bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between serum magnesium and blood lipids: influence of type 2 diabetes and central obesity
Authors: Yu Lianlong , Zhang Junli , Wang Liansen , Li Suyun , Zhang Qian , Xiao Peirui , Wang Kebo , Zhuang Maoqiang , Jiang Ying
Published: May 2018

To assess the changes in the relationship between serum Mg and blood lipids of Chinese adults with type 2 diabetes (T2D) or central obesity, a total of 8163 subjects (mean age 59·6 years, 54·9 % men) were analysed. Participants were classified according to blood Mg (below 0·65 mmol/l, 0·65–0·95 mmol/l and above 0·95 mmol/l), T2D (yes/no) and central obesity (yes/no). Blood lipids (TAG, total cholesterol (TC), HDL-cholesterol and LDL-cholesterol) were determined by standardised methods and conditions. A significant increase in blood lipids, with the exception of HDL-cholesterol, across progressive Mg groups in all subjects was noted (P<0·05). TAG, TC, HDL-cholesterol and LDL-cholesterol were significantly higher among subjects with central obesity compared with those without central obesity (P<0·05). A significant increase in TAG, TC and LDL-cholesterol across progressive Mg groups was observed in subjects without T2D (P<0·05). However, no significant change of HDL-cholesterol and LDL-cholesterol across progressive Mg groups was observed in subjects with T2D (P>0·05). TAG, TC, HDL-cholesterol and LDL-cholesterol were significantly higher among subjects with T2D than those without T2D (P<0·05). Multivariable models for TAG and LDL-cholesterol failed to attain statistical significance in diabetics, by using a generalised linear or parsimonious model. TAG, TC, HDL-cholesterol and LDL-cholesterol were significantly higher among subjects with T2D or central obesity. Blood lipids, with the exception of HDL-cholesterol, were associated with serum Mg, but this association was somehow influenced by T2D in LDL-cholesterol. In addition, multivariable models for both TAG and LDL-cholesterol failed to attain statistical significance among subjects with T2D, different from subjects without T2D.
Prospective association between adherence to dietary recommendations and incident depressive symptoms in the French NutriNet-Santé cohort
Authors: Adjibade Moufidath , Lemogne Cédric , Julia Chantal , Hercberg Serge , Galan Pilar , Assmann Karen E. , Kesse-Guyot Emmanuelle
Published: May 2018

A posteriorihealthier dietary patterns and several nutrients have been associated with lower risks of depression in various studies; however, evidence is lacking with regard to the prospective association between adherence to nutritional recommendations (food-based and nutrient-based recommendations) and incident depression or depressive symptoms. In this study, we investigate such associations in the NutriNet Santé cohort. The study sample included 26 225 participants (aged 18–86 years) who were initially free of depressive symptoms. Adherence to nutritional recommendations was measured by four scores namely modified French Programme National Nutrition Santé-Guideline Score (mPNNS-GS), Alternative Healthy Eating Index-2010 (AHEI-2010), Probability of Adequate Nutrient Intake Dietary Score (PANDiet) and Diet Quality Index-International (DQI-I), using non-consecutive dietary record data during the first 2 years of follow-up (mean number of recording days=8,sd2). Depressive symptoms were defined by a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥17 for men and ≥23 for women. We used Cox proportional hazards models to estimate hazard ratios and 95 % CI, modelling the dietary scores as standardised continuous variables and as tertiles. Over a mean follow-up of 6 years, we identified 2166 incident cases of depressive symptoms. All dietary scores with the exception of the AHEI-2010 were significantly inversely associated with incident depressive symptoms. In the fully adjusted model, an increase of 1sdin the mPNNS-GS, PANDiet and DQI-I was, respectively, associated with an 8 % (95 % CI 4, 13), 5 % (95 % CI 1, 9) and 9 % (95 % CI 5, 13) reduction in the risk of depressive symptoms. Overall, these findings suggest that diet in accordance with national or international guidelines could have beneficial effects with regard to mental health.
The United States and the making of an Arctic nation
Authors: Nilsson Annika E.
Published: May 2018

The United States has sometimes been called a reluctant Arctic actor, but during its chairmanship of the Arctic Council (2015–2017) the US engaged as an active proponent of Arctic cooperation, using the region as a showcase for strong global climate policy. This paper places US Arctic policy development during the Obama presidency within a longer time perspective, with a focus on how US interests towards the region have been formulated in policies and policy statements. The paper uses frame analysis to identify overarching discourses and discusses the extent to which certain themes and political logics recur or shift over time. It highlights economic development and national competitiveness as a prominent recurring frame, but also that the policy discourse has moved from nation-building and military security towards a broader security perspective, with attention to energy supply for the US, and more recently also to the implications of climate change. Over time, there is a clear shift from reluctance towards Arctic regional cooperation to embracing it. Moreover, it highlights how different stands in relation to climate change have affected Arctic cooperation in the past and may do so again in the future.
Comparing the Implications of Expanded Income-Based Measures of Living Standards with an Application to Older Australians
Authors: NAIDOO YUVISTHI
Published: May 2018

