bluuebunny/crossref_metadata_2025 huggingface dataset:
The Influence of Internal Social Capital on Serial Creators’ Success in Crowdfunding
Authors: Skirnevskiy Vitaly , Bendig David , Brettel Malte
Published: January 2017

Interactions between project creators and backers on the crowdfunding platform represent the linchpin of every campaign. However, the resulting internal social capital has received little academic attention. To address this topic, we frame how internal social capital can develop through project track record and how internal social capital can spill over to external online communities. Focusing on the long–term implications of these manifestations of social capital, we empirically assess whether they can increase funding success beyond a single campaign. We test our hypotheses with two data sets derived from platform and survey sources and find support for the proposed relationships.
The threat to coral reefs from more intense cyclones under climate change
Authors: Cheal Alistair J. , MacNeil M. Aaron , Emslie Michael J. , Sweatman Hugh
Published: January 2017

Ocean warming under climate change threatens coral reefs directly, through fatal heat stress to corals and indirectly, by boosting the energy of cyclones that cause coral destruction and loss of associated organisms. Although cyclone frequency is unlikely to rise, cyclone intensity is predicted to increase globally, causing more frequent occurrences of the most destructive cyclones with potentially severe consequences for coral reef ecosystems. While increasing heat stress is considered a pervasive risk to coral reefs, quantitative estimates of threats from cyclone intensification are lacking due to limited data on cyclone impacts to inform projections. Here, using extensive data from Australia's Great Barrier Reef (GBR), we show that increases in cyclone intensity predicted for this century are sufficient to greatly accelerate coral reef degradation. Coral losses on the outer GBR were small, localized and offset by gains on undisturbed reefs for more than a decade, despite numerous cyclones and periods of record heat stress, until three unusually intense cyclones over 5 years drove coral cover to record lows over >1500 km. Ecological damage was particularly severe in the central‐southern region where 68% of coral cover was destroyed over >1000 km, forcing record declines in the species richness and abundance of associated fish communities, with many local extirpations. Four years later, recovery of average coral cover was relatively slow and there were further declines in fish species richness and abundance. Slow recovery of community diversity appears likely from such a degraded starting point. Highly unusual characteristics of two of the cyclones, aside from high intensity, inflated the extent of severe ecological damage that would more typically have occurred over 100s of km. Modelling published predictions of future cyclone activity, the likelihood of more intense cyclones within time frames of coral recovery by mid‐century poses a global threat to coral reefs and dependent societies.
The NLRP3 inflammasome contributes to host protection during Sporothrix schenckii infection
Authors: Gonçalves Amanda Costa , Ferreira Lucas Souza , Manente Francine Alessandra , de Faria Carolina Maria Quinello Gomes , Polesi Marisa Campos , de Andrade Cleverton Roberto , Zamboni Dario Simões , Carlos Iracilda Zeppone
Published: January 2017

Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto. Pattern recognition receptors (PRRs) recognize and respond to pathogen‐associated molecular patterns (PAMPs) and shape the following adaptive immune response. A family of PRRs most frequently associated with fungal recognition is the nucleotide‐binding oligomerization domain‐like receptor (NLR). After PAMP recognition, NLR family pyrin domain‐containing 3 (NLRP3) binds to apoptosis‐associated speck‐like protein containing a caspase recruitment domain (ASC) and caspase‐1 to form the NLRP3 inflammasome. When activated, this complex promotes the maturation of the pro‐inflammatory cytokines interleukin‐1β (IL‐1β) and IL‐18 and cell death through pyroptosis. In this study, we aimed to evaluate the importance of the NLRP3 inflammasome in the outcome of S. schenckii infection using the following three different knockout (KO) mice: NLRP3−/−, ASC−/− and caspase‐1−/−. All KO mice were more susceptible to infection than the wild‐type, suggesting that NLRP3‐triggered responses contribute to host protection during S. schenckii infection. Furthermore, the NLRP3 inflammasome appeared to be critical for the ex vivo release of IL‐1β, IL‐18 and IL‐17 but not interferon‐γ. Additionally, a role for the inflammasome in shaping the adaptive immune response was suggested by the lower frequencies of type 17 helper T (Th17) cells and Th1/Th17 but not Th1 cells in S. schenckii‐infected KO mice. Overall, our results indicate that the NLRP3 inflammasome links the innate recognition of S. schenckii to the adaptive immune response, so contributing to protection against this infection.
Geriatric Infectious Diseases: Current Concepts on Diagnosis and Management
Authors: Yoshikawa Thomas T. , Norman Dean C.
Published: January 2017

New information on infectious diseases in older adults has become available in the past 20 years. In this review, in‐depth discussions on the general problem of geriatric infectious diseases (epidemiology, pathogenesis, age‐related host defenses, clinical manifestations, diagnostic approach); diagnosis and management of bacterial pneumonia, urinary tract infection, and Clostridium difficile infection; and the unique challenges of diagnosing and managing infections in a long‐term care setting are presented.
Factors associated with universal infant free school meal take up and refusal in a multicultural urban community
Authors: Goodchild G. A. , Faulks J. , Swift J. A. , Mhesuria J. , Jethwa P. , Pearce J.
Published: January 2017

Background

Universal infant free school meals (UIFSM) were introduced in September 2014 and are available to all key stage 1 (4–7 years) children attending state‐maintained infant and primary schools in England. The present study aimed to investigate the school‐based factors, child and family socio‐demographic characteristics, and parental beliefs associated with UIFSM take up in an urban community.

