bluuebunny/crossref_metadata_2025_split huggingface dataset:
Caloric restriction lowers endocannabinoid tonus and improves cardiac function in type 2 diabetes
Authors: van Eyk Huub J. , van Schinkel Linda D. , Kantae Vasudev , Dronkers Charlotte E. A. , Westenberg Jos J. M. , de Roos Albert , Lamb Hildo J. , Jukema J. Wouter , Harms Amy C. , Hankemeier Thomas , van der Stelt Mario , Jazet Ingrid M. , Rensen Patrick C. N. , Smit Johannes W. A. 
Published: January 2018

Abstract
Background/Objectives
Endocannabinoids (ECs) are associated with obesity and ectopic fat accumulation, both of which play a role in the development of cardiovascular disease (CVD) in type 2 diabetes (T2D). The effect of prolonged caloric restriction on ECs in relation to fat distribution and cardiac function is still unknown. Therefore, our aim was to investigate this relationship in obese T2D patients with coronary artery disease (CAD).

Subjects/Methods
In a prospective intervention study, obese T2D patients with CAD (n = 27) followed a 16 week very low calorie diet (VLCD; 450–1000 kcal/day). Cardiac function and fat accumulation were assessed with MRI and spectroscopy. Plasma levels of lipid species, including ECs, were measured using liquid chromatography-mass spectrometry.

Results
VLCD decreased plasma levels of virtually all measured lipid species of the class of N-acylethanolamines including the EC anandamide (AEA; −15%, p = 0.016), without decreasing monoacylglycerols including the EC 2-arachidonoylglycerol (2-AG). Baseline plasma AEA levels strongly correlated with the volume of subcutaneous white adipose tissue (SAT; R2 = 0.44, p < 0.001). VLCD decreased the volume of SAT (−53%, p < 0.001), visceral white adipose tissue (VAT) (−52%, p < 0.001), epicardial white adipose tissue (−15%, p < 0.001) and paracardial white adipose tissue (−28%, p < 0.001). VLCD also decreased hepatic (−86%, p < 0.001) and myocardial (−33%, p < 0.001) fat content. These effects were accompanied by an increased left ventricular ejection fraction (54.8 ± 8.7–56.2 ± 7.9%, p = 0.016).

Conclusions
Caloric restriction in T2D patients with CAD decreases AEA levels, but not 2-AG levels, which is paralleled by decreased lipid accumulation in adipose tissue, liver and heart, and improved cardiovascular function. Interestingly, baseline AEA levels strongly correlated with SAT volume. We anticipate that dietary interventions are worthwhile strategies in advanced T2D, and that reduction in AEA may contribute to the improved cardiometabolic phenotype induced by weight loss.
MiR-770 suppresses the chemo-resistance and metastasis of triple negative breast cancer via direct targeting of STMN1
Authors: Li Yaming , Liang Yiran , Sang Yuting , Song Xiaojin , Zhang Hanwen , Liu Ying , Jiang Liyu , Yang Qifeng 
Published: January 2018

AbstractChemo-resistance and metastasis of triple negative breast cancer (TNBC) contributed the most of treatment failure in the clinic. MicroRNAs (miRNAs) have been proved to be involved in many biological processes and diseases. In this study, we aimed to determine the role of miR-770 in the regulation of chemo-resistance and metastasis of TNBC. Clinically, miR-770 was highly expressed in chemo-sensitive tissues and predicted a better prognosis of TNBC. Functionally, ectopic expression of miR-770 suppressed the doxorubicin-resistance of TNBC cell lines via regulation of apoptosis and tumor microenvironment, which was mediated by exosomes. Moreover, miR-770 overexpression inhibited the migration and invasion. Rescue of STMN1 could partly reverse the effect of miR-770 in TNBC behaviors. Furthermore, we also demonstrated that overexpression of miR-770 inhibited DOX resistance and metastasis in vivo. Taken together, our results proved that miR-770 could suppress the doxorubicin-resistance and metastasis of TNBC cells, which broaden our insights into the underlying mechanisms in chemo-resistance and metastasis, and provided a new prognostic marker for TNBC cells.
∆133p53 isoform promotes tumour invasion and metastasis via interleukin-6 activation of JAK-STAT and RhoA-ROCK signalling
Authors: Campbell Hamish , Fleming Nicholas , Roth Imogen , Mehta Sunali , Wiles Anna , Williams Gail , Vennin Claire , Arsic Nikola , Parkin Ashleigh , Pajic Marina , Munro Fran , McNoe Les , Black Michael , McCall John , Slatter Tania L. , Timpson Paul , Reddel Roger , Roux Pierre , Print Cristin , Baird Margaret A. , Braithwaite Antony W. 
Published: January 2018

