bluuebunny/crossref_metadata_2025 huggingface dataset:
A postprocessed flux conserving finite element solution
Authors: Zhang Shangyou , Zhang Zhimin , Zou Qingsong
Published: May 2017

We propose a local postprocessing method to get a new finite element solution whose flux is conservative element‐wise. First, we use the so‐called polynomial preserving recovery (postprocessing) technique to obtain a higher order flux which is continuous across the element boundary. Then, we use special bubble functions, which have a nonzero flux only on one face‐edge or face‐triangle of each element, to correct the finite element solution element by element, guided by the above super‐convergent flux and the element mass. The new finite element solution preserves mass element‐wise and retains the quasioptimality in approximation. The method produces a conservative flux, of high‐order accuracy, satisfying the constitutive law. Numerical tests in 2D and 3D are presented.© 2017 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 33: 1859–1883, 2017
Neonatal Abstinence Syndrome: Update on Diagnostic and Therapeutic Strategies
Authors: Raffaeli Genny , Cavallaro Giacomo , Allegaert Karel , Wildschut Enno Diederik , Fumagalli Monica , Agosti Massimo , Tibboel Dick , Mosca Fabio
Published: May 2017

Substance use among pregnant women is a major public health issue. Both prescription opioid use and illicit opioid abuse have increased dramatically in recent years. Prolonged in utero drug exposure may result in neonatal abstinence syndrome (NAS), an acute multisystemic clinical entity that occurs in the first days of life. This syndrome is caused by abrupt discontinuation of fetal exposure to licit or illicit drugs chronically consumed by the mother during pregnancy and transmitted to the fetus through the placenta. It usually requires prolonged hospitalization and may have long‐term effects. The interplay of many factors contributes to its clinical heterogeneity, and its pathophysiology has not been fully unveiled. The first step in NAS management consists of nonpharmacologic interventions and includes promoting breastfeeding when not contraindicated. If withdrawal signs become severe, pharmacotherapy is needed. The Finnegan scoring system supports care providers across the pharmacotherapy process from initiation through the monitoring phase, until weaning and discontinuation. However, a standardized approach to pharmacotherapy is still lacking. Morphine is usually the first‐line agent to treat NAS. Methadone is a valid option, but its safety profile is not completely known. Phenobarbital, despite its lack of effect on gastrointestinal symptoms and unfavorable pharmacologic features, has been identified as a second‐line agent to be used in infants unresponsive to opiates. Although buprenorphine and clonidine seem promising, their use requires further validation. Long‐term developmental effects of NAS therapy call for more‐comprehensive, longitudinal assessments. In this article, key points for use of recommended therapies are outlined, and directions for future research are suggested.
Proteome analysis of Duck Tembusu virus (DTMUV)‐infected BHK‐21 cells
Authors: Sun Xin , Wang Shengyu , Lin Xian , Zhao Lianzhong , Zhang Dan , Yi Chenyang , Sun Xiaomei , Chen Huanchun , Jin Meilin
Published: May 2017

Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused huge economic losses to the duck industry in China since 2010. Moreover, the infection has spread rapidly, posing a potential public health concern. In this study, iTRAQ approach was first used to quantitatively identify differentially expressed cellular proteins in DTMUV‐infected BHK‐21 cells which are usually employed to produce veterinary vaccines for DTMUV, as well as other flaviviruses by serial passage. We identified 192 differentially expressed cellular proteins, including 11 upregulated and eight downregulated proteins at 24 h postinfection (hpi), as well as 25 upregulated and 151 downregulated proteins at 48 hpi, of which TLR9, DDX3X, and DDX5 may play important roles in virus propagation. Further, DDX3X could inhibit DTMUV replication by modulating the IFN pathway via TBK1. In conclusion, our study is the first to analyze the protein profile of DTMUV‐infected cells by quantitative proteomics. We believe that our findings provide valuable information in better understanding the host response to DTMUV infection. These findings are particularly important in the development of vaccine‐based strategies.
Analogies across auxetic models based on deformation mechanism
Authors: Lim Teik‐Cheng
Published: May 2017

This paper reviews 2D auxetic models, including 3D deformation models with 2D auxetic behavior, from mechanism perspective instead of geometrical perspective. On this basis, auxetic models across different geometrical groups can be regrouped into clusters that exhibit analogy in deformation mechanism. Factors that are taken into consideration include the identification of corresponding (i) rotation and non‐rotation units, as well as (ii) linkages/joints between rotation and non‐rotation units and non‐linkages/non‐joints across various auxetic models. As a result, five clusters of auxetic models have been identified, in which auxetic models within each cluster are analogous to each other. The identified clusters are those that exhibit: (a) double periodicity in the rotation direction of their rotating units, (b) synchronized rotation direction of their rotation units, (c) single periodicity in the rotation direction of their rotating units, (d) random rotation of their rotation units, and (e) non‐rotation of units. Results from this analogy identification place auxetic models in a systematic representation and will enrich future development of auxetic models, particularly those that do not fall within these five clusters. It is proposed that future work includes 3D auxetic models as well as ordering of analogous auxetic models according to their joints or linkage geometries.
The interactive role of eating regulation and stress in the prediction of weight‐related outcomes among college students
Authors: Arsiwalla Dilbur D. , Arnold Amanda W. , Teel Karla P. , Ulrich Pamela V. , Gropper Sareen S.
Published: May 2017

