bluuebunny/crossref_metadata_2025 huggingface dataset:
A role for Ral GTPase‐activating protein subunit β in mitotic regulation
Authors: Personnic Nicolas , Lakisic Goran , Gouin Edith , Rousseau Alix , Gautreau Alexis , Cossart Pascale , Bierne Hélène
Published: May 2014

Ral proteins are small GTPases that play critical roles in normal physiology and in oncogenesis. There is little information on the GTPase‐activating proteins (GAPs) that downregulate their activity. Here, we provide evidence that the noncatalytic β subunit of RalGAPα1/2β complexes is involved in mitotic control. RalGAPβ localizes to the Golgi and nucleus during interphase, and relocalizes to the mitotic spindle and cytokinetic intercellular bridge during mitosis. Depletion of RalGAPβ causes chromosome misalignment and decreases the amount of mitotic cyclin B1, disturbing the metaphase‐to‐anaphase transition. Overexpression of RalGAPβ interferes with cell division, leading to binucleation and multinucleation, and cell death. We propose that RalGAPβ plays an essential role in the sequential progression of mitosis by controlling the spatial and temporal activation of Ral GTPases in the spindle assembly checkpoint (SAC) and cytokinesis. Deregulation of RalGAPβ might cause genomic instability, leading to human carcinogenesis.

Structured digital abstract

RalGAP beta physically interacts with Tubulin beta5, tubulin alpha, Hsp70, EF1a, RalGAP alpha 2, DDX15 and RalGAP alpha 1 by tandem affinity purification (View interaction)

RalGAP beta and GM130 colocalize by fluorescence microscopy (View interaction)
The homeobox transcription factor Irxl1 negatively regulates MyoD expression and myoblast differentiation
Authors: Chuang Han‐Ni , Hsiao Kuang‐Ming , Chang Hui‐Yi , Wu Chia‐Chi , Pan Huichin
Published: May 2014

Irxl1/Mkx (Iroquois homeobox‐like 1/Mohawk) encodes a member of the TALE subfamily of homeodomain proteins. It is expressed in multiple mesoderm‐derived tissues and has recently been shown to regulate tendon differentiation during mouse embryonic development. Previously we showed that knockdown of Irxl1 in zebrafish caused a deficit in neural crest cells which consequently resulted in deformation of craniofacial muscles and arch cartilages. Here, we further demonstrate that loss of Irxl1 function results in deformed somites with disordered muscle fibers and myotendinous junctions. Because expression of myoD is increased in the somites of Irxl1 knockdown morphants, we test whether Irxl1 negatively regulates myoD expression. When stable C2C12 myoblasts overexpressing Irxl1/Mkx were induced to differentiate, myotube formation was inhibited and protein levels of myoD and myosin heavy chain were decreased accordingly. A series of deletion constructs of myoD promoter fragments were tested by luciferase reporter assays, which identified a promoter fragment that is necessary and sufficient for Irxl1‐mediated repression. Direct interaction of Irxl1 and myoD promoter was subsequently elucidated by yeast one‐hybrid assays, electrophoretic mobility shift assays and chromatin immunoprecipitation analysis. Furthermore, mouse Mkx also binds to and represses myoD promoter. These results indicate that Irxl1/Mkx can repress myoD expression through direct binding to its promoter and may thus play a negative regulatory role in muscle differentiation.
LMP1 stimulates the transcription of eIF4E to promote the proliferation, migration and invasion of human nasopharyngeal carcinoma
Authors: Zhao Yi , Pang Tian‐yun , Wang Yan , Wang Sen , Kang Hai‐xian , Ding Wei‐bin , Yong Wei‐wei , Bie Yan‐hong , Cheng Xiao‐guang , Zeng Chao , Yao Yun‐hong , Li Qing , Hu Xin‐rong
Published: May 2014