Abstract∆122p53 mice (a model of ∆133p53 isoform) are tumour-prone, have extensive inflammation and elevated serum IL-6. To investigate the role of IL-6 we crossed ∆122p53 mice with IL-6 null mice. Here we show that loss of IL-6 reduced JAK-STAT signalling, tumour incidence and metastasis. We also show that ∆122p53 activates RhoA-ROCK signalling leading to tumour cell invasion, which is IL-6-dependent and can be reduced by inhibition of JAK-STAT and RhoA-ROCK pathways. Similarly, we show that Δ133p53 activates these pathways, resulting in invasive and migratory phenotypes in colorectal cancer cells. Gene expression analysis of colorectal tumours showed enrichment of GPCR signalling associated with ∆133TP53 mRNA. Patients with elevated ∆133TP53 mRNA levels had a shorter disease-free survival. Our results suggest that ∆133p53 promotes tumour invasion by activation of the JAK-STAT and RhoA-ROCK pathways, and that patients whose tumours have high ∆133TP53 may benefit from therapies targeting these pathways.
Protein phosphatase 5 regulates titin phosphorylation and function at a sarcomere-associated mechanosensor complex in cardiomyocytes
Authors: Krysiak Judith , Unger Andreas , Beckendorf Lisa , Hamdani Nazha , von Frieling-Salewsky Marion , Redfield Margaret M. , dos Remedios Cris G. , Sheikh Farah , Gergs Ulrich , Boknik Peter , Linke Wolfgang A. 
Published: January 2018

AbstractSerine/threonine protein phosphatase 5 (PP5) is ubiquitously expressed in eukaryotic cells; however, its function in cardiomyocytes is unknown. Under basal conditions, PP5 is autoinhibited, but enzymatic activity rises upon binding of specific factors, such as the chaperone Hsp90. Here we show that PP5 binds and dephosphorylates the elastic N2B-unique sequence (N2Bus) of titin in cardiomyocytes. Using various binding and phosphorylation tests, cell-culture manipulation, and transgenic mouse hearts, we demonstrate that PP5 associates with N2Bus in vitro and in sarcomeres and is antagonistic to several protein kinases, which phosphorylate N2Bus and lower titin-based passive tension. PP5 is pathologically elevated and likely contributes to hypo-phosphorylation of N2Bus in failing human hearts. Furthermore, Hsp90-activated PP5 interacts with components of a sarcomeric, N2Bus-associated, mechanosensor complex, and blocks mitogen-activated protein-kinase signaling in this complex. Our work establishes PP5 as a compartmentalized, well-controlled phosphatase in cardiomyocytes, which regulates titin properties and kinase signaling at the myofilaments.
Mechanically-sensitive miRNAs bias human mesenchymal stem cell fate via mTOR signalling
Authors: Frith Jessica E. , Kusuma Gina D. , Carthew James , Li Fanyi , Cloonan Nicole , Gomez Guillermo A. , Cooper-White Justin J. 
Published: January 2018

AbstractMechanotransduction is a strong driver of mesenchymal stem cell (MSC) fate. In vitro, variations in matrix mechanics invoke changes in MSC proliferation, migration and differentiation. However, when incorporating MSCs within injectable, inherently soft hydrogels, this dominance over MSC response substantially limits our ability to couple the ease of application of hydrogels with efficiently directed MSC differentiation, especially in the case of bone generation. Here, we identify differential miRNA expression in response to varying hydrogel stiffness and RhoA activity. We show that modulation of miR-100-5p and miR-143-3p can be used to bias MSC fate and provide mechanistic insight by demonstrating convergence on mTOR signalling. By modulating these mechanosensitive miRNAs, we can enhance osteogenesis in a soft 3D hydrogel. The outcomes of this study provide new understanding of the mechanisms regulating MSC mechanotransduction and differentiation, but also a novel strategy with which to drive MSC fate and significantly impact MSC-based tissue-engineering applications.
The protective role of DOT1L in UV-induced melanomagenesis
Authors: Zhu Bo , Chen Shuyang , Wang Hongshen , Yin Chengqian , Han Changpeng , Peng Cong , Liu Zhaoqian , Wan Lixin , Zhang Xiaoyang , Zhang Jie , Lian Christine G. , Ma Peilin , Xu Zhi-xiang , Prince Sharon , Wang Tao , Gao Xiumei , Shi Yujiang , Liu Dali , Liu Min , Wei Wenyi , Wei Zhi , Pan Jingxuan , Wang Yongjun , Xuan Zhenyu , Hess Jay , Hayward Nicholas K. , Goding Colin R. , Chen Xiang , Zhou Jun , Cui Rutao 
Published: January 2018

