bluuebunny/crossref_metadata_2025_split huggingface dataset:
Title to Territory and Jurisdiction in International Human Rights Law: Three Models for a Fraught Relationship
Authors: RAIBLE LEA 
Published: February 2018

AbstractIt is by now uncontroversial that states may owe human rights obligations to individuals outside their territory. The debate about extraterritoriality has, so far, focused on the concept and interpretation of jurisdiction. The role of territory in general, and title in particular, in the conceptual landscape has received less attention in comparison. This article aims to fill this gap by showing that (a) title to territory continues to shape interpretations of jurisdiction, and (b) that this should be avoided. To this end, the article first defines jurisdiction in international human rights law and title to territory. Jurisdiction is best understood as a threshold criterion that triggers human rights obligations of states towards particular individuals. Title to territory, on the other hand, is a set of claims to territory designed to uphold minimal stability. The article then introduces three models – the approximation model, the differentiation model, and the separation model – of the relationship between title to territory and jurisdiction in international human rights law and evaluates them in light of their fit with the relational nature of human rights. The result is that the approximation and differentiation models – that is, those that maintain title's influence on the interpretation of jurisdiction in various degrees – fail the success criterion, while the separation model satisfies it.
Discussion: the futures of global history
Authors: Drayton Richard , Motadel David 
Published: February 2018

AbstractGlobal history has come under attack. It is charged with neglecting national history and the ‘small spaces’ of the past, with being an elite globalist project made irrelevant by the anti-globalist politics of our age, with focusing exclusively on mobile people and things, and with becoming dangerously hegemonic. This article demonstrates that global history is intertwined with the histories of the nation and the local, individuals, outsiders, and subalterns, and small and isolated places. Moreover, global history has directly addressed immobility and resistances to flow, and remains relatively weak in the discipline, versus the persistent dominance everywhere of national history. The article offers a new short history of the rise of the contemporary idiom of global history, and a prospect for a future in which scholars may find, through collaboration, alternatives to the European weights and measures of the past, and to the dominance of Anglophone historians. It argues that we should no more reverse the ‘global turn’ than we should return history’s gaze only to propertied white men. Rather than a retreat from global history, we need it more than ever to fight against myths of imperial and national pasts, which often underpin nationalist populisms.
Nurses as change agents for a better future in health care: the politics of drift and dilution
Authors: Rafferty Anne M. 
Published: February 2018

AbstractThis paper takes the 70th Anniversary of the National Health Service (NHS) in the United Kingdom as an opportunity to reflect upon the strategic direction of nursing policy and the extent to which nurses can realise their potential as change agents in building a better future for health care. It argues that the policy trajectory set for nursing at the outset of the NHS continues to influence its strategic direction, and that the trajectory needs to be reset with the voices of nurses being more engaged in the design, as much as the delivery of health policy. There is a growing evidence base about the benefits for patients and nurses of deploying well-educated nurses at the top of their skill set, to provide needed care for patients in adequately staffed and resourced units, as well as the value that nurses contribute to decision-making in clinical care. Yet much of this evidence is not being implemented. On the contrary, some of it is being ignored. Policy remains fragmented, driven by short-term financial constraints and underinvestment in high quality care. Nurses need to make their voices heard, and use the evidence base to change the dialogue with the public, policy makers and politicians, in order to build a better future for health care.
Seasonal resource conditions favor a summertime increase in North Pacific diatom–diazotroph associations
Authors: Follett Christopher L , Dutkiewicz Stephanie , Karl David M , Inomura Keisuke , Follows Michael J 
Published: February 2018

Abstract
In the North Pacific Subtropical Gyre (NPSG), an annual pulse of sinking organic carbon is observed at 4000 m between July and August, driven by large diatoms found in association with nitrogen fixing, heterocystous, cyanobacteria: Diatom–Diazotroph Associations (DDAs). Here we ask what drives the bloom of DDAs and present a simplified trait-based model of subtropical phototroph populations driven by observed, monthly averaged, environmental characteristics. The ratio of resource supply rates favors nitrogen fixation year round. The relative fitness of DDA traits is most competitive in early summer when the mixed layer is shallow, solar irradiance is high, and phosphorus and iron are relatively abundant. Later in the season, as light intensity drops and phosphorus is depleted, the traits of small unicellular diazotrophs become more competitive. The competitive transition happens in August, at the time when the DDA export event occurs. This seasonal dynamic is maintained when embedded in a more complex, global-scale, ecological model, and provides predictions for the extent of the North Pacific DDA bloom. The model provides a parsimonious and testable hypothesis for the stimulation of DDA blooms.
Microbial cycling of isoprene, the most abundantly produced biological volatile organic compound on Earth
Authors: McGenity Terry J , Crombie Andrew T , Murrell J Colin 
Published: February 2018