Eukaryotic translation initiation factor 4E (eIF4E) is the rate‐limiting translation initiation factor for many oncogenes. Previous studies have shown eIF4E overexpression in nasopharyngeal carcinoma (NPC). We aimed to study whether viral oncogene latent membrane protein 1 (LMP1) stimulates the transcription of eIF4E to promote NPC malignancy. In NPC cell lines (CNE1 and CNE2), ectopic LMP1 significantly increased the mRNA and protein levels of eIF4E and the transcriptional activity of the eIF4E promoter in a LMP1–plasmid‐transfected dose‐dependent manner. As a backward experiment, knocking down of LMP1 significantly reduced eIF4E mRNA in B95‐8 cells. In the high LMP1 expression condition, knocking down of c‐Myc significantly reduced eIF4E mRNA in both NPC and B95‐8 cells, and knocking down of eIF4E significantly inhibited the tumor proliferation, migration and invasion promoted by LMP1. The results indicated that LMP1 stimulates the transcription of eIF4E via c‐Myc to promote NPC. To the best of our knowledge, this is the first evidence that LMP1 stimulates the transcription of eIF4E. This might be an important cause of the overexpression of eIF4E in NPC and be the novel mechanism by which LMP1 initiates cancer. LMP1‐stimulated eIF4E initiates the translation of those oncogenes transcriptionally activated by LMP1 to amplify and pass down the carcinogenesis signals launched by LMP1.
Temperature‐dependent Li isotope ratios in Appalachian Plateau and Gulf Coast Sedimentary Basin saline water
Authors: Macpherson G. L. , Capo R. C. , Stewart B. W. , Phan T. T. , Schroeder K. , Hammack R. W.
Published: May 2014

Lithium (Li) concentrations of produced water from unconventional (horizontally drilled and hydraulically fractured shale) and conventional gas wells in Devonian reservoirs in the Appalachian Plateau region of western Pennsylvania range from 0.6 to 17 mmol kg−1, and Li isotope ratios, expressed as in δ7Li, range from +8.2 to +15‰. Li concentrations are as high as 40 mmol kg−1 in produced waters from Plio‐Pleistocene through Jurassic‐aged reservoirs in the Gulf Coast Sedimentary Basin analyzed for this study, and δ7Li values range from about +4.2 to +16.6‰. Because of charge‐balance constraints and rock buffering, Li concentrations in saline waters from sedimentary basins throughout the world (including this study) are generally positively correlated with chloride (Cl), the dominant anion in these fluids. Li concentrations also vary with depth, although the extent of depth dependence differs among sedimentary basins. In general, Li concentrations are higher than expected from seawater or evaporation of seawater and therefore require water–mineral reactions that remove lithium from the minerals. Li isotope ratios in these produced waters vary inversely with temperature. However, calculations of temperature‐dependent fractionation of δ7Li between average shale δ7Li (−0.7‰) and water result in δ7Liwater that is more positive than that of most produced waters. This suggests that aqueous δ7Li may reflect transport of water from depth and/or reaction with rocks having δ7Li lighter than average shale.
Transformation of deep‐water methane bubbles into hydrate
Authors: Egorov Alexander V. , Nigmatulin Robert I. , Rozhkov Aleksey N.
Published: May 2014

This study focuses on the mechanics of methane bubble phase behavior in the gas hydrate stability zone. The transformation of deep‐water methane bubbles into solid hydrate was investigated in Lake Baikal in situ. After being released from the lake bottom, methane bubbles were caught by different traps with transparent walls. When bubbles entered the internal spaces of the traps, the bubbles could be transformed into two different solid hydrate structures depending on the ambient conditions. The first structure was hydrate granular matter consisting of solid fragments with sizes on the order of 1 mm. The second structure was a highly porous solid foam consisting of solid bubbles with sizes on the order of 5 mm. The granular matter did not change as it was brought up to the top border of the gas hydrate stability zone, whereas in the solid foam, free methane rapidly exsolved from the sample during depressurization. We conclude that the decrease in depth and the decrease in the bubble flux rate were key factors in the formation of the hydrate granular matter, whereas the increase in the depth of bubble sampling and the increase in the bubble flux rate facilitated the conversion of bubbles into a highly porous solid hydrate foam.
Victoria erupts: the Newer Volcanics Province of south‐eastern Australia
Authors: Boyce J. , Nicholls I. , Keays R. , Hayman P.
Published: May 2014

The Newer Volcanics Province of south‐eastern Australia is often overlooked, though it comprises a multitude of volcanic features worthy of exploration. The province contains > 416 eruption centres varying in nature from simple to complex, ranging from lava shields and scoria cones to some of the largest maar volcanoes in the world. Explorable caves and lava tubes showcase well‐preserved lava flow features, while the province is a fossickers dream, containing abundant mantle xenolith and megacryst collecting localities. As the most recent eruption was ∼5000 bp at Mt. Gambier, the Newer Volcanics is considered an active province, and may yet provide Australia with more eruptions, adding to the glorious volcanic features of the wonderful landscape.
A (virtual) field excursion through the Oman ophiolite
Authors: Rollinson Hugh
Published: May 2014