AbstractThe DOT1L histone H3 lysine 79 (H3K79) methyltransferase plays an oncogenic role in MLL-rearranged leukemogenesis. Here, we demonstrate that, in contrast to MLL-rearranged leukemia, DOT1L plays a protective role in ultraviolet radiation (UVR)-induced melanoma development. Specifically, the DOT1L gene is located in a frequently deleted region and undergoes somatic mutation in human melanoma. Specific mutations functionally compromise DOT1L methyltransferase enzyme activity leading to reduced H3K79 methylation. Importantly, in the absence of DOT1L, UVR-induced DNA damage is inefficiently repaired, so that DOT1L loss promotes melanoma development in mice after exposure to UVR. Mechanistically, DOT1L facilitates DNA damage repair, with DOT1L-methylated H3K79 involvement in binding and recruiting XPC to the DNA damage site for nucleotide excision repair (NER). This study indicates that DOT1L plays a protective role in UVR-induced melanomagenesis.
Qualitative systematic review of barriers and facilitators to self-management of chronic obstructive pulmonary disease: views of patients and healthcare professionals
Authors: Russell Siân , Ogunbayo Oladapo J. , Newham James J. , Heslop-Marshall Karen , Netts Paul , Hanratty Barbara , Beyer Fiona , Kaner Eileen 
Published: January 2018

AbstractSelf-management interventions for chronic obstructive pulmonary disease (COPD) can improve quality of life, reduce hospital admissions, and improve symptoms. However, many factors impede engagement for patients and practitioners. Qualitative research, with its focus on subjective experience, can provide invaluable insights into such factors. Therefore, a systematic review and synthesis of qualitative evidence on COPD self-management from the perspective of patients, carers, and practitioners was conducted. Following a systematic search and screening, 31 studies were appraised and data extracted for analysis. This review found that patients can adapt to COPD; however, learning to self-manage is often a protracted process. Emotional needs are considerable; frustration, depression, and anxiety are common. In addition, patients can face an assortment of losses and limitations on their lifestyle and social interaction. Over time, COPD can consume their existence, reducing motivation. Support from family can prove vital, yet tinged with ambivalence and burden. Practitioners may not have sufficient time, resources, or appropriate skills or confidence to provide effective self-management support, particularly in regard to patients’ psychosocial needs. This can compound patients’ capability to engage in self-management. For COPD self-management to be effective, patients’ psychosocial needs must be prioritised alongside medication and exacerbation management. In addition, patients’ personal beliefs regarding COPD and its management should be reviewed periodically to avoid problematic behaviours and enhance positive adaptions to the disease. Patients with COPD are not a homogenous group and no one intervention will prove effective for all. Finally, practitioners require greater education, training, and support to successfully assist patients.
Expression of the methionine sulfoxide reductase lost during evolution extends Drosophila lifespan in a methionine-dependent manner
Authors: Lee Byung Cheon , Lee Hae Min , Kim Sorah , Avanesov Andrei S. , Lee Aro , Chun Bok-Hwan , Vorbruggen Gerd , Gladyshev Vadim N. 
Published: January 2018

AbstractAccumulation of oxidized amino acids, including methionine, has been implicated in aging. The ability to reduce one of the products of methionine oxidation, free methionine-R-sulfoxide (Met-R-SO), is widespread in microorganisms, but during evolution this function, conferred by the enzyme fRMsr, was lost in metazoa. We examined whether restoration of the fRMsr function in an animal can alleviate the consequences of methionine oxidation. Ectopic expression of yeast fRMsr supported the ability of Drosophila to catalyze free Met-R-SO reduction without affecting fecundity, food consumption, and response to starvation. fRMsr expression also increased resistance to oxidative stress. Moreover, it extended lifespan of flies in a methionine-dependent manner. Thus, expression of an oxidoreductase lost during evolution can enhance metabolic and redox functions and lead to an increase in lifespan in an animal model. More broadly, our study exposes the potential of a combination of genetic and nutritional strategies in lifespan control.
Human brain patterns underlying vigilant attention: impact of sleep debt, circadian phase and attentional engagement
Authors: Maire Micheline , Reichert Carolin F. , Gabel Virginie , Viola Antoine U. , Phillips Christophe , Berthomier Christian , Borgwardt Stefan , Cajochen Christian , Schmidt Christina 
Published: January 2018