The interactive role of eating regulation and perceived stress on weight‐related outcomes was examined among 319 sophomore year college students (110 males and 209 females). Moderated regressions were used to examine interactions between stress and eating regulation on study outcomes including body mass index (BMI) and body fat. Eating regulation moderated associations between stress and BMI and body fat outcomes. Students reporting high perceived stress, high autonomous eating regulation, low controlled regulation, and low amotivation exhibited higher outcomes (BMI and body fat) than those with similar eating regulation but lower perceived stress. Students with lower autonomous eating regulation and higher controlled regulation had no differences in study outcomes across levels of stress. College students who regulate their eating behaviours for health reasons (specifically showing autonomous regulation) exhibit higher BMI and body fat when they report higher levels of perceived stress. Health promotion programs for college students need to target education efforts towards stress reduction and healthy eating behaviours.
Human iPSC-MSC-Derived Xenografts Modulate Immune Responses by Inhibiting the Cleavage of Caspases
Authors: Li Cheng-Lin , Leng Yun , Zhao Bin , Gao Chang , Du Fei-Fei , Jin Ning , Lian Qi-Zhou , Xu Shuang-Yue , Yan Guo-Liang , Xia Jun-Jie , Zhuang Guo-Hong , Fu Qing-Ling , Qi Zhong-Quan
Published: May 2017

Mesenchymal stem cells (MSCs) negatively modulate immune properties. Induced pluripotent stem cells (iPSCs)-derived MSCs are alternative source of MSCs. However, the effects of iPSC-MSCs on T cells phenotypes in vivo remain unclear. We established an iPSC-MSC-transplanted host versus graft reaction mouse model using subcapsular kidney injection. Th1, Th2, regulatory T cells (Treg), and Th17 phenotypes and their cytokines were investigated in vivo and in vitro. The role of caspases and the soluble factors involved in the effects of MSCs were examined. We found that iPSC-MSC grafts led to more cell survival and less infiltration of inflammatory cells in mice. iPSC-MSC transplantation inhibited T cell proliferation, decreased Th1 and Th2 phenotypes and cytokines, upregulated Th17 and Treg subsets. Moreover, iPSC-MSCs inhibited the cleavage of caspases 3 and 8 and inhibition of caspases downregulated Th1, Th2 responses and upregulated Th17, Treg responses. Soluble factors were determined using protein array and TGF-β1/2/3, IL-10, and MCP-1 were found to be highly expressed in iPSC-MSCs. The administration of the soluble factors decreased Th1/2 response, upregulated Treg response and inhibited the cleavage of caspases. Our results demonstrate that iPSC-MSCs regulate T cell responses as a result of a combined action of the above soluble factors secreted by iPSC-MSCs. These factors suppress T cell responses by inhibiting the cleavage of caspases. These data provide a novel immunomodulatory mechanism for the underlying iPSC-MSC-based immunomodulatory effects on T cell responses.
Probing nanostructured materials using X‐ray fluorescence analysis
Authors: Das Gangadhar , Khooha Ajay , Singh A.K. , Tiwari M.K.
Published: May 2017

Dispersion of metal nanoparticles on flat surfaces has attracted considerable interest in many technological applications. Numerous advantages of functionalized patterned nanostructures especially in medical physics, chemistry, biology, and semiconductor quantum dot applications have rapidly driven the growth of this field in the last two decades. In particular, for applications involving biomedical imaging, the nanoparticles have attracted perhaps the greatest attention as these materials provide a direct interface at the subcellular length scale. Reliable characterization methods are thus often needed to infer their detailed structural properties such as average particle size, particle shape, internal structure, surface morphology, distribution of particles, and their chemical composition. As a nondestructive probe, X‐ray fluorescence measurements at grazing incidence provide sensitive information about the physical and chemical nature of the nanoparticles over the large surface area of a substrate. Herein, we demonstrate the potential capabilities of the X‐ray fluorescence technique for reliable and precise determination of surface morphology of metal nanoparticles, dispersed on a flat surface. Our results show that X‐ray standing wave assisted fluorescence measurements are markedly sensitive to the nature of dispersion of nanoparticles on a substrate surface. We have analyzed different types of nanostructured materials; e.g. a W thin film structure and Au nanoparticles deposited on a Si surface. The average size of the Au nanoparticles estimated, using X‐ray standing wave fluorescence analysis, was found to closely agree with the atomic force microscopy measurements. The inherent features of the X‐ray fluorescence technique permit us to analyze distribution of all kinds of metal and metalloid nanoparticles on a flat surface. Copyright © 2017 John Wiley & Sons, Ltd.
Informatics and Technology in Resident Education
Authors: Niehaus William
Published: May 2017