The Oman ophiolite is probably the best preserved and best exposed ophiolite in the world. It forms a range of mountains on the northern coast of Oman which in places rise to over 2000 m and provide three‐dimensional exposure over a distance of about 450 km. Oman is well developed with a good network of tar roads, so that access is relatively easy and the semi‐arid climate means that exposure is excellent. Further, the Oman ophiolite has been intensively studied since the 1970s and there are a large number of maps and published works describing the geology.
A Case Report of Cavernous Sinus Syndrome in a Patient With Takayasu's Arteritis
Authors: Rotstein Dalia L. , Tyndel Felix J. , Tang‐Wai David F.
Published: May 2014

Neurologists must entertain a broad differential diagnosis when considering a patient with cavernous sinus syndrome, including neoplasm, trauma, vascular causes, inflammatory processes, and infections. We report the case of a 37‐year‐old woman initially diagnosed with cavernous sinus syndrome, where subsequent investigations revealed findings of Takayasu's arteritis, a large vessel vasculitis. The patient also tested positive for perinuclear antineutrophil cytoplasmic antibodies, suggesting the possibility of a vasculitic spectrum disorder although no clinical features of Wegener's granulomatosis were present. Criteria for Takayasu's arteritis and its protean neurologic manifestations are reviewed. This case highlights the spectrum of vasculitic conditions that may be associated with cavernous sinus inflammation.
Strong temporal consistency in the individual foraging behaviour of Imperial Shags Phalacrocorax atriceps
Authors: Harris Sabrina , Raya Rey Andrea , Zavalaga Carlos , Quintana Flavio
Published: May 2014

Individual consistency in foraging behaviour can generate behavioural variability within populations and may, ultimately, lead to species diversification. However, individual‐based long‐term behavioural studies are particularly scarce in seabird species. Between 2008 and 2011, breeding Imperial Shags Phalacrocorax atriceps at the Punta León colony, Argentina, were tracked with GPS devices to evaluate behavioural consistency during their foraging trips. Within a breeding season, individuals were highly consistent in the maximum distances they reached from the shore and the colony, as well as in the time invested in flight and diving across consecutive days during early chick rearing. In addition, each individual had its specific foraging area distinct from the foraging area of other individuals. Comparing between early and late chick rearing in the same season, individuals were consistent, to a lesser degree, in the maximum distance they reached from the colony and the shore, increasing in consistency later on in the season. Within the season, females were more consistent than males in the maximum distance they moved from the colony and the shore, the sexes segregated in their foraging areas and individual females were segregated from one another. Twenty‐eight individuals tracked in different breeding seasons were marginally consistent in their trip durations and maximum distance reached from shore across seasons. Among seasons, foraging locations differed between sexes and among individual females. Individuals from this colony exhibited consistency over time in several aspects of foraging behaviour, which may be due to a combination of individual characteristics such as learning abilities, breeding experience or health, as well as targeted prey type and stability of the environment at this location.
A first assessment of genetic variability in the Eurasian Stone‐curlew Burhinus oedicnemus
Authors: Mori Alessia , Baldaccini Natale E. , Baratti Mariella , Caccamo Chiara , Dessì‐Fulgheri Francesco , Grasso Rosario , Nouira Said , Ouni Ridha , Pollonara Enrica , Rodriguez‐Godoy Felipe , Spena Maria T. , Giunchi Dimitri
Published: May 2014

The Eurasian Stone‐curlew is a species of conservation concern in Europe. We investigate for the first time the extent of population structure among populations sampled from six geographical areas, representing four subspecies inhabiting the western part of the species' distribution. Neither mitochondrial nor nuclear markers fully supported current subspecies boundaries. However, both markers support significant differentiation of the Canary Island populations from those sampled from the Mediterranean. Further work is needed to establish the taxonomic status of this potentially distinct Macaronesian taxon. More broadly, further genetic research is required to design and implement an effective conservation plan for this species.
Effect of mixed surfactants on stratum corneum: a drying stress and Raman spectroscopy study
Authors: Purohit P. , Chandar P. , Vilinska A. , Ananthapadmanabhan K. P. , Somasundaran P.
Published: May 2014

