bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apigenin potentiates TRAIL therapy of non-small cell lung cancer via upregulating DR4/DR5 expression in a p53-dependent manner
Authors: Chen Minghui , Wang Xueshi , Zha Daolong , Cai Fangfang , Zhang Wenjing , He Yan , Huang Qilai , Zhuang Hongqin , Hua Zi-Chun 
Published: October 2016

AbstractApigenin (APG) is an edible plant-derived flavonoid that shows modest antitumor activities in vitro and in vivo. APG treatment results in cell growth arrest and apoptosis in various types of tumors by modulating several signaling pathways. In the present study, we evaluated interactions between APG and TRAIL in non-small cell lung cancer (NSCLC) cells. We observed a synergistic effect between APG and TRAIL on apoptosis of NSCLC cells. A549 cells and H1299 cells were resistant to TRAIL treatment alone. The presence of APG sensitized NSCLC cells to TRAIL-induced apoptosis by upregulating the levels of death receptor 4 (DR4) and death receptor 5 (DR5) in a p53-dependent manner. Consistently, the pro-apoptotic proteins Bad and Bax were upregulated, while the anti-apoptotic proteins Bcl-xl and Bcl-2 were downregulated. Meanwhile, APG suppressed NF-κB, AKT and ERK activation. Treatment with specific small-molecule inhibitors of these pathways enhanced TRAIL-induced cell death, mirroring the effect of APG. Furthermore, using a mouse xenograft model, we demonstrated that the combined treatment completely suppressed tumor growth as compared with APG or TRAIL treatment alone. Our results demonstrate a novel strategy to enhance TRAIL-induced antitumor activity in NSCLC cells by APG via inhibition of the NF-κB, AKT and ERK prosurvival regulators.
Diabetes-linked transcription factor HNF4α regulates metabolism of endogenous methylarginines and β-aminoisobutyric acid by controlling expression of alanine-glyoxylate aminotransferase 2
Authors: Burdin Dmitry V. , Kolobov Alexey A. , Brocker Chad , Soshnev Alexey A. , Samusik Nikolay , Demyanov Anton V. , Brilloff Silke , Jarzebska Natalia , Martens-Lobenhoffer Jens , Mieth Maren , Maas Renke , Bornstein Stefan R. , Bode-Böger Stefanie M. , Gonzalez Frank , Weiss Norbert , Rodionov Roman N. 
Published: October 2016

AbstractElevated levels of circulating asymmetric and symmetric dimethylarginines (ADMA and SDMA) predict and potentially contribute to end organ damage in cardiovascular diseases. Alanine-glyoxylate aminotransferase 2 (AGXT2) regulates systemic levels of ADMA and SDMA, and also of beta-aminoisobutyric acid (BAIB)-a modulator of lipid metabolism. We identified a putative binding site for hepatic nuclear factor 4 α (HNF4α) in AGXT2 promoter sequence. In a luciferase reporter assay we found a 75% decrease in activity of Agxt2 core promoter after disruption of the HNF4α binding site. Direct binding of HNF4α to Agxt2 promoter was confirmed by chromatin immunoprecipitation assay. siRNA-mediated knockdown of Hnf4a led to an almost 50% reduction in Agxt2 mRNA levels in Hepa 1–6 cells. Liver-specific Hnf4a knockout mice exhibited a 90% decrease in liver Agxt2 expression and activity, and elevated plasma levels of ADMA, SDMA and BAIB, compared to wild-type littermates. Thus we identified HNF4α as a major regulator of Agxt2 expression. Considering a strong association between human HNF4A polymorphisms and increased risk of type 2 diabetes our current findings suggest that downregulation of AGXT2 and subsequent impairment in metabolism of dimethylarginines and BAIB caused by HNF4α deficiency might contribute to development of cardiovascular complications in diabetic patients.
Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography
Authors: Kerckhofs G. , Durand M. , Vangoitsenhoven R. , Marin C. , Van der Schueren B. , Carmeliet G. , Luyten F. P. , Geris L. , Vandamme K. 
Published: October 2016

AbstractHigh resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging.
Structural characterization of the circadian clock protein complex composed of KaiB and KaiC by inverse contrast-matching small-angle neutron scattering
Authors: Sugiyama Masaaki , Yagi Hirokazu , Ishii Kentaro , Porcar Lionel , Martel Anne , Oyama Katsuaki , Noda Masanori , Yunoki Yasuhiro , Murakami Reiko , Inoue Rintaro , Sato Nobuhiro , Oba Yojiro , Terauchi Kazuki , Uchiyama Susumu , Kato Koichi 
Published: October 2016