Biomedical or clinical informatics is the transdisciplinary field that studies and develops effective uses of biomedical data, information technology innovations, and medical knowledge for scientific inquiry, problem solving, and decision making, with an emphasis on improving human health. Given the ongoing advances in information technology, the field of informatics is becoming important to clinical practice and to residency education. This article will discuss how informatics is specifically relevant to residency education and the different ways to incorporate informatics into residency education, and will highlight applications of current technology in the context of residency education. How informatics can optimize communication for residents, promote information technology use, refine documentation techniques, reduce medical errors, and improve clinical decision making will be reviewed. It is hoped that this article will increase faculty and trainees' knowledge of the field of informatics, awareness of available technology, and will assist practitioners to maximize their ability to provide quality care to their patients. This article will also introduce the idea of incorporating informatics specialists into residency programs to help practitioners deliver more evidenced‐based care and to further improve their efficiency.
Essential Lessons in a Potential Sarin Attack Disaster Plan for a Resource-Constrained Environment
Authors: Watermeyer Matthew John , Dippenaar Nicole , Simo Nelly Clotildea Tchouambou , Buchanan Sean , Laher Abdullah Ebrahim
Published: May 2017

Sarin is a potent nerve agent chemical weapon that was originally designed for military purposes as a fast-acting anti-personnel weapon that would kill or disable large numbers of enemy troops. Its potent toxicity, ease of deployment, and rapid degradation allow for rapid deployment by an attacking force, who can safely enter the area of deployment a short while after its release. Sarin has been produced and stockpiled by a number of countries, and large quantities of it still exist despite collective agreements to cease manufacture and destroy stockpiles. Sarin’s ease of synthesis, which is easily disseminated across the Internet, increases the risk that terrorist organizations may use sarin to attack civilians. Sarin has been used in a number of terrorist attacks in Japan, and more recently in attacks in the Middle East, where nonmilitary organizations have led much of the disaster relief and provision of medical care. In the present article, we examine and discuss the available literature on sarin’s historical use, delivery methods, chemical properties, mechanism of action, decontamination process, and treatment. We present a management guideline to assist with the recognition of an attack and management of victims by medical professionals and disaster relief organizations, specifically in resource-constrained and austere environments. (Disaster Med Public Health Preparedness. 2018;12:249–256)
Lorenz Oken (1779–1851):Naturphilosophieand the reform of natural history
Authors: GAMBAROTTO ANDREA
Published: May 2017

The paper focuses on the work of Lorenz Oken (1779–1851) in an attempt to make sense of the role played by RomanticNaturphilosophiein the development of natural history in Germany at the turn of the nineteenth century. It first focuses on the role played by Schelling and his Würzburg circle in the development of Oken's early views on natural history, then reconstructs Oken's mature programme for a reform of animal classification.
Adverse effects of consuming high fat–sugar diets on cognition: implications for understanding obesity
Authors: Yeomans Martin R.
Published: May 2017

There is increasing evidence for important roles of key cognitive processes, including attention, memory and learning, in the short-term decision making about eating. There is parallel evidence that people who are overweight or obese tend to perform worse on a variety of cognitive tasks. In this review, the evidence for these two ideas is summarised and then the idea that overconsumption of Western-style high-fat (HF)–high-sugar diets may underlie the association between obesity and poorer cognitive performance is explored. In particular, evidence in animals and human subjects that repeated consumption of HF or HF and sugar (HFS) diets leads to specific impairments in the functioning of the hippocampus, which underpin the consequent changes in cognition is summarised. These findings lead into the vicious cycle model (VCM), which suggests that these cognitive changes have knock-on negative effects for future appetite control, and evidence that altered hippocampal function is also associated with impaired appetite control is explored. The review concludes that there is consistent evidence in the animal literature and emerging evidence from human studies that supports this VCM. It is also noted, however, that to date studies lack the nutritional specificity needed to be able to translate these basic research findings into clear nutritional effects, and concludes that there is an urgent need for additional research to clarify the precise nature of the apparent effects of consuming HFS diets on cognition.
Rank-one convexity implies polyconvexity for isotropic, objective and isochoric elastic energies in the two-dimensional case
Authors: Martin Robert J. , Ghiba Ionel-Dumitrel , Neff Patrizio
Published: May 2017

We show that, in the two-dimensional case, every objective, isotropic and isochoric energy function that is rank-one convex on GL+(2) is already polyconvex on GL+(2). Thus, we answer in the negative Morrey's conjecture in the subclass of isochoric nonlinear energies, since polyconvexity implies quasi-convexity. Our methods are based on different representation formulae for objective and isotropic functions in general, as well as for isochoric functions in particular. We also state criteria for these convexity conditions in terms of the deviatoric part of the logarithmic strain tensor.
The International Court of Justice in the Leiden Journal: A Retrospective
Authors: MORGAN-FOSTER JASON , PINZAUTI GIULIA , WEBB PHILIPPA
Published: May 2017

Last year the International Court of Justice (ICJ) marked its seventieth anniversary, and in the most recent issue of the Leiden Journal of International Law, Hugh Thirlway recognized this milestone with a look back through some key developments at the Court, focusing on the last few years. Here, we would like to undertake a retrospective of another sort, paying tribute to the ongoing connection between the Court and the Journal by taking a brief tour through the Journal's coverage of the Court over the years. It is hoped that this retrospective will not only bring back some fond memories but also – by viewing this material as a whole, and pointing out certain gaps in the Journal’s coverage of the Court's work – stimulate future analyses.
“THE UNIVERSAL LANGUAGE OF THE FUTURE”: DECOLONIZATION, DEVELOPMENT, AND THE AMERICAN EMBRACE OF GLOBAL ENGLISH, 1945–1965
Authors: LEMBERG DIANA
Published: May 2017

