bluuebunny/crossref_metadata_2025_split huggingface dataset:
When Health Diplomacy Serves Foreign Policy: Use of Soft Power to Quell Conflict and Crises
Authors: Hosseini Divkolaye Nasim Sadat , Radfar Mohammad Hadi , Seighali Fariba , Burkle Frederick M. 
Published: May 2016

AbstractObjectiveHealth diplomacy has increasingly become a crucial element in forging political neutrality and conflict resolution and the World Health Organization has strongly encouraged its use. Global turmoil has heightened, especially in the Middle East, and with it, political, religious, and cultural differences have become major reasons to incite crises.MethodsThe authors cite the example of the human stampede and the deaths of over 2000 pilgrims during the 2015 annual Haj pilgrimage in Mecca.ResultsThe resulting political conflict between Iran and Saudi Arabia had the potential to escalate into a more severe political and military crisis had it not been for the ministers of health from both countries successfully exercising “soft power” options.ConclusionGlobal health security demands critical health diplomacy skills and training for all health providers. (Disaster Med Public Health Preparedness. 2016;page 1 of 4)
Microstructural characterisation of the Ypresian clays (Kallo-1) at nanometre resolution, using broad-ion beam milling and scanning electron microscopy
Authors: Hemes S. , Desbois G. , Klaver J. , Urai J.L. 
Published: May 2016

AbstractBesides the Oligocene Boom Clay, the Ypresian clays – part of the Eocene Ieper Group (Kortrijk Formation and Kortemark Member) – are currently being investigated as an alternative host rock for the deep geological disposal of radioactive waste in Belgium and the Netherlands. In this study, broad-ion-beam milling and high resolution scanning electron microscopy (BIB-SEM) analyses were carried out to analyse the mineral fabrics and microstructures of representative Ypresian clay samples from different depths of the ON-Kallo-1 borehole (Kallo, Belgium). Qualitative microstructural observations indicate that mineral fabrics and pore morphologies in fine-grained samples are comparable to those found for fine-grained Boom Clay, but most of the Ypresian clay samples analysed also contained a significant silt fraction, which is associated with larger inter-aggregate pores, coated by a thin, very low porous clay layer. Quantitative pore-shape analysis shows lower axial ratios and elongations, as well as higher roundness and circularities for pores in the clay matrix of the more coarse-grained samples, compared to the fine-grained samples. The contribution of large pores (>1 × 107nm² pore area) to the total BIB-SEM observed porosity was found to correlate with the non-clay mineral (NCM) content of a sample. Frequencies of pore sizes within the clay matrix follow a power-law distribution, hinting towards the possibility of up-scaling of the nanometre-scale observations to larger scale (micro-) structural features of the material. Power-law exponents are comparable to values found for power-law pore-size distributions within the clay matrix of the Boom Clay, which indicates similarity of the pore-space morphologies within the clay matrix of the Boom Clay and the Ypresian clays. Wood's metal injection, followed by (cooled BIB)-SEM analysis shows that all visible pores are connected via pore throats of diameter down to ~10 nm.
PGE2 maintains self-renewal of human adult stem cells via EP2-mediated autocrine signaling and its production is regulated by cell-to-cell contact
Authors: Lee Byung-Chul , Kim Hyung-Sik , Shin Tae-Hoon , Kang Insung , Lee Jin Young , Kim Jae-Jun , Kang Hyun Kyoung , Seo Yoojin , Lee Seunghee , Yu Kyung-Rok , Choi Soon Won , Kang Kyung-Sun 
Published: May 2016

AbstractMesenchymal stem cells (MSCs) possess unique immunomodulatory abilities. Many studies have elucidated the clinical efficacy and underlying mechanisms of MSCs in immune disorders. Although immunoregulatory factors, such as Prostaglandin E2 (PGE2) and their mechanisms of action on immune cells have been revealed, their effects on MSCs and regulation of their production by the culture environment are less clear. Therefore, we investigated the autocrine effect of PGE2 on human adult stem cells from cord blood or adipose tissue and the regulation of its production by cell-to-cell contact, followed by the determination of its immunomodulatory properties. MSCs were treated with specific inhibitors to suppress PGE2 secretion and proliferation was assessed. PGE2 exerted an autocrine regulatory function in MSCs by triggering E-Prostanoid (EP) 2 receptor. Inhibiting PGE2 production led to growth arrest, whereas addition of MSC-derived PGE2 restored proliferation. The level of PGE2 production from an equivalent number of MSCs was down-regulated via gap junctional intercellular communication. This cell contact-mediated decrease in PGE2 secretion down-regulated the suppressive effect of MSCs on immune cells. In conclusion, PGE2 produced by MSCs contributes to maintenance of self-renewal capacity through EP2 in an autocrine manner and PGE2 secretion is down-regulated by cell-to-cell contact, attenuating its immunomodulatory potency.
A melanosomal two-pore sodium channel regulates pigmentation
Authors: Bellono Nicholas W. , Escobar Iliana E. , Oancea Elena 
Published: May 2016