AbstractIsoprene (2-methyl-1,3-butadiene), the most abundantly produced biogenic volatile organic compound (BVOC) on Earth, is highly reactive and can have diverse and often detrimental atmospheric effects, which impact on climate and health. Most isoprene is produced by terrestrial plants, but (micro)algal production is important in aquatic environments, and the relative bacterial contribution remains unknown. Soils are a sink for isoprene, and bacteria that can use isoprene as a carbon and energy source have been cultivated and also identified using cultivation-independent methods from soils, leaves and coastal/marine environments. Bacteria belonging to the Actinobacteria are most frequently isolated and identified, and Proteobacteria have also been shown to degrade isoprene. In the freshwater-sediment isolate, Rhodococcus strain AD45, initial oxidation of isoprene to 1,2-epoxy-isoprene is catalyzed by a multicomponent isoprene monooxygenase encoded by the genes isoABCDEF. The resultant epoxide is converted to a glutathione conjugate by a glutathione S-transferase encoded by isoI, and further degraded by enzymes encoded by isoGHJ. Genome sequence analysis of actinobacterial isolates belonging to the genera Rhodococcus, Mycobacterium and Gordonia has revealed that isoABCDEF and isoGHIJ are linked in an operon, either on a plasmid or the chromosome. In Rhodococcus strain AD45 both isoprene and epoxy-isoprene induce a high level of transcription of 22 contiguous genes, including isoABCDEF and isoGHIJ. Sequence analysis of the isoA gene, encoding the large subunit of the oxygenase component of isoprene monooxygenase, from isolates has facilitated the development of PCR primers that are proving valuable in investigating the ecology of uncultivated isoprene-degrading bacteria.
Coral bleaching from a single cell perspective
Authors: Nielsen Daniel Aagren , Petrou Katherina , Gates Ruth D 
Published: February 2018

Abstract
Ocean warming is resulting in increased occurrence of mass coral bleaching; a response in which the intracellular algal endosymbionts (Symbiodinium sp.) are expelled from the coral host due to physiological stress. This detrimental process is often attributed to overproduction of reactive oxygen species (ROS) that leak out of the endosymbionts and causes damage to the host cell, though direct evidence validating this link is limited. Here, for the first time, we used confocal microscopy and fluorescent dyes to investigate if endosymbiont ROS production significantly and predictably affects physiological parameters in its host cell. Heat treatment resulted in a 60% reduction in coral symbiont density, a ~70% increase in median endosymbiont ROS and a small reduction in photosystem efficiency (FV/FM, 11%), indicating absence of severe light stress. Notably, no other physiological parameters were affected in either endosymbionts or host cells, including reduced glutathione and ROS-induced lipid peroxidation. Taken together, the increase in endosymbiont ROS could not be linked to physiological damage in either partner, suggesting that oxidative stress is unlikely to have been the driver for symbiont expulsion in this study.
SPRY2 is a novel MET interactor that regulates metastatic potential and differentiation in rhabdomyosarcoma
Authors: Saini Masum , Verma Aakanksha , Mathew Sam J. 
Published: February 2018