AbstractThe molecular machinery of the cyanobacterial circadian clock consists of three proteins: KaiA, KaiB, and KaiC. Through interactions among the three Kai proteins, the phosphorylation states of KaiC generate circadian oscillations in vitro in the presence of ATP. Here, we characterized the complex formation between KaiB and KaiC using a phospho-mimicking mutant of KaiC, which had an aspartate substitution at the Ser431 phosphorylation site and exhibited optimal binding to KaiB. Mass-spectrometric titration data showed that the proteins formed a complex exclusively in a 6:6 stoichiometry, indicating that KaiB bound to the KaiC hexamer with strong positive cooperativity. The inverse contrast-matching technique of small-angle neutron scattering enabled selective observation of KaiB in complex with the KaiC mutant with partial deuteration. It revealed a disk-shaped arrangement of the KaiB subunits on the outer surface of the KaiC C1 ring, which also serves as the interaction site for SasA, a histidine kinase that operates as a clock-output protein in the regulation of circadian transcription. These data suggest that cooperatively binding KaiB competes with SasA with respect to interaction with KaiC, thereby promoting the synergistic release of this clock-output protein from the circadian oscillator complex.
Specific autoantigens identified by sera obtained from mice that are immunized with testicular germ cells alone
Authors: Terayama Hayato , Hirai Shuichi , Naito Munekazu , Qu Ning , Katagiri Chiaki , Nagahori Kenta , Hayashi Shogo , Sasaki Hiraku , Moriya Shota , Hiramoto Masaki , Miyazawa Keisuke , Hatayama Naoyuki , Li Zhong-Lian , Sakabe Kou , Matsushita Masayuki , Itoh Masahiro 
Published: October 2016

AbstractThere are various autoimmunogenic antigens (AIs) in testicular germ cells (TGCs) recognized as foreign by the body’s immune system. However, there is little information of TGC-specific AIs being available. The aim of this study is to identify TGC-specific AIs. We have previously established that immunization using viable syngeneic TGC can also induce murine experimental autoimmune orchitis (EAO) without using any adjuvant. This study is to identify TGC-specific AIs by TGC liquid chromatography–tandem mass spectrometry analysis, followed by two-dimensional gel electrophoresis that reacted with serum IgG from EAO mice. In this study, we identified 11 TGC-specific AIs that reacted with serum from EAO mice. Real-time RT-PCR analysis showed that the mRNA expressions of seven TGC-specific AIs were significantly higher in only mature testis compared to other organs. Moreover, the recombinant proteins of identified 10 (except unnamed protein) TGC-specific AIs were created by using human embryonic kidney 293 (HEK293) cells and these antigencities were reconfirmed by Western blot using EAO serum reaction. These results indicated Atp6v1a, Hsc70t, Fbp1 and Dazap1 were candidates for TGC-specific AIs. Identification of these AIs will facilitate new approaches for understanding infertility and cancer pathogenesis and may provide a basis for the development of novel therapies.
Activation of heat shock response to treat obese subjects with type 2 diabetes: a prospective, frequency-escalating, randomized, open-label, triple-arm trial
Authors: Kondo Tatsuya , Goto Rieko , Ono Kaoru , Kitano Sayaka , Suico Mary Ann , Sato Miki , Igata Motoyuki , Kawashima Junji , Motoshima Hiroyuki , Matsumura Takeshi , Kai Hirofumi , Araki Eiichi 
Published: October 2016

AbstractActivation of heat shock response (HSR) improves accumulated visceral adiposity and metabolic abnormalities in type 2 diabetes. To identify the optimal intervention strategy of the activation of the HSR provided by mild electrical stimulation (MES) with heat shock (HS) in type 2 diabetes. This study was a prospective, frequency-escalating, randomized, open-label, triple-arm trial in Japan. A total of 60 obese type 2 diabetes patients were randomized into three groups receiving two, four, or seven treatments per week for 12 weeks. No adverse events were identified. MES + HS treatment (when all three groups were combined), significantly improved visceral adiposity, glycemic control, insulin resistance, systemic inflammation, renal function, hepatic steatosis and lipid profile compared to baseline. The reduction in HbA1c was significantly greater among those treated four times per week (−0.36%) or seven times per week (−0.65%) than among those treated two times per week (−0.10%). The relative HbA1c levels in seven times per week group was significantly decreased when adjusted by two times per week group (−0.55%. p = 0.001). This research provides the positive impact of MES + HS to treat obese patients with type 2 diabetes mellitus.
Increased human occupation and agricultural development accelerates the population contraction of an estuarine delphinid
Authors: Lin Wenzhi , Karczmarski Leszek , Xia Jia , Zhang Xiyang , Yu Xinjian , Wu Yuping 
Published: October 2016

