bluuebunny/crossref_metadata_2025 huggingface dataset:
Great power management and ambiguous order in nineteenth-century international society
Authors: Zala Benjamin
Published: September 2016

This article considers what the nineteenth century can tell us about the nature of great power management under conditions of ambiguity in relation to the holders of great power status. It charts the development of an institutionalised role for the great powers as managers of international society but with a specific focus on the mutual recognition, and conferral, of status. Such a focus highlights the changing, and sometimes competing, perceptions of not only which states should be thought of as great powers, but also therefore whether the power structure of international society remained multipolar or shifted towards bipolarity or even unipolarity. The article argues that a ‘golden age’ of great power management existed during a period in which perceptions of great power status were in fact more fluid than the standard literature accounts for. This means that predictions surrounding the imminent demise of the social institution of great power management under an increasingly ambiguous interstate order today may well be misplaced.
DETERMINING THE COINTEGRATION RANK IN HETEROSKEDASTIC VAR MODELS OF UNKNOWN ORDER
Authors: Cavaliere Giuseppe , De Angelis Luca , Rahbek Anders , Robert Taylor A.M.
Published: September 2016

We investigate the asymptotic and finite sample properties of a number of methods for estimating the cointegration rank in integrated vector autoregressive systems of unknown autoregressive order driven by heteroskedastic shocks. We allow for both conditional and unconditional heteroskedasticity of a very general form. We establish the conditions required on the penalty functions such that standard information criterion-based methods, such as the Bayesian information criterion [BIC], when employed either sequentially or jointly, can be used to consistently estimate both the cointegration rank and the autoregressive lag order. In doing so we also correct errors which appear in the proofs provided for the consistency of information-based estimators in the homoskedastic case by Aznar and Salvador (2002,Econometric Theory18, 926–947). We also extend the corpus of available large sample theory for the conventional sequential approach of Johansen (1995,Likelihood-Based Inference in Cointegrated Vector Autoregressive Models. Oxford University Press) and the associated wild bootstrap implementation thereof of Cavaliere, Rahbek, and Taylor (2014,Econometric Reviews33, 606–650) to the case where the lag order is unknown. In particular, we show that these methods remain valid under heteroskedasticity and an unknown lag length provided the lag length is first chosen by a consistent method, again such as the BIC. The relative finite sample properties of the different methods discussed are investigated in a Monte Carlo simulation study. The two best performing methods in this study are a wild bootstrap implementation of the Johansen (1995,Likelihood-Based Inference in Cointegrated Vector Autoregressive Models. Oxford University Press) procedure implemented with BIC selection of the lag length and joint IC approach (cf. Phillips, 1996,Econometrica64, 763–812) which uses the BIC to jointly select the lag order and the cointegration rank.
COMPLEMENTARITY AND IDENTIFICATION
Authors: Twinam Tate
Published: September 2016

This paper examines the identification power of assumptions that formalize the notion of complementarity in the context of a nonparametric bounds analysis of treatment response. I extend the literature on partial identification via shape restrictions by exploiting cross-dimensional restrictions on treatment response when treatments are multidimensional; the assumption of supermodularity can strengthen bounds on average treatment effects in studies of policy complementarity. This restriction can be combined with a statistical independence assumption to derive improved bounds on treatment effect distributions, aiding in the evaluation of complex randomized controlled trials. Complementarities arising from treatment effect heterogeneity can be incorporated through supermodular instrumental variables to strengthen identification in studies with one or multiple treatments. An application examining the long-run impact of zoning on the evolution of urban spatial structure illustrates the value of the proposed identification methods.
How does poverty affect children’s nutritional status in Nairobi slums? A qualitative study of the root causes of undernutrition
Authors: Goudet Sophie M , Kimani-Murage Elizabeth W , Wekesah Frederick , Wanjohi Milka , Griffiths Paula L , Bogin Barry , Madise Nyovani J
Published: September 2016

Objective

Children in slums are at high risk of undernutrition, which has long-term negative consequences on their physical growth and cognitive development. Severe undernutrition can lead to the child’s death. The present paper aimed to understand the causes of undernutrition in children as perceived by various groups of community members in Nairobi slums, Kenya.

Design

Analysis of ten focus group discussions and ten individual interviews with key informants. The main topic discussed was the root causes of child undernutrition in the slums. The focus group discussions and key informant interviews were recorded and transcribed verbatim. The transcripts were coded in NVivo by extracting concepts and using a constant comparison of data across the different categories of respondents to draw out themes to enable a thematic analysis.

Setting

Two slum communities in Nairobi, Kenya.

Subjects

Women of childbearing age, community health workers, elders, leaders and other knowledgeable people in the two slum communities (n 90).

Results

Participants demonstrated an understanding of undernutrition in children.