AbstractRhabdomyosarcoma (RMS) is a predominantly pediatric soft-tissue cancer where the tumor cells exhibit characteristics of the developing skeletal muscle, and the two most common sub-types are embryonal and alveolar RMS. Elevated activation of the receptor tyrosine kinase (RTK) MET is frequent in RMS and is thought to cause increased tumor metastasis and lack of differentiation. However, the reasons underlying dysregulated MET expression and activation in RMS are not well understood. Therefore, we explored the role of Sprouty 2 (SPRY2), a modulator of RTK signaling, in regulating MET. We identify SPRY2 as a novel MET interactor that colocalizes with and binds MET in both embryonal and alveolar RMS. We find that depletion of SPRY2 leads to MET degradation, resulting in reduced migratory and clonogenic potential, and induction of differentiation in both embryonal and alveolar RMS, outcomes that are identical to depletion of MET. Activation of the ERK/MAPK pathway, known to be crucial for regulating cell migration and whose inhibition is required for myogenic differentiation, was downregulated upon depletion of MET or SPRY2. This provides a direct connection to the decreased migration and induction of differentiation upon depletion of MET or SPRY2. Thus, these data indicate that SPRY2 interacts with MET and stabilizes it in order to maintain signaling downstream of MET, which keeps the ERK/MAPK pathway active, resulting in metastatic potential and inhibition of differentiation in RMS. Our results identify a novel mechanism by which MET signaling is stabilized in RMS, and is a potential target for therapeutic intervention in RMS.
The cytotoxicity of coxsackievirus B3 is associated with a blockage of autophagic flux mediated by reduced syntaxin 17 expression
Authors: Tian Lang , Yang Yeyi , Li Chunyun , Chen Jia , Li Zhuoying , Li Xin , Li Shentang , Wu Fang , Hu Zhangxue , Yang Zuocheng 
Published: February 2018

AbstractCoxsackievirus B3 (CVB3) is an important human pathogen linked to cardiac arrhythmias and acute heart failure. CVB3 infection has been reported to induce the formation of autophagosomes that support the viral replication in host cells. Interestingly, our study shows that the accumulation of autophagosomes during CVB3 infection is caused by a blockage of autophagosome–lysosome fusion rather than the induction of autophagosome biogenesis. Moreover, CVB3 decreases the transcription and translation of syntaxin 17 (STX17), a SNARE (soluble N-ethylmaleimide-sensitive factor activating protein receptor) protein involved in autophagosome–lysosome fusion. Overexpression of STX17 restored the autophagic flux, alleviated the virus-induced lysosomal dysfunction, and decreased the apoptosis induced by CVB3 infection in HeLa cells. Taken together, our results suggest that CVB3 infection impairs the autophagic flux by blocking autophagosome–lysosome fusion. These findings thus point to potential new therapeutic strategies targeting STX17 or autophagosome–lysosome fusion for treating CVB3-associated diseases.
BRM270 inhibits cancer stem cell maintenance via microRNA regulation in chemoresistant A549 lung adenocarcinoma cells
Authors: Kwon Taeho , Chandimali Nisansala , Huynh Do Luong , Zhang Jiao Jiao , Kim Nameun , Bak Yesol , Yoon Do-Young , Yu Dae-Yeul , Lee Jae Cheol , Gera Meeta , Ghosh Mrinmoy , Park Yang Ho , Jeong Dong Kee 
Published: February 2018

AbstractChemotherapy is a standard treatment for non-small-cell lung cancer (NSCLC). However, the dose-limiting toxicity of drugs and the development of chemoresistance are major clinical challenges to successful management of NSCLC. Asian traditional medicine is gaining global attention as a non-toxic alternative to chemotherapy. BRM270 is an extract formulated from seven Asian medicinal plants that has been shown to inhibit tumor cell proliferation in diverse cancer types. We previously demonstrated that BRM270 suppresses tumorigenesis by negatively regulating nuclear factor-κB signaling in multidrug-resistant cancer stem cells (CSCs). In this study we report that the growth, migration, and invasion of normal human lung adenocarcinoma cells and their chemoresistant derivatives was inhibited by BRM270 treatment. Notably, BRM270 was found to modulate CSC self-renewal and tumor-initiating capacity via positive regulation of the miRNA-128. Thus, combination therapy with miRNA-128 and BRM270 may be an effective treatment strategy for chemoresistant NSCLC.
Pyruvate kinase M2 regulates photoreceptor structure, function, and viability
Authors: Rajala Ammaji , Wang Yuhong , Brush Richard S. , Tsantilas Kristine , Jankowski Connor S. R. , Lindsay Ken J. , Linton Jonathan D. , Hurley James B. , Anderson Robert E. , Rajala Raju V. S. 
Published: February 2018