The two decades following the Second World War were marked by geopolitical and pedagogical ferment, as researchers and policymakers debated the role of language teaching in a rapidly changing world. As European empires collapsed amid Cold War competition for global influence, limited colonial education systems gave way to new discourses connecting postcolonial educational expansion, international development aid, and language teaching. This article reveals increasing American interest in the connections between development and vehicular English from 1945 to 1965. Drawing on the work of anglophone reformers, American elites promoted English as a development tool, and institutionalized policies designed to spread it abroad. The rise of the idea of global English in the United States, the article shows, was rooted in an instrumental conception of language, which framed English as a politically neutral vehicle for communication, yet this discourse was contradicted by the United States’ strategic ambitions.
Differentiation of Life-History Traits among Palmer Amaranth Populations (Amaranthus palmeri) and Its Relation to Cropping Systems and Glyphosate Sensitivity
Authors: Bravo Washington , Leon Ramon G. , Ferrell Jason A. , Mulvaney Michael J. , Wood C. Wesley
Published: May 2017

Palmer amaranth’s ability to evolve resistance to different herbicides has been studied extensively, but there is little information about how this weed species might be evolving other life-history traits that could potentially make it more aggressive and difficult to control. We characterized growth and morphological variation among 10 Palmer amaranth populations collected in Florida and Georgia from fields with different cropping histories, ranging from continuous short-statured crops (vegetables and peanut) to tall crops (corn and cotton) and from intensive herbicide use history to organic production. Palmer amaranth populations differed in multiple traits such as fresh and dry weight, days to flowering, plant height, and leaf and canopy shape. Differences between populations for these traits ranged from 36% up to 87%. Although glyphosate-resistant (GR) populations collected from cropping systems including GR crops exhibited higher values of the aforementioned variables than glyphosate-susceptible (GS) populations, variation in traits was not explained by glyphosate resistance or distance between populations. Cropping system components such as crop rotation and crop canopy structure better explained the differences among populations. The higher growth of GR populations compared with GS populations was likely the result of multiple selection forces present in the cropping systems in which they grow rather than a pleiotropic effect of the glyphosate resistance trait. Results suggest that Palmer amaranth can evolve life-history traits increasing its growth and reproduction potential in cropping systems, which explains its rapid spread throughout the United States. Furthermore, our findings highlight the need to consider the evolutionary consequences of crop rotation structure and the use of more competitive crops, which might promote the selection of more aggressive biotypes in weed species with high genetic variability.
Hepatocyte polyploidization and its association with pathophysiological processes
Authors: Wang Min-Jun , Chen Fei , Lau Joseph T Y , Hu Yi-Ping
Published: May 2017

A characteristic cellular feature of the mammalian liver is the progressive polyploidization of the hepatocytes, where individual cells acquire more than two sets of chromosomes. Polyploidization results from cytokinesis failure that takes place progressively during the course of postnatal development. The proportion of polyploidy also increases with the aging process or with cellular stress such as surgical resection, toxic stimulation, metabolic overload, or oxidative damage, to involve as much as 90% of the hepatocytes in mice and 40% in humans. Hepatocyte polyploidization is generally considered an indicator of terminal differentiation and cellular senescence, and related to the dysfunction of insulin and p53/p21 signaling pathways. Interestingly, the high prevalence of hepatocyte polyploidization in the aged mouse liver can be reversed when the senescent hepatocytes are serially transplanted into young mouse livers. Here we review the current knowledge on the mechanism of hepatocytes polyploidization during postnatal growth, aging, and liver diseases. The biologic significance of polyploidization in senescent reversal, within the context of new ways to think of liver aging and liver diseases is considered.
A miRNA-101-3p/Bim axis as a determinant of serum deprivation-induced endothelial cell apoptosis
Authors: Kim Ji-Hee , Lee Dong-Keon , Kim Joohwan , Choi Seunghwan , Park Wonjin , Ha Kwon-Soo , Kim Tae-Hoon , Choe Jongseon , Won Moo-Ho , Kwon Young-Guen , Kim Young-Myeong
Published: May 2017

Serum deprivation or withdrawal induces apoptosis in endothelial cells, resulting in endothelial cell dysfunction that is associated with cardiovascular disease. However, there is still limited information on the role of miRNA in serum deprivation-induced apoptosis. Here we found that serum deprivation increased caspase-dependent apoptosis through miRNA-101-3p downregulation, without altering expression of its host gene RNA 3′-terminal phosphate cyclase-like 1, which was highly correlated with suppressed expression levels of Dicer and Argonaute 2 (Ago2), indicating that miR-101-3p is post-transcriptionally elevated in serum-deprived conditions. The decreased miR-101-3p caused elevated Bim expression by targeting its 3′-untranslated region (3′-UTR). This resulted in activation of the intrinsic pathway of apoptosis via interaction with Bcl-2, decreased mitochondrial membrane potential, cytochrome c release, mitochondrial reactive oxygen species (ROS) production, and caspase activation. These events were abrogated by miR-101-3p mimic and the proapoptotic Bim siRNA, which suggest a determinant role of the miR-101-3p/Bim axis in serum deprivation-induced apoptosis. The apoptosis induced by miR-101-3p-mediated Bim expression is mediated by both caspase-3 and -1, which are activated by two distinct intrinsic mechanisms, cytochrome c release and ROS-induced inflammasome activation, respectively. In other words, the antioxidant inhibited endothelial cell death mediated by caspase-1 that activated caspase-7, but not caspase-3. These findings provide mechanistic insight into a novel function of miR-101-3p in serum withdrawal-induced apoptosis triggered by activating two different intrinsic or mitochondrial apoptosis pathways, implicating miR-101-3p as a therapeutic target that limits endothelial cell death associated with vascular disorders.
Betulin exhibits anti-inflammatory activity in LPS-stimulated macrophages and endotoxin-shocked mice through an AMPK/AKT/Nrf2-dependent mechanism
Authors: Ci Xinxin , Zhou Junfeng , Lv Hongming , Yu Qinlei , Peng Liping , Hua Shucheng
Published: May 2017

Continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including cancer. Nuclear factor erythroid 2-related factor (Nrf2), a critical transcriptional activator for antioxidative responses, has envolved to be an attractive drug target for the treatment or prevention of human diseases. In the present study, we investigated the effects and mechanisms of betulin on Nrf2 activation and its involvement in the lipopolysaccharide (LPS)-triggered inflammatory system. In macrophages, betulin activated the Nrf2 signaling pathway and increased Nrf2-targeted antioxidant and detoxifying enzymes, including NADPH, quinine oxidoreductase 1 (NQO1), heme oxygenase-1 (HO-1), γ-glutamyl cysteine synthetase catalytic subunit (GCLC) and modifier subunit (GCLM) in a dose and time dependent manner. Importantly, we found betulin-induced activation of Nrf2 is AMPK/AKT/GSK3β dependent, as pharmacologically inactivating AMPK blocked the activating effect of betulin on AKT, GSK3β and Nrf2. Furthermore, betulin attenuated LPS-induced inflammatory mediators (iNOS and COX-2) and MAPK inflammatory signaling pathway. The effect of betulin on HO-1 and NQO1 upregulation, iNOS and COX-2 the downregulation, and survival time extension was largely weakened when Nrf2 was depleted in vitro and in vivo. Our results demonstrate that the AMPK/AKT/Nrf2 pathways are essential for the anti-inflammatory effects of betulin in LPS-stimulated macrophages and endotoxin-shocked mice.
Maternal age-dependent APC/C-mediated decrease in securin causes premature sister chromatid separation in meiosis II
Authors: Nabti Ibtissem , Grimes Rosanna , Sarna Hema , Marangos Petros , Carroll John
Published: May 2017

Sister chromatid attachment during meiosis II (MII) is maintained by securin-mediated inhibition of separase. In maternal ageing, oocytes show increased inter-sister kinetochore distance and premature sister chromatid separation (PSCS), suggesting aberrant separase activity. Here, we find that MII oocytes from aged mice have less securin than oocytes from young mice and that this reduction is mediated by increased destruction by the anaphase promoting complex/cyclosome (APC/C) during meiosis I (MI) exit. Inhibition of the spindle assembly checkpoint (SAC) kinase, Mps1, during MI exit in young oocytes replicates this phenotype. Further, over-expression of securin or Mps1 protects against the age-related increase in inter-sister kinetochore distance and PSCS. These findings show that maternal ageing compromises the oocyte SAC–APC/C axis leading to a decrease in securin that ultimately causes sister chromatid cohesion loss. Manipulating this axis and/or increasing securin may provide novel therapeutic approaches to alleviating the risk of oocyte aneuploidy in maternal ageing.
Tunable Polarons in Bose-Einstein Condensates
Authors: Compagno E. , De Chiara G. , Angelakis D. G. , Palma G. M.
Published: May 2017

A toolbox for the quantum simulation of polarons in ultracold atoms is presented. Motivated by the impressive experimental advances in the area of ultracold atomic mixtures, we theoretically study the problem of ultracold atomic impurities immersed in a Bose-Einstein condensate mixture (BEC). The coupling between impurity and BEC gives rise to the formation of polarons whose mutual interaction can be effectively tuned using an external laser driving a quasi-resonant Raman transition between the BEC components. Our scheme allows one to change the effective interactions between polarons in different sites from attractive to zero. This is achieved by simply changing the intensity and the frequency of the two lasers. Such arrangement opens new avenues for the study of strongly correlated condensed matter models in ultracold gases.
The Plasmodium PI(4)K inhibitor KDU691 selectively inhibits dihydroartemisinin-pretreated Plasmodium falciparum ring-stage parasites
Authors: Dembele L. , Ang X. , Chavchich M. , Bonamy G. M. C. , Selva J. J. , Lim M. Yi-Xiu , Bodenreider C. , Yeung B. K. S. , Nosten F. , Russell B. M. , Edstein M. D. , Straimer J. , Fidock D. A. , Diagana T. T. , Bifani P.
Published: May 2017

