bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interrupted reprogramming of alveolar type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis
Authors: Guo Li , Karoubi Golnaz , Duchesneau Pascal , Aoki Fabio Gava , Shutova Maria V. , Rogers Ian , Nagy Andras , Waddell Thomas K. 
Published: August 2018

AbstractWe describe here an interrupted reprogramming strategy to generate “induced progenitor-like (iPL) cells” from alveolar epithelial type II (AEC-II) cells. A carefully defined period of transient expression of reprogramming factors (Oct4, Sox2, Klf4, and c-Myc (OSKM)) is able to rescue the limited in vitro clonogenic capacity of AEC-II cells, potentially by activation of a bipotential progenitor-like state. Importantly, our results demonstrate that interrupted reprogramming results in controlled expansion of cell numbers yet preservation of the differentiation pathway to the alveolar epithelial lineage. When transplanted to the injured lungs, AEC-II-iPL cells are retained in the lung and ameliorate bleomycin-induced pulmonary fibrosis. Interrupted reprogramming can be used as an alternative approach to produce highly specified functional therapeutic cell populations and may lead to significant advances in regenerative medicine.
Understanding the effects of education through the lens of biology
Authors: Sokolowski H. Moriah , Ansari Daniel 
Published: August 2018

AbstractEarly educational interventions aim to close gaps in achievement levels between children. However, early interventions do not eliminate individual differences in populations and the effects of early interventions often fade-out over time, despite changes of the mean of the population immediately following the intervention. Here, we discuss biological factors that help to better understand why early educational interventions do not eliminate achievement gaps. Children experience and respond to educational interventions differently. These stable individual differences are a consequence of biological mechanisms that support the interplay between genetic predispositions and the embedding of experience into our biology. Accordingly, we argue that it is not plausible to conceptualize the goals of educational interventions as both a shifting of the mean and a narrowing of the distribution of a particular measure of educational attainment assumed to be of utmost importance (such as a standardized test score). Instead of aiming to equalize the performance of students, the key goal of educational interventions should be to maximize potential at the individual level and consider a kaleidoscope of educational outcomes across which individuals vary. Additionally, in place of employing short-term interventions in the hope of achieving long-term gains, educational interventions need to be sustained throughout development and their long-term, rather than short-term, efficacy be evaluated. In summary, this paper highlights how biological research is valuable for driving a re-evaluation of how educational success across development can be conceptualized and thus what policy implications may be drawn.
Application of the fragment molecular orbital method to discover novel natural products for prion disease
Authors: Choi Jiwon , Kim Hyo-Jin , Jin Xuemei , Lim Hocheol , Kim Songmi , Roh In-Soon , Kang Hae-Eun , No Kyoung Tai , Sohn Hyun-Joo 
Published: August 2018

AbstractConformational conversion of the normal cellular isoform of the prion protein PrPC into an infectious isoform PrPSc causes pathogenesis in prion diseases. To date, numerous antiprion compounds have been developed to block this conversion and to detect the molecular mechanisms of prion inhibition using several computational studies. Thus far, no suitable drug has been identified for clinical use. For these reasons, more accurate and predictive approaches to identify novel compounds with antiprion effects are required. Here, we have applied an in silico approach that integrates our previously described pharmacophore model and fragment molecular orbital (FMO) calculations, enabling the ab initio calculation of protein-ligand complexes. The FMO-based virtual screening suggested that two natural products with antiprion activity exhibited good binding interactions, with hotspot residues within the PrPC binding site, and effectively reduced PrPSc levels in a standard scrapie cell assay. Overall, the outcome of this study will be used as a promising strategy to discover antiprion compounds. Furthermore, the SAR-by-FMO approach can provide extremely powerful tools in quickly establishing virtual SAR to prioritise compounds for synthesis in further studies.
A novel, non-invasive model for diagnosing liver fibrosis stage in patients with hepatocellular carcinoma
Authors: Ouyang Gao-Xiong , Zhang Yu-mei , Zhu Shao-Liang , Wang Peng , Ren Yuan , Li Jia-Hao , Liu Yu-Kai , Chen Jun , Xiang Bang-De , Li Le-Qun , Liu Jian-Yong , Zhang Zhi-Ming 
Published: August 2018

