bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing energy intake misreporting and its effects on intake estimations, in the Portuguese adult population
Authors: Magalhães Vânia , Severo Milton , Torres Duarte , Ramos Elisabete , Lopes Carla ,   by IAN-AF Consortium
Published: September 2019

AbstractObjective:The aim of the current study was to evaluate energy intake misreporting prevalence, its associated factors and its effects on nutrient intake, in the Portuguese population aged from 18 to 84 years.Design:Cross-sectional study.Setting:Portugal.Subjects:Adults participants from the National Food, Nutrition and Physical Activity Survey, IAN-AF, 2015–2016, who provided two complete 24 h dietary recall and complete covariate information.Results:Under, plausible and over-reporters were identified according to the Goldberg method. Total misreporting prevalence was 29·9 %, being 28·5 % of under-reporting and 1·4 % of over-reporting. The current study found higher odds of being classified as an under-reporter especially in participants with higher BMI and in those who self-reported health perception status as non-favourable. Energy intake estimation increases by 853.5 kJ/d (204 kcal/d) when misreporters are excluded, and the same tendency is observed for macro and micronutrients. It is worth mentioning that the prevalence of inadequacy for protein intake decreases by about 5 % when considering plausible reporters.Conclusions:The exclusion of misreporters has a small impact on the crude energy and nutrient estimates as well as on assessing the contribution of nutrients to total energy intake. However, a moderate impact was observed in the estimation of nutrient inadequacy prevalence.
Food cultures and aging: a qualitative study of grandparents’ food perceptions and influence of food choice on younger generations
Authors: Criss Shaniece , Horhota Michelle , Wiles Kayla , Norton Julia , St. Hilaire Kyle J , Short Mary Anne , Blomquist Kerstin K 
Published: September 2019

AbstractObjective:To explore food perceptions among grandparents and understand the influence of these perceptions on food choice for the younger generations in their family.Design:Qualitative methodology, thematic analysis of the transcripts from fourteen focus groups.Setting:Grandparents in the southern region of the United States.Subjects:Participants were fifty-eight Black, Hispanic, and White grandparents, predominantly women (72%), ranging in age from 44–86 years (mean age = 65·4 (sd 9·97) years).Results:Grandparents’ perceptions related to personal food choice were related to health issues and the media. Grandparents’ perceived influence on their children’s and grandchildren’s food choices was described through the themes of proximity and power (level of influence based on an interaction of geographic proximity to grandchildren and the power given to them by their children and grandchildren to make food decisions), healthy v. unhealthy spoiling, cultural food tradition, and reciprocal exchange of knowledge.Conclusion:Our results highlight areas for future research including nutrition interventions for older adults as well as factors that may be helpful to consider when engaging grandparents concerning food decisions for younger generations to promote health. Specifically, power should be assessed as part of a holistic approach to addressing dietary influence, the term ‘healthy spoiling’ can be used to reframe notions of traditional spoiling, and the role of cultural food tradition should be adapted differently by race.
Aberrant HER3 ligand heregulin-expressing head and neck squamous cell carcinoma is resistant to anti-EGFR antibody cetuximab, but not second-generation EGFR-TKI
Authors: Yonesaka Kimio , Tanaka Kaoru , Kitano Mutsukazu , Kawakami Hisato , Hayashi Hidetoshi , Takeda Masayuki , Sakai Kazuko , Nishio Kazuto , Doi Katsumi , Nakagawa Kazuhiko 
Published: September 2019