Methods

A cross‐sectional questionnaire survey was completed in October to November 2015, amongst parents whose children attended eligible schools in Leicester, England. A questionnaire about school meals was also completed by each school.

Results

Parents reported their child did not take (non‐UIFSM, n = 159) or took (UIFSM, n = 517) a UIFSM on most days. The non‐UIFSM group were more likely to be White‐British, have a higher socio‐economic status, have English as a first language, and involve their child in the decision over whether or not to take UIFSM, compared to the UIFSM group. Cluster analysis revealed that non‐UIFSM parents were either concerned over quality of meals and what/how much their child ate, concerned only by what/how much their child ate or whether their child did not like the food provided. Two subsets of parents in the UIFSM group were either very positive about UIFSM or appeared to take meals because they were free. Schools used a variety of measures to increase and maintain UIFSM take up.

Conclusions

Parents like to have control over what their child eats at school and children need to enjoy their school meals. Using a range of interventions to target subsets of parents may help local authorities, schools and caterers to increase UIFSM take up.
WHAT MAKES CITIES MORE PRODUCTIVE? EVIDENCE FROM FIVE OECD COUNTRIES ON THE ROLE OF URBAN GOVERNANCE
Authors: Ahrend Rudiger , Farchy Emily , Kaplanis Ioannis , Lembcke Alexander C.
Published: January 2017

In estimating agglomeration benefits across five OECD countries, this paper represents the first empirical analysis that contrasts cross‐country evidence on agglomeration benefits with the productivity impact of metropolitan governance structures, while taking into account the potential sorting of individuals across cities. The comparability of results in a multicountry setting is supported through the use of a new internationally harmonised definition of cities based on economic linkages rather than administrative boundaries. The analysis finds that cities with fragmented governance structures tend to have lower levels of productivity. The estimated elasticity for an increase in the number of local jurisdiction is 0.06, which is halved by the existence of a metropolitan governance body. The productivity effect is sizeable and at least as important as the agglomeration benefit found due to city size.
Interspecific and intraspecific variation in corolla tube length in Pedicularis species achieved by both cell anisotropy and division
Authors: Wang Xiang‐Ping , Huang Shuang‐Quan
Published: January 2017

The association between plants with long corolla tubes and pollinators with long tongues has evolved repeatedly in diverse pollination systems. However, the morphogenesis of long corolla tubes involved in diverse plant groups remains largely unexplored, limiting our understanding of the evolution and maintenance of long corolla tubes. Corolla tubes of Himalayan Pedicularis species exhibit striking length diversity, ranging from less than 10 mm to more than 120 mm. We investigated the role of cell division and cell expansion in determining the corolla tube morphology in eight Pedicularis species and in an experimental population of P. siphonantha Don in which corolla tubes were elongated under shading and watering treatments. Among species, the corolla tube length was positively correlated with both cell number and cell length but not cell width. Our analyses of intraspecific variation in corolla tube length indicated that it was positively correlated with cell length in all eight species but with cell number in only four of the species, indicating that corolla tube development in Pedicularis generally involves anisotropic cell expansion. The elongation of corolla tubes in P. siphonantha under experimental conditions was caused by the anisotropic elongation of cells; cell number of tube‐elongated flowers was not significantly increased. Our results showed that intraspecific variation in corolla tube length in Pedicularis species was largely attributable to changes in cell anisotropy, but the evolutionary innovation underlying the rapid radiation of Pedicularis corolla tubes was attributable to both cell division and cell expansion.
Sensory and analytical characterization of the “cool‐melting” perception of commercial spreads
Authors: Galindo‐Cuspinera Verónica , Valenҁa de Sousa Joana , Knoop Marcia
Published: January 2017

Butters, margarines and table spreads are water‐in‐oil emulsions. Melting characteristics of these products are important for flavor release and consumer acceptance. One characteristic that is believed to discriminate butters from margarines is a cooling sensation perceived in‐mouth while consuming these products. Here, we investigated different methods to characterize sensorically and analytically the “cool‐melting” properties of commercial butter and margarines. Our results show that butter indeed can be distinguished from margarines based on their “cool‐melting” properties. Furthermore, changes in enthalpy as measured through DSC and solid fat content are good predictors of the “cool‐melting” effect of spreads.

Practical applications

By understanding the mechanisms of the “cool‐melting” perception of spreads, and linking them to analytical measurements, we can create an in‐vitro quantification method of “cool‐melting.” This method can eventually help directing product development to achieve the desire product profile and increase consumer acceptance and liking of margarines and low‐fat spread products. In this study we did not assess the impact of “cool‐melting” on consumer perception, which would be the next step in understanding the drivers of liking of spread products.
Effects of Leukoreduction and Storage on Erythrocyte Phosphatidylserine Expression and Eicosanoid Concentrations in Units of Canine Packed Red Blood Cells
Authors: Muro S.M. , Lee J.H. , Stokes J.V. , Ross M.K. , Archer T.M. , Wills R.W. , Mackin A.J. , Thomason J.M.
Published: January 2017

Background

Storage of canine packed red blood cells (pRBCs) can increase erythrocyte phosphatidylserine (PS) expression and eicosanoid concentrations.

Hypothesis/Objectives

To determine the effects of leukoreduction on erythrocyte PS expression and eicosanoid concentrations in stored units of canine pRBCs. Our hypothesis was that leukoreduction would decrease PS expression and eicosanoid concentrations.