Conclusions

Findings inform target criteria at community and household level that can be used to identify children at risk of undernutrition. To tackle the immediate and underlying causes of undernutrition, interventions recommended should aim to: (i) improve maternal health and nutrition; (ii) promote optimal infant and young children feeding practices; (iii) support mothers in their working role; (iv) increase access to family planning; (v) improve water, sanitation and hygiene (WASH); (vi) address alcohol problems at all levels; and (vii) address street food issues with infant feeding counselling.
Some Useful Sources
Authors: McGann Michael , Bowman Dina , Biggs Simon , Kimberley Helen
Published: September 2016

Issues related to population ageing and longer working lives span diverse research areas and are linked to a number of conceptual and policy debates. Here we provide details of texts which allow quick access to key debates in the different domains covered by the contributions. We focus first on social policy, retirement and pensions. We then provide key sources on the changing experiences and perceptions of retirement; age-discrimination, human resource management and older workers; and early exit, mature-age unemployment and activating older workers.
Mortality forecasting using a modified Continuous Mortality Investigation Mortality Projections Model for China I: methodology and country-level results
Authors: Huang Fei , Browne Bridget
Published: September 2016

In this paper, we project future mortality rates for actuarial use with Chinese data using a modified Continuous Mortality Investigation (CMI) Mortality Projections Model. The model adopts a convergence structure from “initial” to “long-term” rates of mortality improvement as the process of projection. The initial rates of mortality improvement are derived using two-dimensional P-spline methodology. Given the short history of Chinese data, the long-term rates of mortality improvement are determined by borrowing information from international experience. K-means clustering with dynamic time warping distance is used to classify populations, which is novel in the actuarial mortality research field. The original CMI approach is deterministic, however, in this paper we make it stochastic using techniques outlined by Koller and described by Browne et al. Comparing our results with a pure extrapolative approach, we find that the CMI Mortality Projections Model is more suitable for long-term projections for China.
What Factors Moderate Self-Other Discrepancies in Decision Making? Results from a Vaccination Scenario
Authors: Petrova Dafina , Garcia-Retamero Rocio , van der Pligt Joop
Published: September 2016

When we make risky decisions for others, we tend to follow social norms about risks. This often results in making different decisions for others than we would make for ourselves in a similar situation (i.e., self-other discrepancies). In an experiment, we investigated self-other discrepancies in young adults’ decisions to purchase a vaccine against a sexually-transmitted virus for themselves or for another person (i.e., the target of the decision). When the target’s preferences were in line with social norms, surrogates showed large self-other discrepancies in line with these norms. When the target’s preferences were contrary to social norms, surrogates did not show self-other discrepancies in line with these preferences; instead they still followed social norms,F(1, 140) = 21.45,p <.001, ηp2= .13. Surrogates with lower numeracy,F(2, 128) = 3.44,p =.035, ηp2= .05, and higher empathy,F(2, 128) = 3.72,p =.027, ηp2= .06, showed self-other discrepancies more in line with the target’s preferences, even when these were contrary to the norm. Surrogates whose own risk attitudes were contrary to social norms showed larger self-other discrepancies,F(1, 128) = 5.38,p =.022, ηp2= .04. These results demonstrate that perceived social norms about risk can predict self-other discrepancies in risky decisions, even when the target’s preferences are known and at odds with the social norm. Further, the surrogates’ numeracy, empathy, and propensity to take risks influence the extent to which risky decisions for others resemble risky decisions for oneself.
Impact of Participation in Decision Making on Job Satisfaction: An Organizational Communication Perspective
Authors: Xia Ying , Zhang Li , Zhao Ning
Published: September 2016

Participation in organizational decision-making has received considerable attention from scholars. Beyond the perspectives proposed in past studies, we offer a new account, based upon a communication perspective, to explain why and when participation in decision-making can influence job satisfaction. Drawing from social capital theory, we examine whether communication openness mediates the relationship between participation in decision-making and job satisfaction. We also investigate how information adequacy moderates this mediated process. Results from a sample of 184 employees in China showed that the four-factor model was the best fitting solution (CFI = .91, GFI = .90, RMSEA = .09). The analyses indicated that employees’ participation in decision-making positively affected their job satisfaction (β = .32,p< .001), and the effect was mediated by communication openness (direct effect became non-significant when communication openness was included: β = .06,n.s.). Results also found that decision-making information adequacy positively moderated the relationship between participation in decision-making and communication openness (β = .13,p< .05). Thus, open communication and the free flow of information within organizations should be encouraged.
Chronischer Husten
Authors: Rothe Thomas
Published: September 2016

Zusammenfassung. Dauert Husten länger als 8 Wochen an, wird er als chronisch bezeichnet. Patienten mit Husten sind stark in ihrer Lebensqualität eingeschränkt. Der Besuch eines Konzerts kann verunmöglicht werden, Mitmenschen vermuten teilweise eine infektiöse Ursache und ziehen sich zurück. Bei massivem Husten kann es zu Urininkontinenz, Hustensynkopen und zur Entwicklung von Abdominal- bzw. Leistenhernien kommen. Einem chronischen Husten liegen meist mehrere kausale Faktoren zugrunde. Nach Identifizierung und Elimination sistiert der Hustenreiz oft. Allerdings fällt auf, dass die gleichen Faktoren im selben Masse bei einer anderen Person vorhanden sein können, ohne dass chronischer Husten auftritt. Es muss davon ausgegangen werden, dass Menschen mit chronischem Husten an einem Hypersensitivitäts-Syndrom leiden, das zu diesem Phänotyp führt. Therapieversuche mit Gabapentin wurden unternommen. Noch wirksamere Substanzen sind in der Erprobung.
Vorhofflimmern
Authors: Schön Tobias , Kühne Michael
Published: September 2016