AbstractThe aim of this study was to investigate the diagnostic value of the platelet count-to-spleen volume ratio (PSR) for diagnosing hepatic fibrosis in patients with hepatocellular carcinoma (HCC). In this interim analysis of an on-going prospective study, 117 patients with HCC and with or without cirrhosis or fibrosis in different stages were analyzed. Fibrosis staging negatively correlated with PSR and the liver volume-to-spleen volume ratio (LSR), while it positively correlated with aspartate aminotransferase-to-platelet ratio index (APRI), Frons’ index, S-index and a fibrosis index based on four factors (FIB-4). The area under the receiver operating characteristic curve (AUROC) was significantly larger for PSR (0.777) than LSR (0.633, P = 0.002). Among patients with significant fibrosis, AUROC for PSR did not differ significantly from the AUROCs for APRI (0.789, P = 0.825), Frons’ index (0.674, P = 0.102), FIB-4 (0.704, P = 0.251) or S-index (0.696, P = 0.204). Among patients with severe fibrosis, AUROC was significantly higher for PSR (0.808) than for LSR (0.685, P = 0.003), Frons’ index (0.673, P = 0.014), FIB-4 (0.684, P = 0.029), or S-index (0.672, P = 0.016); in contrast, the AUROC for PSR was not significantly different from that for APRI (0.739, P = 0.215). Among patients with cirrhosis, AUROC was significantly higher for PSR (0.814) than for LSR (0.671, P = 0.001) or S-index (0.679, P = 0.022), while the AUROC for PSR did not differ significantly from those for APRI (0.711, P = 0.105), Frons’ index (0.722, P = 0.061) or FIB-4 (0.708, P = 0.079). Our results suggest that PSR may be a useful non-invasive model for diagnosing liver fibrosis stage in patients with HCC in China.
Exploring the potential of NTME/GC-MS, in the establishment of urinary volatomic profiles. Lung cancer patients as case study
Authors: Porto-Figueira Priscilla , Pereira Jorge , Miekisch Wolfram , Câmara José S. 
Published: August 2018

AbstractThe growing cancer incidence and mortality worldwide claims for the development of novel diagnostic strategies. In this study we aimed to explore the potential of an innovative methodology, based on a needle trap microextraction (NTME), combined with gas chromatography-mass spectrometry (GC-MS), as new approach to isolate and profile urinary volatile organic metabolites (VOMs) from lung cancer (LC) patients and healthy individuals (CTRL). In this context, different experimental parameters with influence of NTME extraction efficiency including, temperature, equilibration time, headspace volume, ionic strength, pH, effects of sample volume and stirring, were investigated and optimized. For the DVB/CarX/Car1000 needle trap device (NTD), the best results were obtained using 40 mL headspace of a 4-mL acidified (pH = 2) urine sample with 20% NaCl and an extraction temperature of 50 °C for 40 min of equilibration time. The stability of the isolated VOMs was investigated up to 72 h after extraction. From the VOMs identified, belonging namely to ketones, sulphur and benzene derivatives, 98 presented a frequency of occurrence above 90%. Data were processed by discriminant analysis, retrieving differentiated clusters for LC and CTRL groups. As far we are aware, this is the first study using NTME/GC-MS to establish urinary volatomic profiles. Preliminary results are very promising, as broad and comprehensive volatile profiles were obtained. Moreover, the extended storage stability of the NTD devices opens new opportunities for sampling other matrices in a wide range of applications.
Strengthening the efficacy of official food control improves Listeria monocytogenes prevention in fish-processing plants
Authors: Aalto-Araneda Mariella , Korkeala Hannu , Lundén Janne 
Published: August 2018

AbstractVacuum-packaged cold-salted and cold-smoked fish products are considered typical vehicles forListeria monocytogenes, the causative agent of the food-borne disease listeriosis, which is increasingly prevalent in the European Union. Efficacy of both the fish processing plant self-checking system and official food control conducted by authorities are crucial forL.monocytogenesprevention in the processing of these risky products. However, the impact of official control onL.monocytogenesprevention in the processing of fish products has not been extensively studied. We investigated the occurrence, control measures, and correction of non-compliances predisposing toL.monocytogenesin Finnish fish processing plants. The following features were associated withL.monocytogenesoccurrence: (a) frequency of non-compliances concerning processing machinery, (b) recurrence of non-compliances, and (c) frequency of non-compliances for which official control measures were requested by inspecting authorities. Official control of fish processing plants had focused on risky areas, but non-compliances were common and their correction exhibited deficiencies. We conclude thatL.monocytogenesprevention in fish processing can be enhanced by strengthening official food control measures and processing plant compliance. In particular, timely correction of all food safety violations must be improved.
Induction of Ptp2 and Cmp2 protein phosphatases is crucial for the adaptive response to ER stress in Saccharomyces cerevisiae
Authors: Mizuno Tomoaki , Nakamura Meyu , Irie Kenji 
Published: August 2018