AbstractPyruvate kinase M2 (PKM2) is a glycolytic enzyme that is expressed in cancer cells. Its role in tumor metabolism is not definitively established, but investigators have suggested that regulation of PKM2 activity can cause accumulation of glycolytic intermediates and increase flux through the pentose phosphate pathway. Recent evidence suggests that PKM2 also may have non-metabolic functions, including as a transcriptional co-activator in gene regulation. We reported previously that PKM2 is abundant in photoreceptor cells in mouse retinas. In the present study, we conditionally deleted PKM2 (rod-cre PKM2-KO) in rod photoreceptors and found that the absence of PKM2 causes increased expression of PKM1 in rods. Analysis of metabolic flux from U-13C glucose shows that rod-cre PKM2-KO retinas accumulate glycolytic intermediates, consistent with an overall reduction in the amount of pyruvate kinase activity. Rod-cre PKM2-KO mice also have an increased NADPH availability could favor lipid synthesis, but we found no difference in phospholipid synthesis between rod-cre PKM2 KO and PKM2-positive controls. As rod-cre PKM2-KO mice aged, we observed a significant loss of rod function, reduced thickness of the photoreceptor outer segment layer, and reduced expression of photoreceptor proteins, including PDE6β. The rod-cre PKM2-KO retinas showed greater TUNEL staining than wild-type retinas, indicating a slow retinal degeneration. In vitro analysis showed that PKM2 can regulate transcriptional activity from the PDE6β promoter in vitro. Our findings indicate that both the metabolic and transcriptional regulatory functions of PKM2 may contribute to photoreceptor structure, function, and viability.
Glycogen synthase kinase-3β inhibition promotes lysosome-dependent degradation of c-FLIPL in hepatocellular carcinoma
Authors: Zhang Na , Liu Xiaojia , Liu Lu , Deng Zhesong , Zeng Qingxuan , Pang Weiqiang , Liu Yang , Song Danqing , Deng Hongbin 
Published: February 2018

AbstractGlycogen synthase kinase-3β (GSK-3β) is a ubiquitously expressed serine/threonine kinase involved in a variety of functions ranging from the control of glycogen metabolism to transcriptional regulation. We recently demonstrated that GSK-3β inhibition triggered ASK1-JNK-dependent apoptosis in human hepatocellular carcinoma (HCC) cells. However, the comprehensive picture of downstream GSK-3β-regulated pathways/functions remains elusive. In this study, we showed that GSK-3β was aberrantly activated in HCC. Pharmacological inhibition and genetic depletion of GSK-3β suppressed the growth and induced caspase-dependent apoptosis in HCC cells. In addition, GSK-3β inhibition-induced apoptosis through downregulation of c-FLIPL in HCC, which was caused by biogenesis of functional lysosomes and subsequently c-FLIPL translocated to lysosome for degradation. This induction of the lysosome-dependent c-FLIPL degradation was associated with nuclear translocation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis. Moreover, GSK-3β inhibition-induced TFEB translocation acts through activation of AMPK and subsequently suppression of mTOR activity. Thus our findings reveal a novel mechanism by which inhibition of GSK-3β promotes lysosome-dependent degradation of c-FLIPL. Our study shows that GSK-3β may become a promising therapeutic target for HCC.
Baicalin administration attenuates hyperglycemia-induced malformation of cardiovascular system
Authors: Wang Guang , Liang Jianxin , Gao Lin-rui , Si Zhen-peng , Zhang Xiao-tan , Liang Guo , Yan Yu , Li Ke , Cheng Xin , Bao Yongping , Chuai Manli , Chen Li-guo , Lu Da-xiang , Yang Xuesong 
Published: February 2018