Zusammenfassung. Vorhofflimmern ist die häufigste Herzrhythmusstörung mit einer Prävalenz von 1 – 2 % in der Bevölkerung und lässt sich im Elektrokardiogramm diagnostizieren. Wichtige Risikofaktoren sind Alter, arterielle Hypertonie und Adipositas. Jeder vierte bis fünfte Schlaganfall ist mit Vorhofflimmern assoziiert. Durch eine orale Antikoagulation (OAK), die heute ohne Gerinnungskontrollen mit Nicht-Vitamin K-abhängigen oralen Antikoagulantien (NOAKs) durchgeführt werden kann, lässt sich das Schlaganfallrisiko und die Gesamtmortalität senken. Das Risiko intrakranieller Blutungen ist unter NOAKs gegenüber Vitamin K-Antagonisten (VKA) geringer. Die meisten Patienten benötigen nach Risiko-Nutzenanalyse eine lebenslange OAK. Ähnlich wie bei VKA kann die antikoagulatorische Wirkung von NOAKs mit neuen Antidots innerhalb von Minuten antagonisert werden. Liegen Kontraindikation für eine lebenslange OAK vor, kann ein (interventioneller) Verschluss des Vorhofohrs erwogen werden. Leiden Patienten unter der Symptomatik des Vorhofflimmerns oder führt die Arrhythmie zu einer Tachykardiomyopathie, ist besonders in der Frühphase der Arrhythmie eine rhythmuserhaltene Therapie indiziert, die mit Antiarrhythmika, Kardioversion oder Katheterablation umgesetzt werden kann. Dabei ist die Pulmonalvenenisolation zu einem hochstandardisierten Verfahren geworden. Ist eine rhythmuserhaltene Therapie nicht mehr möglich und auch die Frequenzkontrolle nicht ausreichend umsetzbar, bleibt als Ultima ratio die AV-Knotenablation.
Subjektive Einschätzung und objektive kognitive Leistung bei psychisch Gesunden
Authors: Diener Carsten , Bornschlegl Mona , Menke Barbara , Petermann Franz
Published: September 2016

Zusammenfassung. Neuropsychologische Untersuchungen verweisen auf uneinheitliche Zusammenhänge zwischen der subjektiven und objektiven kognitiven Leistungsbeurteilung. Bei 286 psychisch Gesunden wurden objektive kognitive Leistungswerte in der deutschen Adaptation der Neuropsychological Assessment Battery (NAB) sowie der Fragebogen zur subjektiven Einschätzung der geistigen Leistungsfähigkeit (FLei) erhoben. Trotz sehr guter Reliabilitäten des FLei limitierten Bodeneffekte die Aufdeckung richtungskonformer Zusammenhänge mit objektiven Leistungswerten in den Bereichen Aufmerksamkeit, Gedächtnis und exekutiven Funktionen. Dennoch erwies sich die Gedächtnisleistung als sensitivste Einzeldomäne für einen positiven Zusammenhang zwischen subjektiver und objektiver Leistungseinschätzung. Dabei moderierte das subjektive Wohlbefinden (WHO-5-Index) den Zusammenhang beider (subjektiver/objektiver) Ebenen im Gedächtnisbereich und in der kognitiven Gesamtleistung. Vor dem Hintergrund dieses Ergebnismusters sollten zukünftige Zusammenhangsanalysen insbesondere bei Personen mit psychischen Belastungen zu weiteren klinisch relevanten Befunden führen.
All Earthquakes Are Created Equal
Authors: Crane Leah
Published: September 2016

A study of the development of earthquakes shows that the size of the initial rupture does not determine its intensity or range later on.
Obama Unveils First Marine National Monument in the Atlantic
Authors: Showstack Randy
Published: September 2016

The new designation follows the administration's expansion last month of a marine sanctuary in the Pacific Ocean near Hawaii into the world's largest protected ocean area.
Bone–cartilage crosstalk: a conversation for understanding osteoarthritis
Authors: Findlay David M , Kuliwaba Julia S
Published: September 2016

Although cartilage degradation is the characteristic feature of osteoarthritis (OA), it is now recognized that the whole joint is involved in the progression of OA. In particular, the interaction (crosstalk) between cartilage and subchondral bone is thought to be a central feature of this process. The interface between articular cartilage and bone of articulating long bones is a unique zone, which comprises articular cartilage, below which is the calcified cartilage sitting on and intercalated into the subchondral bone plate. Below the subchondral plate is the trabecular bone at the end of the respective long bones. In OA, there are well-described progressive destructive changes in the articular cartilage, which parallel characteristic changes in the underlying bone. This review examines the evidence that biochemical and biomechanical signaling between these tissue compartments is important in OA disease progression and asks whether such signaling might provide possibilities for therapeutic intervention to halt or slow disease development.
Distinctive expression of interleukin‐23 receptor subunits on human Th17 and γδ T cells
Authors: Wines Bruce D , Yap May L , Powell Maree S , Tan Peck‐Szee , Ko K Kerry , Orlowski Eva , Hogarth P Mark
Published: September 2016