AbstractExpression control of the protein phosphatase is critically involved in crosstalk and feedback of the cellular signaling. In the budding yeast ER stress response, multiple signaling pathways are activated and play key roles in adaptive reactions. However, it remains unclear how the expression level of the protein phosphatase is modulated during ER stress response. Here, we show that ER stress increases expression of Ptp2 tyrosine phosphatase and Cmp2 calcineurin phosphatase. Upregulation of Ptp2 is due to transcriptional activation mediated by Mpk1 MAP kinase and Rlm1 transcription factor. This induction is important for Ptp2 to effectively downregulate the activity of Hog1 MAP kinase. The budding yeast genome possesses two genes, CMP2 and CNA1, encoding the catalytic subunit of calcineurin phosphatase. CMP2 is more important than CNA1 not only in ER stress response, but also in salt stress response. Higher promoter activity of CMP2 contributes to its relative functional significance in ER stress response, but is less important for salt stress response. Thus, our results suggest that expression control of Ptp2 and Cmp2 protein phosphatases at the promoter level is crucial for adaptive responses to ER stress.
Groupwise image registration based on a total correlation dissimilarity measure for quantitative MRI and dynamic imaging data
Authors: Guyader Jean-Marie , Huizinga Wyke , Poot Dirk H. J. , van Kranenburg Matthijs , Uitterdijk André , Niessen Wiro J. , Klein Stefan 
Published: August 2018

AbstractThe most widespread technique used to register sets of medical images consists of selecting one image as fixed reference, to which all remaining images are successively registered. This pairwise scheme requires one optimization procedure per pair of images to register. Pairwise mutual information is a common dissimilarity measure applied to a large variety of datasets. Alternative methods, called groupwise registrations, have been presented to register two or more images in a single optimization procedure, without the need of a reference image. Given the success of mutual information in pairwise registration, we adapt one of its multivariate versions, called total correlation, in a groupwise context. We justify the choice of total correlation among other multivariate versions of mutual information, and provide full implementation details. The resulting total correlation measure is remarkably close to measures previously proposed by Huizinga et al. based on principal component analysis. Our experiments, performed on five quantitative imaging datasets and on a dynamic CT imaging dataset, show that total correlation yields registration results that are comparable to Huizinga’s methods. Total correlation has the advantage of being theoretically justified, while the measures of Huizinga et al. were designed empirically. Additionally, total correlation offers an alternative to pairwise mutual information on quantitative imaging datasets.
Stationary log-normal distribution of weights stems from spontaneous ordering in adaptive node networks
Authors: Uzan Herut , Sardi Shira , Goldental Amir , Vardi Roni , Kanter Ido 
Published: August 2018

AbstractExperimental evidence recently indicated that neural networks can learn in a different manner than was previously assumed, using adaptive nodes instead of adaptive links. Consequently, links to a node undergo the same adaptation, resulting in cooperative nonlinear dynamics with oscillating effective link weights. Here we show that the biological reality of stationary log-normal distribution of effective link weights in neural networks is a result of such adaptive nodes, although each effective link weight varies significantly in time. The underlying mechanism is a stochastic restoring force emerging from a spontaneous temporal ordering of spike pairs, generated by strong effective link preceding by a weak one. In addition, for feedforward adaptive node networks the number of dynamical attractors can scale exponentially with the number of links. These results are expected to advance deep learning capabilities and to open horizons to an interplay between adaptive node rules and the distribution of network link weights.
Yeast quality in juvenile diet affects Drosophila melanogaster adult life traits
Authors: Grangeteau Cédric , Yahou Fairouz , Everaerts Claude , Dupont Sébastien , Farine Jean-Pierre , Beney Laurent , Ferveur Jean-François 
Published: August 2018