AbstractThe anti-epidermal growth factor receptor (EGFR) antibody cetuximab is standard therapy for head and neck squamous cell carcinoma (HNSCC). However, most HNSCC tumors are resistant to it and require alternative treatments. Here, we explored the mechanism of cetuximab resistance and evaluated its clinical relevance in HNSCC. An unbiased comprehensive transcriptome analysis was performed on cetuximab-resistant HNSCC FaDuCR cells. The causative resistance genome was knocked down with siRNA, cell signaling was immunologically analyzed, and drug efficacy was evaluated in vitro and in vivo. The mRNA in situ hybridization (ISH) of the causative genome was performed using 28 excised HNSCC tumors and its relationship with cetuximab efficacy was analyzed. FaDuCR cells were resistant to cetuximab, whereas parental FaDu cells were susceptible to it. FaDuCR cells expressed consistently higher levels of phosphorylated Akt than FaDu cells despite cetuximab exposure. A comprehensive transcriptome analysis revealed that the HER3-ligand heregulin was upregulated in FaDuCR cells compared to FaDu cells. Heregulin knockdown in FaDuCR cells repressed HER3 and Akt phosphorylation and recovered cetuximab anticancer efficacy. In contrast, pan-HER family tyrosine kinase inhibitors such as afatinib decreased HER3 and Akt phosphorylation in FaDuCR cells and inhibited FaDuCR tumor growth. Two of the 28 HNSCC tumor samples presented aberrant heregulin expression comparable to that of FaDuCR cells and were resistant to cetuximab therapy. In HNSCC, heregulin-mediated HER3-Akt activation causes resistance to cetuximab but not to second-generation EGFR-tyrosine kinase inhibitors. Subpopulations with aberrant heregulin-expressing HNSCC might be resistant to cetuximab.
TXNDC12 promotes EMT and metastasis of hepatocellular carcinoma cells via activation of β-catenin
Authors: Yuan Kefei , Xie Kunlin , Lan Tian , Xu Lin , Chen Xiangzheng , Li Xuefeng , Liao Mingheng , Li Jiaxin , Huang Jiwei , Zeng Yong , Wu Hong 
Published: September 2019

Abstract
Metastasis is one of the main contributors to the poor prognosis of hepatocellular carcinoma (HCC). However, the underlying mechanism of HCC metastasis remains largely unknown. Here, we showed that TXNDC12, a thioredoxin-like protein, was upregulated in highly metastatic HCC cell lines as well as in portal vein tumor thrombus and lung metastasis tissues of HCC patients. We found that the enforced expression of TXNDC12 promoted metastasis both in vitro and in vivo. Subsequent mechanistic investigations revealed that TXNDC12 promoted metastasis through upregulation of the ZEB1-mediated epithelial–mesenchymal transition (EMT) process. We subsequently showed that TXNDC12 overexpression stimulated the nuclear translocation and activation of β-catenin, a positive transcriptional regulator of ZEB1. Accordingly, we found that TXNDC12 interacted with β-catenin and that the thioredoxin-like domain of TXNDC12 was essential for the interaction between TXNDC12 and β-catenin as well as for TXNDC12-mediated β-catenin activation. Moreover, high levels of TXNDC12 in clinical HCC tissues correlated with elevated nuclear β-catenin levels and predicted worse overall and disease-free survival. In summary, our study demonstrated that TXNDC12 could activate β-catenin via protein–protein interaction and promote ZEB1-mediated EMT and HCC metastasis.
LncRNA SNHG14/miR-5590-3p/ZEB1 positive feedback loop promoted diffuse large B cell lymphoma progression and immune evasion through regulating PD-1/PD-L1 checkpoint
Authors: Zhao Lina , Liu Ye , Zhang Jingbo , Liu Yan , Qi Qi 
Published: September 2019

AbstractDiffuse large B cell lymphoma (DLBCL) is the commonest disorder derived from the B-lymphocytes. Inhibiting the immune checkpoint through naturalizing programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) is proved to be a successful therapeutic regime for lymphoma. Long non-coding RNAs (lncRNAs) are unceasingly reported to be promising biological targets for the cancer therapies. This study planned to explore the regulation of small nucleolar RNA host gene 14 (SNHG14) on DLBCL. SNHG14 level in DLBCL samples and cell lines was analyzed by GEPIA bioinformatics tool and RT-qPCR. Biological functions of SNHG14 in DLBCL were detected by CCK-8, colony formation, and transwell invasion assays. Molecular interaction was determined by RNA immunoprecipitation (RIP) and luciferase reporter assays. MiR-5590-3p-related pathway was identified through KEGG pathway analysis applying DAVID6.8 online bioinformatics tool. Effect of SNHG14 on CD8+ T cells was detected by flow cytometry. Results depicted that SNHG14 was upregulated in DLBCL and its depletion retarded proliferation, migration and epithelial-to-mesenchymal transition (EMT). Mechanistically, SNHG14 sponged miR-5590-3p to upregulate Zinc finger E-box binding homeobox 1 (ZEB1), and ZEB1 transcriptionally activated SNHG14 and PD-L1 to promote the immune evasion of DLBCL cells. In conclusion, we firstly showed that SNHG14/miR-5590-3p/ZEB1 positive feedback loop promoted diffuse large B cell lymphoma progression and immune evasion through regulating PD-1/PD-L1 checkpoint, indicating that targeting SNHG14 was a potential approach to improve the efficacy of immunotherapy in DLBCL.
MiR-532-3p suppresses colorectal cancer progression by disrupting the ETS1/TGM2 axis-mediated Wnt/β-catenin signaling
Authors: Gu Chuncai , Cai Jianqun , Xu Zhijun , Zhou Shiming , Ye Liangying , Yan Qun , Zhang Yue , Fang Yuxin , Liu Yongfeng , Tu Chenge , Wang Xinke , He Juan , Li Qingyuan , Han Lu , Lin Xin , Li Aimin , Liu Side 
Published: September 2019