AbstractIntracellular organelles mediate complex cellular functions that often require ion transport across their membranes. Melanosomes are organelles responsible for the synthesis of the major mammalian pigment melanin. Defects in melanin synthesis result in pigmentation defects, visual deficits, and increased susceptibility to skin and eye cancers. Although genes encoding putative melanosomal ion transporters have been identified as key regulators of melanin synthesis, melanosome ion transport and its contribution to pigmentation remain poorly understood. Here we identify two-pore channel 2 (TPC2) as the first reported melanosomal cation conductance by directly patch-clamping skin and eye melanosomes. TPC2 has been implicated in human pigmentation and melanoma, but the molecular mechanism mediating this function was entirely unknown. We demonstrate that the vesicular signaling lipid phosphatidylinositol bisphosphate PI(3,5)P2 modulates TPC2 activity to control melanosomal membrane potential, pH, and regulate pigmentation.
MgZnO/ZnO heterostructures with electron mobility exceeding 1 × 106 cm2/Vs
Authors: Falson Joseph , Kozuka Yusuke , Uchida Masaki , Smet Jurgen H. , Arima Taka-hisa , Tsukazaki Atsushi , Kawasaki Masashi 
Published: May 2016

AbstractThe inherently complex chemical and crystallographic nature of oxide materials has suppressed the purities achievable in laboratory environments, obscuring the rich physical degrees of freedom these systems host. In this manuscript we provide a systematic approach to defect identification and management in oxide molecular beam epitaxy grown MgZnO/ZnO heterostructures which host two-dimensional electron systems. We achieve samples displaying electron mobilities in excess of 1 × 106 cm2/Vs. This data set for the MgZnO/ZnO system firmly establishes that the crystalline quality has become comparable to traditional semiconductor materials.
NAMPT knockdown attenuates atherosclerosis and promotes reverse cholesterol transport in ApoE KO mice with high-fat-induced insulin resistance
Authors: Li Shengbing , Wang Cong , Li Ke , Li Ling , Tian Mingyuan , Xie Jing , Yang Mengliu , Jia Yanjun , He Junying , Gao Lin , Boden Guenther , Liu Hua , Yang Gangyi 
Published: May 2016

AbstractNAMPT has been suggested association with atherosclerosis and insulin resistance. However, the impact of NAMPT on atherosclerosis remained unknown. Therefore, the objective of this study was to use a NAMPT loss-of-function approach to investigate the effect of NAMPT on atherosclerosis in hypercholesterolemic mice. We demonstrated that a specific NAMPT knockdown increased plasma HDL-C levels, reduced the plaque area of the total aorta en face and the cross-sectional aortic sinus, decreased macrophage number and apoptosis and promoted RCT in HFD-fed ApoE KO mice. These changes were accompanied by increased PPARα, LXRα, ABCA1 and ABCG1 expressions in the liver. NAMPT knockdown also facilitated cholesterol efflux in RAW264.7 cells. We further investigated the effect of NAMPT knockdown on the PPARα-LXRα pathway of cholesterol metabolism with MK886 (a selective inhibitor of PPARα) in RAW264.7 macrophages. MK886 abolished the ability of NAMPT knockdown to decrease intracellular cholesterol levels to enhance the rate of 3H-cholesterol efflux and to increase ABCA1/G1 and LXRα expressions in RAW264.7 macrophages. Our observations demonstrate that NAMPT knockdown exerted antiatherogenic effects by promoting cholesterol efflux and macrophage RCT through the PPARα- LXRα- ABCA1/G1pathway in vitro and in vivo.
Experimental evidence for beneficial effects of projected climate change on hibernating amphibians
Authors: Üveges Bálint , Mahr Katharina , Szederkényi Márk , Bókony Veronika , Hoi Herbert , Hettyey Attila 
Published: May 2016

