contamination level of alpha emitters exceeded 4 Bq/cm2.
A Matched Case-Control Study on the Association Between Colds, Depressive Symptoms during Pregnancy and Congenital Heart Disease in Northwestern China
Authors: Guo Leqian , Zhao Doudou , Zhang Ruo , Li Shanshan , Liu Rong , Wang Hongli , Dang Shaonong , Yan Hong 
Published: January 2019

AbstractThe purpose of this study was to explore the association between colds, depressive symptoms during pregnancy and offspring congenital heart disease (CHD). A 1:2 matching case-control study was conducted in Northwest China. Information was gathered by a structured questionnaire and was reviewed by investigators on the spot. Multivariate logistic regressions and nonlinear mixed effect model were performed. 614 cases and 1228 controls were available in this study. After adjusting for potential confounders, the colds during the entire pregnancy were associated with increased risk of offspring CHD (OR = 1.44(1.12–1.85)). Similarly, there was a higher depression score in CHD group than the control group (OR = 1.89(1.48–2.41)). In addition, the women with both colds and higher depression scores had a higher risk of offspring CHD (OR = 2.72(1.87–3.93)) than their counterparts with only colds (OR = 1.48(1.04–2.09)) or with only higher depression scores (OR = 1.94(1.37–2.74)). The combined effects were significant in the multiplication model (OR = 2.04(1.47–2.83)) but not in the additive model (S = 1.40(0.70–2.81), AP = 0.19(−0.15–0.53) and RERI = 0.55(−0.54–1.64)). In conclusion, the colds and depressive symptoms during pregnancy were found associated with increased risk of offspring CHD and we found for the first time that there existed a statistically multiplying interaction effect of colds and depression on increasing risk of offspring CHD.
Membrane damage mechanism contributes to inhibition of trans-cinnamaldehyde on Penicillium italicum using Surface-Enhanced Raman Spectroscopy (SERS)
Authors: Huang Fei , Kong Jie , Ju Jian , Zhang Ying , Guo Yahui , Cheng Yuliang , Qian He , Xie Yunfei , Yao Weirong 
Published: January 2019

AbstractThe antifungal mechanism of essential oils against fungi remains in the shallow study. In this paper, antifungal mechanism of trans-cinnamaldehyde against Penicillium italicum was explored. Trans-cinnamaldehyde exhibited strong mycelial growth inhibition against Penicillium italicum, with minimum inhibitory concentration of 0.313 μg/mL. Conventional analytical tests showed that trans-cinnamaldehyde changed the cell membrane permeability, which led to the leakage of some materials. Meanwhile, the membrane integrity and cell wall integrity also changed. Surface-enhanced Raman spectroscopy, an ultrasensitive and fingerprint method, was served as a bran-new method to study the antifungal mechanism. Characteristic peaks of supernatant obviously changed at 734, 1244, 1330, 1338 and 1466 cm−1. The Raman intensity represented a strong correlation with results from conventional methods, which made SERS an alternative to study antifungal process. All evidences implied that trans-cinnamaldehyde exerts its antifungal capacity against Penicillium italicum via membrane damage mechanism.
Screening Pyridine Derivatives against Human Hydrogen Sulfide-synthesizing Enzymes by Orthogonal Methods
Authors: Zuhra Karim , Sousa Pedro M. F. , Paulini Giulia , Lemos Ana Rita , Kalme Zenta , Bisenieks Imants , Bisenieks Egils , Vigante Brigita , Duburs Gunars , Bandeiras Tiago M. , Saso Luciano , Giuffrè Alessandro , Vicente João B. 
Published: January 2019

AbstractBiosynthesis of hydrogen sulfide (H2S), a key signalling molecule in human (patho)physiology, is mostly accomplished by the human enzymes cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (MST). Several lines of evidence have shown a close correlation between increased H2S production and human diseases, such as several cancer types and amyotrophic lateral sclerosis. Identifying compounds selectively and potently inhibiting the human H2S-synthesizing enzymes may therefore prove beneficial for pharmacological applications. Here, the human enzymes CBS, CSE and MST were expressed and purified from Escherichia coli, and thirty-one pyridine derivatives were synthesized and screened for their ability to bind and inhibit these enzymes. Using differential scanning fluorimetry (DSF), surface plasmon resonance (SPR), circular dichroism spectropolarimetry (CD), and activity assays based on fluorimetric and colorimetric H2S detection, two compounds (C30 and C31) sharing structural similarities were found to weakly inhibit both CBS and CSE: 1 mM C30 inhibited these enzymes by approx. 50% and 40%, respectively, while 0.5 mM C31 accounted for CBS and CSE inhibition by approx. 40% and 60%, respectively. This work, while presenting a robust methodological platform for screening putative inhibitors of the human H2S-synthesizing enzymes, highlights the importance of employing complementary methodologies in compound screenings.
The factors affecting a native obligate parasite, Cuscuta australis, in selecting an exotic weed, Humulus scandens, as its host
Authors: Wu Ai-Ping , Zhong Wen , Yuan Jin-Rui , Qi Liang-Yu , Chen Fa-Lin , Liang Yun-Shan , He Fei-Fei , Wang Yan-Hong 
Published: January 2019