AbstractThe expression panel of plasma microRNA defined miR-532-3p as a valuable biomarker for colorectal adenoma (CRA). However, its expression pattern and function in colorectal cancer (CRC) have remained unclear. The present study investigated the expression levels of miR-532-3p and found that it was in situ downregulated both in CRA and CRC. Moreover, it functioned as a sensitizer for chemotherapy in CRC by inducing cell cycle arrest and early apoptosis via its activating effects on p53 and apoptotic signaling pathways. In addition, miR-532-3p was found to restrain cell growth, metastasis, and epithelial–mesenchymal transition (EMT) phenotype of CRC. A study on the mechanism behind these effects revealed that miR-532-3p directly binds to 3′UTR regions of ETS1 and TGM2, ultimately repressing the canonical Wnt/β-catenin signaling. Further investigation showed that TGM2 was transcriptionally regulated by ETS1 and ETS1/TGM2 axis served as a vital functional target of miR-532-3p in suppressing CRC progression. To conclude, miR-532-3p mimics could act as potential candidate for molecular therapy in CRC through inactivation of the canonical Wnt/β-catenin signaling and enhancement of chemosensitivity.
Dissociation of mitochondrial HK-II elicits mitophagy and confers cardioprotection against ischemia
Authors: Tan Valerie P. , Smith Jeffrey M. , Tu Michelle , Yu Justin D. , Ding Eric Y. , Miyamoto Shigeki 
Published: September 2019

AbstractPreservation of mitochondrial integrity is critical for maintaining cellular homeostasis. Mitophagy is a mitochondria-specific type of autophagy which eliminates damaged mitochondria thereby contributing to mitochondrial quality control. Depolarization of the mitochondrial membrane potential is an established mechanism for inducing mitophagy, mediated through PINK1 stabilization and Parkin recruitment to mitochondria. Hexokinase-II (HK-II) which catalyzes the first step in glucose metabolism, also functions as a signaling molecule to regulate cell survival, and a significant fraction of cellular HK-II is associated with mitochondria (mitoHK-II). We demonstrate here that pharmacological interventions and adenoviral expression of a mitoHK-II dissociating peptide which reduce mitoHK-II levels lead to robust increases in mitochondrial Parkin and ubiquitination of mitochondrial proteins in cardiomyocytes and in a human glioblastoma cell line 1321N1, independent of mitochondrial membrane depolarization or PINK1 accumulation. MitoHK-II dissociation-induced mitophagy was demonstrated using Mito-Keima in cardiomyocytes and in 1321N1 cells. Subjecting cardiomyocytes or the in vivo heart to ischemia leads to modest dissociation of mitoHK-II. This response is potentiated by expression of the mitoHK-II dissociating peptide, which increases Parkin recruitment to mitochondria and, importantly, provides cardioprotection against ischemic stress. These results suggest that mitoHK-II dissociation is a physiologically relevant cellular event that is induced by ischemic stress, the enhancement of which protects against ischemic damage. The mechanism which underlies the effects of mitoHK-II dissociation can be attributed to the ability of Bcl2-associated athanogene 5 (BAG5), an inhibitor of Parkin, to localize to mitochondria and form a molecular complex with HK-II. Overexpression of BAG5 attenuates while knockdown of BAG5 sensitizes the effect of mitoHK-II dissociation on mitophagy. We suggest that HK-II, a glycolytic molecule, can function as a sensor for metabolic derangements at mitochondria to trigger mitophagy, and modulating the intracellular localization of HK-II could be a novel way of regulating mitophagy to prevent cell death induced by ischemic stress.
Regulation of the Notch-ATM-abl axis by geranylgeranyl diphosphate synthase inhibition
Authors: Agabiti Sherry S. , Li Jin , Dong Willie , Poe Michael M. , Wiemer Andrew J. 
Published: September 2019