Synopsis

Objective

Stratum corneum (SC) lipids are known to play an important role in barrier properties of skin by maintaining the optimal hydration levels. The disruption of SC lipids by cleanser surfactants is believed to lead to dry skin damage which can be a precursor to other skin disorders. The purpose of this study is to investigate the effects of commonly used anionic and zwitterionic surfactants sodium lauryl ether sulphate (SLES) and cocoamidopropyl betaine (CAPB) on the generation of drying stresses in SC and the role played by lipids.

Methods

Stratum corneum separated from pig skin was treated with various surfactants (SDS, SLES and CAPB) their mixtures and solvents. The tensile response to these treatments was measured by using a dynamic mechanical thermal analyzer. A Raman spectroscopy study of the treated samples was performed to investigate the effects of lipid modification (lipid chain conformational order and lipid removal) on stress generation in SC.

Results

The effects of commonly used anionic and zwitterionic surfactants on the generation of drying stresses in SC were studied. Although known to be milder in comparison with SDS, both SLES and CAPB generated high drying stresses individually. In mixtures, SLES–CAPB at 4 : 1 ratio leads to lower drying stress as compared to water alone. A Raman spectroscopic study of surfactant‐treated SC shows changes in lipid chain conformational order as well as a decrease in lipid–protein ratio in SC. A chloroform–methanol 2 : 1 treatment leads to the highest drying stress as well delipidization of SC.

Conclusion

The results show a correlation between generation of drying stress in SC and extent of lipid modification. We propose that the changes in lipid conformational order and removal of lipid components affect the stress relaxation properties of SC leading to high drying stresses.
Genome‐wide gene expression profiling reveals unsuspected molecular alterations in pemphigus foliaceus
Authors: Malheiros Danielle , Panepucci Rodrigo A. , Roselino Ana M. , Araújo Amélia G. , Zago Marco A. , Petzl‐Erler Maria Luiza
Published: May 2014

Pemphigus foliaceus (PF) is a complex autoimmune disease characterized by bullous skin lesions and the presence of antibodies against desmoglein 1. In this study we sought to contribute to a better understanding of the molecular processes in endemic PF, as the identification of factors that participate in the pathogenesis is a prerequisite for understanding its biological basis and may lead to novel therapeutic interventions. CD4+ T lymphocytes are central to the development of the disease. Therefore, we compared genome‐wide gene expression profiles of peripheral CD4+ T cells of various PF patient subgroups with each other and with that of healthy individuals. The patient sample was subdivided into three groups: untreated patients with the generalized form of the disease, patients submitted to immunosuppressive treatment, and patients with the localized form of the disease. Comparisons between different subgroups resulted in 135, 54 and 64 genes differentially expressed. These genes are mainly related to lymphocyte adhesion and migration, apoptosis, cellular proliferation, cytotoxicity and antigen presentation. Several of these genes were differentially expressed when comparing lesional and uninvolved skin from the same patient. The chromosomal regions 19q13 and 12p13 concentrate differentially expressed genes and are candidate regions for PF susceptibility genes and disease markers. Our results reveal genes involved in disease severity, potential therapeutic targets and previously unsuspected processes involved in the pathogenesis. Besides, this study adds original information that will contribute to the understanding of PF's pathogenesis and of the still poorly defined in vivo functions of most of these genes.
How Aging and Intergeneration Disparity Influence Consumption Inequality in China
Authors: Zhang Juwei , Xiang Jing
Published: May 2014

Concurrent with market economic reforms, China is facing an increasing income gap and an aging population. The question addressed in the present paper is how much aging contributes to the rising disparity in consumption. Based on the model established by Ohtake and Saito (1998), our study shows that cohort effects contribute close to 60 percent of the rising consumption inequality, while approximately 10 percent is the result of aging. The growth of aggregate consumption inequality caused by the cohort effect has various implications. Strengthening the redistribution system, especially the tax system, may enable the economy to avoid further increases in income inequality.
A delineation of the cognitive processes manifested in a social annotation environment
Authors: Li S.C. , Pow J.W.C. , Cheung W.C.
Published: May 2014