The interleukin‐23 (IL‐23) pathway, T helper 17 (Th17) cells and γδ T cells, which respond to IL‐23, have major pro‐inflammatory roles. We have used unique IL‐23 receptor (IL‐23R) subunit‐specific monoclonal antibodies, X67 and X68, and IL‐12 receptor beta‐1 subunit (IL‐12Rβ1) expression levels to evaluate the IL‐23R complex on CD4 αβ TCR Th17 cells and on γδ T cells. Both IL‐23R and IL‐12Rβ1 subunits constitute the functional IL‐23R. Expression of the IL‐23R subunit by cultured Th17 cells was heterogeneous. Th17 cells expressed consistent high levels of the IL‐12Rβ1 subunit, which appeared a better predictor of responsiveness to IL‐23 than the expression of the IL‐23R subunit. Moreover, sorting memory CD4 T cells by high IL‐12Rβ1 expression selectively enriched cells committed to IL‐17 production from the blood. IL‐23R expression was also observed on freshly isolated and cultured γδ T cells and the cultured γδ T cells were not responsive to IL‐23.
Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis
Authors: Meisel Marlies , Mayassi Toufic , Fehlner-Peach Hannah , Koval Jason C , O’Brien Sarah L , Hinterleitner Reinhard , Lesko Kathryn , Kim Sangman , Bouziat Romain , Chen Li , Weber Christopher R , Mazmanian Sarkis K , Jabri Bana , Antonopoulos Dionysios A
Published: September 2016

Dysbiosis resulting in gut-microbiome alterations with reduced butyrate production are thought to disrupt intestinal immune homeostasis and promote complex immune disorders. However, whether and how dysbiosis develops before the onset of overt pathology remains poorly defined. Interleukin-15 (IL-15) is upregulated in distressed tissue and its overexpression is thought to predispose susceptible individuals to and have a role in the pathogenesis of celiac disease and inflammatory bowel disease (IBD). Although the immunological roles of IL-15 have been largely studied, its potential impact on the microbiota remains unexplored. Analysis of 16S ribosomal RNA-based inventories of bacterial communities in mice overexpressing IL-15 in the intestinal epithelium (villin-IL-15 transgenic (v-IL-15tg) mice) shows distinct changes in the composition of the intestinal bacteria. Although some alterations are specific to individual intestinal compartments, others are found across the ileum, cecum and feces. In particular, IL-15 overexpression restructures the composition of the microbiota with a decrease in butyrate-producing bacteria that is associated with a reduction in luminal butyrate levels across all intestinal compartments. Fecal microbiota transplant experiments of wild-type and v-IL-15tg microbiota into germ-free mice further indicate that diminishing butyrate concentration observed in the intestinal lumen of v-IL-15tg mice is the result of intrinsic alterations in the microbiota induced by IL-15. This reconfiguration of the microbiota is associated with increased susceptibility to dextran sodium sulfate-induced colitis. Altogether, this study reveals that IL-15 impacts butyrate-producing bacteria and lowers butyrate levels in the absence of overt pathology, which represent events that precede and promote intestinal inflammatory diseases.
A dendritic disinhibitory circuit mechanism for pathway-specific gating
Authors: Yang Guangyu Robert , Murray John D. , Wang Xiao-Jing
Published: September 2016

While reading a book in a noisy café, how does your brain ‘gate in’ visual information while filtering out auditory stimuli? Here we propose a mechanism for such flexible routing of information flow in a complex brain network (pathway-specific gating), tested using a network model of pyramidal neurons and three classes of interneurons with connection probabilities constrained by data. We find that if inputs from different pathways cluster on a pyramidal neuron dendrite, a pathway can be gated-on by a disinhibitory circuit motif. The branch-specific disinhibition can be achieved despite dense interneuronal connectivity, even with random connections. Moreover, clustering of input pathways on dendrites can naturally emerge through synaptic plasticity regulated by dendritic inhibition. This gating mechanism in a neural circuit is further demonstrated by performing a context-dependent decision-making task. The model suggests that cognitive flexibility engages top-down signalling of behavioural rule or context that targets specific classes of inhibitory neurons.
Delayed glial clearance of degenerating axons in aged Drosophila is due to reduced PI3K/Draper activity
Authors: Purice Maria D. , Speese Sean D. , Logan Mary A.
Published: September 2016

Advanced age is the greatest risk factor for neurodegenerative disorders, but the mechanisms that render the senescent brain vulnerable to disease are unclear. Glial immune responses provide neuroprotection in a variety of contexts. Thus, we explored how glial responses to neurodegeneration are altered with age. Here we show that glia–axon phagocytic interactions change dramatically in the aged Drosophila brain. Aged glia clear degenerating axons slowly due to low phosphoinositide-3-kinase (PI3K) signalling and, subsequently, reduced expression of the conserved phagocytic receptor Draper/MEGF10. Importantly, boosting PI3K/Draper activity in aged glia significantly reverses slow phagocytic responses. Moreover, several hours post axotomy, early hallmarks of Wallerian degeneration (WD) are delayed in aged flies. We propose that slow clearance of degenerating axons is mechanistically twofold, resulting from deferred initiation of axonal WD and reduced PI3K/Draper-dependent glial phagocytic function. Interventions that boost glial engulfment activity, however, can substantially reverse delayed clearance of damaged neuronal debris.
A physical zero-knowledge object-comparison system for nuclear warhead verification
Authors: Philippe Sébastien , Goldston Robert J. , Glaser Alexander , d’Errico Francesco
Published: September 2016