AbstractOver the past few thousand years, human development and population expansion in southern China have led to local extirpation and population contraction of many terrestrial animals. At what extent this early human-induced environmental change has also affected coastal marine species remains poorly known. We investigated the demographic history of the Indo-Pacific humpback dolphin (Sousa chinensis) in the Pearl River Delta (PRD); an obligatory inshore species known for its susceptibility to anthropogenic impacts in one of China’s most developed coastal regions. Although the deltaic evolution of PRD has been influenced by climate since the Holocene, ~74% reduction of the dolphin’s effective population size occurred within the last 2000 years, consistent with ~61% habitat contraction during this period. This considerable and recent population contraction may have been due to land use practices and deforestation in the upper/middle Pearl River region, all leading to increasing sedimentation rate in the estuarine area. As anthropogenic impacts within the drainage of Pearl River affected a vast area, coastal dolphins and large terrestrial mammals in southern China may share a similar demographic history, whilst the demographic and biogeographic history of the PRD humpback dolphins may be symptomatic of similar processes that this species may have undergone elsewhere in the region.
Association between polygenic risk for schizophrenia, neurocognition and social cognition across development
Authors: Germine L , Robinson E B , Smoller J W , Calkins M E , Moore T M , Hakonarson H , Daly M J , Lee P H , Holmes A J , Buckner R L , Gur R C , Gur R E 
Published: October 2016

AbstractBreakthroughs in genomics have begun to unravel the genetic architecture of schizophrenia risk, providing methods for quantifying schizophrenia polygenic risk based on common genetic variants. Our objective in the current study was to understand the relationship between schizophrenia genetic risk variants and neurocognitive development in healthy individuals. We first used combined genomic and neurocognitive data from the Philadelphia Neurodevelopmental Cohort (4303 participants ages 8–21 years) to screen 26 neurocognitive phenotypes for their association with schizophrenia polygenic risk. Schizophrenia polygenic risk was estimated for each participant based on summary statistics from the most recent schizophrenia genome-wide association analysis (Psychiatric Genomics Consortium 2014). After correction for multiple comparisons, greater schizophrenia polygenic risk was significantly associated with reduced speed of emotion identification and verbal reasoning. These associations were significant by age 9 years and there was no evidence of interaction between schizophrenia polygenic risk and age on neurocognitive performance. We then looked at the association between schizophrenia polygenic risk and emotion identification speed in the Harvard/MGH Brain Genomics Superstruct Project sample (695 participants ages 18–35 years), where we replicated the association between schizophrenia polygenic risk and emotion identification speed. These analyses provide evidence for a replicable association between polygenic risk for schizophrenia and a specific aspect of social cognition. Our findings indicate that individual differences in genetic risk for schizophrenia are linked with the development of aspects of social cognition and potentially verbal reasoning, and that these associations emerge relatively early in development.
Exome chip analyses in adult attention deficit hyperactivity disorder
Authors: Zayats T , Jacobsen K K , Kleppe R , Jacob C P , Kittel-Schneider S , Ribasés M , Ramos-Quiroga J A , Richarte V , Casas M , Mota N R , Grevet E H , Klein M , Corominas J , Bralten J , Galesloot T , Vasquez A A , Herms S , Forstner A J , Larsson H , Breen G , Asherson P , Gross-Lesch S , Lesch K P , Cichon S , Gabrielsen M B , Holmen O L , Bau C H D , Buitelaar J , Kiemeney L , Faraone S V , Cormand B , Franke B , Reif A , Haavik J , Johansson S 
Published: October 2016

AbstractAttention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E−06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E−08), whereNT5DC1andCOL10A1reside; theSEC23IPlocus (P=6.47E−07); thePSDlocus (P=7.58E−08) andZCCHC4locus (P=1.79E−06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 inPPP2R2B(odds ratio=0.81,P=1.61E−05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1,PSD,SEC23IPandZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.
Relations causales entre santé et travail
Authors: Barnay Thomas 
Published: October 2016

Les économistes s’intéressent aux liens entre santé et travail en examinant en particulier trois relations : l’effet négatif de la santé dégradée sur la position sur le marché du travail, l’influence positive du travail sur la santé mais aussi le rôle délétère de certaines conditions de travail et d’emploi sur l’état de santé. Si la littérature internationale est abondante sur la question, la littérature française est plus récente. En France, les effets d’événements de santé sont plus pénalisants sur la trajectoire professionnelle lorsqu’ils surviennent en seconde partie de carrière invitant à la mise en place d’une prévention précoce en entreprise. Les études soulignent aussi des populations fragiles face aux ruptures de trajectoires professionnelles ou de santé telles que les hommes anxieux.
Zur Verwendung des sozioökonomischen Status in der Gesundheitsforschung am Beispiel Rückenschmerz – systematisches Review
Authors: Fliesser M , Klipker K , Wippert P.-M 
Published: October 2016