AbstractNotch proteins drive oncogenesis of many cancers, most prominently T-cell acute lymphoblastic leukemia (T-ALL). Because geranylgeranylated Rab proteins regulate Notch processing, we hypothesized that inhibition of geranylgeranyl diphosphate synthase (GGDPS) would impair Notch processing and reduce viability of T-ALL cells that express Notch. Here, we show that GGDPS inhibition reduces Notch1 expression and impairs the proliferation of T-ALL cells. GGDPS inhibition also reduces Rab7 membrane association and depletes Notch1 mRNA. GGDPS inhibition increases phosphorylation of histone H2A.X, and inhibitors of ataxia telangiectasia-mutated kinase (ATM) mitigate GGDPS inhibitor-induced apoptosis. GGDPS inhibition also influences c-abl activity downstream of caspases, and inhibitors of these enzymes prevent GGDPS inhibitor-induced apoptosis. Surprisingly, induction of apoptosis by GGDPS inhibition is reduced by co-treatment with γ-secretase inhibitors. While inhibitors of γ-secretase deplete one specific form of the Notch1 intracellular domain (NICD), they also increase Notch1 mRNA expression and increase alternate forms of Notch1 protein expression in cells treated with a GGDPS inhibitor. Furthermore, inhibitors of γ-secretase and ATM increase Notch1 mRNA stability independent of GGDPS inhibition. These results provide a model by which T-ALL cells use Notch1 to avoid DNA-damage-induced apoptosis, and can be overcome by inhibition of GGDPS through effects on Notch1 expression and its subsequent response.
Tissue-regenerative potential of the secretome of γ-irradiated peripheral blood mononuclear cells is mediated via TNFRSF1B-induced necroptosis
Authors: Simader Elisabeth , Beer Lucian , Laggner Maria , Vorstandlechner Vera , Gugerell Alfred , Erb Michael , Kalinina Polina , Copic Dragan , Moser Doris , Spittler Andreas , Tschachler Erwin , Jan Ankersmit Hendrik , Mildner Michael 
Published: September 2019

AbstractPeripheral blood mononuclear cells (PBMCs) have been shown to produce and release a plethora of pro-angiogenetic factors in response to γ-irradiation, partially accounting for their tissue-regenerative capacity. Here, we investigated whether a certain cell subtype of PBMCs is responsible for this effect, and whether the type of cell death affects the pro-angiogenic potential of bioactive molecules released by γ-irradiated PBMCs. PBMCs and PBMC subpopulations, including CD4+ and CD8+ T cells, B cells, monocytes, and natural killer cells, were isolated and subjected to high-dose γ-irradiation. Transcriptome analysis revealed subpopulation-specific responses to γ-irradiation with distinct activation of pro-angiogenic pathways, cytokine production, and death receptor signalling. Analysis of the proteins released showed that interactions of the subsets are important for the generation of a pro-angiogenic secretome. This result was confirmed at the functional level by the finding that the secretome of γ-irradiated PBMCs displayed higher pro-angiogenic activity in an aortic ring assay. Scanning electron microscopy and image stream analysis of γ-irradiated PBMCs revealed distinct morphological changes, indicative for apoptotic and necroptotic cell death. While inhibition of apoptosis had no effect on the pro-angiogenic activity of the secretome, inhibiting necroptosis in stressed PBMCs abolished blood vessel sprouting. Mechanistically, we identified tumor necrosis factor (TNF) receptor superfamily member 1B as the main driver of necroptosis in response to γ-irradiation in PBMCs, which was most likely mediated via membrane-bound TNF-α. In conclusion, our study demonstrates that the pro-angiogenic activity of the secretome of γ-irradiated PBMCs requires interplay of different PBMC subpopulations. Furthermore, we show that TNF-dependent necroptosis is an indispensable molecular process for conferring tissue-regenerative activity and for the pro-angiogenic potential of the PBMC secretome. These findings contribute to a better understanding of secretome-based therapies in regenerative medicine.
Essential role of glucokinase in the protection of pancreatic β cells to the glucose energetic status
Authors: Marqués Patricia , Kamitz Anne , Bartolomé Alberto , Burillo Jesús , Martínez Helena , Jiménez Beatriz , Fernández-Rhodes María , Guillén Carlos , Benito Manuel 
Published: September 2019