Zero-knowledge proofs are mathematical cryptographic methods to demonstrate the validity of a claim while providing no further information beyond the claim itself. The possibility of using such proofs to process classified and other sensitive physical data has attracted attention, especially in the field of nuclear arms control. Here we demonstrate a non-electronic fast neutron differential radiography technique using superheated emulsion detectors that can confirm that two objects are identical without revealing their geometry or composition. Such a technique could form the basis of a verification system that could confirm the authenticity of nuclear weapons without sharing any secret design information. More broadly, by demonstrating a physical zero-knowledge proof that can compare physical properties of objects, this experiment opens the door to developing other such secure proof-systems for other applications.
Inferences of drug responses in cancer cells from cancer genomic features and compound chemical and therapeutic properties
Authors: Wang Yongcui , Fang Jianwen , Chen Shilong
Published: September 2016

Accurately predicting the response of a cancer patient to a therapeutic agent is a core goal of precision medicine. Existing approaches were mainly relied primarily on genomic alterations in cancer cells that have been treated with different drugs. Here we focus on predicting drug response based on integration of the heterogeneously pharmacogenomics data from both cell and drug sides. Through a systematical approach, named as PDRCC (Predict Drug Response inCancerCells), the cancer genomic alterations and compound chemical and therapeutic properties were incorporated to determine the chemotherapeutic response in cancer patients. Using the Cancer Cell Line Encyclopedia (CCLE) study as the benchmark dataset, all pharmacogenomics data exhibited their roles in inferring the relationships between cancer cells and drugs. When integrating both genomic resources and compound information, the prediction coverage was significantly increased. The validity of PDRCC was also supported by its effective in uncovering the unknown cell-drug associations with database and literature evidences. It set the stage for clinical testing of novel therapeutic strategies, such as the sensitive association between cancer cell ‘A549_LUNG’ and compound ‘Topotecan’. In conclusion, PDRCC offers the possibility for faster, safer, and cheaper the development of novel anti-cancer therapeutics in the early-stage clinical trails.
Hypermetabolism in B–lymphocytes from malignant hyperthermia susceptible individuals
Authors: Hoppe Kerstin , Hack Guido , Lehmann–Horn Frank , Jurkat–Rott Karin , Wearing Scott , Zullo Alberto , Carsana Antonella , Klingler Werner
Published: September 2016

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism which is characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca2+ release in myotubes via the ryanodine receptor type 1 (RyR1). As RyR1 is also expressed in B–lymphocytes, this study investigated whether cellular metabolism of native B–lymphocytes was also altered in MH susceptible (MHS) individuals. A potent activator of RyR1, 4–chloro–m–cresol (4-CmC) was used to challenge native B-lymphocytes in a real–time, metabolic assay based on a pH–sensitive silicon biosensor chip. At the cellular level, a dose–dependent, phasic acidification occurred with 4–CmC. The acidification rate, an indicator of metabolic activation, was significantly higher in B–lymphocytes from MHS patients and required 3 to 5 fold lower concentrations of 4–CmC to evoke similar acidification rates to MHN. Native B–lymphocytes from MHS individuals are more sensitive to 4–CmC than those from MHN, reflecting a greater Ca2+ turnover. The acidification response, however, was less pronounced than in muscle cells, presumably reflecting the lower expression of RyR1 in B–lymphocytes.
Prostate tumor attenuation in the nu/nu murine model due to anti-sarcosine antibodies in folate-targeted liposomes
Authors: Heger Zbynek , Polanska Hana , Merlos Rodrigo Miguel Angel , Guran Roman , Kulich Pavel , Kopel Pavel , Masarik Michal , Eckschlager Tomas , Stiborova Marie , Kizek Rene , Adam Vojtech
Published: September 2016

Herein, we describe the preparation of liposomes with folate-targeting properties for the encapsulation of anti-sarcosine antibodies (antisarAbs@LIP) and sarcosine (sar@LIP). The competitive inhibitory effects of exogenously added folic acid supported the role of folate targeting in liposome internalization. We examined the effects of repeated administration on mice PC-3 xenografts. Sar@LIP treatment significantly increased tumor volume and weight compared to controls treated with empty liposomes. Moreover, antisarAbs@LIP administration exhibited a mild antitumor effect. We also identified differences in gene expression patterns post-treatment. Furthermore, Sar@LIP treatment resulted in decreased amounts of tumor zinc ions and total metallothioneins. Examination of the spatial distribution across the tumor sections revealed a sarcosine-related decline of the MT1X isoform within the marginal regions but an elevation after antisarAbs@LIP administration. Our exploratory results demonstrate the importance of sarcosine as an oncometabolite in PCa. Moreover, we have shown that sarcosine can be a potential target for anticancer strategies in management of PCa.
Weyl semimetals in optical lattices: moving and merging of Weyl points, and hidden symmetry at Weyl points
Authors: Hou Jing-Min , Chen Wei
Published: September 2016

We propose to realize Weyl semimetals in a cubic optical lattice. We find that there exist three distinct Weyl semimetal phases in the cubic optical lattice for different parameter ranges. One of them has two pairs of Weyl points and the other two have one pair of Weyl points in the Brillouin zone. For a slab geometry with (010) surfaces, the Fermi arcs connecting the projections of Weyl points with opposite topological charges on the surface Brillouin zone is presented. By adjusting the parameters, the Weyl points can move in the Brillouin zone. Interestingly, for two pairs of Weyl points, as one pair of them meet and annihilate, the originial two Fermi arcs coneect into one. As the remaining Weyl points annihilate further, the Fermi arc vanishes and a gap is opened. Furthermore, we find that there always exists a hidden symmetry at Weyl points, regardless of anywhere they located in the Brillouin zone. The hidden symmetry has an antiunitary operator with its square being −1.
Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito
Authors: Hart Robert J. , Cornillot Emmanuel , Abraham Amanah , Molina Emily , Nation Catherine S. , Ben Mamoun Choukri , Aly Ahmed S. I.
Published: September 2016