Animals

Eight healthy dogs.

Methods

In a cross‐over study, units of whole blood were leukoreduced (LR) or non‐LR and stored (10 and 21 days) as pRBCs. Samples were collected at donation, and before and after a simulated transfusion. PS expression was measured by flow cytometry, and concentrations of arachidonic acid (AA), prostaglandin F2α (PGF2α), prostaglandin E2 (PGE2), prostaglandin D2 (PGD2), thromboxane B2 (TXB2), 6‐keto‐prostaglandin F1α (6‐keto‐PGF1α), and leukotriene B4 (LTB4) were quantified by liquid chromatography–mass spectrometry.

Results

There was no change in PS expression during leukoreduction, storage, and simulated transfusion for non‐LR and LR units. Immediately after leukoreduction, there was a significant increase in TXB2 and PGF2α concentrations, but during storage, these eicosanoids decreased to non‐LR concentrations. In both LR and non‐LR units, 6‐keto‐PGF1α concentrations increased during storage and simulated transfusion, but there was no difference between unit type. There was no difference in AA, LTB4, PGE2, and PGD2 concentrations between unit types.

Conclusions and Clinical Importance

Leukoreduction, storage, and simulated transfusion do not alter erythrocyte PS expression. Leukoreduction causes an immediate increase in concentrations of TXB2 and PGF2α, but concentrations decrease to non‐LR concentrations with storage. Leukoreduction does not decrease the accumulation of 6‐keto‐PGF1α during storage.
Testing a general approach to assess the degree of disturbance in tropical forests
Authors: Sellan Giacomo , Simini Filippo , Maritan Amos , Banavar Jayanth R. , de Haulleville Thalès , Bauters Marijn , Doucet Jean‐Louis , Beeckman Hans , Anfodillo Tommaso
Published: January 2017

Questions

Is there any theoretical model enabling predictions of the optimal tree size distribution in tropical communities? Can we use such a theoretical framework for quantifying the degree of disturbance?

Location

Reserve of Yangambi, northeast region of the Democratic Republic of Congo.

Methods

We applied an allometric model based on the assumption that a virtually undisturbed forest uses all available resources. In this condition, the forest structure (e.g. the tree size distribution) is theoretically predictable from the scaling of the tree crown with tree height at an individual level. The degree of disturbance can be assessed through comparing the slopes of the tree size distribution curves in the observed and predicted conditions. We tested this tool in forest stands subjected to different degrees of disturbance. We inventoried trees >1.3 m in height by measuring the DBH in three plots of 1 ha each, and measured tree height, crown radius and crown length in a sub‐sample of trees.

Results

All tree species, independently of the site, shared the same exponents of allometric relationships: tree height vs tree diameter, crown radius vs tree height, crown length vs tree height and consequently crown volume vs tree height, suggesting that similar trajectories of biomass allocation have evolved irrespective of species. The observed tree size distributions appeared to be power laws (excluding the finite size effect) and, as predicted, the slope was steeper in the less disturbed forest (−2.34) compared to the most disturbed (−1.99). The difference in the slope compared to the theoretical fully functional forest (−2.65) represents the metric for assessing the degree of disturbance.

Conclusions

We developed a simple tool for operationalizing the concept of ‘disturbance’ in tropical forests. This approach is species‐independent, needs minimal theoretical assumptions, the measurement of only a few structural traits and requires a low investment in equipment, time and computer skills. Its simple implementation opens new perspectives for effectively addressing initiatives of forest protection and/or restoration.
The next frontier of plant–soil feedback research: unraveling context dependence across biotic and abiotic gradients
Authors: Smith‐Ramesh Lauren M. , Reynolds Heather L.
Published: January 2017

Question

Plant–soil feedback (PSF) has emerged as a ubiquitous phenomenon and a potentially important predictor of plant community structure and dynamics. However, the predictive power of PSF in field contexts is mixed, and ecologists do not yet understand its relative importance compared to other factors that structure communities. Further progress requires a more nuanced understanding of how PSF interacts with other biotic and abiotic factors. Environmental factors (e.g. natural enemies, moisture, light, nutrients) are known to affect plant interactions with soil and soil organisms, leading to an expectation of environmental context dependence in plant–soil feedback. Such context dependence could explain when PSF is expected to be an important driver of community dynamics, and under what conditions PSF is likely to be positive (destabilizing) vs negative (stabilizing).

Methods

We conducted a literature review of studies that examined PSF across biotic and abiotic gradients.

Results

Although few relevant studies have been conducted in this emerging research area, results to date suggest that plant–soil feedback is sensitive to biotic factors, such as above‐ and below‐ground herbivory, and abiotic factors, such as nutrients and light.

Conclusions

We develop a conceptual framework to predict variation in the direction and strength of PSF depending on the biotic or abiotic drivers of feedback (e.g. pathogens, nutrients) and the environmental context (e.g. intensity of herbivory, soil fertility). We explore the utility of our predictive framework through discussion of case studies from the literature on context dependence in PSF. We also consider how different experimental approaches might yield different insights about PSF–environment interactions, and suggest key future research directions.
External validation of the Donor Risk Index and the Eurotransplant Donor Risk Index on the French liver transplantation registry
Authors: Winter Audrey , Féray Cyrille , Audureau Etienne , Écochard René , Jacquelinet Christian , Roudot‐Thoraval Françoise , Duvoux Christophe , Daurès Jean‐Pierre , Landais Paul
Published: January 2017

Background & Aims

A major limitation to liver transplantation is organ shortage leading to the use of non‐optimal liver grafts. The Donor Risk Index has been validated and recommended to select donors/organs. The Eurotransplant Donor Risk Index was derived from the Donor Risk Index. The objective of our study was to perform an external validation of both Donor Risk Index and Eurotransplant‐Donor Risk Index against the French liver transplantation Cristal registry according to recommendations of the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis.