Malaria control and elimination are threatened by the emergence and spread of resistance to artemisinin-based combination therapies (ACTs). Experimental evidence suggests that when an artemisinin (ART)-sensitive (K13 wild-type) Plasmodium falciparum strain is exposed to ART derivatives such as dihydroartemisinin (DHA), a small population of the early ring-stage parasites can survive drug treatment by entering cell cycle arrest or dormancy. After drug removal, these parasites can resume growth. Dormancy has been hypothesized to be an adaptive physiological mechanism that has been linked to recrudescence of parasites after monotherapy with ART and, possibly contributes to ART resistance. Here, we evaluate the in vitro drug sensitivity profile of normally-developing P. falciparum ring stages and DHA-pretreated dormant rings (DP-rings) using a panel of antimalarial drugs, including the Plasmodium phosphatidylinositol-4-OH kinase (PI4K)-specific inhibitor KDU691. We report that while KDU691 shows no activity against rings, it is highly inhibitory against DP-rings; a drug effect opposite to that of ART. Moreover, we provide evidence that KDU691 also kills DP-rings of P. falciparum ART-resistant strains expressing mutant K13.
Analytical consideration of liquid droplet impingement on solid surfaces
Authors: Yonemoto Yukihiro , Kunugi Tomoaki
Published: May 2017

In industrial applications involving spray-cooling, combustion, and so on, prediction of the maximum spreading diameter of a droplet impinging on a solid surface permits a quantitative estimation of heat removal and energy consumption. However, although there are many experimental studies regarding droplet impingement behaviour, theoretical models have an applicability limit for predicting the maximum spreading diameter. In the present study, we have developed an analytical model for droplet impingement based on energy conservation that considers adhesion energy in both horizontal and vertical directions at the contact line. The theory is validated by our experiment and existing experimental data possessing a wide range of Weber numbers. We demonstrate that our model can predict βm (i.e., the maximum spreading diameter normalised in terms of initial droplet diameter) for various Newtonian liquids ranging from micro- to millimetre-sized droplets on different solid surfaces and can determine the transition between capillary and viscous regimes. Furthermore, theoretical relations for scaling laws observed by many researchers are derived.
A novel gravity-driven nanofibrous membrane for point-of-use water disinfection: polydopamine-induced in situ silver incorporation
Authors: Wang Jianqiang , Wu Yichao , Yang Zhe , Guo Hao , Cao Bin , Tang Chuyang Y.
Published: May 2017

We report a facile method for preparing silver-loaded membranes for point-of-use disinfection and disaster relief applications. A bio-inspired material, polydopamine, was coated onto a highly porous nanofibrous polyacrylonitrile substrate. We then take advantage of the redox properties of polydopamine to form silver nanoparticles in situ. These nanoparticles were uniformly distributed on the surface of nanofibers with no apparent agglomeration at a silver loading up to 4.36 wt.% (cPAN-Ag1.5). The silver-incorporated membrane cPAN-Ag1.5 achieved a high pure water flux of 130 Lm−2 h−1 at 10-cm water head, demonstrating the feasibility of energy-efficient gravity-driven filtration and eliminating the need for electrical power. The strong anti-bacterial activity and high physical rejection of the membrane led to an excellent disinfection power, with no viable bacterial cells detected in its permeate water. The membrane exhibited >7 log reduction for E. coli and >6 log reduction for B. subtilis. The strategy reported here provides an efficient and green route to synthesize point-of-use membranes. Combining their excellent permeability and disinfection effectiveness, these membranes offer an ideal solution to water supply in disaster-affected areas.
Nano-assembly of amyloid β peptide: role of the hairpin fold
Authors: Maity Sibaprasad , Hashemi Mohtadin , Lyubchenko Yuri L.
Published: May 2017

Structural investigations have revealed that β hairpin structures are common features in amyloid fibrils, suggesting that these motifs play an important role in amyloid assembly. To test this hypothesis, we characterized the effect of the hairpin fold on the aggregation process using a model β hairpin structure, consisting of two Aβ(14–23) monomers connected by a turn forming YNGK peptide. AFM studies of the assembled aggregates revealed that the hairpin forms spherical structures whereas linear Aβ(14–23) monomers form fibrils. Additionally, an equimolar mixture of the monomer and the hairpin assembles into non-fibrillar aggregates, demonstrating that the hairpin fold dramatically changes the morphology of assembled amyloid aggregates. To understand the molecular mechanism underlying the role of the hairpin fold on amyloid assembly, we performed single-molecule probing experiments to measure interactions between hairpin and monomer and two hairpin complexes. The studies reveal that the stability of hairpin-monomer complexes is much higher than hairpin-hairpin complexes. Molecular dynamics simulations revealed a novel intercalated complex for the hairpin and monomer and Monte Carlo modeling further demonstrated that such nano-assemblies have elevated stability compared with stability of the dimer formed by Aβ(14–23) hairpin. The role of such folding on the amyloid assembly is also discussed.
Using bicistronic constructs to evaluate the chaperone activities of heat shock proteins in cells
Authors: San Gil Rebecca , Berg Tracey , Ecroyd Heath
Published: May 2017