AbstractDiet quality is critical for animal development and survival. Fungi can provide nutrients that are essential to organisms that are unable to synthetize them, such as ergosterol in Drosophila melanogaster. Drosophila studies examining the influence of yeast quality in the diet have generally either provided the diet over the whole life span (larva to adult) or during the adult stage and have rarely focussed on the juvenile diet. Here, we tested the effect of yeast quality in the larval diet on pre-adult development and adult weight, survival, reproduction and food preference. The yeast Saccharomyces cerevisiae was added in three forms in three treatments—live, heated or dried—to food used as the juvenile diet or was not added (empty treatment). Adults resulting from the larvae raised on these four juvenile diets were all maintained on a similar standard laboratory food diet. Our data indicate that yeast quality in the juvenile diet affects larva-to-pupa—but not pupa-to-adult—development. Importantly, adult survival, food preference, mating behaviour and cuticular pheromones strongly varied with the juvenile diet. Therefore, the variation of yeast quality in the pre-adult Drosophila diet affects key adult life traits involved in food search, reproduction and survival.
Diabetes und Revaskularisation
Authors: Reith Sebastian , Schächinger Volker 
Published: August 2018

ZusammenfassungPatienten mit Diabetes mellitus haben im Vergleich zur Normalpopulation ein signifikant erhöhtes Risiko, kardiovaskuläre Ereignisse zu erleiden. Durch spezifische diabetesassoziierte pathophysiologische Veränderungen schreitet die koronare Atherosklerose bei Patienten mit Diabetes mellitus in der Regel schneller und diffuser voran. Mithilfe des SYNTAX-Scores können der morphologische Schweregrad der koronaren Herzerkrankung graduiert und somit die optimale Revaskularisationsstrategie festgelegt werden. Diabetische Patienten mit einer komplexen Koronar- und Stenoseanatomie profitieren, sofern das operative Risiko vertretbar ist, am ehesten von einer aortokoronaren Bypassoperation. Bei weniger komplexer KHK stellt die perkutane Koronarintervention eine valide Therapiealternative dar, hier sollten heutzutage aber ausschließlich medikamentenbeschichtete Stents der 2. Generation verwendet werden.
Metabolic Determinants of Impaired Pulmonary Function in Patients with Newly Diagnosed Type 2 Diabetes Mellitus
Authors: Röhling Martin , Pesta Dominik , Markgraf Daniel , Strassburger Klaus , Knebel Birgit , Burkart Volker , Szendroedi Julia , Müssig Karsten , Roden Michael ,   for the GDS study group
Published: August 2018

Abstract
Aims Impaired lung function associates with deterioration of glycemic control and diabetes-related oxidative stress in long-standing type 2 diabetes. We hypothesized that recent-onset type 2 diabetes patients exhibit abnormal pulmonary function when compared to glucose-tolerant controls and that the frequencies of single-nucleotide polymorphisms (SNPs), known to associate with lung dysfunction, are different between both groups.
Methods Type 2 diabetes patients with a known disease duration<1 year (n=34) had similar age, sex distribution and BMI as overweight controls (n=26). Lung function was assessed by spirometry comprising predicted forced vital capacity (FVC%), predicted forced expiratory volume in one second (FEV1%) and the FEV1/FVC ratio. Multivariable linear regressions were performed to investigate group differences, which were adjusted for potential confounders such as age, sex, BMI, height and smoking status. SNP genotyping was conducted using real-time polymerase chain reaction-based allelic discrimination.
Results Patients with type 2 diabetes had lower FEV1%, FEV1/FVC and VO2max (all p<0.05). Among patients with type 2 diabetes, FEV1% correlated positively with VO2max (r=0.40, p<0.05) and FEV1/FVC correlated negatively with HbA1c (r=−0.49, p<0.01). Regression analyses across the whole cohort indicated that the group differences in FEV1/FVC can be explained by the confounding effect of HbA1c. The frequencies of the SNPs rs1042713, rs1079572, rs11172113, rs12504628, rs1422795, rs1481345, rs2235910, rs2277027, rs2284746, rs4341, rs7068966, rs925284, rs993925 and rs3824658 did not differ between both groups.
Conclusions Recent-onset type 2 diabetes patients exhibit reductions in features of pulmonary function, which might be at least in part resulting from glucotoxicity.
Levels of Glucagon-like Peptide 1 are Decreased in Macrosomic Neonates from Non-Diabetic Mothers
Authors: Aktulay Ayla , Engin-Ustun Yaprak , Yasar Ozlem , Yilmaz Canan , Erkaya Salim , Ozgu-Erdinc A. 
Published: August 2018