Zusammenfassung
Ziel der Studie Welche Indikatoren zur Messung des SES werden in sozialepidemiologischen Studien zum Thema Rückenschmerzen wie häufig eingesetzt, wie wird dies begründet und zeigen sich systematische Unterschiede in den Ergebnissen abhängig von der verwendeten Operationalisierungsweise?
Methodik Um diese Frage zu beantworten wurde ein systematisches Literaturreview durchgeführt.
Ergebnisse 13 Aufsätze genügten den Einschlusskriterien. Dabei zeigt sich, dass Bildung am häufigsten als Indikator für den SES verwendet wird gefolgt von Einkommen, Berufsklasse, Berufskategorie und mehrdimensionalem Index. 8 Studien verwendeten mehr als einen Indikator. Begründet wurde die Auswahl in 2 Studien. Ein Vergleich der Effektgrößen der in den unterschiedlichen Studien verwendeten Indikatoren zeigt kein einheitliches Bild.
Schlussfolgerungen Es ist zu hinterfragen, inwieweit die Verwendung des SES als globales Maß sinnvoll ist. Gemäß den hier vorliegenden Ergebnissen ist zu empfehlen anstelle des SES die jeweils verwendeten Indikatoren zu benennen und, gerade aufgrund der selten erfolgten Begründung, keine über die jeweiligen Indikatoren hinausgehenden Vermutungen anzustellen.
CLIL and SLA
Authors: García Mayo María del Pilar , Basterrechea María 
Published: October 2016

Abstract
The Interaction Hypothesis is one of the explanations for second language acquisition (SLA) (Hatch 1978; Long 1983). Numerous studies have shown that interaction facilitates SLA because learners have the opportunity to negotiate language input, receive feedback and modify their output (Long 1996; Pica 2013). However, there is little experimental research on interaction from this perspective in Content and Language Integrated Learning (CLIL) settings. The main goal of this chapter is to provide an overview of the main constructs of the interactionist framework and to see how they have been researched in studies that analyze the interlanguage of CLIL learners regarding their negotiation routines, attention to form and corrective feedback episodes.
Genre and appraisal in CLIL history texts
Authors: McCabe Anne , Whittaker Rachel 
Published: October 2016

Abstract
This chapter offers a perspective on texts written in a CLIL class, highlighting the role of the interpersonal meanings covered by the appraisal framework (Martin & White 2005) in constructing the different genres of history, which are not only factual, but also include assigning value and indicating point of view. An analysis of appraisal in an 11,000-word longitudinal corpus of CLIL secondary student writing shows how texts are more or less successful in their selection of features from the Appraisal systems as they respond to prompts, the higher-rated texts creating a more appropriate voice for the genre (Coffin 2006). Awareness of the categories of interpersonal meanings can allow teachers to make genre expectations explicit, helping improve student writing.
Assessment for learning in CLIL classroom discourse
Authors: Pascual Irene , Basse Rachel 
Published: October 2016

Abstract
This chapter explores the significance of metacognitive questions in primary CLIL classrooms in which teachers implement Assessment for Learning (AfL), a methodology which requires the teacher to help students assess learning gaps and work toward closing them (Black & Wiliam 1998a, 1998b; Black et al. 2003). We present illustrative data from a study comprising 9 AfL lessons belonging to a larger corpus. These sessions were analyzed qualitatively, focusing on extracts featuring metacognitive questions and how they affected teacher-student interaction. Using examples from the data, we show how metacognitive questions, as essential to an AfL approach, encourage students to reflect upon and verbalize their learning processes. Furthermore, they engage students in peer‑ and self-assessment, which also contributes to the awareness of learning gaps and prompts motivation to fill these gaps.
Problems for Mainstream Evidentialism
Authors: Piazza Tommaso 
Published: October 2016

AbstractEvidentialism says that a subject S’s justification is entirely determined by S’s evidence. The plausibility of evidentialism depends on (1) what kind of entities constitute a subject S’s evidence and (2) what one takes the support relation to consist in. Conee and Feldman’s mainstream evidentialism (ME) incorporates a psychologist answer to (1) and an explanationist answer to (2). ME naturally accommodates perceptual justification. However, it does not accommodate intuitive cases of inferential justification. In the second part of the paper, I consider and reject a reply based on a refined explanationist theory of the support relation proposed by K McCain.