The standard of living of older people is a critical policy matter, given Australia's ageing population. Conventional living standard assessments continue to rely on disposable income as a defining indicator, despite it not encompassing the full range of potential consumption possibilities that affect an individual's economic living standard. This article proposes a series of three economic resource metrics that sequentially append the disposable income metric with the value of non-cash benefits and services arising from the receipt of public goods and/or services from home ownership in the form of a ‘full’ income metric, and then the inclusion of wealth in the form of two derived ‘potential consumption’ metrics. Using data from the Household, Income and Labour Dynamics in Australia Survey, the findings demonstrate that augmenting disposable income with income streams from non-cash services and annuitised wealth substantially improves the relative economic position of older Australians. It also highlights the heterogeneity in economic living standard outcomes for different demographic sub-groups of older people that would otherwise be drawn using a disposable income analytic lens. The article argues that an expanded economic resource perspective is necessary for informing ageing and social policy.
Networking, lobbying and bargaining for pensions: trade union power in the Norwegian pension reform
Authors: Grødem Anne Skevik , Hippe Jon M.
Published: May 2018

Norway reformed its pension system in 2011, introducing a Swedish-style, NDC system. Contrary to expectations, the reform was largely supported by the dominant confederation of trade unions, the LO. In this article, we look at LO involvement in the process at different stages. Through qualitative interviews with key reform architects, we have traced the process between 2005 and 2008, emphasising actors, meeting places and interests. Starting from the insight that unions can influence through lobbying, bargaining and (the threat of) mobilising, we suggest that lobbying can be a mutual process, where parties and unions move each other’s positions. In addition, bargaining can take the form of behind-the-scenes cooperation, as well as of negotiations in the classic, Nordic-style industrial relations sense. Expanding on this framework, we suggest that the literature on pension reforms should pay more attention to negotiated and voluntary labour market occupational schemes, and to the importance of expertise and networks.
RESPONSE TO JOAQUIN AND AGREGADO
Authors: Shenefelt Michael , White Heidi
Published: May 2018

Why do logical truths exist at all, and how can our belief in them be justified? In an earlier article (‘What on Earth is Logic?', THINK 45) we contended that at least some aspects of logic must always be assumed, without argument, and that ‘logic is a horizon beyond which none of our earnest and self-reflecting arguments can help us see’. We also contended that logical truths are independent of physical facts, of social rules, and of the anatomical features of our brains. Nevertheless, in a further article in this volume, Jeremiah Joven Joaquin and Jose Emmanuel Agregado have challenged our view. We respond to their criticisms.
FATALISM: A DIALOGUE
Authors: Garrett Brian
Published: May 2018

In this dialogue I discuss the connection between eternalism (the view that past, present and future are equally real) and fatalism. I do not think, as some do, that eternalism implies fatalism, but I do think that eternalists can avoid fatalism only by denying a seemingly intuitive claim about what a traveller to the past cannot do.
Standard And Non-Standard Latin
Authors: Moran Jerome
Published: May 2018

Readers would do well to keep in mind at all times the following distinctions when reading this article: standard/classical and non-standard; native and non-native speaker; literate and illiterate. I use ‘second’ and ‘foreign’ interchangeably of a language, as any distinction that may be made is not relevant in the context of a world in which there were no nation-states (or notions of political correctness). If I were to prefer one to the other it would be ‘foreign’: native speakers of Latin regarded everyone else but Greek-speakers as foreigners, or, as they called them, barbari. The foreigners came to have a higher regard for Latin than the native speakers of Latin had for their languages; but unlike the British in more recent times the latter never sought to impose their language on the former, nor even to encourage its adoption by them.
Management of the left subclavian artery during TEVAR – complications and mid-term follow-up
Authors: Youssef Akram , Ghazy Tamer , Kersting Stephan , Leip Jennifer Lynne , Hoffmann Ralf-Thorsten , Kappert Utz , Matschke Klaus , Weiss Norbert , Mahlmann Adrian
Published: May 2018

Abstract. Background: Numerous conditions that affect the boundary between the aortic arch and descending aorta are treated with thoracic endovascular aortic repair (TEVAR). In 40 % of cases, coverage of the left subclavian artery (LSA) cannot be prevented. Subsequently, neurological complications such as stroke or ischemia of the left upper extremity may develop. However, the actual risk of these complications is subject to considerable controversy. The optimal treatment approach, specifically the question whether primary revascularization of the LSA should be performed in all cases, is unclear. Patients and methods: The present retrospective study analyzed the short- and mid-term results of patients treated with TEVAR with complete coverage of the LSA. The postoperative protocol consisted of clinical and noninvasive examinations as well as morphological imaging. Survival, complication, and reintervention rates were recorded. Results: A total of 40 patients, undergoing TEVAR with complete coverage of the LSA between January 2010 and December 2014 were analyzed retrospectively. The 30-day survival rate was 95 %, the survival one year after performed TEVAR was 67.5 %. The average follow-up was 1.5 years. After TEVAR procedure with complete coverage of the LSA, only one patient (2.5 %) developed critical ischemia of the left arm immediately after aortic stent implantation, requiring revascularization by transposition of the LSA. Anterior spinal artery syndrome occurred in another patient (2.5 %) immediately following TEVAR. During follow-up examinations, all patients showed a compensated arterial arm status. None of the patients developed new neurological deficits during the follow-up period. Conclusions: The study shows that performing TEVAR without primary revascularization of the LSA was justifiable in our cohort. An important risk factor of developing cerebral ischemia seems to be insufficient collateralization through the circle of Willis.
Furchen im Herzen – ein Zufallsbefund bei	parainfektiöser Myokarditis
Authors: Berger Florian , Hansi Christopher , Niemann Tilo
Published: May 2018