AbstractAmphibians are the most threatened vertebrates today, experiencing worldwide declines. In recent years considerable effort was invested in exposing the causes of these declines. Climate change has been identified as such a cause; however, the expectable effects of predicted milder, shorter winters on hibernation success of temperate-zone Amphibians have remained controversial, mainly due to a lack of controlled experimental studies. Here we present a laboratory experiment, testing the effects of simulated climate change on hibernating juvenile common toads (Bufo bufo). We simulated hibernation conditions by exposing toadlets to current (1.5 °C) or elevated (4.5 °C) hibernation temperatures in combination with current (91 days) or shortened (61 days) hibernation length. We found that a shorter winter and milder hibernation temperature increased survival of toads during hibernation. Furthermore, the increase in temperature and shortening of the cold period had a synergistic positive effect on body mass change during hibernation. Consequently, while climate change may pose severe challenges for amphibians of the temperate zone during their activity period, the negative effects may be dampened by shorter and milder winters experienced during hibernation.
Prolonged mitotic arrest induces a caspase-dependent DNA damage response at telomeres that determines cell survival
Authors: Hain Karolina O. , Colin Didier J. , Rastogi Shubhra , Allan Lindsey A. , Clarke Paul R. 
Published: May 2016

AbstractA delay in the completion of metaphase induces a stress response that inhibits further cell proliferation or induces apoptosis. This response is thought to protect against genomic instability and is important for the effects of anti-mitotic cancer drugs. Here, we show that mitotic arrest induces a caspase-dependent DNA damage response (DDR) at telomeres in non-apoptotic cells. This pathway is under the control of Mcl-1 and other Bcl-2 family proteins and requires caspase-9, caspase-3/7 and the endonuclease CAD/DFF40. The gradual caspase-dependent loss of the shelterin complex protein TRF2 from telomeres promotes a DDR that involves DNA-dependent protein kinase (DNA-PK). Suppression of mitotic telomere damage by enhanced expression of TRF2, or the inhibition of either caspase-3/7 or DNA-PK during mitotic arrest, promotes subsequent cell survival. Thus, we demonstrate that mitotic stress is characterised by the sub-apoptotic activation of a classical caspase pathway, which promotes telomere deprotection, activates DNA damage signalling and determines cell fate in response to a prolonged delay in mitosis.
Interconnection of post-transcriptional regulation: The RNA-binding protein Hfq is a novel target of the Lon protease in Pseudomonas aeruginosa
Authors: Fernández Lucía , Breidenstein Elena B. M. , Taylor Patrick K. , Bains Manjeet , de la Fuente-Núñez César , Fang Yuan , Foster Leonard J. , Hancock Robert E. W. 
Published: May 2016

AbstractBesides being a major opportunistic human pathogen, Pseudomonas aeruginosa can be found in a wide range of environments. This versatility is linked to complex regulation, which is achieved through the action of transcriptional regulators, and post-transcriptional regulation by intracellular proteases including Lon. Indeed, lon mutants in this species show defects in motility, biofilm formation, pathogenicity and fluoroquinolone resistance. Here, the proteomic approach stable isotope labeling by amino acids in cell culture (SILAC) was used to search for novel proteolytic targets. One of the proteins that accumulated in the lon mutant was the RNA-binding protein Hfq. Further experiments demonstrated the ability of Lon to degrade Hfq in vitro. Also, overexpression of the hfq gene in the wild-type strain led to partial inhibition of swarming, swimming and twitching motilities, indicating that Hfq accumulation could contribute to the phenotypes displayed by Lon mutants. Hfq overexpression also led to the upregulation of the small regulatory RNA PhrS. Analysis of the phenotypes of strains lacking or overexpressing this sRNA indicated that the Lon protease might be indirectly regulating the levels and activity of sRNAs via Hfq. Overall, this study revealed new links in the complex regulatory chain that controls multicellular behaviours in P. aeruginosa.
Determinants of the N content of Quercus wutaishanica leaves in the Loess Plateau: a structural equation modeling approach
Authors: Xing Kaixiong , Kang Muyi , Chen Han Y. H. , Zhao Mingfei , Wang Yuhang , Wang Guoyi , Chen Chen , Liu Yang , Dong Xiaobin 
Published: May 2016

