bluuebunny/crossref_metadata_2025 huggingface dataset:
Curcumin Induces ABCA1 Expression and Apolipoprotein A-I-Mediated Cholesterol Transmembrane in the Chronic Cerebral Hypoperfusion Aging Rats
Authors: Tian Mingyuan , Zhang Xiong , Wang Linhui , Li Yu
Published: October 2013

Cerebral hypoperfusion or aging often results in the disturbances of cholesterol and lipoprotein, which have been well depicted as a common pathological status contributing to neurodegenerative diseases such as vascular dementia (VaD) and Alzheimer's dementia (AD). The pathway of the liver X receptor-β (LXR-β)/retinoic X receptor-α (RXR-α)/ABCA1 plays a vital role in lipoprotein metabolism. Curcumin, a kind of phenolic compound, has been widely used. It has been reported that curcumin can reduce the levels of cholesterol in serum, but the underlying mechanisms are poorly understood. In this study, we evaluated the effects of curcumin on the cholesterol level in brain, vascular cognitive impairment and explored whether the mechanisms for those effects are through activating LXR-β/RXR-α and ABCA1 expression and apoA-I. With a Morris water test, we found that curcumin treatment could attenuate cognitive impairment. With HE and Nissl staining, we found that curcumin could significantly ameliorate the abnormal changes of pyramidal neurons. Meanwhile, the expression of LXR-β, RXR-α, ABCA1 and apoA-I mRNA and protein were increased in a dose-dependent manner after curcumin treatment. Interestingly, both serum HDL cholesterol and total cholesterol levels were statistically higher in the curcumin treatment group than those other groups. We conclude that curcumin has the ability to activate permissive LXR-β/RXR-α signaling and thereby modulate ABCA1 and apoA-I-mediated cholesterol transmembrane transportation, which is a new preventive and therapeutic strategy for cerevascular diseases.
Salvia miltiorrhiza (Dan Shen) Significantly Ameliorates Colon Inflammation in Dextran Sulfate Sodium Induced Colitis
Authors: Wen Xiao-Dong , Wang Chong-Zhi , Yu Chunhao , Zhang Zhiyu , Calway Tyler , Wang Yunwei , Li Ping , Yuan Chun-Su
Published: October 2013

Inflammatory bowel disease increases the risks of human colorectal cancer. In this study, the effects of Salvia miltiorrhiza extract (SME) on chemically-induced colitis in a mouse model were evaluated. Chemical composition of SME was determined by HPLC analysis. A/J mice received a single injection of AOM 7.5 mg/kg. After one week, these mice received 2.5% DSS for eight days, or DSS plus SME (25 or 50 mg/kg). DSS-induced colitis was scored with the disease activity index (DAI). Body weight and colon length were also measured. The severity of inflammatory lesions was further evaluated by colon tissue histological assessment. HPLC assay showed that the major constituents in the tested SME were danshensu, protocatechuic aldehyde, salvianolic acid D, and salvianolic acid B. In the model group, the DAI score reached its highest level on Day 8, while the SME group on both doses showed a significantly reduced DAI score (both p < 0.01). As an objective index of the severity of inflammation, colon length was significantly shorter in the model group than the vehicle group. Treatment with 25 and 50 mg/kg of SME inhibited the shortening of colon in a dose-related manner (p < 0.05 and p < 0.01, respectively). SME groups also significantly reduced weight reduction (p < 0.05). Colitis histological data supported the pharmacological observations. Thus, Salvia miltiorrhiza could be a promising candidate in preventing and treating colitis and in reducing the risks of inflammation-associated colorectal cancer.
Moringa Fruit Inhibits LPS-InducedNO/iNOSExpression through Suppressing theNF-κBActivation in RAW264.7 Cells
Authors: Lee Hyo-Jin , Jeong Yun-Jeong , Lee Tae-Sung , Park Yoon-Yub , Chae Whi-Gun , Chung Il-Kyung , Chang Hyeun-Wook , Kim Cheorl-Ho , Choi Yung-Hyun , Kim Wun-Jae , Moon Sung-Kwon , Chang Young-Chae
Published: October 2013

In this study, we evaluated the anti-inflammatory effects of moringa (Moringa oleifera Lam.), a natural biologically active substance, by determining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Extracts from different parts of moringa (root, leaf, and fruit) reduced LPS-induced nitric oxide (NO) release in a dose-dependent manner. The moringa fruit extract most effectively inhibited LPS-induced NO production and levels of inducible nitric oxide synthase (iNOS). The moringa fruit extract also was shown to suppress the production of inflammatory cytokines including IL-1β, TNF-α, and IL-6. Furthermore, moringa fruit extract inhibited the cytoplasmic degradation of I κ B -α and the nuclear translocation of p65 proteins, resulting in lower levels of NF -κ B transactivation. Collectively, the results of this study demonstrate that moringa fruit extract reduces the levels of pro-inflammatory mediators including NO , IL-1β, TNF-α, and IL-6 via the inhibition of NF -κ B activation in RAW264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of moringa fruit extract.
Wedelia chinensisInhibits Nasopharyngeal Carcinoma CNE-1 Cell Growth by Inducing G2/M Arrest in a Chk1-Dependent Pathway
Authors: Liu Manyu , Wang Weizhang , Li Xiaobo , Shi Dayu , Mei Hanfang , Jin Xiaobao , Zhu Jiayong
Published: October 2013