Zusammenfassung. Wir berichten über den Fall einer 23-jährigen Patientin, bei der im Rahmen der Bilanzierung einer para­infektiösen Myokarditis eine transthorakale Echokardiografie durchgeführt wurde. Als Zufallsbefund zeigte sich eine kleine ­lokale Aussparung im linken Herzventrikel basal inferior. Zur weiteren Abklärung bei unklarer Situation wurde eine kardiale Magnetresonanztomografie durchgeführt, bei der eine Furche des Myokards, eine Normvariante des Wandaufbaus des Herzens, festgestellt wurde. Bei einer kardialen Magnetresonanztomografie handelt es sich um eine nicht-invasive Bildgebungsmodalität mit hoher räumlicher und zeitlicher Bildauflösung, die eine genaue Darstellung der Anatomie des Herzens und somit eine Unterscheidung zwischen Normvarianten und pathologischen Veränderungen des Herzens ermöglicht.
Advance Research Directives in Germany
Authors: Scholten Matthé , Gieselmann Astrid , Gather Jakov , Vollmann Jochen
Published: May 2018

Abstract. The fourth amendment to the German Medicinal Products Act (Arzneimittelgesetz) states that nontherapeutic research in incompetent populations is permissible under the condition that potential research participants expressly declare their wish to participate in scientific research in an advance research directive. This article explores the implementation of advance research directives in Germany against the background of the international legal and ethical framework for biomedical research. In particular, it addresses a practical problem that arises from the disclosure requirement for advance research directives. We show that, if the disclosure standard for advance research directives is set at a token level, nontherapeutic research in incompetent populations becomes practically impossible. To resolve this issue, we suggest the disclosure standard be set at a type level.
EarthN: A New Earth System Nitrogen Model
Authors: Johnson Benjamin W. , Goldblatt Colin
Published: May 2018

The amount of nitrogen in the atmosphere, oceans, crust, and mantle have important ramifications for Earth's biologic and geologic history. Despite this importance, the history and cycling of nitrogen in the Earth system is poorly constrained over time. For example, various models and proxies contrastingly support atmospheric mass stasis, net outgassing, or net ingassing over time. In addition, the amount available to and processing of nitrogen by organisms is intricately linked with and provides feedbacks on oxygen and nutrient cycles. To investigate the Earth system nitrogen cycle over geologic history, we have constructed a new nitrogen cycle model: EarthN. This model is driven by mantle cooling, links biologic nitrogen cycling to phosphate and oxygen, and incorporates geologic and biologic fluxes. Model output is consistent with large (2‐4x) changes in atmospheric mass over time, typically indicating atmospheric drawdown and nitrogen sequestration into the mantle and continental crust. Critical controls on nitrogen distribution include mantle cooling history, weathering, and the total Bulk Silicate Earth + atmosphere nitrogen budget. Linking the nitrogen cycle to phosphorous and oxygen levels, instead of carbon as has been previously done, provides new and more dynamic insight into the history of nitrogen on the planet.
In Situ Quantitative Raman Detection of Dissolved Carbon Dioxide and Sulfate in Deep‐Sea High‐Temperature Hydrothermal Vent Fluids
Authors: Li Lianfu , Zhang Xin , Luan Zhendong , Du Zengfeng , Xi Shichuan , Wang Bing , Cao Lei , Lian Chao , Yan Jun
Published: May 2018

Carbon dioxide emitted from hydrothermal vents, as an important part of the global carbon cycle, can directly affect hydrothermal ecosystems. However, traditional chemical analysis methods cannot directly measure the concentrations of dissolved CO2 in high‐temperature hydrothermal fluids. Although in situ mass spectrometry has been applied to the measurements of deep sea, it cannot be used to detect high‐temperature fluids. In this study, an in situ Raman quantitative method for measuring dissolved CO2 suitable for a hydrothermal environment is established. The Raman relative intensity of CO2 displayed a linear relationship with increasing concentration of CO2 under the investigated conditions (up to 300°C and 40 MPa), allowing this in situ measurement method to be applied to most hydrothermal fields worldwide. Moreover, we find that the quantitative calibration curve for
for high‐temperature and high‐pressure conditions is identical to that of
for room temperature and atmospheric pressure. The concentrations of CO2 in mid‐Okinawa Trough hydrothermal fluids determined by in situ Raman measurement are 188.4–532.3 mmol/kg, which are about 3 times higher than those obtained by traditional sampling methods (59–198 mmol/kg). However, the concentrations of
calculated from in situ Raman spectra were near zero, indicating that the in situ Raman measurement avoids hydrothermal fluids contaminated with seawater.
Reconfigurable elastomeric graded-index optical elements controlled by light
Authors: Angelini Angelo , Pirani Federica , Frascella Francesca , Descrovi Emiliano
Published: May 2018