Methods

Liver transplantations performed in France between 2009 and 2013 were used to perform the validation study for the Donor Risk Index and the Eurotransplant‐Donor Risk Index respectively. We applied on the French data the models used to construct the Donor Risk Index and the Eurotransplant‐Donor Risk Index respectively.

Results

Neither the Donor Risk Index nor the Eurotransplant‐Donor Risk Index were validated against this dataset. Discrimination and calibration of these scores were not preserved according to our data. Important donor and candidates differences between our dataset and the Organ Procurement and Transplantation Network or the Eurotransplant datasets may explain why the Donor Risk Index and the Eurotransplant‐Donor Risk Index appeared unadapted to the French transplant registry.

Conclusion

Neither of these risk indexes were suitable to optimize the French liver allocation system. Thus, our next step will be to propose a general adaptive model for a Donor Risk Index.
A combination of sexual and ecological divergence contributes to rearrangement spread during initial stages of speciation
Authors: Kozak Genevieve M. , Wadsworth Crista B. , Kahne Shoshanna C. , Bogdanowicz Steven M. , Harrison Richard G. , Coates Brad S. , Dopman Erik B.
Published: January 2017

Chromosomal rearrangements between sympatric species often contain multiple loci contributing to assortative mating, local adaptation and hybrid sterility. When and how these associations arise during the process of speciation remains a subject of debate. Here, we address the relative roles of local adaptation and assortative mating on the dynamics of rearrangement evolution by studying how a rearrangement covaries with sexual and ecological trait divergence within a species. Previously, a chromosomal rearrangement that suppresses recombination on the Z (sex) chromosome was identified in European corn borer moths (Ostrinia nubilalis). We further characterize this recombination suppressor and explore its association with variation in sex pheromone communication and seasonal ecological adaptation in pairs of populations that are divergent in one or both of these characteristics. Direct estimates of recombination suppression in pedigree mapping families indicated that more than 39% of the Z chromosome (encompassing up to ~10 megabases and ~300 genes) resides within a nonrecombining unit, including pheromone olfactory receptor genes and a major quantitative trait locus that contributes to ecotype differences (Pdd). Combining direct and indirect estimates of recombination suppression, we found that the rearrangement was occasionally present between sexually isolated strains (E vs. Z) and between divergent ecotypes (univoltine vs. bivoltine). However, it was only consistently present when populations differed in both sexual and ecological traits. Our results suggest that independent of the forces that drove the initial establishment of the rearrangement, a combination of sexual and ecological divergence is required for rearrangement spread during speciation.
Transcriptomic responses to seawater acidification among sea urchin populations inhabiting a natural pH mosaic
Authors: Evans Tyler G. , Pespeni Melissa H. , Hofmann Gretchen E. , Palumbi Stephen R. , Sanford Eric
Published: January 2017

Increasing awareness of spatial and temporal variation in ocean pH suggests some marine populations may be adapted to local pH regimes and will therefore respond differently to present‐day pH variation and to long‐term ocean acidification. In the Northeast Pacific Ocean, differences in the strength of coastal upwelling cause latitudinal variation in prevailing pH regimes that are hypothesized to promote local adaptation and unequal pH tolerance among resident populations. In this study, responses to experimental seawater acidification were compared among embryos and larvae from six populations of purple sea urchins (Strongylocentrotus purpuratus) inhabiting areas that differ in their frequency of low pH exposure and that prior research suggests are locally adapted to seawater pH. Transcriptomic analyses demonstrate urchin populations most frequently exposed to low pH seawater responded to experimental acidification by expressing genes within major ATP‐producing pathways at greater levels than populations encountering low pH less often. Multiple genes within the tricarboxylic acid cycle, electron transport chain and fatty acid beta oxidation pathways were upregulated in urchin populations experiencing low pH conditions most frequently. These same metabolic pathways were significantly over‐represented among genes both expressed in a population‐specific manner and putatively under selection to enhance low pH tolerance. Collectively, these data suggest natural selection is acting on metabolic gene networks to redirect ATP toward maintaining acid–base homeostasis and enhance tolerance of seawater acidification. As a trade‐off, marine populations more tolerant of low pH may have less energy to put towards other aspects of fitness and to respond to additional ocean change.
Cryphonectria parasitica, the causal agent of chestnut blight: invasion history, population biology and disease control
Authors: Rigling Daniel , Prospero Simone
Published: January 2017

Chestnut blight, caused by Cryphonectria parasitica, is a devastating disease infecting American and European chestnut trees. The pathogen is native to East Asia and was spread to other continents via infected chestnut plants. This review summarizes the current state of research on this pathogen with a special emphasis on its interaction with a hyperparasitic mycovirus that acts as a biological control agent of chestnut blight.