Although Wedelia chinensis, an herb in traditional Chinese medicine, has been widely used for the treatment of inflammation, the effects of W. chinensis on cancer cell growth and the related molecular mechanisms behind these effects have largely remained unexplored to date. In the present study, W. chinensis plant extracts were obtained using either ethanol (E), petroleum ether (PE), ethyl acetate (EA) or butyl alcohol (BA). Then, extracts were examined for bioactivity in vitro via MTT assay in five human cancer cell lines. Our results showed that one subfraction of the EA extract (EA6) was cytotoxic to nasopharyngeal carcinoma (NPC) CNE-1 cells, among all cell lines evaluated. Treatment of CNE-1 cells with EA6 resulted in significant G2/M cell cycle arrest and modest apoptosis. EA6 induced Chk1 activation and inhibition of Chk1 in CNE-1 cells by RNA interference (RNAi) markedly abrogated EA6-mediated G2/M arrest and abolished EA6-induced cytotoxicity. EA6 treatment resulted in notable reduction of c-myc expression in CNE-1 cells, whereas silencing Chk1 inhibited such effects of EA6. Our results indicate that Chk1 is a novel molecular target of EA6 in NPC cells and also suggest an intervention strategy for NPC by EA6 exploring its molecular mechanisms of action.
EXTERNAL SUPPORT, INNOVATION AND ECONOMIC PERFORMANCE: WHAT FIRM LEVEL FACTORS MATTER FOR HIGH-TECH SMEs? HOW?
Authors: Bala Subrahmanya M. H.
Published: October 2013

This paper probes the factors which determine or enable SMEs to acquire external support, to achieve technological innovation outputs (in the form of innovation sales) and to enhance economic performance (in the form of sales growth). At the outset a conceptual framework (based on literature survey) is formulated by identifying the key variables relevant to the research objectives. Subsequently based on primary data gathered from 157 innovative SMEs covering auto components, electronics and machine tool industries in the Bangalore city region of India, we analyzed the three objectives. By means of logistic regression analysis, we ascertained that SMEs which have internal technical competence in the form of technically qualified owner/manager and an exclusive design office, which innovate frequently, particularly focusing on both product and process innovations obtained external support relative to the rest. Backward elimination multiple regression analysis revealed that firms which are able to obtain and complement external support to their internal technical competence, and which are "entrepreneurial firms" achieved more innovation sales. Finally, backward elimination multiple regression analysis ascertained that innovation sales, objective of firm origin, age of firms and nature of innovations significantly influenced the sales growth of SMEs.
CORPORATE CULTURE AS AN ANTECEDENT OF SUCCESSFUL EXPLORATION AND EXPLOITATION
Authors: MATZLER KURT , ABFALTER DAGMAR E. , MOORADIAN TODD A. , BAILOM FRANZ
Published: October 2013

Organisational culture is a decisive factor for a firm's innovativeness and performance. Our empirical model explores the relationship between organisational culture — based on the competing values model — as an antecedent of exploration and exploitation, innovation success and firm performance. It is tested on a sample of 232 CEOs of corporations in the US. Relationships between the constructs were analysed through path modelling, using the Partial Least Squares (PLS) method, employing the SmartPLS software. The results reveal a strong influence of corporate culture on exploration and exploitation, innovation success and performance. More specifically, we find significant positive relationships between hierarchy culture and market culture and exploitation. A clan culture negatively impacts exploration. Only an adhocracy culture positively influences both exploitation and exploration. Exploration and exploitation are positively related to innovation success and firm performance. Theoretical and managerial implications, limitations, and an agenda for further research are discussed.
High-permittivity polymer nanocomposites: Influence of interface on dielectric properties
Authors: Dang Zhi-Min , Yuan Jin-Kai , Zha Jun-Wei , Hu Peng-Hao , Wang Dong-Rui , Cheng Zhong-Yang
Published: October 2013

Flexible dielectric composites with high permittivity have been extensively studied due to their potential applications in high-density energy capacitors. In this review, effects of interface characteristics on the dielectric properties in the polymer-based nanocomposites with high permittivity are analyzed. The polymer-based dielectric composites are classified into two types: dielectric–dielectric (DD, ceramic particle-polymer) composites and conductor–dielectric (CD, conductive particle-polymer) composites. It is highly desirable for the dielectric–dielectric composites to exhibit high permittivity at low content of ceramic particles, which requires a remarkable interface interaction existing in the composite. For conductor–dielectric composites, a high permittivity can be achieved in composite with a small amount of conductor particle, but associated with a high loss. In this case, the interface between conductor and polymer with a good insulating characteristic is very important. Different methods can be used to modify the surface of ceramic/conductor particles before these particles are dispersed into polymers. The experimental results are summarized on how to design and make the desirable interface, and recent achievements in the development of these nanocomposites are presented. The challenges facing the fundamental understanding on the role of interface in high-permittivity polymer nanocomposites should be paid a more attention.
Relaxor ferroelectric properties of 85PZN–15BT transparent ceramic at low temperatures
Authors: Huang Lizhu , Zhao Wei , Ruan Wei , Yang Heji , Zeng Jiangtao , Li Guorong
Published: October 2013