This study aims to examine how students' learning trajectories progress in an online social annotation environment, and how their cognitive processes and levels of interaction correlate with their learning outcomes. Three different types of activities (cognitive, metacognitive and social) were identified in the online environment. The time series of different levels of cognitive and metacognitive activities correlate with one another, indicating that a kind of symbiotic or ecological relationship exists among the cognitive and metacognitive processes. The multiple regression results show that low‐cognitive level activities mediate the effect of high‐cognitive level activities on student's performance in the group inquiry learning project. The results of multilevel analysis indicate that the average number of highlighted texts posted per person in a group accounted for over 50% of the variance of the group inquiry learning project scores. Further, the results also indicate that the level of collaboration within a group explains over 70% of the variance of the high‐level cognitive and metacognitive activities across different groups. In sum, group collaboration is found to be conducive to fostering high‐level cognitive and metacognitive activities.
Is gingival bleeding a symptom of patients with type 1 von Willebrand disease? A case–control study
Authors: Weickert Lisa , Miesbach Wolfgang , Alesci Sonja Rosa , Eickholz Peter , Nickles Katrin
Published: May 2014

Background

Von Willebrand disease (VWD) is the most common inherent bleeding disorder resulting in prolonged bleeding time. Gingival bleeding is a frequently reported symptom of VWD. However, gingival bleeding is also known as a leading symptom of plaque‐induced gingivitis and untreated periodontal disease. Gingival bleeding in VWD patients (VWD) may be triggered by gingival inflammation and not a genuine symptom. Thus, this study evaluated whether type 1 VWD determines an increased susceptibility to gingival bleeding in response to the oral biofilm.

Methods

Fifty cases and 40 controls were examined haematologically (VWF antigen, VWF Ristocetin cofactor, factor VIII activity) and periodontally [Gingival Bleeding Index (GBI), bleeding on probing (BOP), Plaque Control Record (PCR), periodontal inflamed surface area (PISA), vertical probing attachment level].

Results

GBI was significantly higher in controls (12.2%) than in VWD (10%). The study failed to find a significant difference regarding BOP between VWD (17%) and controls (17.2%). Multiple regressions identified PCR and PISA to be associated with GBI and BOP. VWD was negatively associated with GBI. Smoking and number of remaining teeth was negatively associated with BOP.

Conclusion

VWD is not associated with a more pronounced inflammatory response to the oral biofilm in terms of GBI and BOP.
The diets of school‐aged Aboriginal youths in Canada: a systematic review of the literature
Authors: Gates A. , Skinner K. , Gates M.
Published: May 2014

Background

Most national surveys examining diet leave large segments of the Aboriginal population under‐represented. The present study aimed to: (i) review primary research studies that investigated the dietary intakes of Canadian school‐aged Aboriginal youths; (ii) summarise the tools and methodologies currently used to measure diet in this population; and (iii) identify knowledge gaps and suggest areas of future research.

Methods

A systematic review of research published between January 2004 and January 2014 related to the diets of Canadian school‐aged (6–18 years) Aboriginal youths was undertaken, including Medline, Scopus, ERIC, Web of Science and Google Scholar databases. Studies were summarised based on purpose, year, sample population, setting, dietary assessment method and main findings.

Results

Twenty‐four studies were reviewed, all of which were cross‐sectional in design. Most (n = 16; 67%) were from Ontario or Quebec, investigated the diets of First Nations (n = 21; 88%) youths and took place in remote or isolated settings (n = 18; 75%). Almost all of the studies used the 24‐h recall to assess intake (n = 19; 79%), of which 89% used a single recall. The findings suggest that the diets of Aboriginal youths could be improved. Of particular concern are inadequate intakes of vegetables and fruit, milk and alternatives, fibre, folate, vitamin A, vitamin C, calcium and vitamin D, concomitant with an excess consumption of sugar sweetened beverages, snacks and fast foods. Traditional foods remain important but tend to be consumed infrequently.