The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and knockout parasites demonstrate an important role for these genes in the regulation of expression of other CoA biosynthesis genes. Together, our data provide the first genetic evidence for the importance of the early steps of pantothenate utilization in the regulation of CoA biosynthesis and malaria parasite transmission to Anopheles mosquitoes.
Ultrafast in cellulo photoinduced dynamics processes of the paradigm molecular light switch [Ru(bpy)2dppz]2+
Authors: De la Cadena Alejandro , Davydova Dar’ya , Tolstik Tatiana , Reichardt Christian , Shukla Sapna , Akimov Denis , Heintzmann Rainer , Popp Jürgen , Dietzek Benjamin
Published: September 2016

An in cellulo study of the ultrafast excited state processes in the paradigm molecular light switch [Ru(bpy)2dppz]2+ by localized pump-probe spectroscopy is reported for the first time. The localization of [Ru(bpy)2dppz]2+ in HepG2 cells is verified by emission microscopy and the characteristic photoinduced picosecond dynamics of the molecular light switch is observed in cellulo. The observation of the typical phosphorescence stemming from a 3MLCT state suggests that the [Ru(bpy)2dppz]2+ complex intercalates with the DNA in the nucleus. The results presented for this benchmark coordination compound reveal the necessity to study the photoinduced processes in coordination compounds for intracellular use, e.g. as sensors or as photodrugs, in the actual biological target environment in order to derive a detailed molecular mechanistic understanding of the excited-state properties of the systems in the actual biological target environment.
Remote Actuation of Magnetic Nanoparticles For Cancer Cell Selective Treatment Through Cytoskeletal Disruption
Authors: Master Alyssa M. , Williams Philise N. , Pothayee Nikorn , Pothayee Nipon , Zhang Rui , Vishwasrao Hemant M. , Golovin Yuri I. , Riffle Judy S. , Sokolsky Marina , Kabanov Alexander V.
Published: September 2016

Motion of micron and sub-micron size magnetic particles in alternating magnetic fields can activate mechanosensitive cellular functions or physically destruct cancer cells. However, such effects are usually observed with relatively large magnetic particles (>250 nm) that would be difficult if at all possible to deliver to remote sites in the body to treat disease. Here we show a completely new mechanism of selective toxicity of superparamagnetic nanoparticles (SMNP) of 7 to 8 nm in diameter to cancer cells. These particles are coated by block copolymers, which facilitates their entry into the cells and clustering in the lysosomes, where they are then magneto-mechanically actuated by remotely applied alternating current (AC) magnetic fields of very low frequency (50 Hz). Such fields and treatments are safe for surrounding tissues but produce cytoskeletal disruption and subsequent death of cancer cells while leaving healthy cells intact.
Circulating miR-185 might be a novel biomarker for clinical outcome in patients with dilated cardiomyopathy
Authors: Yu Miao , Liang Wei , Xie Yu , Long Qi , Cheng Xiang , Liao Yu-Hua , Yuan Jing
Published: September 2016

B cells contribute to the development of dilated cardiomyopathy (DCM) by inducing myocyte injuries and myocardial fibrosis. Our recent research indicated that microRNA (miR) -185 participated in human B-cell activation. Thus, this study was aimed to explore the relationship between miR-185 and DCM progression. Forty-one healthy volunteers and fifty newly diagnosed DCM patients were enrolled. The levels of plasma miR-185, TNF-α secreting B cells and anti-heart autoantibody were detected. We found that the mean levels of plasma miR-185 in DCM patients were significantly higher than those in healthy controls. Furthermore, these DCM patients could be divided into miR-185high and miR-185low groups according to the cluster distribution. During one-year follow-up period, the miR-185high group showed apparent improvements in left ventricular ejection fraction, left ventricular end diastolic diameter and NT-proBNP, accompanied by significant declines in both cardiovascular mortality and total admissions for heart failure re-hospitalizations. In addition, the levels of anti-β1-AR antibody and TNF-α secreting B cells were also reduced in miR-185high group. These findings suggested that high miR-185 levels might be associated with a favorable prognosis by repressing B cell function in DCM. The findings of this study need to be confirmed with larger sample size and longer duration of observation.
Adenovirus-mediated expression of orphan nuclear receptor NR4A2 targeting hepatic stellate cell attenuates liver fibrosis in rats
Authors: Chen Pengguo , Li Jie , Huo Yan , Lu Jin , Wan Lili , Yang Quanjun , Huang Jinlu , Gan Run , Guo Cheng
Published: September 2016