AbstractEnergy sensing is indispensable to balance anabolic and catabolic processes for the maintenance of cell viability. Pancreatic β cells are especially relevant because of their involvement in the coordination of insulin secretion when glucose concentration arises in the local milieu. In this work, we uncover the increased susceptibility of pancreatic β cells to cell death in response to different energy stressors. Upon glucose decline, from 25 to 5 mM, caused by stimulation with either 2-deoxyglucose or metformin, only pancreatic β cells showed an increase in cell death. Very interestingly, when we transfected either mouse insulinoma cell or human embryo kidney cells with a phospho-mutant form of B cell lymphoma 2 associated agonist of cell death at serine 155 (BAD S155D), an increase in the pro-survival factor B cell lymphoma 2 was detected in pancreatic β cells and not in human embryonic kidney cells in the presence of the energetic stressors. This data suggests that the protective capacity of this mutant form is only present in cells that present glucokinase. In contrast, upon hyperactivation of mechanistic target of rapamycin complex 1 signaling by knocking-down tuberous sclerosis complex protein, we observed increased susceptibility to cell death in response to energy stress in both pancreatic and non-pancreatic β cells. Therefore, mechanistic target of rapamycin complex 1 signaling presents a dual effect on cell viability. On the one hand, a chronic inhibition of mechanistic target of rapamycin complex 1 activity in response to the energy status is deleterious for pancreatic β cells, being attenuated by the overexpression of B cell lymphoma 2 associated agonist of cell death S155D. On the other hand, mechanistic target of rapamycin complex 1 hyperactivity provokes a susceptibility to energetic stress-induced cell death. Taken together, these results may open potential implications for the use of glucokinase activators or mechanistic target of rapamycin complex 1 modulators for the maintenance of pancreatic β cells for longer periods of time avoiding its loss in different pathologies such as type 2 diabetes mellitus.
Neurogenomic insights into paternal care and its relation to territorial aggression
Authors: Bukhari Syed Abbas , Saul Michael C. , James Noelle , Bensky Miles K. , Stein Laura R. , Trapp Rebecca , Bell Alison M. 
Published: September 2019

AbstractMotherhood is characterized by dramatic changes in brain and behavior, but less is known about fatherhood. Here we report that male sticklebacks—a small fish in which fathers provide care—experience dramatic changes in neurogenomic state as they become fathers. Some genes are unique to different stages of paternal care, some genes are shared across stages, and some genes are added to the previously acquired neurogenomic state. Comparative genomic analysis suggests that some of these neurogenomic dynamics resemble changes associated with pregnancy and reproduction in mammalian mothers. Moreover, gene regulatory analysis identifies transcription factors that are regulated in opposite directions in response to a territorial challenge versus during paternal care. Altogether these results show that some of the molecular mechanisms of parental care might be deeply conserved and might not be sex-specific, and suggest that tradeoffs between opposing social behaviors are managed at the gene regulatory level.
Transport mechanisms during the high-temperature oxidation of ternary γ/γ′ Co-base model alloys
Authors: Weiser Martin , Chater Richard J. , Shollock Barbara A. , Virtanen Sannakaisa 
Published: September 2019

AbstractOver a decade ago, γ′-strengthened Co-base alloys were introduced as potential replacement for conventional Ni-base Superalloys. Insufficient resistance against high-temperature oxidation restricts the number of possible applications. The present study contributes to the understanding of elementary mechanisms such as material transport during extensive oxide scale formation on γ/γ′ Co-base alloys to explain their inferior oxidation behaviour. A clear dependency of the scale growth kinetics on W content and oxidation temperature is demonstrated by thermogravimetry and subsequent analysis of cross-sections. By means of electron backscattered diffraction (EBSD), the evolution of microstructures in the outer oxide layers were examined depending on the oxidation temperature. Sequential exposure of samples in 16O2- and 18O2-containing atmospheres proved counter-current material transport. The combination of focused ion beam (FIB) and secondary ion mass spectroscopy (SIMS) visualised the formation of new oxide phases mainly on the outer and inner interface of the oxide scale. An elaborate review of available transport paths for oxygen is given during the discussion of results. All experimental findings were combined to a coherent explanation of the inferior oxidation resistance of this relatively new class of high-temperature materials at temperatures above 800 °C.