Conclusions

The diets of Canadian Aboriginal youths are energy‐dense and nutrient‐poor. The diets of Inuit and Métis youths, in particular, and perceptions of a balanced diet warrant further investigation.
Comparisons of phenotype and immunomodulatory capacity among rhesus bone‐marrow‐derived mesenchymal stem/stromal cells, multipotent adult progenitor cells, and dermal fibroblasts
Authors: Sindberg Gregory M. , Lindborg Beth A. , Wang Qi , Clarkson Christina , Graham Melanie , Donahue Robert , Hering Bernhard J. , Verfaillie Catherine M. , Bansal‐Pakala Pratima , O'Brien Timothy D.
Published: May 2014

Background

Potent immunomodulatory effects have been reported for mesenchymal stem/stromal cells (MSCs), multipotent adult progenitor cells (MAPCs), and fibroblasts. However, side‐by‐side comparisons of these cells specifically regarding immunophenotype, gene expression, and suppression of proliferation of CD4+ and CD8+ lymphocyte populations have not been reported.

Methods

We developed MAPC and MSC lines from rhesus macaque bone marrow and fibroblast cell lines from rhesus dermis and assessed phenotypes based upon differentiation potential, flow cytometric analysis of immunophenotype, and quantitative RT‐PCR analysis of gene expression. Using allogeneic lymphocyte proliferation assays, we compared the in vitro immunomodulatory potency of each cell type.

Results and Conclusions

Extensive phenotypic similarities exist among each cell type, although immunosuppressive potencies are distinct. MAPCs are most potent, and fibroblasts are the least potent cell type. All three cell types demonstrated immunomodulatory capacity such that each may have potential therapeutic applications such as in organ transplantation, where reduced local immune response is desirable.
Multifocal motor neuropathy: correlation of nerve ultrasound, electrophysiological, and clinical findings
Authors: Kerasnoudis Antonios , Pitarokoili Kalliopi , Behrendt Volker , Gold Ralf , Yoon Min‐Suk
Published: May 2014

We present nerve ultrasound findings in multifocal motor neuropathy (MMN) and examine their correlation with electrophysiology and functional disability. Eighty healthy controls and 12 MMN patients underwent clinical, sonographic, and electrophysiological evaluation a mean of 3.5 years (standard deviation [SD] ± 2.1) after disease onset. Nerve ultrasound revealed significantly higher cross‐sectional area (CSA) values of the median (forearm, p < 0.001), ulnar (p < 0.001), and tibial nerve (ankle, p < 0.001) when compared with controls. Electroneurography documented signs of significantly lower values of the motor conduction velocity and compound muscle action potentials (cMAPs) in the upper arm nerves (median, ulnar, radial, p < 0.001). A significant correlation between sonographic and electrophysiological findings in the MMN group was found only between cMAP and CSA of the median nerve at the upper arm (r = 0.851, p < 0.001). Neither nerve sonography nor electrophysiology correlated with functional disability. MMN seems to show inhomogeneous CSA enlargement in various peripheral nerves, with weak correlation to electrophysiological findings. Neither nerve sonography nor electrophysiology correlated with functional disability. Multicentre, prospective studies are required to prove the applicability and diagnostic values of these findings.
ARE WOMEN REALLY MORE RISK‐AVERSE THAN MEN? A RE‐ANALYSIS OF THE LITERATURE USING EXPANDED METHODS
Authors: Nelson Julie A.
Published: May 2014

While a substantial literature in economics and finance has concluded that ‘women are more risk averse than men’, this conclusion merits investigation. After briefly clarifying the difference between making generalizations about groups, on the one hand, and making valid inferences from samples, on the other, this essay suggests improvements to how economists communicate our research results. Supplementing findings of statistical significance with quantitative measures of both substantive difference (Cohen's d, a measure in common use in non‐Economics literatures) and of substantive overlap (the Index of Similarity, newly proposed here) adds important nuance to the discussion of sex differences. These measures are computed from the data on men, women and risk used in 35 scholarly works from economics, finance and decision science. The results are considerably more mixed and overlapping than would commonly be inferred from the broad claims made in the literature, with standardized differences in means mostly amounting to considerably less than one standard deviation, and the degree of overlap between male and female distributions generally exceeding 80%. In addition, studies that look at contextual influences suggest that these contribute importantly to observations of differences both between and within the sexes.
CANNABIS USE AND ITS EFFECTS ON HEALTH, EDUCATION AND LABOR MARKET SUCCESS
Authors: van Ours Jan C. , Williams Jenny
Published: May 2014