Taxonomy

Cryphonectria parasitica (Murr.) Barr. is a Sordariomycete (ascomycete) fungus in the family Cryphonectriaceae (Order Diaporthales). Closely related species that can also be found on chestnut include Cryphonectria radicalis, Cryphonectria naterciae and Cryphonectria japonica.

Host range

Major hosts are species in the genus Castanea (Family Fagaceae), particularly the American chestnut (C. dentata), the European chestnut (C. sativa), the Chinese chestnut (C. mollissima) and the Japanese chestnut (C. crenata). Minor incidental hosts include oaks (Quercus spp.), maples (Acer spp.), European hornbeam (Carpinus betulus) and American chinkapin (Castanea pumila).

Disease symptoms

Cryphonectria parasitica causes perennial necrotic lesions (so‐called cankers) on the bark of stems and branches of susceptible host trees, eventually leading to wilting of the plant part distal to the infection. Chestnut blight cankers are characterized by the presence of mycelial fans and fruiting bodies of the pathogen. Below the canker the tree may react by producing epicormic shoots. Non‐lethal, superficial or callusing cankers on susceptible host trees are usually associated with mycovirus‐induced hypovirulence.

Disease control

After the introduction of C. parasitica into a new area, eradication efforts by cutting and burning the infected plants/trees have mostly failed. In Europe, the mycovirus Cryphonectria hypovirus 1 (CHV‐1) acts as a successful biological control agent of chestnut blight by causing so‐called hypovirulence. CHV‐1 infects C. parasitica and reduces its parasitic growth and sporulation capacity. Individual cankers can be therapeutically treated with hypovirus‐infected C. parasitica strains. The hypovirus may subsequently spread to untreated cankers and become established in the C. parasitica population. Hypovirulence is present in many chestnut‐growing regions of Europe, either resulting naturally or after biological control treatments. In North America, disease management of chestnut blight is mainly focused on breeding with the goal to backcross the Chinese chestnut's blight resistance into the American chestnut genome.
Silencing of OTUB1 inhibits migration of human glioma cells in vitro
Authors: Xu Li , Li Jinquan , Bao Zhen , Xu Peng , Chang Hao , Wu Jingjing , Bei Yuanqi , Xia Liuwan , Wu Peizhang , Yan Ke , Lu Bing , Cui Gang
Published: January 2017

OTU domain‐containing ubiquitin aldehyde‐binding protein 1 (OTUB1) protein, a deubiquitinating enzyme (DUB) which belongs to the ovarian tumor (OTU) family, was reported to be associated with the development of various malignancies. However, the potential function of OTUB1 in human gliomas was still unclear. In this study, we sought to investigate the function of OTUB1 in the pathological process of gliomas and analyze its related clinical significance. Western blot and immunohistochemistry analyses demonstrated that OTUB1 was overexpressed in glioma tissues, and statistical analysis suggested the expression level of OTUB1 was significantly correlated with the WHO grades of human gliomas (P < 0.05). Moreover, Kaplan–Meier curve also indicated that high expression of OTUB1 was correlated with a poor prognosis. In vitro, silencing OTUB1 retarded the migration ability of glioma cells. Knockdown of OTUB1 increases epithelial‐mesenchymal transition‐related protein E‐cadherin expression, but decreases simultaneously the expression of vimentin and snail. Furthermore, down‐regulated expression of OTUB1 also resulted in decreased expression of some extracellular matrix degradation‐related proteins, such as matrix metallopeptidase (MMP)2 and MMP9. All results suggested that OTUB1 was a valuable marker in the pathogenesis of human gliomas and could be used as a novel biomarker for glioma therapy in the future.
MicroRNA‐125a promotes resistance to BRAF inhibitors through suppression of the intrinsic apoptotic pathway
Authors: Koetz‐Ploch Lisa , Hanniford Douglas , Dolgalev Igor , Sokolova Elena , Zhong Judy , Díaz‐Martínez Marta , Bernstein Emily , Darvishian Farbod , Flaherty Keith T. , Chapman Paul B. , Tawbi Hussein , Hernando Eva
Published: January 2017

Melanoma patients with BRAFV600E‐mutant tumors display striking responses to BRAF inhibitors (BRAFi); however, almost all invariably relapse with drug‐resistant disease. Here, we report that microRNA‐125a (miR‐125a) expression is upregulated in human melanoma cells and patient tissues upon acquisition of BRAFi resistance. We show that miR‐125a induction confers resistance to BRAFV600E melanoma cells to BRAFi by directly suppressing pro‐apoptotic components of the intrinsic apoptosis pathway, including BAK1 and MLK3. Apoptotic suppression and prolonged survival favor reactivation of the MAPK and AKT pathways by drug‐resistant melanoma cells. We demonstrate that miR‐125a inhibition suppresses the emergence of resistance to BRAFi and, in a subset of resistant melanoma cell lines, leads to partial drug resensitization. Finally, we show that miR‐125a upregulation is mediated by TGFβ signaling. In conclusion, the identification of this novel role for miR‐125a in BRAFi resistance exposes clinically relevant mechanisms of melanoma cell survival that can be exploited therapeutically.
Impact of exacerbations on adherence and outcomes of pulmonary rehabilitation in patients with COPD
Authors: Braeken Dionne C.W. , Spruit Martijn A. , Houben‐Wilke Sarah , Smid Dionne E. , Rohde Gernot G.U. , Wouters Emiel F.M. , Franssen Frits M.E.
Published: January 2017

ABSTRACT

Background and objective

Dropout or lack of response is an important issue in pulmonary rehabilitation (PR), which underlines the need to identify predictors of dropout and response. Acute exacerbations (AEs) of COPD may influence dropout rates and PR response. We aimed to assess differences in dropout and outcomes of PR between COPD with and without AEs.