Dielectric, hysteresis (P–E) loops and TSDC properties of transparent 85PZN–15BT ceramic over -150–150°C were investigated. The sample was found to exhibit a strong relaxor behavior and a relatively small remanent polarization. TSDC studies showed that there existed an electric field-dependent peak in the p versus T. Such interesting features were attributed to the electric field-induced transition and coexistence of polar nanoregion, long-range ordered polar region and nonpolarizable BZN-rich region.
Tectonometamorphic evolution of the Åreskutan Nappe – Caledonian history revealed by SIMS U–Pb zircon geochronology
Authors: Ladenberger Anna , Be'eri-Shlevin Yaron , Claesson Stefan , Gee David G. , Majka Jarosław , Romanova Irina V.
Published: October 2013

Secondary ionization mass spectrometry (SIMS) U–Pb dating of zircons from the Åreskutan Nappe in the central part of the Seve Nappe Complex of western central Jämtland provides new constraints on the timing of granulite–amphibolite-facies metamorphism and tectonic stacking of the nappe during the Caledonian orogeny. Peak-temperature metamorphism in garnet migmatites is constrained to
c.
442±4 Ma, very similar to the ages of leucogranites at 442±3 and 441±4 Ma. Within a migmatitic amphibolite, felsic segregations crystallized at 436±2 Ma. Pegmatites, cross-cutting the dominant Caledonian foliation in the Nappe, yield 428±4 and 430±3 Ma ages. The detrital zircon cores in the migmatites and leucogranites provide evidence of Late Palaeoproterozoic, Mesoproterozoic to Early Neoproterozoic source terranes for the metasedimentary rocks. The formation of the ductile and hot Seve migmatites, with their inverted metamorphism and thinning towards the hinterland, can be explained by an extrusion model in which the allochthon stayed ductile for a period of at least 10 million years during cooling from peak-temperature metamorphism early in the Silurian.

In our model, Baltica–Laurentia collision occurred in the Late Ordovician–earliest Silurian, with emplacement of the nappes far on to the Baltoscandian platform during the Silurian and early Devonian, Scandian Orogeny lasting until
c.
390 Ma.
Annotated checklist and keys for cumaceans (Crustacea: Peracarida) from the Tropical Eastern Pacific, with six new species from the Southern Mexican Pacific
Authors: JARQUÍN-GONZÁLEZ JANI , GARCÍA-MADRIGAL MARÍA DEL SOCORRO
Published: October 2013

In the Tropical Eastern Pacific (TEP) 23 species of cumaceans are known, however none of these species has been previously registered in the southern Pacific coast of Mexico. The examination of 378 specimens resulted in six new species, belonging to two families and five genera, Coricuma zurai sp. nov., Cyclaspis boquillensis sp. nov., Cyclaspis hyalinus sp. nov., Cumella (Cumewingia) carmeinae sp. nov., Elassocumella krakeri sp. nov. and Nannastacus corallinus sp. nov. The genus Coricuma Watling & Breedy, 1988, increases its geographical range from Costa Rica to Mexico, and a second species is described. Recorded for the first time in the Eastern Pacific are the genera Elassocumella Watling, 1991 and Nannastacus Bate, 1865. An annotated checklist and illustrated key to all species of cumaceans recognised from the Tropical Eastern Pacific are included.
Caught in speciation? A new host for Conchodytes meleagrinae Peters, 1852 (Decapoda, Caridea, Palaemonidae)
Authors: Fransen Charles H.J.M. , Reijnen Bastian T.
Published: October 2013

During fieldwork in 2009 at Ternate, Indonesia, a pair of a pontoniine shrimp species belonging to the genus Conchodytes was collected from a bivalve mollusk of the genus Spondylus. This constitutes the first record of a species of the genus Conchodytes associated with a spondylid host. The specimens can be distinguished from other known Conchodytes species based on both morphology and colour pattern. Its COI barcode however, strongly resembles those obtained from three specimens of C. meleagrinae and is nested in the C. meleagrinae clade of the reconstructed phylogeny. Based on morphology and colouration only the specimens associated with the Spondylus bivalve would have been described as a species new to science. The modest conflicting molecular data have lead the authors to fully describe and figure the Spondylus associated specimens and compare them with the Pinctada associated specimens. Based on the present information it is decided not to give the Spondylus associated specimens the status as a distinct species but regard them as host-related (colour)morph of Conchodytes meleagrinae.
New species of the genus Ontholestes Ganglbauer, 1895
(Coleoptera: Staphylinidae: Staphylininae) from Yakutia
Authors: SMETANA ALEŠ , SHAVRIN ALEXEY V.
Published: October 2013

Recently, the junior author had an opportunity to study material of Staphylinidae, which was given to him by the Yakutian entomologist Dr. Sargylana Nogovitsyna (Institute of Biological Problems of Cryolithozone, Yakutsk, Russia). Three species of the genus Ontholestes Ganglbauer, 1895 were included in this material from South-western and North-eastern Yakutia (Republic of Sakha, Russia): O. inauratus Mannerheim, 1830, O. murinus (Linnaeus, 1758) and one additional, new species in three specimens (Shavrin et al. 2008), all from north-eastern part of Yakutia (Cherskiy Mts., Suntar-Khayata Mts.). Subsequently, during one of the annual Meetings on Biology and Systematics of Staphylinidae, the junior author presented two males of this new species to the senior author who concurred that it is a new species. The goal of our paper is to give the description of this new species.
Cicero, Against Verres, 2.1.53–86
Authors: Gildenhard Ingo
Published: October 2013