In many optical applications, there is an increasing need for dynamically tunable optical elements that are able to shape the wavefront of light ‘on demand’. In this work, an elastomeric easy-to-fabricate optical element whose transmission functions can be reversibly phase configured by visible light is demonstrated. The light responsivity of proper azopolymers incorporated within an elastomeric matrix is exploited to induce a light-controlled graded refractive index (GRIN) distribution within the bulk compound. The induced refractive index distribution is continuous and conformal to the intensity profile of the illumination at moderate power. A 100 mW doubled-frequency Nd:YAG Gaussian beam focused to a 650 μm waist is shown to induce a maximum relative refractive index change of ~0.4% in the elastomeric matrix, with an approximately parabolic profile. The restoring characteristics of the elastomeric matrix enable full recovery of the initial homogeneous refractive index distribution within a few seconds when the incident laser is switched off. As an exemplary application, the configurable GRIN element is used in a microscope-based imaging system for light control of the effective focal length.
Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor
Authors: Wang Zhuo , Stuckey Daniel J. , Murdoch Colin E. , Camelliti Patrizia , Lip Gregory Y. H. , Griffin Martin
Published: May 2018

Cardiac fibrosis is implicit in all forms of heart disease but there are no effective treatments. In this report, we investigate the role of the multi-functional enzyme Transglutaminase 2 (TG2) in cardiac fibrosis and assess its potential as a therapeutic target. Here we describe the use a highly selective TG2 small-molecule inhibitor to test the efficacy of TG2 inhibition as an anti-fibrotic therapy for heart failure employing two different in vivo models of cardiac fibrosis: Progressively induced interstitial cardiac fibrosis by pressure overload using angiotensin II infusion: Acutely induced focal cardiac fibrosis through myocardial infarction by ligation of the left anterior descending coronary artery (AMI model). In the AMI model, in vivo MRI showed that the TG2 inhibitor 1–155 significantly reduced infarct size by over 50% and reduced post-infarct remodelling at 20 days post insult. In both models, Sirius red staining for collagen deposition and levels of the TG2-mediated protein crosslink ε(γ-glutamyl)lysine were significantly reduced. No cardiac rupture or obvious signs of toxicity were observed. To provide a molecular mechanism for TG2 involvement in cardiac fibrosis, we show that both TGFβ1-induced transition of cardiofibroblasts into myofibroblast-like cells and TGFβ1-induced EndMT, together with matrix deposition, can be attenuated by the TG2 selective inhibitor 1–155, suggesting a new role for TG2 in regulating TGFβ1 signalling in addition to its role in latent TGFβ1 activation. In conclusion, TG2 has a role in cardiac fibrosis through activation of myofibroblasts and matrix deposition. TG2 inhibition using a selective small-molecule inhibitor can attenuate cardiac fibrosis.
Critical role of OX40 in the expansion and survival of CD4 T-cell-derived double-negative T cells
Authors: Sun Guangyong , Sun Xiaojing , Li Wei , Liu Kai , Tian Dan , Dong Yiran , Sun Xuelian , Xu Hufeng , Zhang Dong
Published: May 2018

CD4+T-cell-converted CD4−CD8−double negative (cDNT) have strong suppressive activity in the maintenance of immune tolerance, whereas IL-2 promotes cDNT proliferation and enhances cDNT resistance to apoptosis. However, the intrinsic mechanisms that regulate the survival of cDNT are still unknown. Here we demonstrate that theOX40molecule was highly expressed on cDNT. The expression ofOX40was necessary to promote proliferation and inhibit apoptosis of cDNT in vivo and in vitro.OX40promoted the survival of cDNT by regulating the expression of Bcl-2, Bcl-xL, Survivin, and BCL2L11. Canonical NF-κB cell signaling played an important role in the transmission of essential division and survival signals throughOX40in cDNT. IL-2 promoted the survival of cDNT in part via elevating the expression of theOX40molecule. IL-2 promotedOX40expression via downregulating the PPARα expression. In conclusion, we elucidated thatOX40is a key molecule that regulates cDNT proliferation and survival. IL-2 promotedOX40expression by downregulating the PPARα binding to theOX40promoter, leading to the elevated expression of Bcl-2, Bcl-xL, and Survivin in cDNT, which finally resulted in the promoted proliferation and decreased apoptosis of cDNT.
DNMT1 mediates metabolic reprogramming induced by Epstein–Barr virus latent membrane protein 1 and reversed by grifolin in nasopharyngeal carcinoma
Authors: Luo Xiangjian , Hong Liping , Cheng Can , Li Namei , Zhao Xu , Shi Feng , Liu Jikai , Fan Jia , Zhou Jian , Bode Ann M. , Cao Ya
Published: May 2018