Methods

Clinically stable patients with moderate‐to‐very severe COPD (age: 64.1 ± 9.1 years, 55.6% males, forced expiratory volume in 1 s (FEV1
): 48.6 ± 20.0% predicted) were assessed during PR (inpatient and outpatient). Mild‐to‐moderate AEs were defined as ‘the prescription of systemic glucocorticosteroids and/or antibiotics, following an acute increase in respiratory symptoms’. Severe AEs were defined as ‘a hospital admission due to an AE’. Health status was measured by COPD Assessment Test (CAT), COPD‐specific version of the St George's Respiratory Questionnaire (SGRQ‐C) and Clinical COPD Questionnaire (CCQ). Symptoms of anxiety and depression were measured by Hospital Anxiety and Depression Scale (HADS). Exercise capacity was measured with the 6‐min walking test (6MWT) and constant work rate test (CWRT).

Results

A total of 518 patients were assessed during a pre‐rehabilitation assessment. Four hundred and seventy‐six patients started PR, of whom 419 (88.0%) completed it. A larger proportion of patients who dropped out had a severe AE during PR (20.0% vs 3.5%, P < 0.001). Completers with severe AE showed a deterioration in 6MWT, while completers without AE and with mild‐to‐moderate AE improved (−24.8 (95% CI: −94.0 to 44.5) vs 24.2 (95% CI: 16.0 to 32.5) vs 25.1 (95% CI: 14.0 to 36.3) metres, P = 0.042). No other significant differences were observed in outcomes comparing completers with and without AE during PR.

Conclusion

Mild‐to‐moderate AEs do not affect dropout or response of PR, although severe AEs are associated with dropout. AEs should not lead to discontinuation of PR, as response is in general not affected.
Coexistence of fusion and concrescence of primary teeth: in a child with Down syndrome
Authors: Singh Akshara , Bhatia Hind Pal , Sharma Naresh
Published: January 2017

Down syndrome is one of the most common congenital anomaly. It is most frequently caused by trisomy of chromosome 21. Other causes can be mosaicism and translocation. Such patients are commonly encountered in routine dental practice. This syndrome has wide range of medical and dental abnormalities. This paper presents a unique case of fusion and concrescence of retained primary teeth in a child with Down syndrome. The incidence of such anomalies is quite low in these cases. Thus, a better awareness of such conditions on part of a dental practitioner will aid in the provision of enhanced dental care to these patients.
Plasma volume reduction and hematological fluctuations in high‐level athletes after an increased training load
Authors: Bejder J. , Andersen A. B. , Goetze J. P. , Aachmann‐Andersen N. J. , Nordsborg N. B.
Published: January 2017

The time course of plasma volume (PV) reduction following an increased training load period is unknown and was investigated. The accompanying fluctuations in [Hb] and OFF‐hr score were analyzed in the Athlete Biological Passport. Further, whether fluctuations in plasma albumin, soluble transferrin receptors (sTfR), and pro‐atrial natriuretic peptide (proANP) concentrations correlate with PV fluctuations was investigated. Eleven high‐level competitive cyclists were investigated for 3 weeks. After initial measurements in week 1, training load was increased ~250% in week 2 followed by a reversion to baseline training load in week 3. PV and hematological variables were determined frequently during all weeks. The higher training load in week 2 increased (P<.001) PV 10%, while [Hb] and OFF‐hr score decreased ~6% (P<.01) and ~16% (P<.001), respectively. PV and [Hb] returned to baseline within 2 and 4 days after week 2, respectively, while OFF‐hr score remained reduced for 6 days. Further, one and three atypical blood profiles of the ABP occurred during weeks 2 and 3, respectively. Individual changes in albumin, sTfR, and proANP only correlated weakly (R2<.20) with PV fluctuations. In conclusion, PV and [Hb] fluctuations caused by an elevated training load period were reverted within 2 and 4 days after returning to baseline training load, respectively, while OFF‐hr remained altered for 6 days. Furthermore, some atypical blood profiles were induced during and subsequent to the increased training load, demonstrating the importance of knowledge on naturally occurring hematological fluctuations. Finally, concentrations of albumin, sTfR, and proANP could not explain PV fluctuations.
The twisted structure of the Achilles tendon unraveled: A detailed quantitative and qualitative anatomical investigation
Authors: Pękala P. A. , Henry B. M. , Ochała A. , Kopacz P. , Tatoń G. , Młyniec A. , Walocha J. A. , Tomaszewski K. A.
Published: January 2017