Looting, despoiling temples, attempted rape and judicial murder: these are just some of the themes of this classic piece of writing by one of the world’s greatest orators. This particular passage is from the second book of Cicero’s Speeches against Verres, who was a former Roman magistrate on trial for serious misconduct. Cicero presents the lurid details of Verres’ alleged crimes in exquisite and sophisticated prose. This volume provides a portion of the original text of Cicero’s speech in Latin, a detailed commentary, study aids, and a translation. As a literary artefact, the speech gives us insight into how the supreme master of Latin eloquence developed what we would now call rhetorical "spin”. As an historical document, it provides a window into the dark underbelly of Rome’s imperial expansion and exploitation of the Near East. Ingo Gildenhard’s illuminating commentary on this A-Level set text will be of particular interest to students of Latin at both high school and undergraduate level. It will also be a valuable resource to Latin teachers and to anyone interested in Cicero, language and rhetoric, and the legal culture of Ancient Rome.
Economic Fables
Authors: Rubinstein Ariel
Published: October 2013

I had the good fortune to grow up in a wonderful area of Jerusalem, surrounded by a diverse range of people: Rabbi Meizel, the communist Sala Marcel, my widowed Aunt Hannah, and the intellectual Yaacovson. As far as I'm concerned, the opinion of such people is just as authoritative for making social and economic decisions as the opinion of an expert using a model. Part memoir, part crash-course in economic theory, this deeply engaging book by one of the world's foremost economists looks at economic ideas through a personal lens. Together with an introduction to some of the central concepts in modern economic thought, Ariel Rubinstein offers some powerful and entertaining reflections on his childhood, family and career. In doing so, he challenges many of the central tenets of game theory, and sheds light on the role economics can play in society at large. The book is as thought-provoking for seasoned economists as it is enlightening for newcomers to the field. Sylvia Nasar, author of A Beautiful Mind, describes Economics Fables as a "wonderfully inviting introduction to game theory, rich in personalities, history and sense of place. Ariel Rubinstein is not only a brilliant theorist with a knack for lucid exposition, but a gifted storyteller. Students will find the ideas surprisingly accessible. Aspiring scholars, wondering whether a life of the mind is worth pursuing, will find his personal journey of intellectual discovery thrilling."
Temporal Variation in Stable Isotopic Composition of Rainfall and Groundwater in a Tropical Dry Forest in the Northeastern Caribbean
Authors: Govender Y. , Cuevas E. , Sternberg L. D. S. , Jury M. R.
Published: October 2013

Karst topography links rainfall to groundwater recharge; therefore, possible changes in the hydrology can play an important role in ecosystem function especially in tropical dry forests where water is the most limiting resource. This study investigates the temporal variation in isotopic composition (δ18O and δD values) of rainwater and groundwater in the Guánica Dry Forest of southwestern Puerto Rico. The study not only establishes a dataset of oxygen and hydrogen isotopic composition of rainwater to assist in local ecohydrological studies but also establishes the origin of rainfall in the semiarid region of the island. The geographical position of Puerto Rico in the northeastern Caribbean causes the study site to receive marine air masses from the North Atlantic Ocean and Caribbean Sea. This research documents the monthly to annual variability in stable isotopic composition of rainwater and estimates the source of groundwater recharge in the Guánica Dry Forest.

To calculate the local meteoric water line (LMWL), the authors analyzed the isotopic signatures of rainwater, collected at near-monthly intervals from January 2008 to December 2011. The LMWL (δD = 7.79δ18O + 10.85) is close to the global meteoric water line (δD = 8.17δ18O + 11.27). Isotopic signatures of rainwater for the Guánica Dry Forest are consistent with southeastern Caribbean, where rainfall is of marine origin with an annual cycle contributed by sea surface temperature (SST) and significant intermonthly fluctuations due to rainfall and winds during tropical weather events. The d-excess values in the period of data collection (2008–11) respond to the rainfall–evaporation balance, with little seasonal cycle and strong pulsing events. Comparison of rain and groundwater isotopic compositions in the United Nations Educational, Scientific and Cultural Organization (UNESCO) Man and the Biosphere Programme (MAB) Guánica Dry Forest indicates that groundwater recharge is confined to rainfall events of more than 90 mm. Imbalances between rainfall and drought place cumulative stresses on ecosystems where plants and animals synchronize their growth phenology and reproduction to climatic patterns, especially in areas with variable annual cycles. Therefore, it is useful in ecohydrological studies to determine the origins and temporal dynamics of rainfall and groundwater recharge in the Caribbean, where predictions of climate models indicate drying trends.
Introducing Hysteresis in Snow Depletion Curves to Improve the Water Budget of a Land Surface Model in an Alpine Catchment
Authors: Magand Claire , Ducharne Agnès , Le Moine Nicolas , Gascoin Simon
Published: October 2013

The Durance watershed (14 000 km2), located in the French Alps, generates 10% of French hydropower and provides drinking water to 3 million people. The Catchment land surface model (CLSM), a distributed land surface model (LSM) with a multilayer, physically based snow model, has been applied in the upstream part of this watershed, where snowfall accounts for 50% of the precipitation. The CLSM subdivides the upper Durance watershed, where elevations range from 800 to 4000 m within 3580 km2, into elementary catchments with an average area of 500 km2. The authors first show the difference between the dynamics of the accumulation and ablation of the snow cover using Moderate Resolution Imaging Spectroradiometer (MODIS) images and snow-depth measurements. The extent of snow cover increases faster during accumulation than during ablation because melting occurs at preferential locations. This difference corresponds to the presence of a hysteresis in the snow-cover depletion curve of these catchments, and the CLSM was adapted by implementing such a hysteresis in the snow-cover depletion curve of the model. Different simulations were performed to assess the influence of the parameterizations on the water budget and the evolution of the extent of the snow cover. Using six gauging stations, the authors demonstrate that introducing a hysteresis in the snow-cover depletion curve improves melting dynamics. They conclude that their adaptation of the CLSM contributes to a better representation of snowpack dynamics in an LSM that enables mountainous catchments to be modeled for impact studies such as those of climate change.
Outside-the-(Cavity-prep)-Box Thinking
Authors: Thompson V.P. , Watson T.F. , Marshall G.W. , Blackman B.R.K. , Stansbury J.W. , Schadler L.S. , Pearson R.A. , Libanori R.
Published: October 2013