Cancer cells frequently adapt fundamentally altered metabolism to support tumorigenicity and malignancy. Epigenetic and metabolic networks are closely interactive, in which DNA methyltransferases (DNMTs) play important roles. Epstein–Barr virus (EBV)-encoded latent membrane protein 1 (EBV-LMP1) is closely associated with nasopharyngeal carcinoma (NPC) pathogenesis because it can trigger multiple cell signaling pathways that promote cell transformation, proliferation, immune escape, invasiveness, epigenetic modification, and metabolic reprogramming. Our current findings reveal for the first time that LMP1 not only upregulates DNMT1 expression and activity, but also promotes its mitochondrial translocation. This induces epigenetic silencing of pten and activation of AKT signaling as well as hypermethylation of the mtDNA D-loop region and downregulation of oxidative phosphorylation (OXPHOS) complexes, consequently, leading to metabolic reprogramming in NPC. Furthermore, we demonstrate that grifolin, a natural farnesyl phenolic compound originated from higher fungi, is able to attenuate glycolytic flux and recover mitochondrial OXPHOS function by inhibiting DNMT1 expression and activity as well as its mitochondrial retention in NPC cells. Therefore, our work establishes a mechanistic connection between epigenetics and metabolism in EBV-positive NPC and provides further evidence for pathological classification based on CpG island methylator phenotype (CIMP) in EBV-associated malignancies. In addition, grifolin might be a promising lead compound in the intervention of high-CIMP tumor types. The availability of this natural product could hamper tumor cell metabolic reprogramming by targeting DNMT1.
Renal inhibition of miR-181a ameliorates 5-fluorouracil-induced mesangial cell apoptosis and nephrotoxicity
Authors: Liu Xiao-Yun , Zhang Fei-Ran , Shang Jin-Yan , Liu Ying-Ying , Lv Xiao-Fei , Yuan Jia-Ni , Zhang Ting-Ting , Li Kai , Lin Xiao-Chun , Liu Xiu , Lei Qingqing , Fu Xiao-Dong , Zhou Jia-Guo , Liang Si-Jia
Published: May 2018

The development of nephrotoxicity largely limits the clinical use of chemotherapy. MiRNAs are able to target various genes and involved in the regulation of diverse cellular processes, including cell apoptosis and death. Our study showed that miR-181a expression was significantly increased after 5-fluorouracil (5-FU) treatment in renal mesangial cells and kidney tissue, which was associated with decreased baculoviral inhibition of apoptosis protein repeat-containing 6 (BIRC6) expression and increased apoptotic rate. Enforced miR-181a expression enhanced 5-FU-induced p53-dependent mitochondrial apoptosis, including declined Bcl-2/Bax ratio, loss of mitochondrial membrane potential, cytochrome c release, and caspase-9 and caspase-3 activation. However, inhibition of miR-181a was associated with reduced p53-mediated mitochondrial apoptosis induced by 5-FU. Moreover, miR-181a increased BIRC6 downstream gene p53 protein expression and transcriptional activity by reducing ubiquitin-mediated protein degradation. We found that miR-181a directly targeted 3′-UTR of BIRC6 mRNA and negatively regulated BIRC6 expression. In vivo study, knockdown of miR-181a with adeno-associated virus harboring miR-181a-tough decoy attenuated 5-FU-induced renal cell apoptosis, inflammation and kidney injury. In conclusion, these results demonstrate that miR-181a increases p53 protein expression and transcriptional activity by targeting BIRC6 and promotes 5-FU-induced apoptosis in mesangial cells. Inhibition of miR-181a ameliorates 5-FU-induced nephrotoxicity, suggesting that miR-181a may be a novel therapeutic target for nephrotoxicity treatment during chemotherapy.
Pharmacologic inhibition of protein phosphatase-2A achieves durable immune-mediated antitumor activity when combined with PD-1 blockade
Authors: Ho Winson S. , Wang Herui , Maggio Dominic , Kovach John S. , Zhang Qi , Song Qi , Marincola Francesco M. , Heiss John D. , Gilbert Mark R. , Lu Rongze , Zhuang Zhengping
Published: May 2018

Mounting evidence suggests that inhibition of protein phosphatase-2A (PP2A), a serine/threonine phosphatase, could enhance anticancer immunity. However, drugs targeting PP2A are not currently available. Here, we report that a PP2A inhibitor, LB-100, when combined with anti-PD-1 (aPD-1) blockade can synergistically elicit a durable immune-mediated antitumor response in a murine CT26 colon cancer model. This effect is T-cell dependent, leading to regression of a significant proportion of tumors. Analysis of tumor lymphocytes demonstrates enhanced effector T-cell and reduced suppressive regulatory T-cell infiltration. Clearance of tumor establishes antigen-specific secondary protective immunity. A synergistic effect of LB-100 and aPD-1 blockade is also observed in B16 melanoma model. In addition, LB-100 activates the mTORC1 signaling pathway resulting in decreased differentiation of naive CD4 cells into regulatory T cells. There is also increased expression of Th1 and decreased expression of Th2 cytokines. These data highlight the translational potential of PP2A inhibition in combination with checkpoint inhibition.
Are autonomous cities our urban future?
Authors: Norman Barbara
Published: May 2018

Cities are rapidly expanding in size, wealth and power, with some now larger than nation states. Smart city solutions and strong global urban networks are developing to manage massive urban growth. However, cities exist within a wider system and it may take more than technological advances, innovation and city autonomy to develop a sustainable urban future.
Different combination strategies for prophylaxis of venous thromboembolism in patients: A prospective multicenter randomized controlled study
Authors: Sang Cui-Qin , Zhao Na , Zhang Jian , Wang Shu-Zhen , Guo Shu-Li , Li Shu-Hong , Jiang Ying , Li Bin , Wang Jian-Liu , Song Lei , Zhai Jian-Jun , Zhang Zhen-Yu
Published: May 2018