The Achilles tendon (AT) consists of fibers originating from the soleus muscle (SOL), which lies deep, and the medial (GM) and lateral (GL) heads of the gastrocnemius muscle, which lie superficial. As the fibers descend toward the insertion of the AT, the individual subtendons twist around each other. The aim of this study was to investigate the twisted structure of the AT and its individual subtendons. Specimens of the AT, with preserved calcaneal bone and a fragment of the triceps surae muscle, were obtained from 53 fresh‐frozen, male cadavers (n=106 lower limbs). The angle of torsion of each of the AT's subtendons was measured using a specially designed and 3D‐printed tool. The mean distance between the most distal fibers of the triceps surae muscle and the superior border of the calcaneal bone was 60.77±14.15 mm. The largest component of the AT at the level of its insertion into the calcaneal bone is the subtendon from the GL (44.43%), followed by the subtendon from SOL (27.89%), and the subtendon from GM (27.68%). The fibers originating from the GM rotate on average 28.17±15.15°, while the fibers originating from the GL and SOL twist 135.98±33.58° and 128.58±29.63°, respectively. The torsion of superficial fibers (GM) comprising the AT is significantly lower than that of deeper fibers (GL and SOL). The cross‐sectional area of the AT is smaller at the level of the musculo‐tendinous junction than at the level of its insertion. This study illustrates the three types of the AT with differently twisting subtendons, as well as a generalized model of the AT. Types of AT torsion may potentially alter the biomechanical properties of the tendon, thus possibly influencing the pathophysiologic mechanisms leading to the development of various tendinopathies.
CATALYTIC SURFACE MODIFICATION OF ALUMINA MEMBRANE FOR OXYGEN SEPARATION
Authors: Sihar ‘Ainun Sailah , Shahrudin Munawar Zaman , Alias Nur Hashimah , Che Abdul Rahim 'Azzah Nazihah , Othman Nur Hidayati , A. Rahman Mukhlis
Published: January 2017

Two types of alumina ceramic membrane in hollow fibre shape was used in this study. Both alumina hollow fibres (AHF) were sintered at different temperatures; (a) 1350oC and (b) 1450oC. In order to improve the catalytic activity of the alumina membrane for oxygen separation purposes, surface modification of the membranes was carried out using La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) perovskite catalyst. LSCF was synthesised using simple Pechini sol-gel method. The evaporation time and temperature of the LSCF-sol were varied to obtain various viscosity of catalytic sol. From XRD analysis, pure LSCF perovskite structure formed at temperature at 850oC. The morphological of unmodified and surface-modified alumina hollow fibre membranes (AHF) were studied using FESEM. The effect of LSCF catalytic sol viscosity was studied and it was found that as the viscosity of the sol increases, the amount of catalyst deposited on the alumina hollow fibre were increased.  Besides, the amount of catalyst deposited on 1350 AHF was found to be higher than 1450 AHF. This result is supported by the result of pore distribution data whereby 1350 AHF was observed to be more porous than 1450 AHF, with porosity percentage of 40.38% and 28.80%, respectively. Although higher viscosity of catalytic sol could lead to a high amount of catalyst deposited on the AHF substrate, there is a tendency for micro-cracks to develop. Thus, the viscosity of the catalytic sol is important to control in order to have higher oxygen permeation flux.
MEMBRANE FROM PLASTIC WASTE FOR THE TREATMENT OF CONTAMINATED RIVER WATER
Authors: Zukimin Nur Wafaa , Jullok Nora , Mat Razi Al Nazifah , Fadzilah Muhd Hanif Harif
Published: January 2017

Excessive plastic waste and river water pollution are both never ending environmental problems faced by every country around the world. In this paper, polymeric membrane was synthesized from plastic waste of high density polyethylene (HDPE) type to treat contaminated river water. The plastic waste was grinded into powder of different particle sizes before synthesizing the membrane by sintering method. The membranes were synthesized both with and without the addition of solvents. The heating temperature during membrane synthesis was also being study for membrane performance in terms of percentage of permeate rejection and permeate flux. HDPE membrane produced from average particle size of 270.7±178.6 μm achieved the highest permeate rejection and has highest heating temperature (180ºC). Field Emission Scanning Electron Microscopic (FESEM) analysis showed that the sintered membranes exhibit a porous asymmetric structure. Meanwhile, Fourier Transform Infrared Spectroscopy (FTIR) analysis denote the HDPE membranes in grouped as alkanes and aromatics compounds.
EFFECT OF SYNTHESIS REACTION TIME AND DOPING ON UV/VIS ABSORPTION OF POLYENE COATING
Authors: Norizan Mohd Nurazzi , Mohamed Rahmah
Published: January 2017

Absorbance spectra and energy band gap of synthesizing polyene from dechlorination of polyvinyl chloride (PVC) with varying synthesizing reaction times and doping percentages were examined in this paper. The reaction time of dechlorination was varied from 30 minutes, 1 hour, 2 hours and 4 hours. Polyene obtained from the dechlorination reaction was doped with potassium iodide (KI). Sample for UV/Vis test was prepared in the form of film. Modified EO film as control sample showed that there is only a single absorption peak around 327nm. The C-Cl adsorption band link from source link polymer was observed at 422nm and all polyene film samples and new bands absorption were observed from 422nm to 590nm, and 683nm upon the increase in reaction time. The lower energy band gap was observed at 683.18nm absorption with 1.08eV.
URSODEOXYCHOLIC ACID REGULATES CASPASE-9 AND ROS PRODUCTION IN PROTECTING CARDIOMYOCYTES AGAINST HYPOXIA
Authors: Hanafi Noorul Izzati , Sheikh Abdul Kadir Siti Hamimah , Mohamed Anis Syamimi , Md Noor Julina , Osman Nora Julianna , Siran Rosfaiizah , Ab Rahim Sharaniza , Abdul Hamid Hasani Narimah
Published: January 2017