AbstractMost terrestrial ecosystems are nitrogen (N)-limited. The elucidation of the multivariate relationships among environmental drivers, leaf morphological traits, and foliar N of dominant species which are critical to the functioning of forests remains a critical challenge for ecologists. We sampled leaves of Quercus wutaishanica across a broad natural gradient in the Loess Plateau, China, and employed structural equation modelling to evaluate the causal pathways and the relative importance of drivers of the foliar N per unit area (Narea) and per unit mass (Nmass). We found that (1) Nmass and Narea were primarily affected by leaf morphological traits instead of environmental variables and that leaf morphological traits accounted for most of their variations; (2) the total soil potassium and phosphorus and mean annual precipitation had different effects on Nmass and Narea via different pathways and path coefficients, whereas the mean annual temperature and total soil N had non-significant effects on Nmass and Narea. Our results demonstrated that variations in Nmass and Narea within Quercus wutaishanica were strongly linked to their leaf morphological traits and that the leaf N was also influenced by mean annual precipitation and soil phosphorus and potassium instead of soil N in the Loess Plateau, China.
Exploring the Inhibitory Mechanism of Approved Selective Norepinephrine Reuptake Inhibitors and Reboxetine Enantiomers by Molecular Dynamics Study
Authors: Zheng Guoxun , Xue Weiwei , Wang Panpan , Yang Fengyuan , Li Bo , Li Xiaofeng , Li Yinghong , Yao Xiaojun , Zhu Feng 
Published: May 2016

AbstractSelective norepinephrine reuptake inhibitors (sNRIs) provide an effective class of approved antipsychotics, whose inhibitory mechanism could facilitate the discovery of privileged scaffolds with enhanced drug efficacy. However, the crystal structure of human norepinephrine transporter (hNET) has not been determined yet and the inhibitory mechanism of sNRIs remains elusive. In this work, multiple computational methods were integrated to explore the inhibitory mechanism of approved sNRIs (atomoxetine, maprotiline, reboxetine and viloxazine), and 3 lines of evidences were provided to verify the calculation results. Consequently, a binding mode defined by interactions between three chemical moieties in sNRIs and eleven residues in hNET was identified as shared by approved sNRIs. In the meantime, binding modes of reboxetine’s enantiomers with hNET were compared. 6 key residues favoring the binding of (S, S)-reboxetine over that of (R, R)-reboxetine were discovered. This is the first study reporting that those 11 residues are the common determinants for the binding of approved sNRIs. The identified binding mode shed light on the inhibitory mechanism of approved sNRIs, which could help identify novel scaffolds with improved drug efficacy.
Enhanced Flexible Tubular Microelectrode with Conducting Polymer for Multi-Functional Implantable Tissue-Machine Interface
Authors: Tian Hong-Chang , Liu Jing-Quan , Kang Xiao-Yang , Tang Long-Jun , Wang Ming-Hao , Ji Bo-Wen , Yang Bin , Wang Xiao-Lin , Chen Xiang , Yang Chun-Sheng 
Published: May 2016

AbstractImplantable biomedical microdevices enable the restoration of body function and improvement of health condition. As the interface between artificial machines and natural tissue, various kinds of microelectrodes with high density and tiny size were developed to undertake precise and complex medical tasks through electrical stimulation and electrophysiological recording. However, if only the electrical interaction existed between electrodes and muscle or nerve tissue without nutrition factor delivery, it would eventually lead to a significant symptom of denervation-induced skeletal muscle atrophy. In this paper, we developed a novel flexible tubular microelectrode integrated with fluidic drug delivery channel for dynamic tissue implant. First, the whole microelectrode was made of biocompatible polymers, which could avoid the drawbacks of the stiff microelectrodes that are easy to be broken and damage tissue. Moreover, the microelectrode sites were circumferentially distributed on the surface of polymer microtube in three dimensions, which would be beneficial to the spatial selectivity. Finally, the in vivo results confirmed that our implantable tubular microelectrodes were suitable for dynamic electrophysiological recording and simultaneous fluidic drug delivery, and the electrode performance was further enhanced by the conducting polymer modification.
The novel compound Sul-121 inhibits airway inflammation and hyperresponsiveness in experimental models of chronic obstructive pulmonary disease
Authors: Han Bing , Poppinga Wilfred J. , Zuo Haoxiao , Zuidhof Annet B. , Bos I. Sophie T. , Smit Marieke , Vogelaar Pieter , Krenning Guido , Henning Robert H. , Maarsingh Harm , Halayko Andrew J. , van Vliet Bernard , Stienstra Stef , Graaf Adrianus Cornelis van der , Meurs Herman , Schmidt Martina 
Published: May 2016