Direct placement restorative materials must interface with tooth structures that are often compromised by caries or trauma. The material must seal the interface while providing sufficient strength and wear resistance to assure function of the tooth for, ideally, the lifetime of the patient. Needed are direct restorative materials that are less technique-sensitive than current resin-based composite systems while having improved properties. The ideal material could be successfully used in areas of the world with limited infrastructure. Advances in our understanding of the interface between the restoration adhesive system and the stages of carious dentin can be used to promote remineralization. Application of fracture mechanics to adhesion at the tooth-restoration interface can provide insights for improvement. Research in polymer systems suggests alternatives to current composite resin matrix systems to overcome technique sensitivity, while advances in nano- and mesoparticle reinforcement and alignment in composite systems can increase material strength, toughness, and wear resistance, foreshadowing dental application.
Detection of serum antibodies against Bartonella species in cats with sporotrichosis from Rio de Janeiro, Brazil
Authors: Kitada Amanda AB , Favacho Alexsandra RM , Oliveira Raquel VC , Pessoa Adonai A , Gomes Raphael , Honse Carla O , Gremião Isabella DF , Lemos Elba RS , Pereira Sandro A
Published: October 2013

Cat scratch disease is a zoonosis caused by Bartonella species, transmitted to humans through scratches or bites from infected cats and via direct contact with infected feces. Sporotrichosis, caused by the fungal complex Sporothrix, is transmitted by traumatic inoculation of the fungus. Cats are important in zoonotic transmission. Serum samples from 112 domestic cats with sporotrichosis and 77 samples from healthy cats were analyzed by indirect immunofluorescence assay (IFA), using the commercial kit Bartonella henselae IFA IgG (Bion). The presence of antibodies against feline leukemia virus (FeLV) and of feline immunodeficiency virus (FIV) core antigens was detected using the commercial kit Snap Combo FIV–FeLV (Idexx). The group of animals with sporotrichosis contained 93 males with a median age of 22 months, eight (7.1%) of which were positive for FIV and 15 (13.4%) for FeLV. The group of animals without sporotrichosis contained 36 males with a median age 48 months, 10 (13.0%) of which were positive for FIV and eight (10.4%) for FeLV. Of the 112 cats with sporotrichosis and 77 cats without mycosis, 72 (64.3%) and 35 (45.5%), respectively, were IFA reactive. No association was found between age, sex, FIV/FeLV and the presence of antibodies to Bartonella species. The results suggest that the study population can be considered a potential source of zoonotic infection for both diseases.
Collaborative action around implementation in Collaborations for Leadership in Applied Health Research and Care: towards a programme theory
Authors: Rycroft-Malone Jo , Wilkinson Joyce , Burton Christopher R , Harvey Gill , McCormack Brendan , Graham Ian , Staniszewska Sophie
Published: October 2013

Objectives

In theory, greater interaction between researchers and practitioners should result in increased potential for implementation. However, we know little about whether this is the case, or what mechanisms might operate to make it happen. This paper reports findings from a study that is identifying and tracking implementation mechanisms, processes, influences and impacts in real time, over time in the Collaborations for Leadership in Applied Health Research and Care (CLAHRCs).

Methods

This is a longitudinal, realist evaluation case study. The development of the conceptual framework and initial hypotheses involved literature reviewing and stakeholder consultation. Primary data were collected through interviews, observations and documents within three CLAHRCs, and analysed thematically against the framework and hypotheses.

Results

The first round of data collection shows that the mechanisms of collaborative action, relationship building, engagement, motivation, knowledge exchange and learning are important to the processes and outcomes of CLAHRCs' activity, including their capacity for implementation. These mechanisms operated in different contexts such as competing agendas, availability of resources and the CLAHRCs’ brand. Contexts and mechanisms result in different impact, including the CLAHRCs’ approach to implementation, quality of collaboration, commitment and ownership, and degree of sharing and managing knowledge.

Conclusion

Emerging features of a middle range theory of implementation within collaboration include alignment in organizational structures and cognitive processes, history of partnerships, responsiveness and resilience in rapidly changing contexts. CLARHCs’ potential to mobilize knowledge may be further realized by how they develop insights into their function as collaborative entities.
Inversion effects in the perception of the moving human form: A comparison of adolescents with autism spectrum disorder and typically developing adolescents
Authors: Cleary Laura , Looney Kathy , Brady Nuala , Fitzgerald Michael
Published: October 2013