The aim was to evaluate the efficacy and safety of different combination strategies for prophylaxis of venous thromboembolism (VTE) after gynecologic surgery in patients at different levels of risk. This was a prospective multicenter randomized controlled study, in which 625 women who would undergo pelvic surgery for gynecologic diseases were stratified into three risk groups and then randomized into four groups to receive graduated compression stockings (GCS) alone (group A), GCS + low molecular weight heparin (LMWH) (group B), GCS + intermittent pneumatic compression (IPC) (group C), and GCS + IPC + LMWH (group C), respectively. The overall incidence of DVT was 5.1%. Group A had the highest incidence of DVT (8.8%), followed by group C (5.2%), group B (3.8%), and group D (2.6%). There was a significant difference in the incidence of DVT between groups A and D. The incidence of DVT was significantly lower in LMWH-treated patients (group B + group D) than in non-LMWH-treated patients (group A + group C). In conclusion, combination prophylaxis, especially LMWH-containing strategies, is better than monoprophylaxis in reducing VTE after gynecologic surgery. Risk-stratified prophylactic strategies should be implemented in patients undergoing gynecologic surgery, with LMWH-containing strategies being recommended for high-risk and very-high-risk patients.
The Evolution of Molecular Compatibility between Bacteriophage ΦX174 and its Host
Authors: Kula Alexander , Saelens Joseph , Cox Jennifer , Schubert Alyxandria M. , Travisano Michael , Putonti Catherine
Published: May 2018

Viruses rely upon their hosts for biosynthesis of viral RNA, DNA and protein. This dependency frequently engenders strong selection for virus genome compatibility with potential hosts, appropriate gene regulation and expression necessary for a successful infection. While bioinformatic studies have shown strong correlations between codon usage in viral and host genomes, the selective factors by which this compatibility evolves remain a matter of conjecture. Engineered to include codons with a lesser usage and/or tRNA abundance within the host, three different attenuated strains of the bacterial virus ФX174 were created and propagated via serial transfers. Molecular sequence data indicate that biosynthetic compatibility was recovered rapidly. Extensive computational simulations were performed to assess the role of mutational biases as well as selection for translational efficiency in the engineered phage. Using bacteriophage as a model system, we can begin to unravel the evolutionary processes shaping codon compatibility between viruses and their host.
The effect of N-acetyl-l-cysteine (NAC) on liver toxicity and clinical outcome after hematopoietic stem cell transplantation
Authors: El-Serafi Ibrahim , Remberger Mats , El-Serafi Ahmed , Benkessou Fadwa , Zheng Wenyi , Martell Eva , Ljungman Per , Mattsson Jonas , Hassan Moustapha
Published: May 2018

Busulphan (Bu) is a myeloablative drug used for conditioning prior to hematopoietic stem cell transplantation. Bu is predominantly metabolized through glutathione conjugation, a reaction that consumes the hepatic glutathione. N-acetyl-l-cysteine (NAC) is a glutathione precursor used in the treatment of acetaminophen hepatotoxicity. NAC does not interfere with the busulphan myeloablative effect. We investigated the effect of NAC concomitant treatment during busulphan conditioning on the liver enzymes as well as the clinical outcome. Prophylactic NAC treatment was given to 54 patients upon the start of busulphan conditioning. These patients were compared with 54 historical matched controls who did not receive NAC treatment. In patients treated with NAC, aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were significantly (P < 0.05) decreased after conditioning compared to their start values. Within the NAC-group, liver enzymes were normalized in those patients (30%) who had significantly high start values. No significant decrease in enzyme levels was observed in the control group. Furthermore, NAC affected neither Bu kinetics nor clinical outcome (sinusoidal obstruction syndrome incidence, graft-versus-host disease and/or graft failure). In conclusion: NAC is a potential prophylactic treatment for hepatotoxicity during busulphan conditioning. NAC therapy did not alter busulphan kinetics or affect clinical outcome.
Induction of ganglioside synthesis in Drosophila brain accelerates assembly of amyloid β protein
Authors: Yamasaki Yasutoyo , Tsuda Leo , Suzuki Akemi , Yanagisawa Katsuhiko
Published: May 2018

The assembly and deposition of amyloid β protein (Aβ) is a fundamental event during the early stages of Alzheimer’s disease (AD) and cerebral amyloid angiopathy. A growing body of evidence indicates that gangliosides form a pathological platform for the generation of ganglioside-bound Aβ, which facilitates the assembly of soluble Aβs; however, the molecular mechanisms underlying the binding of Aβ to gangliosides in the brain remain unclear due to the lack of an in vivo system that may address this issue. In insects, including the fruit fly Drosophila melanogaster, gangliosides are not intrinsically present at a detectable level. We herein demonstrate that ganglioside expression is inducible in Drosophila via the expression of transgenes of ganglioside synthesis enzymes and the feeding of exogenous sialic acid, and also that the induction of ganglioside synthesis significantly accelerates Aβ assembly in vivo. Our results support the hypothesis that gangliosides are responsible for Aβ assembly in vivo and also provide an opportunity to develop a valuable model for basic research as well as a therapeutic strategy for AD.
Metagenomic insights into the microbial diversity in manganese-contaminated mine tailings and their role in biogeochemical cycling of manganese
Authors: Ghosh Shreya , Das Alok Prasad
Published: May 2018