AbstractSleepiness and cognitive function vary over the 24-h day due to circadian and sleep-wake-dependent mechanisms. However, the underlying cerebral hallmarks associated with these variations remain to be fully established. Using functional magnetic resonance imaging (fMRI), we investigated brain responses associated with circadian and homeostatic sleep-wake-driven dynamics of subjective sleepiness throughout day and night. Healthy volunteers regularly performed a psychomotor vigilance task (PVT) in the MR-scanner during a 40-h sleep deprivation (high sleep pressure) and a 40-h multiple nap protocol (low sleep pressure). When sleep deprived, arousal-promoting thalamic activation during optimal PVT performance paralleled the time course of subjective sleepiness with peaks at night and troughs on the subsequent day. Conversely, task-related cortical activation decreased when sleepiness increased as a consequence of higher sleep debt. Under low sleep pressure, we did not observe any significant temporal association between PVT-related brain activation and subjective sleepiness. Thus, a circadian modulation in brain correlates of vigilant attention was only detectable under high sleep pressure conditions. Our data indicate that circadian and sleep homeostatic processes impact on vigilant attention via specific mechanisms; mirrored in a decline of cortical resources under high sleep pressure, opposed by a subcortical “rescuing” at adverse circadian times.
The early conversion of deep-sea wood falls into chemosynthetic hotspots revealed by in situ monitoring
Authors: Kalenitchenko D. , Péru E. , Contreira Pereira L. , Petetin C. , Galand P. E. , Le Bris N. 
Published: January 2018

AbstractWood debris on the ocean floor harbor flourishing communities, which include invertebrate taxa thriving in sulfide-rich habitats belonging to hydrothermal vent and methane seep deep-sea lineages. The formation of sulfidic niches from digested wood material produced by woodborers has been known for a long time, but the temporal dynamics and sulfide ranges encountered on wood falls remains unknown. Here, we show that wood falls are converted into sulfidic hotpots, before the colonization by xylophagaid bivalves. Less than a month after immersion at a depth of 520 m in oxygenated seawater the sulfide concentration increased to millimolar levels inside immersed logs. From in situ experiments combining high-frequency chemical and video monitoring, we document the rapid development of a microbial sulfur biofilm at the surface of wood. These findings highlight the fact that sulfide is initially produced from the labile components of wood and supports chemosynthesis as an early pathway of energy transfer to deep-sea wood colonists, as suggested by recent aquarium studies. The study furthermore reveals that woodborers promote sulfide-oxidation at the periphery of their burrows, thus, not only facilitating the development of sulfidic zones in the surrounding of degraded wood falls, but also governing sulfur-cycling within the wood matrix.
Effects of straw application on nitrate leaching in fields in the Yellow River irrigation zone of Ningxia, China
Authors: Yang Shiqi , Wang Yongsheng , Liu Ruliang , Li Quanxin , Yang Zhengli 
Published: January 2018

AbstractA five-year field experiment was conducted to investigate the effects of straw application on nitrate leaching loss. Treatments included soil that was not treated (control), soil treated with straw at a low rate (4,500 kg ha−2, T1) and soil treated with straw at a high rate (9,000 kg ha−2, T2). Nitrate-nitrogen leaching in the 10, 20, 30, 60, and 90 cm soil layers was measured using the resin-core method. The results indicated that straw application could reduce soil nitrate leaching losses in the 0–30 cm layer. In this layer, the nitrate leaching values for T1 (13.76 kg ha−2) and T2 (13.74 kg ha−2) were both significantly lower than those of the control (15.76 kg ha−2) (P < 0.05); the soil nitrate leaching losses decreased by 12.71% and 12.84% for those two treatments, respectively. However, no significant differences in losses were observed (P > 0.05) between T1 and T2. The effects of straw application were apparent only in the ploughing layer (30 cm-depth soil layer). In the deeper layers (60 and 90 cm), no significant differences were observed between the treatments and the control, and the same results were observed in the topsoil layers (10 and 20 cm).
Impact of Concurrent Genomic Alterations Detected by Comprehensive Genomic Sequencing on Clinical Outcomes in East-Asian Patients with EGFR-Mutated Lung Adenocarcinoma
Authors: Sato Seijiro , Nagahashi Masayuki , Koike Terumoto , Ichikawa Hiroshi , Shimada Yoshifumi , Watanabe Satoshi , Kikuchi Toshiaki , Takada Kazuki , Nakanishi Ryota , Oki Eiji , Okamoto Tatsuro , Akazawa Kouhei , Lyle Stephen , Ling Yiwei , Takabe Kazuaki , Okuda Shujiro , Wakai Toshifumi , Tsuchida Masanori 
Published: January 2018