Cannabis is the most popular illegal drug. Its legal status is typically justified on the grounds that cannabis use has harmful consequences. Empirically investigating this issue has been a fertile topic for research in recent times. We provide an overview of this literature, focusing on studies which seek to establish the causal effect of cannabis use on health, education, and labor market success. We conclude that there do not appear to be serious harmful health effects of moderate cannabis use. Nevertheless, there is evidence of reduced mental well‐being for heavy users who are susceptible to mental health problems. While there is robust evidence that early cannabis use reduces educational attainment, there remains substantial uncertainty as to whether using cannabis has adverse labor market effects.
Immunoglobulins IgG1, IgM and IgA: a synergistic team influencing survival in sepsis
Authors: Bermejo‐Martín J. F. , Rodriguez‐Fernandez A. , Herrán‐Monge R. , Andaluz‐Ojeda D. , Muriel‐Bombín A. , Merino P. , García‐García M. M. , Citores R. , Gandía F. , Almansa R. , Blanco J. ,   the GRECIA Group (Grupo de Estudios y Análisis en Cuidados Intensivos)
Published: May 2014

Objective

The impact of endogenous immunoglobulin isotypes on the prognosis of patients with severe sepsis has not been sufficiently explored. The aim of this study was to evaluate the association between immunoglobulin levels in plasma and survival in patients with this condition.

Design and patients

A prospective multicentre cohort study was conducted. A total of 172 adult patients admitted to the intensive care unit (ICU) with severe sepsis or septic shock were recruited. Patients were classified based on deciles of immunoglobulin concentrations at diagnosis of sepsis. Categorical variables were created and tested for their association with survival during hospitalization in the ICU.

Results

Overall, 42 patients died in the ICU during the study. Kaplan–Meier analysis showed that immunoglobulin concentrations below 300 mg dL−1 for IgG1, 35 mg dL−1 for IgM and 150 mg dL−1 for IgA were associated with shorter survival times. Multivariate regression analysis showed that IgG1 < 300 mg dL−1 was a risk factor for mortality [odds ratio (OR) 2.50, 95% confidence interval (CI) 1.04–6.03; P = 0.042]. The combined presence of IgG1, IgM and IgA levels below the described thresholds had a synergistic impact on mortality risk (OR 5.27, 95% CI 1.41–19.69; P = 0.013). A similar effect was observed for combined low levels of IgG1 and IgA (OR 4.10, 95% CI 1.28–13.12; P = 0.018) and also of IgG1 and IgM (OR 3.10. 95% CI 1.13–8.49; P = 0.028).

Conclusions

The combined presence of low levels of the endogenous immunoglobulins IgG1, IgM and IgA in plasma is associated with reduced survival in patients with severe sepsis or septic shock. Assessment of the concentrations of these immunoglobulins could improve the results of treatment with exogenous immunoglobulins in patients with sepsis.
Trends in 28‐day and 1‐year mortality rates in patients hospitalized for a first acute myocardial infarction in Norway during 2001–2009: a “Cardiovascular disease in Norway” (CVDNOR) project
Authors: Sulo E. , Vollset S. E. , Nygård O. , Sulo G. , Igland J. , Egeland G. M. , Ebbing M. , Tell G. S.
Published: May 2014

Objective

The aim of this study was to investigate the trends in 28‐day and 1‐year mortality rates in patients hospitalized for a first acute myocardial infarction (AMI) in Norway during the period 2001–2009. Potential age group and gender differences in these trends were also examined.

Design, subjects and setting

In this retrospective nationwide cohort study, patients hospitalized for a first AMI between 2001 and 2009 were identified in the Cardiovascular Disease in Norway 1994–2009 (CVDNOR) project and followed for 1 year.

Main outcome measures

Trends in 28‐day and 1‐year mortality [both all‐cause and cardiovascular disease (CVD) mortality] were investigated.

Results

A total of 115 608 patients (60.6% men) were hospitalized for a first AMI during the study period. Mortality at 28 days was reduced annually by 3.8% overall and by 6.7%, 4.1% and 2.6% in patients aged 25–64, 65–84 and ≥85 years, respectively (all Ptrend < 0.001). In addition, 1‐year all‐cause mortality was reduced annually by 2.0% overall (Ptrend < 0.001) and by 3.7% (Ptrend = 0.02), 2.5% (Ptrend < 0.001) and 1.1% (Ptrend < 0.001) in patients aged 25–64, 65–84 and ≥85 years, respectively. Furthermore, 1‐year CVD mortality was reduced overall by 6.2% annually; a reduction was observed in all age groups. Finally, 1‐year non‐CVD mortality increased annually overall by 3.9% due to an increase in patients aged ≥65 years.