Liver fibrosis is a wound-healing response characterized with the accumulation of extracellular matrix (ECM). And hepatic stellate cells (HSCs) are the principal cell source of ECM. NR4A2 (Nurr1) is a member of orphan nuclear receptor NR4A family and acts as transcription factor. It participates in regulating cell differentiation, proliferation and apoptosis. We previously demonstrated that NR4A2 expression in fibrotic liver reduced significantly compared with normal liver and NR4A2 knockout in HSCs promoted ECM production. In the present study we explored the role of NR4A2 on liver fibrosis. Studies in cultured HSCs demonstrated that NR4A2 over-expression suppressed the activation of HSCs, such as ECM production and invasion ability. Moreover cell cycle was arrested, cell apoptosis was promoted and cell signaling pathway was influenced. Adenovirus-mediated delivery of NR4A2 in rats ameliorated significantly dimethylnitrosamine (DMN) induced liver fibrosis. The In vivo experiments produced results consistent with in vitro experiments. Taken together these results demonstrate NR4A2 enhancement attenuates liver fibrosis via suppressing the activation of HSCs and NR4A2 may be an ideal target for anti-fibrotic therapy.
pH/NIR Light-Controlled Multidrug Release via a Mussel-Inspired Nanocomposite Hydrogel for Chemo-Photothermal Cancer Therapy
Authors: GhavamiNejad Amin , SamariKhalaj Melisa , Aguilar Ludwig Erik , Park Chan Hee , Kim Cheol Sang
Published: September 2016

This study reports on an intelligent composite hydrogel with both pH-dependent drug release in a cancer environment and heat generation based on NIR laser exposure, for the combined application of photothermal therapy (PTT) and multidrug chemotherapy. For the first time in the literature, Dopamine nanoparticle (DP) was incorporated as a highly effective photothermal agent as well as anticancer drug, bortezomib (BTZ) carrier inside a stimuli responsive pNIPAAm-co-pAAm hydrogel. When light is applied to the composite hydrogel, DP nanoparticle absorbs the light, which is dissipated locally as heat to impact cancer cells via hyperthermia. On the other hand, facile release of the anticancer drug BTZ from the surface of DP encapsulated hydrogel could be achieved due to the dissociation between catechol groups of DP and the boronic acid functionality of BTZ in typical acidic cancer environment. In order to increase the synergistic effect by dual drug delivery, Doxorubicin (DOXO) were also loaded to pNIPAAm-co-pAAm/DP-BTZ hydrogel and the effect of monotherapy as well as combined therapy were detailed by a complete characterization. Our results suggest that these mussel inspired nanocomposite with excellent heating property and controllable multidrug release can be considered as a potential material for cancer therapy.
Activation of Adenosine 2A receptor inhibits neutrophil apoptosis in an autophagy-dependent manner in mice with systemic inflammatory response syndrome
Authors: Liu Yang-Wuyue , Yang Ting , Zhao Li , Ni Zhenhong , Yang Nan , He Fengtian , Dai Shuang-Shuang
Published: September 2016

Systemic inflammatory response syndrome (SIRS) is an overwhelming whole body inflammation caused by infectious diseases or sterile insults. Neutrophils are the dominant participants during inflammation, and their survival and death determine the initiation as well as resolution of SIRS. Apoptosis and autophagy are two fundamental cellular processes that modulating cell fate, but their correlation and regulators in neutrophils under SIRS condition have not been elucidated. In this study, we demonstrated that high dose of LPS induced both apoptosis and autophagy of neutrophils in a mouse SIRS model and LPS-stimulated neutrophils in vitro. Moreover, we found that the adenosine 2A receptor (A2AR), a known anti-inflammatory G protein-coupled receptor (GPCR), could inhibit LPS-induced neutrophil apoptosis by suppressing the LPS-induced autophagy. Activation of A2AR suppressed LPS-induced autophagy by inhibiting the ROS-JNK pathway as well as promoting GPCR βϒ subunit–AKT signaling. The A2AR-inhibited autophagy suppressed apoptosis of neutrophils by blocking caspase8, caspase3 and PARP signaling. These findings not only increase our understandings of neutrophils’ fate and function in response to systemic inflammation, but also identify a novel anti-inflammatory role of A2AR in modulating neutrophils’ survival during inflammation.
Absence of apolipoprotein E protects mice from cerebral malaria
Authors: Kassa Fikregabrail Aberra , Van Den Ham Kristin , Rainone Anthony , Fournier Sylvie , Boilard Eric , Olivier Martin
Published: September 2016

Cerebral malaria claims the life of millions of people each year, particularly those of children and is a major global public health problem. Thus, the identification of novel malaria biomarkers that could be utilized as diagnostic or therapeutic targets is becoming increasingly important. Using a proteomic approach, we previously identified unique biomarkers in the sera of malaria-infected individuals, including apolipoprotein E (ApoE). ApoE is the dominant apolipoprotein in the brain and has been implicated in several neurological disorders; therefore, we were interested in the potential role of ApoE in cerebral malaria. Here we report the first demonstration that cerebral malaria is markedly attenuated in ApoE−/−mice. The protection provided by the absence of ApoE was associated with decreased sequestration of parasites and T cells within the brain and was determined to be independent from the involvement of ApoE receptors and from the altered lipid metabolism associated with the knock-out mice. Importantly, we demonstrated that treatment of mice with the ApoE antagonist heparin octasaccharide significantly decreased the incidence of cerebral malaria. Overall, our study indicates that the reduction of ApoE could be utilized in the development of therapeutic treatments aimed at mitigating the neuropathology of cerebral malaria.
Structural basis for disruption of claudin assembly in tight junctions by an enterotoxin
Authors: Shinoda Takehiro , Shinya Naoko , Ito Kaori , Ohsawa Noboru , Terada Takaho , Hirata Kunio , Kawano Yoshiaki , Yamamoto Masaki , Kimura-Someya Tomomi , Yokoyama Shigeyuki , Shirouzu Mikako
Published: September 2016