The “body inversion effect” refers to superior recognition of upright than inverted images of the human body and indicates typical configural processing. Previous research by Reed et al. using static images of the human body shows that people with autism fail to demonstrate this effect. Using a novel task in which adults, adolescents with autism, and typically developing adolescents judged whether walking stick figures—created from biological motion recordings and shown at seven orientations between 0° and 180°—were normal or distorted, this study shows clear effects of stimulus inversion. Reaction times and “inverse efficiency” increased with orientation for normal but not distorted walkers, and sensitivity declined with rotation from upright for all groups. Notably, the effect of stimulus inversion was equally detrimental to both groups of adolescents suggesting intact configural processing of the body in motion in autism spectrum disorder.
Alleles of the homologous recombination gene, RAD59, identify multiple responses to disrupted DNA replication in Saccharomyces cerevisiae
Authors: Liddell Lauren C , Manthey Glenn M , Owens Shannon N , Fu Becky XH , Bailis Adam M
Published: October 2013

Background

In Saccharomyces cerevisiae, Rad59 is required for multiple homologous recombination mechanisms and viability in DNA replication-defective rad27 mutant cells. Recently, four rad59 missense alleles were found to have distinct effects on homologous recombination that are consistent with separation-of-function mutations. The rad59-K166A allele alters an amino acid in a conserved α-helical domain, and, like the rad59 null allele diminishes association of Rad52 with double-strand breaks. The rad59-K174A and rad59-F180A alleles alter amino acids in the same domain and have genetically similar effects on homologous recombination. The rad59-Y92A allele alters a conserved amino acid in a separate domain, has genetically distinct effects on homologous recombination, and does not diminish association of Rad52 with double-strand breaks.

Results

In this study, rad59 mutant strains were crossed with a rad27 null mutant to examine the effects of the rad59 alleles on the link between viability, growth and the stimulation of homologous recombination in replication-defective cells. Like the rad59 null allele, rad59-K166A was synthetically lethal in combination with rad27. The rad59-K174A and rad59-F180A alleles were not synthetically lethal in combination with rad27, had effects on growth that coincided with decreased ectopic gene conversion, but did not affect mutation, unequal sister-chromatid recombination, or loss of heterozygosity. The rad59-Y92A allele was not synthetically lethal when combined with rad27, stimulated ectopic gene conversion and heteroallelic recombination independently from rad27, and was mutually epistatic with srs2. Unlike rad27, the stimulatory effect of rad59-Y92A on homologous recombination was not accompanied by effects on growth rate, cell cycle distribution, mutation, unequal sister-chromatid recombination, or loss of heterozygosity.

Conclusions

The synthetic lethality conferred by rad59 null and rad59-K166A alleles correlates with their inhibitory effect on association of Rad52 with double-strand breaks, suggesting that this may be essential for rescuing replication lesions in rad27 mutant cells. The rad59-K174A and rad59-F180A alleles may fractionally reduce this same function, which proportionally reduced repair of replication lesions by homologous recombination and growth rate. In contrast, rad59-Y92A stimulates homologous recombination, perhaps by affecting association of replication lesions with the Rad51 recombinase. This suggests that Rad59 influences the rescue of replication lesions by multiple recombination factors.
Decreased miR-106a inhibits glioma cell glucose uptake and proliferation by targeting SLC2A3 in GBM
Authors: Dai Dong-Wei , Lu Qiong , Wang Lai-Xing , Zhao Wen-Yuan , Cao Yi-Qun , Li Ya-Nan , Han Guo-Sheng , Liu Jian-Min , Yue Zhi-Jian
Published: October 2013

Background

MiR-106a is frequently down-regulated in various types of human cancer. However the underlying mechanism of miR-106a involved in glioma remains elusive.

Methods

The association of miR-106a with glioma grade and patient survival was analyzed. The biological function and target of miR-106a were determined by bioinformatic analysis and cell experiments (Western blot, luciferase reporter, cell cycle, ntracellular ATP production and glucose uptake assay). Finally, rescue expression of its target SLC2A3 was used to test the role of SLC2A3 in miR-106a-mediated cell glycolysis and proliferation.

Results

Here we showed that miR-106a was a tumor suppressor miRNA was involved in GBM cell glucose uptake and proliferation. Decreased miR-106a in GBM tissues and conferred a poor survival of GBM patients. SLC2A3 was identified as a core target of miR-106a in GBM cells. Inhibition of SLC2A3 by miR-106a attenuated cell proliferation and inhibited glucose uptake. In addition, for each biological process we identified ontology-associated transcripts that significantly correlated with SLC2A3 expression. Finally, the expression of SLC2A3 largely abrogated miR-106a-mediated cell proliferation and glucose uptake in GBM cells.

Conclusions

Taken together, miR-106a and SLC2A3 could be potential therapeutic approaches for GBM.
Implementing disability evaluation and welfare services based on the framework of the international classification of functioning, disability and health: experiences in Taiwan
Authors: Chiu Wen-Ta , Yen Chia-Feng , Teng Sue-Wen , Liao Hua-Fang , Chang Kwang-Hwa , Chi Wen-Chou , Wang Yen-Ho , Liou Tsan-Hon
Published: October 2013

Background

Before 2007, the disability evaluation was based on the medical model in Taiwan. According to the People with Disabilities Rights Protection Act, from 2012 the assessment of a person’s eligibility for disability benefits has to be determined based on the International Classification of Functioning, Disability, and Health (ICF) framework nationwide. The purposes of this study were to: 1) design the evaluation tools for disability eligibility system based on the ICF/ICF-Children and Youth; 2) compare the differences of grades of disability between the old and new evaluation systems; 3) analyse the outcome of the new disability evaluation system.