AbstractGlucagon-like peptide 1 (GLP-1) is a gut-derived peptide with insulin-like effects. Our aim was to analyze cord blood GLP-1 levels of macrosomic and appropriate-gestational-age (AGA) neonates from non-diabetic mothers. A case-control study was conducted with 22 term macrosomic neonates (birth weight≥4000 g) and 22 AGA (birth weight>10th percentile and<4000 g) pregnancies. Cord blood GLP-1 levels of neonates were measured. There were no significant differences in maternal age, gestational age and gravida between the 2 groups. Umbilical cord blood GLP-1 levels were significantly lower in macrosomic neonates (6.9±2.9 pg/mL) compared with control group (10.3±3.7 pg/mL) (p=0.002). Binary logistic regression analysis showed only the maternal BMI to be an independent statistically significant predictor of macrosomia (odds ratio=2.459; 95% CI, 1.170–5.170; P=0.018). The results of our study revealed decreased GLP-1 levels in macrosomic neonates, and maternal BMI was an independent predictor of macrosomia.
Prostaglandin E2 Activates NLRP3 Inflammasome in Endothelial Cells to Promote Diabetic Retinopathy
Authors: Wang Yixin , Tao Jianxin , Yao Yong 
Published: August 2018

AbstractProliferative diabetic retinopathy (PDR) is the leading cause of blindness and accounts for approximately 12% of all new cases of blindness. Prostaglandin E2 (PGE2) and nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inﬂammasomes have been long considered to be associated with PDR. Levels of pro-inflammatory mediators were examined by Enzyme-linked immunosorbent assay (ELISA) measurements. PGE2 levels were analyzed by using the Prostaglandin E2 Monoclonal EIA Kit. Human retinal microvascular endothelial cells (HRMECs) were stained with Annexin V/propidium iodide and analyzed by ﬂow cytometry for testing the apoptosis. Expression levels of NLRP3 inflammasome components under various conditions were detected by Western blot and real-time PCR. Inﬂammasome markers and PGE2 were highly expressed in the vitreous of PDR patients. PGE2 and NLRP3 induced apoptosis of HRMECs. PGE2 upregulated the expression of NLRP3 inﬂammasome components and inﬂammatory chemokines. Knockdown of NLRP3 attenuated the expression of NLRP3 inﬂammasome components and inhibited the effect of PGE2. Our results suggest that PGE2 levels and NLRP3 inﬂammasome activation are closely related to the pathogenesis of PDR and nonsteroidal anti-inﬂammatory drugs may have a potential therapeutic effect on PDR.
Mechanism of Cepharanthine Cytotoxicity in Human Ovarian Cancer Cells
Authors: Payon Vilawan , Kongsaden Chanaporn , Ketchart Wannarasmi , Mutirangura Apiwat , Wonganan Piyanuch 
Published: August 2018

AbstractCepharanthine (CEP), a medicinal product derived from Stephania cephalantha Hayata, possesses a potent cytotoxicity against several types of cancers. Recently, we have found that CEP could efficiently inhibit the growth of mutated p53 colon cancer cells, which are often resistant to commonly used chemotherapeutic agents. In this study, we evaluated the cytotoxic effect and the underlying mechanisms of CEP on both chemosensitive CaOV-3 and chemoresistant OVCAR-3 ovarian cancer cell lines. The present study demonstrated that CEP significantly inhibited the growth of CaOV-3 and OVCAR-3 cells in a time- and concentration-dependent manner. CEP arrested CaOV-3 and OVCAR-3 cells in the G1 phase and S phase of cell cycle, respectively. Western blot analysis demonstrated that CEP markedly increased the expression of p21Waf1 protein and decreased the expression of cyclins A and D proteins in both CaOV-3 and OVCAR-3 cells. Additionally, CEP triggered apoptotic cell death in OVCAR-3 cells. Taken together, the above results suggest that CEP is a promising anticancer drug for ovarian cancer.