To extend the knowledge on the microbial diversity of manganese rich environments, we performed a clone library based study using metagenomic approach. Pyrosequencing based analysis of 16S rRNA genes were carried out on an Illumina platform to gain insights into the bacterial community inhabiting in a manganese mining site and the taxonomic profiles were correlated with the inherent capacities of these strains to solubilise manganese. The application of shot gun sequencing in this study yielded results which revealed the highest prevalence of Proteobacteria (42.47%), followed by Actinobacteria (23.99%) in the area of study. Cluster of orthologous group (COG) functional category has 85,066 predicted functions. Out of which 11% are involved in metabolism of amino acid, 9% are involved in production and conversion of energy while Keto Encyclopedia of Gene and Genomes (KEGG) functional category has 107,388 predicted functions, out of which 55% are involved in cellular metabolism, 15% are environmental and information processing and 12% are genetic information processing in nature. The isolated microbial consortia demonstrated visible growth in presence of high concentrations of Mn. Solubilisation studies resulted in 86% of manganese recovery after 20 days. The result presented in this study has important implications in understanding the microbial diversity in manganese contaminated mine tailings and their role in natural geochemical cycling of Mn.
Temperature and the vertical movements of oceanic whitetip sharks, Carcharhinus longimanus
Authors: Andrzejaczek Samantha , Gleiss Adrian C. , Jordan Lance K. B. , Pattiaratchi Charitha B. , Howey Lucy A. , Brooks Edward J. , Meekan Mark G.
Published: May 2018

Large-bodied pelagic ectotherms such as sharks need to maintain internal temperatures within a favourable range in order to maximise performance and be cost-efficient foragers. This implies that behavioural thermoregulation should be a key feature of the movements of these animals, although field evidence is limited. We used depth and temperature archives from pop-up satellite tags to investigate the role of temperature in driving vertical movements of 16 oceanic whitetip sharks,Carcharhinus longimanus, (OWTs). Spectral analysis, linear mixed modelling, segmented regression and multivariate techniques were used to examine the effect of mean sea surface temperature (SST) and mixed layer depth on vertical movements. OWTs continually oscillated throughout the upper 200 m of the water column. In summer when the water column was stratified with high SSTs, oscillations increased in amplitude and cycle length and sharks reduced the time spent in the upper 50 m. In winter when the water column was cooler and well-mixed, oscillations decreased in amplitude and cycle length and sharks frequently occupied the upper 50 m. SSTs of 28 oC marked a distinct change in vertical movements and the onset of thermoregulation strategies. Our results have implications for the ecology of these animals in a warming ocean.
Publisher Correction: Examining a Thermodynamic Order Parameter of Protein Folding
Authors: Chong Song-Ho , Ham Sihyun
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Characterizing co-expression networks underpinning maize stalk rot virulence in Fusarium verticillioides through computational subnetwork module analyses
Authors: Kim Man S. , Zhang Huan , Yan Huijuan , Yoon Byung-Jun , Shim Won Bo
Published: May 2018

Fusarium verticillioidesis recognized as an important stalk rot pathogen of maize worldwide, but our knowledge of genetic mechanisms underpinning this pathosystem is limited. Previously, we identified a striatin-like protein Fsr1 that plays an important role in stalk rot. To further characterize transcriptome networks downstream of Fsr1, we performed next-generation sequencing (NGS) to investigate relative read abundance and also to infer co-expression networks utilizing the preprocessed expression data through partial correlation. We used a probabilistic pathway activity inference strategy to identify functional subnetwork modules likely involved in virulence. Each subnetwork modules consisted of multiple correlated genes with coordinated expression patterns, but the collective activation levels were significantly different inF. verticillioideswild type versusfsr1mutant. We also identified putative hub genes from predicted subnetworks for functional validation and network robustness studies through mutagenesis, virulence and qPCR assays. Our results suggest that these genes are important virulence genes that regulate the expression of closely correlated genes, demonstrating that these are important hubs of their respective subnetworks. Lastly, we used keyF. verticillioidesvirulence genes to computationally predict a subnetwork of maize genes that potentially respond to fungal genes by applying cointegration-correlation-expression strategy.
Quality control of the traditional Chinese medicine Ruyi jinhuang powder based on high-throughput sequencing and real-time PCR
Authors: Li Qiang , Sun Ying , Guo Huijun , Sang Feng , Ma Hongyu , Peng Hai , Zheng Na , Xu Liran
Published: May 2018

Traditional Chinese medicine (TCM) has been practiced for thousands of years, although concerns about the efficacy, legality, and safety of TCM continue to be raised. Chromatographic studies have detected the presence of heavy metals and plant toxins within some TCM preparations. However, chromatography is not able to identify all of the compounds of TCM, particularly those items that are not clearly labeled on the packaging. The present study aimed to establish a supplemental method that better assesses the ingredient components of TCM preparations.We established an effective approach to screen the biological and toxical composition of TCM based on high-throughput sequencing (HTS), as well as fast detection and validation of the toxical species by real-time PCR, based on ITS2 DNA barcoding. Ruyi jinhuang powder (RHP), a classical herbal prescription containing the toxical herb Arisaematis rhizoma, was chosen to test the method. This method could determine whether the Arisaematis Rhizoma had been replaced by Pinellia pedatisecta in the RHP. The results were validated by real-time PCR. 90% compositions of RHP were identified by ITS2 DNA barcoding, suggesting that more DNA barcoding markers are needed for TCM identification. The strategy of high-throughput sequencing has the potential for comprehensive ingredient profiling for TCM preparations. Real-time PCR provides a expeditious metehod for monitoring the safety and legality of TCM preparations.
Dexamethasone-induced Intra-Uterine Growth Restriction impacts NOSTRIN and its downstream effector genes in the rat mesometrial uterus
Authors: Chakraborty Shreeta , Islam Safirul , Saha Sarbani , Ain Rupasri
Published: May 2018