Ursodeoxycholic acid (UDCA) is known as a therapeutic agent in treating cholestasis and liver diseases. Recently, UDCA has been suggested as a therapeutic drug for heart related diseases. Cardioprotective effect of UDCA against the development of ischemia has been studied. Yet, the mechanism of UDCA-cardioprotection is not clearly understood. Therefore, this study aimed to elucidate the mechanisms of UDCA cardioprotection against hypoxia by investigating the expression of caspase -3/-9 and ROS generation using an in vitro hypoxic heart model. A newborn (0-2 days old) rat heart was isolated for primary cell culture of cardiomyocytes. Hypoxia was chemically induced by using CoCl2. Cardiomyocytes were then incubated with UDCA. The treated cardiomyocytes were subjected for ROS generation detection assay, QuantiGene Plex assay for caspase-3/-9 gene expression and ELISA for caspase-3/-9 protein expression. The data were analyzed by using sample paired t-test and One-way ANOVA. Our results showed that UDCA abolishes the effects on CoCl2 in ROS production and UDCA downregulates caspase-9 protein  expression in CoCl2 treated cardiomyocytes. This study provides an insight of UDCA in protecting cardiomyocytes against hypoxia mediated by anti-apoptosis mechanism.
Exploring the Cham Script to Develop the Transliteration Application for Cham Latin to Cham Script
Authors: Sang Van Ngoc , Bilal Ali Mohamad , Abd Halim Noor Dayana
Published: January 2017

The main purpose of this research is to explore the preferable Cham script and Cham Latin; to develop application and evaluate the application products. Research sample is divided into two groups and the research instrument distributed into two forms of survey. The application was developed using ADDIE model. This survey, the acceptance of Cham script by religious group is 100%, Cham script online voting by student is 90.09%, Cham script by online questionnaire is 98.3%. EFEO Cham Latin by religious group is 100%, EFEO Cham Latin by online questionnaire is 95.4%. Viewed by sixteen experts using Fuzzy Delphi the results show that percentage of all items are 100%, more than what required (75%), the value of d for total construct is 0.02 (required ≤ 0.2). For conversion application, we have checked the accuracy percentage of four Cham poems and results Ariya Gleng Anak 99.88% (n=2459); Nai Mai Mang Makah 100% (n=2523); Ariya Cam Bini 100% (n=1823); Ariya Po Ceng 99.91% (n=2202). Using technologies to preserve the Cham language heritage is not only theoretically significant but also practically significant.
Rarefied gas flow into vacuum through short tubes at variable wall temperatures
Authors: Zhang Mingxing , Day Christian , Varoutis Stylianos , Cai Guobiao
Published: January 2017

Rarefied gas flow into vacuum through short tubes at variable wall temperatures was studied numerically with the direct simulation Monte Carlo method. A wide range of tube wall temperatures varying from 120 to 1200 K was considered, as well as several rarefaction parameters and tube aspect ratios. The mass flow rate, specific impulse, thrust, and characteristics of the gas flow field were analyzed. The results showed that the tube wall temperature, as well as the aspect ratio and rarefaction parameter, had a significant influence on the characteristics of the tube flow. The mass flow rate was found to decrease with increasing wall temperature, while the specific impulse increased. This paper reveals the combinations of rarefaction parameter and aspect ratio whereby the wall temperature has the strongest influence on the flow field of the gas, as well as on the overall macroscopic parameters.
PDZRN3 destabilizes endothelial cell-cell junctions through a PKCζ-containing polarity complex to increase vascular permeability
Authors: Sewduth Raj N. , Kovacic Héléna , Jaspard-Vinassa Béatrice , Jecko Vincent , Wavasseur Thomas , Fritsch Nicolas , Pernot Mathieu , Jeaningros Sylvie , Roux Etienne , Dufourcq Pascale , Couffinhal Thierry , Duplàa Cécile
Published: January 2017

Inhibiting the E3 ubiquitin ligase PDZRN3 could stabilize endothelial cell connections to prevent vascular leakage.
A Short Double-Stapled Peptide Inhibits Respiratory Syncytial Virus Entry and Spreading
Authors: Gaillard Vanessa , Galloux Marie , Garcin Dominique , Eléouët Jean-François , Le Goffic Ronan , Larcher Thibaut , Rameix-Welti Marie-Anne , Boukadiri Abdelhak , Héritier Julien , Segura Jean-Manuel , Baechler Elodie , Arrell Miriam , Mottet-Osman Geneviève , Nyanguile Origène
Published: January 2017

Synthetic peptides derived from the heptad repeat (HR) of fusion (F) proteins can be used as dominant negative inhibitors to inhibit the fusion mechanism of class I viral F proteins. Here, we have performed a stapled-peptide scan across the HR2 domain of the respiratory syncytial virus (RSV) F protein with the aim to identify a minimal domain capable of disrupting the formation of the postfusion six-helix bundle required for viral cell entry. Constraining the peptides with a single staple was not sufficient to inhibit RSV infection. However, the insertion of double staples led to the identification of novel short stapled peptides that display nanomolar potency in HEp-2 cells and are exceptionally robust to proteolytic degradation. By replacing each amino acid of the peptides by an alanine, we found that the substitution of residues 506 to 509, located in a patch of polar contacts between HR2 and HR1, severely affected inhibition. Finally, we show that intranasal delivery of the most potent peptide to BALB/c mice significantly decreased RSV infection in upper and lower respiratory tracts. The discovery of this minimal HR2 sequence as a means for inhibition of RSV infection provides the basis for further medicinal chemistry efforts toward developing RSV fusion antivirals.