Heat shock proteins (Hsps) are molecular chaperones that prevent the aggregation of client proteins by facilitating their refolding, or trafficking them for degradation. The chaperone activities of Hsps are dependent on dynamic protein-protein interactions, including their oligomerisation into large multi-subunit complexes. Thus, tagging Hsps with fluorescent proteins can interfere with their chaperone activity. To overcome this limitation, we have exploited bicistronic constructs for the concurrent expression of a non-tagged Hsp and fluorescent reporter from a single mRNA in cells. We used the Hsp-encoding bicistronic constructs in a cell-based model of protein aggregation, using a destabilised (mutant) form of firefly luciferase (mFluc) that forms inclusion bodies in cells. Expression of Hsp40, Hsp70, or Hsp40 and Hsp70 in cells expressing mFluc decreased the formation of inclusion bodies by 25–46% compared to controls. Moreover, there was a concentration-dependent decrease in the proportion of cells with inclusions when Hsp70, or Hsp40 and Hsp70 were co-expressed with mFluc in cells. The Hsp-encoding bicistronic constructs enable transfection efficiencies and concentration-dependent effects of Hsp expression to be determined using fluorescence based techniques, without the need to tag the Hsp with a fluorescent protein.
Deletion of Runx2 in Articular Chondrocytes Decelerates the Progression of DMM-Induced Osteoarthritis in Adult Mice
Authors: Liao Lifan , Zhang Shanxing , Gu Jianhong , Takarada Takeshi , Yoneda Yukio , Huang Jian , Zhao Lan , Oh Chun-do , Li Jun , Wang Baoli , Wang Meiqing , Chen Di
Published: May 2017

Runx2 may play an important role in development of osteoarthritis (OA). However, the specific role of Runx2 in articular chondrocyte function and in OA development in adult mice has not been fully defined. In this study, we performed the destabilization of the medial meniscus (DMM) surgery at 12-week-old mice to induce OA in adult Runx2
Agc1CreER
mice, in which Runx2 was specifically deleted in Aggrecan-expressing chondrocytes by administering tamoxifen at 8-weeks of age. Knee joint samples were collected 8- and 12-weeks post-surgery and analyzed through histology, histomorphometry and micro-computed tomography (μCT). Our results showed that severe OA-like defects were observed after DMM surgery in Cre-negative control mice, including articular cartilage degradation and subchondral sclerosis, while the defects were significantly ameliorated in Runx2
Agc1CreER
KO mice. Immunohistochemical (IHC) results showed significantly reduced expression of MMP13 in Runx2
Agc1CreER
KO mice compared to that in Cre-negative control mice. Results of quantitative reverse-transcription PCR (qRT-PCR) demonstrated that expression of the genes encoding for matrix degradation enzymes was significantly decreased in Runx2
Agc1CreER
KO mice. Thus, our findings suggest that inhibition of Runx2 in chondrocytes could at least partially rescue DMM-induced OA-like defects in adult mice.
The “inherent vice” in the anti-angiogenic theory may cause the highly metastatic cancer to spread more aggressively
Authors: Wang Denian , Tan Chun , Xiao Fei , Zou Lan , Wang Lijun , Wei Yong’gang , Yang Hanshuo , Zhang Wei
Published: May 2017

Although anti-angiogenic (AA) therapy is widely used in clinical practice, it is often challenged by insufficient efficacy and intrinsic resistance. Some studies have reported that AA therapy can even increase tumor metastasis. However, whether this is due to a specific AA drug causing a specific tumor to metastasize or because the anti-angiogenic theory has some “inherent vice” that may inevitably lead to tumor dissemination remains a mystery. Herein, we designed a model that completely blocks tumor blood supply using a physical barrier to examine tumor behavior in such circumstances. Surprisingly, we found that cutting off the blood supply could neither eliminate the primary tumor cells nor prevent local invasion or formation of distant metastases. By using a mathematical method to simulate tumor behavior, we found that blocking tumor blood supply may lead to an inevitable consequence: the cells that can tolerate blood deficiency are “naturally selected” and survive, whereas a portion of cells are promoted to escape from the “starvation” area by the consistent environmental stress until they are spread throughout the body. This may be an intrinsic disadvantage of the AA strategy, which will inevitably cause the tumor, particularly highly metastatic tumors, to spread more aggressively.
Component analysis of somatosensory evoked potentials for identifying spinal cord injury location
Authors: Wang Yazhou , Li Guangsheng , Luk Keith D. K. , Hu Yong
Published: May 2017

This study aims to determine whether the time-frequency components (TFCs) of somatosensory evoked potentials (SEPs) can be used to identify the specific location of a compressive spinal cord injury using a classification technique. Waveforms of SEPs after compressive injuries at various locations (C4, C5 and C6) in rat spinal cords were decomposed into a series of TFCs using a high-resolution time-frequency analysis method. A classification method based on support vector machine (SVM) was applied to the distributions of these TFCs among different pathological locations. The difference among injury locations manifests itself in different categories of SEP TFCs. High-energy TFCs of normal-state SEPs have significantly higher power and frequency than those of injury-state SEPs. The location of C5 is characterized by a unique distribution pattern of middle-energy TFCs. The difference between C4 and C6 is evidenced by the distribution pattern of low-energy TFCs. The proposed classification method based on SEP TFCs offers a discrimination accuracy of 80.2%. In this study, meaningful information contained in various SEP components was investigated and used to propose a new application of SEPs for identification of the location of pathological changes in the cervical spinal cord.
ANO1 inhibits cardiac fibrosis after myocardial infraction via TGF-β/smad3 pathway
Authors: Gao Yao , Zhang Yan Mei , Qian Li Jun , Chu Ming , Hong Jian , Xu Di
Published: May 2017