AbstractIn this study, the effects of Baicalin on the hyperglycemia-induced cardiovascular malformation during embryo development were investigated. Using early chick embryos, an optimal concentration of Baicalin (6 μM) was identified which could prevent hyperglycemia-induced cardiovascular malformation of embryos. Hyperglycemia-enhanced cell apoptosis was reduced in embryos and HUVECs in the presence of Baicalin. Hyperglycemia-induced excessive ROS production was inhibited when Baicalin was administered. Analyses of SOD, GSH-Px, MQAE and GABAA suggested Baicalin plays an antioxidant role in chick embryos possibly through suppression of outwardly rectifying Cl(−) in the high-glucose microenvironment. In addition, hyperglycemia-enhanced autophagy fell in the presence of Baicalin, through affecting the ubiquitin of p62 and accelerating autophagy flux. Both Baicalin and Vitamin C could decrease apoptosis, but CQ did not, suggesting autophagy to be a protective function on the cell survival. In mice, Baicalin reduced the elevated blood glucose level caused by streptozotocin (STZ). Taken together, these data suggest that hyperglycemia-induced embryonic cardiovascular malformation can be attenuated by Baicalin administration through suppressing the excessive production of ROS and autophagy. Baicalin could be a potential candidate drug for women suffering from gestational diabetes mellitus.
The oncogene Etv5 promotes MET in somatic reprogramming and orchestrates epiblast/primitive endoderm specification during mESCs differentiation
Authors: Zhang Jinglong , Cao Hongxia , Xie Jing , Fan Chen , Xie Youlong , He Xin , Liao Mingzhi , Zhang Shiqiang , Wang Huayan 
Published: February 2018

AbstractUnipotent spermatogonial stem cells (SSCs) can be efficiently reprogrammed into pluripotent stem cells only by manipulating the culture condition, without introducing exogenous reprogramming factors. This phenotype raises the hypothesis that the endogenous transcription factors (TFs) in SSCs may facilitate reprogramming to acquire pluripotency. In this study, we screened a pool of SSCs TFs (Bcl6b, Lhx1, Foxo1, Plzf, Id4, Taf4b, and Etv5), and found that oncogene Etv5 could dramatically increase the efficiency of induced pluripotent stem cells (iPSCs) generation when combined with Yamanaka factors. We also demonstrated that Etv5 could promote mesenchymal-epithelial transition (MET) at the early stage of reprogramming by regulating Tet2-miR200s-Zeb1 axis. In addition, Etv5 knockdown in mouse embryonic stem cells (mESCs) could decrease the genomic 5hmC level by downregulating Tet2. Furthermore, the embryoid body assay revealed that Etv5 could positively regulate primitive endoderm specification through regulating Gata6 and negatively regulate epiblast specification by inhibiting Fgf5 expression. In summary, our findings provide insights into understanding the regulation mechanisms of Etv5 under the context of somatic reprogramming, mESCs maintenance, and differentiation.
Uncoupling FoxO3A mitochondrial and nuclear functions in cancer cells undergoing metabolic stress and chemotherapy
Authors: Celestini Valentina , Tezil Tugsan , Russo Luciana , Fasano Candida , Sanese Paola , Forte Giovanna , Peserico Alessia , Lepore Signorile Martina , Longo Giovanna , De Rasmo Domenico , Signorile Anna , Gadaleta Raffaella Maria , Scialpi Natasha , Terao Mineko , Garattini Enrico , Cocco Tiziana , Villani Gaetano , Moschetta Antonio , Grossi Valentina , Simone Cristiano 
Published: February 2018

AbstractWhile aberrant cancer cell growth is frequently associated with altered biochemical metabolism, normal mitochondrial functions are usually preserved and necessary for full malignant transformation. The transcription factor FoxO3A is a key determinant of cancer cell homeostasis, playing a dual role in survival/death response to metabolic stress and cancer therapeutics. We recently described a novel mitochondrial arm of the AMPK-FoxO3A axis in normal cells upon nutrient shortage. Here, we show that in metabolically stressed cancer cells, FoxO3A is recruited to the mitochondria through activation of MEK/ERK and AMPK, which phosphorylate serine 12 and 30, respectively, on FoxO3A N-terminal domain. Subsequently, FoxO3A is imported and cleaved to reach mitochondrial DNA, where it activates expression of the mitochondrial genome to support mitochondrial metabolism. Using FoxO3A−/− cancer cells generated with the CRISPR/Cas9 genome editing system and reconstituted with FoxO3A mutants being impaired in their nuclear or mitochondrial subcellular localization, we show that mitochondrial FoxO3A promotes survival in response to metabolic stress. In cancer cells treated with chemotherapeutic agents, accumulation of FoxO3A into the mitochondria promoted survival in a MEK/ERK-dependent manner, while mitochondrial FoxO3A was required for apoptosis induction by metformin. Elucidation of FoxO3A mitochondrial vs. nuclear functions in cancer cell homeostasis might help devise novel therapeutic strategies to selectively disable FoxO3A prosurvival activity.