AbstractIn weed management, using native parasites to control exotic weeds is considered a better alternative than classical biological control. But the risk must be assessed because of the potential damage caused by these agents. We conducted this project to investigate the mechanism driving the choice of a native obligate parasite, Cuscuta australis, between the exotic, Humulus scandens, and native plants as its host through field and pot experiments. The results showed that C. australis preferred the exotic weed over native (naturalized) hosts and caused a notable reduction in the biomass of H. scandens in the field. In contrast, the results of the pot experimentindicated that C. australis preferred a mix of native (naturalized) hosts over the exotic weed. Both texperiments indicated that the parasitic preference of C. australis was induced more by light irradiance than plant water, carbon (C), nitrogen (N) and phosphorus (P) contents, indicating that the native parasite can only be used to control H. scandens when the exotic weed forms mono-cultures or dominates the community. Accordingly, induction and release of C. australis to control H. scandens should be conducted with great caution.
Incorporation of ifosfamide into various essential oils -based nanoemulsions ameliorates its apoptotic effect in the cancers cells
Authors: Alkhatib Mayson H. , AlMotwaa Sahar M. , Alkreathy Huda M. 
Published: January 2019

AbstractThe chemotherapeutic drugs, loaded in nanocarriers, have recently attracted the pharmaceutical industries due to their limited adverse side effects. The objective of the current study was to incorporate the ifosfamide (IFO) into two different essential oils-based nanoemulsions, lemon (LEM-IFO) and salvia (SAL-IFO). The antiproliferation activities of the resulted formulas were evaluated in the MCF-7 breast cancer cells and HeLa cervical cancers cells. The cytotoxic effect of the NE formulas was detected by the MTT assay, DAPI stain and light microscopy. The z-average diameters range of LEM-IFO and SAL-IFO, determined by the zetasizer, were 49.15–61.81 nm and 56.64–64.62 nm, respectively. The half maximal inhibitory concentration (IC50) of LEM-IFO and SAL-IFO, applied into the HeLa cells, were 0.165 ± 0.025 and 0.141 ± 0.035 mM, respectively, whereas the IC50 of LEM-IFO and SAL-IFO subjected into the MCF-7 cells were 0.200 ± 0.005 mM and 0.270 ± 0.025 mM, respectively. The IC50 of the free IFO was markedly larger than LEM-IFO and SAL-IFO when applied into MCF-7 cells (9.20 ± 2.01 mM) and HeLa cells (7.69 ± 1.88 mM). Among the tested formulas, LEM-IFO and SAL-IFO have the greatest apoptotic effect on the MCF-7 and HeLa cells, respectively. Solubilizing the IFO in the essential oils-based NE has ameliorated the antitumor efficacy of IFO.
Sulfur isotopes ratio of atmospheric carbonyl sulfide constrains its sources
Authors: Angert Alon , Said-Ahmad Ward , Davidson Chen , Amrani Alon 
Published: January 2019

AbstractCarbonyl sulfide (COS) is the major long-lived sulfur bearing gas in the atmosphere, and is used to estimate the rates of regional and global (both past and current) photosynthesis. Sulfur isotope measurements (34S/32S ratio, δ34S) of COS may offer a way for improved determinations of atmospheric COS sources. However, measuring the COS δ34S at the atmospheric concentrations of ~0.5 ppb is challenging. Here we present high-accuracy δ34S measurements of atmospheric COS done by gas chromatograph (GC) connected to a multicollector inductively coupled plasma mass spectrometer (MC-ICPMS), after pre-concentrating from 2-liters of air. We showed that the precision of COS δ34S measurement for gas standards is ≤0.2‰, and that N2and CO2in the gas standard mixture had no effect on the measured δ34S. Natural air samples were collected in Israel and in the Canary Islands. The COS δ34S values in both locations were found to be 13.2 ± 0.6‰, and are believed to represent the background tropospheric value. This δ34S value is markedly different from the previously reported value of 4.9‰. We estimate the expected isotopic signature of COS sources and sinks, and use the δ34S value of atmospheric COS we measured to estimate that ~48% of it originates from the ocean.
Electronic and optical properties of lead-free hybrid double perovskites for photovoltaic and optoelectronic applications
Authors: Roknuzzaman Md , Zhang Chunmei , Ostrikov Kostya , Du Aijun , Wang Hongxia , Wang Lianzhou , Tesfamichael Tuquabo 
Published: January 2019

AbstractDeveloping of lead-free double perovskites have drawn significant interest for photovoltaics and optoelectronics as the materials have the potential to avoid toxicity and instability issues associated with lead-based organometallic perovskites. In this study, we report the optoelectronic properties of a new group of non-toxic lead-free organic-inorganic halide double perovskites composed of caesium (Cs), methylammonium (MA) or formamidinium (FA) with bismuth (Bi) and metal copper (Cu). We perform density functional theory investigations to calculate the structural, electronic and optical properties of 18 Pb-free compounds, ABiCuX6 [A = Cs2, (MA)2, (FA)2, CsMA, CsFA, MAFA; X = I, Br, Cl] to predict their suitability in photovoltaic and optoelectronic applications. We found that the considered compounds are semiconductors with a tunable band gap characteristics that are suitable for some devices like light emitting diodes. In addition to this, the high dielectric constant, high absorption, high optical conductivity and low reflectivity suggest that the materials have the potential in a wide range of optoelectronic applications including solar cells. Furthermore, we predict that the organic-inorganic hybrid double perovskite (FA)2BiCuI6 is the best candidate in photovoltaic and optoelectronic applications as the material has superior optical and electronic properties.