Methods

To develop evaluation tools and procedure for disability determination, we formed an implementation taskforce, including 199 professional experts, and conducted a small-scale field trial to examine the feasibility of evaluation tools in Phase I. To refine the evaluation tools and process and to compare the difference of the grades of disability between new and old systems, 7,329 persons with disabilities were randomly recruited in a national population-based study in Phase II. To implement the new system smoothly and understand the impact of the new system, the collaboration mechanism was established and data of 168,052 persons who applied for the disability benefits was extracted from the information system and analysed in Phase III.

Results

The measures of the 43 categories for body function/structure components, the Functioning Scale of Disability Evaluation System for activities/participation components, and the needs assessment have been developed and used in the field after several revisions. In Phase II, there was 49.7% agreement of disability grades between the old and new systems. In Phase III, 110,667 persons with a disability received their welfare services through the new system. Among them, 77% received basic social welfare support, 89% financial support, 24% allowance for assistive technology, 7% caregiver support, 8% nursing care and rehabilitation services at home, and 47% were issued parking permits for persons with disability.

Conclusion

This study demonstrated that disability evaluation system based on the ICF could provide a common language between disability assessment, needs assessment and welfare services. However, the proposed assessment protocol and tools require additional testing and validation.
The Aeromonas salmonicida subsp. salmonicida exoproteome: global analysis, moonlighting proteins and putative antigens for vaccination against furunculosis
Authors: Vanden Bergh Philippe , Heller Manfred , Braga-Lagache Sophie , Frey Joachim
Published: October 2013

Background

Aeromonas salmonicida subsp. salmonicida, the etiologic agent of furunculosis, is a major pathogen of fisheries worldwide. Despite the identification of several virulence factors the pathogenesis is still poorly understood. We have used high-throughput proteomics to display the differences between in vitro secretome of A. salmonicida wild-type (wt, hypervirulent, JF5054) and T3SS-deficient (isogenic ΔascV, extremely low-virulent, JF2747) strains in exponential (GP) and stationary (SP) phases of growth.

Results

Among the different experimental conditions we obtained semi-quantitative values for a total of 2136 A. salmonicida proteins. Proteins of specific A. salmonicida species were proportionally less detected than proteins common to the Aeromonas genus or those shared with other Aeromonas species, suggesting that in vitro growth did not induce the expression of these genes. Four detected proteins which are unidentified in the genome of reference strains of A. salmonicida were homologous to components of the conjugative T4SS of A. hydrophila pRA1 plasmid. Polypeptides of three proteins which are specific to the 01-B526 strain were also discovered. In supernatants (SNs), the number of detected proteins was higher in SP (326 for wt vs 329 for mutant) than in GP (275 for wt vs 263 for mutant). In pellets, the number of identified proteins (a total of 1536) was approximately the same between GP and SP. Numerous highly conserved cytoplasmic proteins were present in A. salmonicida SNs (mainly EF-Tu, EF-G, EF-P, EF-Ts, TypA, AlaS, ribosomal proteins, HtpG, DnaK, peptidyl-prolyl cis-trans isomerases, GAPDH, Enolase, FbaA, TpiA, Pgk, TktA, AckA, AcnB, Mdh, AhpC, Tpx, SodB and PNPase), and several evidences support the theory that their extracellular localization was not the result of cell lysis. According to the Cluster of Orthologous Groups classification, 29% of excreted proteins in A. salmonicida SNs were currently poorly characterized.

Conclusions

In this part of our work we elucidated the whole in vitro exoproteome of hypervirulent A. salmonicida subsp. salmonicida and showed the secretion of several highly conserved cytoplasmic proteins with putative moonlighting functions and roles in virulence. All together, our results offer new information about the pathogenesis of furunculosis and point out potential candidates for vaccine development.
Proteomic profiling of serum samples from chikungunya-infected patients provides insights into host response
Authors: Puttamallesh Vinuth N , Sreenivasamurthy Sreelakshmi K , Singh Pradeep Kumar , Harsha H C , Ganjiwale Anjali , Broor Shobha , Pandey Akhilesh , Narayana Jayasuryan , Prasad T S Keshava
Published: October 2013

Background

Chikungunya is a highly debilitating febrile illness caused by Chikungunya virus, a single-stranded RNA virus, which is transmitted by Aedes aegypti or Aedes albopictus mosquito species. The pathogenesis and host responses in individuals infected with the chikungunya virus are not well understood at the molecular level. We carried out proteomic profiling of serum samples from chikungunya patients in order to identify molecules associated with the host response to infection by this virus.

Results

Proteomic profiling of serum obtained from the infected individuals resulted in identification of 569 proteins. Of these, 63 proteins were found to be differentially expressed (≥ 2-fold) in patient as compared to control sera. These differentially expressed proteins were involved in various processes such as lipid metabolism, immune response, transport, signal transduction and apoptosis.

Conclusions

This is the first report providing a global proteomic profile of serum samples from individuals infected with the chikungunya virus. Our data provide an insight into the proteins that are involved as host response factors during an infection. These proteins include clusterin, apolipoproteins and S100A family of proteins.
Inflammation induces neuro-lymphatic protein expression in multiple sclerosis brain neurovasculature
Authors: Chaitanya Ganta Vijay , Omura Seiichi , Sato Fumitaka , Martinez Nicholas E , Minagar Alireza , Ramanathan Murali , Guttman Bianca Weinstock , Zivadinov Robert , Tsunoda Ikuo , Alexander Jonathan S
Published: October 2013

Background

Multiple sclerosis (MS) is associated with ectopic lymphoid follicle formation. Podoplanin+(lymphatic marker) T helper17 (Th17) cells and B cell aggregates have been implicated in the formation of tertiary lymphoid organs (TLOs) in MS and experimental autoimmune encephalitis (EAE). Since podoplanin expressed by Th17 cells in MS brains is also expressed by lymphatic endothelium, we investigated whether the pathophysiology of MS involves inductions of lymphatic proteins in the inflamed neurovasculature.