As a newly identified factor in calcium-activated chloride channel, ANO1 participates in various physiological processes like proliferation and differentiation, and expresses in human cardiac fibroblasts. In this experiment, we investigated the function of ANO1 in cardiac fibrosis after myocardial infraction (MI) with methods of Western blotting, Quantitative real-time PCR (qRT-PCR), metabolic reduction of 3-(4,5-dimethylthiozol-2-yl)-2, 5-diphenyltetrazo-lium bromide (MTT), immunofluorescence and confocal imaging, and Masson’s trichrome staining. The results showed that the expression of ANO1 significantly increased in neonatal rats’ cardiac fibroblasts after hypoxia and in cardiac tissues after MI. After ANO1 over-expression, cardiac fibrosis was reduced in vitro and in vivo. Moreover, the expression of TGF-β and p-smad3 declined after ANO1over-expression in cardiac fiborblasts. In conclusion, ANO1 inhibits cardiac fibrosis after MI via TGF-β/smad3 pathway in rats.
The PB2 mutation with lysine at 627 enhances the pathogenicity of avian influenza (H7N9) virus which belongs to a non-zoonotic lineage
Authors: Li Weixuan , Lee Horace Hok Yeung , Li Run Feng , Zhu Huachen Maria , Yi Guan , Peiris Joseph Sriyal Malik , Yang Zi Feng , Mok Chris Ka Pun
Published: May 2017

A novel avian-origin influenza A (H7N9) virus emerged in China in 2013 and has caused zoonotic disease in over 1123 persons with an overall mortality around 30%. Amino acid changes at the residues 591, 627 and 701 of polymerase basic protein 2 (PB2) have been found frequently in the human H7N9 isolates but not in viruses isolated from avian species. We have recently identified a cluster of H7N9 viruses in ducks which circulated in China prior to the first recognition of zoonotic disease in 2013. These duck viruses have genetic background distinct from the zoonotic H7N9 lineage. We found that the introduction of PB2 mutation with K at 627 but not K at 591 or N at 701 to the duck H7N9 virus led to increased pathogenicity in mice. We also found that the induction of pro-inflammatory cytokines including TNF-α, IP-10, MCP-1 and MIP-1α were associated with increased severity of infection. We conclude that introduction of the mammalian adaptation mutations into the PB2 gene of duck H7N9 viruses, which are genetically unrelated to the zoonotic H7N9 lineage, can also enhance pathogenicity in mice.
Characterization of porcine simple sequence repeat variation on a population scale with genome resequencing data
Authors: Liu Congcong , Liu Yan , Zhang Xinyi , Xu Xuewen , Zhao Shuhong
Published: May 2017

Simple sequence repeats (SSRs) are used as polymorphic molecular markers in many species. They contribute very important functional variations in a range of complex traits; however, little is known about the variation of most SSRs in pig populations. Here, using genome resequencing data, we identified ~0.63 million polymorphic SSR loci from more than 100 individuals. Through intensive analysis of this dataset, we found that the SSR motif composition, motif length, total length of alleles and distribution of alleles all contribute to SSR variability. Furthermore, we found that CG-containing SSRs displayed significantly lower polymorphism and higher cross-species conservation. With a rigorous filter procedure, we provided a catalogue of 16,527 high-quality polymorphic SSRs, which displayed reliable results for the analysis of phylogenetic relationships and provided valuable summary statistics for 30 individuals equally selected from eight local Chinese pig breeds, six commercial lean pig breeds and Chinese wild boars. In addition, from the high-quality polymorphic SSR catalogue, we identified four loci with potential loss-of-function alleles. Overall, these analyses provide a valuable catalogue of polymorphic SSRs to the existing pig genetic variation database, and we believe this catalogue could be used for future genome-wide genetic analysis.
Physiological concentrations of soluble uric acid are chondroprotective and anti-inflammatory
Authors: Lai Jenn-Haung , Luo Shue-Fen , Hung Li-Feng , Huang Chuan-Yueh , Lien Shiu-Bii , Lin Leou-Chyr , Liu Feng-Cheng , Yen B. Linju , Ho Ling-Jun
Published: May 2017

High uric acid levels are a risk factor for cardiovascular disorders and gout; however, the role of physiological concentrations of soluble uric acid (sUA) is poorly understood. This study aimed to clarify the effects of sUA in joint inflammation. Both cell cultures of primary porcine chondrocytes and mice with collagen-induced arthritis (CIA) were examined. We showed that sUA inhibited TNF-α- and interleukin (IL)-1β–induced inducible nitric oxide synthase, cyclooxygenase-2 and matrix metalloproteinase (MMP)-13 expression. Examination of the mRNA expression of several MMPs and aggrecanases confirmed that sUA exerts chondroprotective effects by inhibiting the activity of many chondro-destructive enzymes. These effects attenuated collagen II loss in chondrocytes and reduced proteoglycan degradation in cartilage explants. These results were reproduced in chondrocytes cultured in three-dimensional (3-D) alginate beads. Molecular studies revealed that sUA inhibited the ERK/AP-1 signalling pathway, but not the IκBα-NF-κB signalling pathway. Increases in plasma uric acid levels facilitated by the provision of oxonic acid, a uricase inhibitor, to CIA mice exerted both anti-inflammatory and arthroprotective effects in these animals, as demonstrated by their arthritis severity scores and immunohistochemical analysis results. Our study demonstrated that physiological concentrations of sUA displayed anti-inflammatory and chondroprotective effects bothin vitroandin vivo.