AbstractCOPD is characterized by persistent airflow limitation, neutrophilia and oxidative stress from endogenous and exogenous insults. Current COPD therapy involving anticholinergics, β2-adrenoceptor agonists and/or corticosteroids, do not specifically target oxidative stress, nor do they reduce chronic pulmonary inflammation and disease progression in all patients. Here, we explore the effects of Sul-121, a novel compound with anti-oxidative capacity, on hyperresponsiveness (AHR) and inflammation in experimental models of COPD. Using a guinea pig model of lipopolysaccharide (LPS)-induced neutrophilia, we demonstrated that Sul-121 inhalation dose-dependently prevented LPS-induced airway neutrophilia (up to ~60%) and AHR (up to ~90%). Non-cartilaginous airways neutrophilia was inversely correlated with blood H2S and LPS-induced attenuation of blood H2S (~60%) was prevented by Sul-121. Concomitantly, Sul-121 prevented LPS-induced production of the oxidative stress marker, malondialdehyde by ~80%. In immortalized human airway smooth muscle (ASM) cells, Sul-121 dose-dependently prevented cigarette smoke extract-induced IL-8 release parallel with inhibition of nuclear translocation of the NF-κB subunit, p65 (each ~90%). Sul-121 also diminished cellular reactive oxygen species production in ASM cells and inhibited nuclear translocation of the anti-oxidative response regulator, Nrf2. Our data show that Sul-121 effectively inhibits airway inflammation and AHR in experimental COPD models, prospectively through inhibition of oxidative stress.
Binding of Human Fibrinogen to MRP Enhances Streptococcus suis Survival in Host Blood in a αXβ2 Integrin-dependent Manner
Authors: Pian Yaya , Li Xueqin , Zheng Yuling , Wu Xiaohong , Yuan Yuan , Jiang Yongqiang 
Published: May 2016

AbstractThe Gram-positive bacterium Streptococcus suis serotype 2 (S. suis 2), an important zoonotic pathogen, induces strong systemic infections in humans; sepsis and meningitis are the most common clinical manifestations and are often accompanied by bacteremia. However, the mechanisms of S. suis 2 survival in human blood are not well understood. In our previous study, we identified muramidase-released protein (MRP), a novel human fibrinogen (hFg)-binding protein (FBP) in S. suis 2 that is an important epidemic infection marker with an unknown mechanism in pathogenesis. The present study demonstrates that the N-terminus of MRP (a.a. 283–721) binds to both the Aα and Bβ chains of the D fragment of hFg. Strikingly, the hFg-MRP interaction improved the survival of S. suis 2 in human blood and led to the aggregation and exhaustion of polymorphonuclear neutrophils (PMNs) via an αXβ2 integrin-dependent mechanism. Other Fg-binding proteins, such as M1 (GAS) and FOG (GGS), also induced PMNs aggregation; however, the mechanisms of these FBP-hFg complexes in the evasion of PMN-mediated innate immunity remain unclear. MRP is conserved across highly virulent strains in Europe and Asia and these data shed new light on the function of MRP in S. suis pathogenesis.
The NKD1/Rac1 feedback loop regulates the invasion and migration ability of hepatocarcinoma cells
Authors: Li Jie , Zhang Sheng , Hu Qing , Zhang Kang , Jin Jianbin , Zheng Xuqing , Yin Zhenyu , Wang Xiaomin 
Published: May 2016

AbstractHepatocellular carcinoma (HCC) is complicated by aggressive migration and invasion, which contribute to the increased mortality of HCC patients. The NKD1 protein is abnormally expressed in many neoplasms and plays an important role in tumor progression. However, the regulation and underlying molecular mechanisms of NKD1 in HCC cell invasion and migration remain poorly understood. In the present study, ectopic expression of NKD1 in HCC cells attenuated migration and invasionin vitroandin vivoby down-regulating Rac1 expression level and activity, which affected the HCC cell cytoskeleton and E-cadherin expression. Mechanistic studies showed that NKD1 interacted with Rac1 in the cytoplasm and promoted its degradation by the ubiquitin-proteasome pathway. Over-expression of Rac1 enhanced the transcription of theNKD1gene and protein expression conversely owing to its negative regulation of EZH2. Analysis of clinical samples showed that abnormal expression of NKD1 and Rac1 was associated with the poor prognosis of HCC patients. In summary, our data indicate a new role for NKD1 as a regulator of HCC cell invasion and migration via a feedback loop involving Rac1.