Methods

We assessed the protein levels of lymphatic vessel endothelial hyaluronan receptor and podoplanin, which are specific to the lymphatic system and prospero-homeobox protein-1, angiopoietin-2, vascular endothelial growth factor-D, vascular endothelial growth factor receptor-3, which are expressed by both lymphatic endothelium and neurons. Levels of these proteins were measured in postmortem brains and sera from MS patients, in the myelin proteolipid protein (PLP)-induced EAE and Theiler’s murine encephalomyelitis virus (TMEV) induced demyelinating disease (TMEV-IDD) mouse models and in cell culture models of inflamed neurovasculature.

Results and conclusions

Intense staining for LYVE-1 was found in neurons of a subset of MS patients using immunohistochemical approaches. The lymphatic protein, podoplanin, was highly expressed in perivascular inflammatory lesions indicating signaling cross-talks between inflamed brain vasculature and lymphatic proteins in MS. The profiles of these proteins in MS patient sera discriminated between relapsing remitting MS from secondary progressive MS and normal patients. Thein vivofindings were confirmed in thein vitrocell culture models of neuroinflammation.
Estimating the contribution of the gut to plasma viral load in early SIV infection
Authors: Petravic Janka , Vanderford Thomas H , Silvestri Guido , Davenport Miles
Published: October 2013

Background

There is significant debate about whether the gut plays a major role in viral replication and pathology in HIV infection. Here we aimed to estimate the contribution of the gut to the total virus observed in plasma, by comparing the frequency of different viral mutants in plasma and gut in SIV infection.

Results

We found that the maximum contribution of gut to plasma viral load estimated from rectal biopsy at day 28 post-infection had a median of 10%. The estimated values for individual animals ranged from nearly 100% to <3% in 4/14 animals. Importantly, these are maximum estimates, so that a value of 90%, for example, means that the real contribution may be anything between 0 and 90%, just not higher than 90%.

We also studied the contribution of gut at the peak of plasma viral load (day 14). However, since there was very little escape in most animals at this time point, we could only estimate the maximal contribution of gut in 4 animals, in two of which it was <15%.

Conclusions

The role of the gut in HIV is a controversial area, with many suggesting that it plays a dominant role in driving early infection. Our analysis suggests that, at least by day 28 post-infection, the gut is not contributing greatly to the plasma viral load.
Phase II clinical trial of whole-brain irradiation plus three-dimensional conformal boost with concurrent topotecan for brain metastases from lung cancer
Authors: Ge Xiao-hui , Lin Qiang , Ren Xiao-cang , Liu Yue-e , Chen Xue-ji , Wang Dong-ying , Wang Yong-qiang , Cao Bin , Li Zhi-gang , Liu Miao-ling
Published: October 2013

Background

Patients with brain metastases from lung cancer have poor prognoses and short survival time, and they are often excluded from clinical trials. Whole-cranial irradiation is considered to be the standard treatment, but its efficacy is not satisfactory. The purpose of this phase II clinical trial was to evaluate the preliminary efficacy and safety of the treatment of whole-brain irradiation plus three-dimensional conformal boost combined with concurrent topotecan for the patients with brain metastases from lung cancer.

Methods

Patients with brain metastasis from lung cancer received concurrent chemotherapy and radiotherapy: conventional fractionated whole-brain irradiation, 2 fields/time, 1 fraction/day, 2 Gy/fraction, 5 times/week, and DT 40 Gy/20 fractions; for the patients with ≤ 3 lesions with diameter ≥ 2 cm, a three-dimensional (3-D) conformal localised boost was given to increase the dosage to 56–60 Gy; and during radiotherapy, concurrent chemotherapy with topotecan was given (the chemoradiotherapy group, CRT). The patients with brain metastasis from lung cancer during the same period who received radiotherapy only were selected as the controls (the radiotherapy-alone group, RT).

Results

From March 2009 to March 2012, both 38 patients were enrolled into two groups. The median progression-free survival(PFS) time , the 1- and 2-year PFS rates of CRT group and RT group were 6 months, 42.8%, 21.6% and 3 months, 11.6%, 8.7% (χ2 = 6.02, p = 0.014), respectively. The 1- and 2-year intracranial lesion control rates of CRT and RT were 75.9% , 65.2% and 41.6% , 31.2% (χ2 = 3.892, p = 0.049), respectively. The 1- and 2-year overall survival rates (OS) of CRT and RT were 50.8% , 37.9% and 40.4% , 16.5% (χ2 = 1.811, p = 0.178), respectively. The major side effects were myelosuppression and digestive toxicities, but no differences were observed between the two groups.

Conclusion

Compared with radiotherapy alone, whole-brain irradiation plus 3-D conformal boost irradiation and concurrent topotecan chemotherapy significantly improved the PFS rate and the intracranial lesion control rate of patients with brain metastases from lung cancer, and no significant increases in side effects were observed. Based on these results, this treatment method is recommended for phase III clinical trial.