Intra-Uterine Growth Restriction (IUGR) is a major cause of fetal and neonatal mortality. Understanding the impact of IUGR on utero-placental gene expression is key to developing effective therapy. In this report we elucidated the impact of IUGR on NOSTRIN and its downstream effector gene expression in the utero-placental compartments. We showed here that induction of IUGR by maternal dexamethasone administration in rats led to up-regulation of NOSTRIN transcript and protein in the mesometrial triangle of the uterus (MG) and not in other utero-placental compartments as compared to control. This was associated with down-regulation of twelve genes and four cytokines that were known to be regulated by NOSTRIN and also required for maintenance of pregnancy. Interestingly, there was remarkable decrease in phosphorylation of RelA transcription factor in the MG during IUGR in line with the fact that the down regulated genes harbour RelA transcription activation domain in their promoters. Furthermore, HIF-1α level was reciprocal to NOSTRIN expression pattern in the mesometrial compartment during IUGR and also in CoCl2 treated endothelial cells. Over-expression of HIF-1α led to a decrease in NOSTRIN levels suggesting inhibition of Nostrin transcription by HIF-1α. Our findings highlight the importance of NOSTRIN in uterine pathophysiology during IUGR.
Asymmetric distribution of biomolecules of maternal origin in the Xenopus laevis egg and their impact on the developmental plan
Authors: Sindelka Radek , Abaffy Pavel , Qu Yanyan , Tomankova Silvie , Sidova Monika , Naraine Ravindra , Kolar Michal , Peuchen Elizabeth , Sun Liangliang , Dovichi Norman , Kubista Mikael
Published: May 2018

Asymmetric cell division is a ubiquitous feature during the development of higher organisms. Asymmetry is achieved by differential localization or activities of biological molecules such as proteins, and coding and non-coding RNAs. Here, we present subcellular transcriptomic and proteomic analyses along the animal-vegetal axis of Xenopus laevis eggs. More than 98% of the maternal mRNAs could be categorized into four localization profile groups: animal, vegetal, extremely vegetal, and a newly described group of mRNAs that we call extremely animal, which are mRNAs enriched in the animal cortex region. 3′UTRs of localized mRNAs were analyzed for localization motifs. Several putative motifs were discovered for vegetal and extremely vegetal mRNAs, while no distinct conserved motifs for the extremely animal mRNAs were identified, suggesting different localization mechanisms. Asymmetric profiles were also found for proteins, with correlation to those of corresponding mRNAs. Based on unexpected observation of the profiles of the homoeologous genes exd2 we propose a possible mechanism of genetic evolution.
Extended investigation of tube-gel sample preparation: a versatile and simple choice for high throughput quantitative proteomics
Authors: Muller Leslie , Fornecker Luc , Chion Marie , Van Dorsselaer Alain , Cianférani Sarah , Rabilloud Thierry , Carapito Christine
Published: May 2018

Sample preparation for quantitative proteomics is a crucial step to ensure the repeatability and the accuracy of the results. However, there is no universal method compatible with the wide variety of protein extraction buffers currently used. We have recently demonstrated the compatibility of tube-gel with SDS-based buffers and its efficiency for label-free quantitative proteomics by comparing it to stacking gel and liquid digestion. Here, we investigated the compatibility of tube-gel with alternatives to SDS-based buffers allowing notably the extraction of proteins in various pH conditions. We also explored the use of photopolymerization to extend the number of possibilities, as it is compatible with a wide range of pH and is non-oxidative. To achieve this goal, we compared six extraction buffers in combination with two polymerization conditions to further optimize the tube-gel protocol and evaluate its versatility. Identification and quantitative results demonstrated the compatibility of tube-gel with all tested conditions by overall raising quite comparable results. In conclusion, tube-gel is a versatile and simple sample preparation method for large-scale quantitative proteomics applications. Complete datasets are available via ProteomeXchange with identifier PXD008656.
Sedimentary environment and depositional evolution of the Mesoproterozoic Bingmagou Formation on the southern margin of the North China Craton
Authors: Yue Liang , Liu ZiLiang , Ma Yongsheng
Published: May 2018

The Precambrian sedimentary strata on the southern margin of the North China Craton are well developed and widely exposed, making the region ideal for the study of depositional processes. However, because of the length of the depositional history and the lack of biogenic criteria, interpretations of the sedimentary environments of the Precambrian strata are often based on the tectonic background, geographical environment, rock type and sedimentary structures, resulting in controversies in the literature. In this study of the Bingmagou Formation in the Ruyang Group on the southern margin of the North China Craton, analysis of petrologic features, palaeocurrents and sedimentary facies is combined with regional correlation of relevant strata and the reconstruction of ancient landforms to explain the depositional environments and environmental transitions. Dominated by marine deposits on the southern margin of the North China Craton, the sedimentary strata of the Ruyang Group unconformably overlie the Archean crystalline basement or Proterozoic Xionger Group. As the lowermost unit of the Ruyang Group, the Bingmagou Formation, which was depositionally controlled by topography and faults and received abundant detrital material, is a highly distinctive set of sedimentary strata and represents an environmental transition from alluvial fan to sandy coast.