The food-poisoning bacterium Clostridium perfringens produces an enterotoxin (~35 kDa) that specifically targets human claudin-4, among the 26 human claudin proteins, and causes diarrhea by fluid accumulation in the intestinal cavity. The C-terminal domain of the Clostridium perfringens enterotoxin (C-CPE, ~15 kDa) binds tightly to claudin-4, and disrupts the intestinal tight junction barriers. In this study, we determined the 3.5-Å resolution crystal structure of the cell-free synthesized human claudin-4•C-CPE complex, which is significantly different from the structure of the off-target complex of an engineered C-CPE with mouse claudin-19. The claudin-4•C-CPE complex structure demonstrated the mechanism underlying claudin assembly disruption. A comparison of the present C-CPE-bound structure of claudin-4 with the enterotoxin-free claudin-15 structure revealed sophisticated C-CPE-induced conformation changes of the extracellular segments, induced on the foundation of the rigid four-transmembrane-helix bundle structure. These conformation changes provide a mechanistic model for the disruption of the lateral assembly of claudin molecules. Furthermore, the present novel structural mechanism for selecting a specific member of the claudin family can be used as the foundation to develop novel medically important technologies to selectively regulate the tight junctions formed by claudin family members in different organs.
Species identification by experts and non-experts: comparing images from field guides
Authors: Austen G. E. , Bindemann M. , Griffiths R. A. , Roberts D. L.
Published: September 2016

Accurate species identification is fundamental when recording ecological data. However, the ability to correctly identify organisms visually is rarely questioned. We investigated how experts and non-experts compared in the identification of bumblebees, a group of insects of considerable conservation concern. Experts and non-experts were asked whether two concurrent bumblebee images depicted the same or two different species. Overall accuracy was below 60% and comparable for experts and non-experts. However, experts were more consistent in their answers when the same images were repeated and more cautious in committing to a definitive answer. Our findings demonstrate the difficulty of correctly identifying bumblebees using images from field guides. Such error rates need to be accounted for when interpreting species data, whether or not they have been collected by experts. We suggest that investigation of how experts and non-experts make observations should be incorporated into study design and could be used to improve training in species identification.
Origin of the plant Tm-1-like gene via two independent horizontal transfer events and one gene fusion event
Authors: Yang Zefeng , Liu Li , Fang Huimin , Li Pengcheng , Xu Shuhui , Cao Wei , Xu Chenwu , Huang Jinling , Zhou Yong
Published: September 2016

TheTomato mosaic virus(ToMV) resistance geneTm-1encodes a direct inhibitor of ToMV RNA replication to protect tomato from infection. The plant Tm-1-like (Tm-1L) protein is predicted to contain an uncharacterized N-terminal UPF0261 domain and a C-terminal TIM-barrel signal transduction (TBST) domain. Homologous searches revealed that proteins containing both of these two domains are mainly present in charophyte green algae and land plants but absent from glaucophytes, red algae and chlorophyte green algae. Although Tm-1 homologs are widely present in bacteria, archaea and fungi, UPF0261- and TBST-domain-containing proteins are generally encoded by different genes in these linages. A co-evolution analysis also suggested a putative interaction between UPF0261- and TBST-domain-containing proteins. Phylogenetic analyses based on homologs of these two domains revealed that plants have acquired UPF0261- and TBST-domain-encoding genes through two independent horizontal gene transfer (HGT) events before the origin of land plants from charophytes. Subsequently, gene fusion occurred between these two horizontally acquired genes and resulted in the origin of theTm-1Lgene in streptophytes. Our results demonstrate a novel evolutionary mechanism through which the recipient organism may acquire genes with functional interaction through two different HGT events and further fuse them into one functional gene.
Synthesis of Highly Polymerized Water-soluble Cellulose Acetate by the Side Reaction in Carboxylate Ionic Liquid 1-ethyl-3-methylimidazolium Acetate
Authors: Pang Jinhui , Liu Xin , Yang Jun , Lu Fachuang , Wang Bo , Xu Feng , Ma Mingguo , Zhang Xueming
Published: September 2016

In the present study, we describe a novel one-step method to prepare water-soluble cellulose acetate (WSCA) with higher degree of polymerization values (DP = 650–680) by in situ activation of carboxyl group in ionic liquid. First of all, cellulose was dissolved in 1-ethyl-3-methylimidazolium acetate (EmimAc) and reacted with dichloroacetyl chloride (Cl2AcCl) in order to make cellulose dichloroacetate. Under various conditions, a series of water soluble products were produced. Elemental analysis and NMR results confirmed that they were cellulose acetate with DS (degree of substitution) values in the range from 0.30 to 0.63. NMR studies demonstrated that Cl2AcCl reacted with acetate anion of EmimAc producing a mixed anhydride that acetylated cellulose. Other acylating reagents such as benzoyl chloride, chloroacetyl chloride can also work similarly. 2D NMR characterization suggested that 6-mono-O-acetyl moiety, 3,6-di-O-acetylcellulose and 2,6-di-O-acetyl cellulose were all synthesized and the reactivity of hydroxyl groups in anhydro-glucose units was in the order C-6>C-3>C-2. This work provides an alternative way to make WSCA, meanwhile, also services as a reminder that the activity of EmimAc toward carbohydrate as acylating reagents could be a problem, because the expected acylated products may not be resulted and recycling of this ionic liquid could also be difficult.