AbstractNext-generation sequencing (NGS) has enabled comprehensive detection of genomic alterations in lung cancer. Ethnic differences may play a critical role in the efficacy of targeted therapies. The aim of this study was to identify and compare genomic alterations of lung adenocarcinoma between Japanese patients and the Cancer Genome Atlas (TCGA), which majority of patients are from the US. We also aimed to examine prognostic impact of additional genomic alterations in patients harboring EGFR mutations. Genomic alterations were determined in Japanese patients with lung adenocarcinoma (N = 100) using NGS-based sequencing of 415 known cancer genes, and correlated with clinical outcome. EGFR active mutations, i.e., those involving exon 19 deletion or an L858R point mutation, were seen in 43% of patients. Some differences in driver gene mutation prevalence were observed between the Japanese cohort described in the present study and the TCGA. Japanese cohort had significantly more genomic alterations in cell cycle pathway, i.e., CDKN2B and RB1 than TCGA. Concurrent mutations, in genes such as CDKN2B or RB1, were associated with worse clinical outcome in patients with EGFR active mutations. Our data support the utility of comprehensive sequencing to detect concurrent genomic variations that may affect clinical outcomes in this disease.
Use of nanoparticle concentration as a tool to understand the structural properties of colloids
Authors: Ribeiro Lígia Nunes de Morais , Couto Verônica Muniz , Fraceto Leonardo Fernandes , de Paula Eneida 
Published: January 2018

AbstractElucidation of the structural properties of colloids is paramount for a successful formulation. However, the intrinsic dynamism of colloidal systems makes their characterization a difficult task and, in particular, there is a lack of physicochemical techniques that can be correlated to their biological performance. Nanoparticle tracking analysis (NTA) allows measurements of size distribution and nanoparticle concentration in real time. Its analysis over time also enables the early detection of physical instability in the systems not assessed by subtle changes in size distribution. Nanoparticle concentration is a parameter with the potential to bridge the gap between in vitro characterization and biological performance of colloids, and therefore should be monitored in stability studies of formulations. To demonstrate this, we have followed two systems: extruded liposomes exposed to increasing CHCl3 concentrations, and solid lipid nanoparticles prepared with decreasing amounts of poloxamer 188. NTA and dynamic light scattering (DLS) were used to monitor changes in nanoparticle number and size, and to estimate the number of lipid components per particle. The results revealed a strong negative correlation between particle size (determined by DLS) and concentration (assessed by NTA) in diluted samples, which should be adopted to monitor nanocolloidal stability, especially in drug delivery.
Experimental infection of cattle with Mycobacterium tuberculosis isolates shows the attenuation of the human tubercle bacillus for cattle
Authors: Villarreal-Ramos Bernardo , Berg Stefan , Whelan Adam , Holbert Sebastien , Carreras Florence , Salguero Francisco J. , Khatri Bhagwati L. , Malone Kerri , Rue-Albrecht Kevin , Shaughnessy Ronan , Smyth Alicia , Ameni Gobena , Aseffa Abraham , Sarradin Pierre , Winter Nathalie , Vordermeier Martin , Gordon Stephen V. 
Published: January 2018

AbstractThe Mycobacterium tuberculosis complex (MTBC) is the collective term given to the group of bacteria that cause tuberculosis (TB) in mammals. It has been reported that M. tuberculosis H37Rv, a standard reference MTBC strain, is attenuated in cattle compared to Mycobacterium bovis. However, as M. tuberculosis H37Rv was isolated in the early 1930s, and genetic variants are known to exist, we sought to revisit this question of attenuation of M. tuberculosis for cattle by performing a bovine experimental infection with a recent M. tuberculosis isolate. Here we report infection of cattle using M. bovis AF2122/97, M. tuberculosis H37Rv, and M. tuberculosis BTB1558, the latter isolated in 2008 during a TB surveillance project in Ethiopian cattle. We show that both M. tuberculosis strains caused reduced gross pathology and histopathology in cattle compared to M. bovis. Using M. tuberculosis H37Rv and M. bovis AF2122/97 as the extremes in terms of infection outcome, we used RNA-Seq analysis to explore differences in the peripheral response to infection as a route to identify biomarkers of progressive disease in contrast to a more quiescent, latent infection. Our work shows the attenuation of M. tuberculosis strains for cattle, and emphasizes the potential of the bovine model as a ‘One Health’ approach to inform human TB biomarker development and post-exposure vaccine development.