Conclusion

Mortaity at 28 days after the first AMI declinedin Norway between 2001 and 2009 in both men and women and in all age groups. All‐cause mortality at 1 year also declined both in men and women due to decreases in CVD mortality rates, whilst non‐CVD mortality rates increased amongst patients ≥65 years of age.
Exploring composition and behaviour of fish fauna by in situ observations in the Bari Canyon (Southern Adriatic Sea, Central Mediterranean)
Authors: D'Onghia Gianfranco , Capezzuto Francesca , Carluccio Angela , Carlucci Roberto , Giove Agnese , Mastrototaro Francesco , Panza Michele , Sion Letizia , Tursi Angelo , Maiorano Porzia
Published: May 2014

Canyons play a fundamental role in enhancing the abundance and diversity of marine organisms through the transport of organic matter and food resources, the presence of complex physical habitats and the absence of trawl fishing. During four baited lander deployments carried out in the Bari Canyon (Southern Adriatic Sea, Central Mediterranean), at depths of 443–788 m, about 43 h of video records were taken, for a total of 619,200 video frames. A total of 12 benthopelagic fish species (five chondrichthyes and seven osteichthyes) were identified. The blackspot seabream (Pagellus bogaraveo) was the most often observed fish species. The depth of 787 m represents a new depth record for this fish in the Adriatic Sea. Groups of up to 40 individuals of P. bogaraveo were attracted to the bait and were shown in single frames. The individuals were observed both exploring the area and feeding actively on the bait. The European conger (Conger conger) was recorded at each deployment. Clear scavenger behaviour was also observed in this teleost fish and in the shark Etmopterus spinax. The shark species Centrophorus granulosus and Hexanchus griseus, which are considered ‘vulnerable’ on the published IUCN Mediterranean Regional Red List, were also recorded but, although attracted by the bait, they were never seen feeding on it. Other fish species, harvested on fishing grounds, such as Merluccius merluccius, Helicolenus dactylopterus and Polyprion americanus, were also recorded. This study represents the first in situ documentation, at very low impact, of the fish fauna in the Bari Canyon, providing new insights into its small scale distribution and behaviour, the first in situ direct observation of the variable feeding behaviour of P. bogaraveo and its gregarious habits, as well as indicating that this canyon could act as a refuge area for species that are vulnerable to fishing on the open slope.
Clonal genetic structure and diversity in populations of an aquatic plant with combined vs. separate sexes
Authors: Yakimowski Sarah B. , Barrett Spencer C. H.
Published: May 2014

Clonality is often implicated in models of the evolution of dioecy, but few studies have explicitly compared clonal structure between plant sexual systems, or between the sexes in dioecious populations. Here, we exploit the occurrence of monoecy and dioecy in clonal Sagittaria latifola (Alismataceae) to evaluate two main hypotheses: (i) clone sizes are smaller in monoecious than dioecious populations, because of constraints imposed on clone size by costs associated with geitonogamy; (ii) in dioecious populations, male clones are larger and flower more often than female clones because of sex‐differential reproductive costs. Differences in clone size and flowering could result in discordance between ramet‐ and genet‐based sex ratios. We used spatially explicit sampling to address these hypotheses in 10 monoecious and 11 dioecious populations of S. latifolia at the northern range limit in Eastern North America. In contrast to our predictions, monoecious clones were significantly larger than dioecious clones, probably due to their higher rates of vegetative growth and corm production, and in dioecious populations, there was no difference in clone size between females and males; ramet‐ and genet‐based sex ratios were therefore highly correlated. Genotypic diversity declined with latitude for both sexual systems, but monoecious populations exhibited lower genotypic richness. Differences in life history between the sexual systems of S. latifolia appear to be the most important determinants of clonal structure and diversity.
Chronic Central Nervous System Expression of HIV‐1 Tat Leads to Accelerated Rarefaction of Neocortical Capillaries and Loss of Red Blood Cell Velocity Heterogeneity
Authors: Silva Jharon N. , Polesskaya Oksana , Wei Helen S. , Rasheed Izad‐Yar D. , Chamberlain Jeffrey M. , Nishimura Christopher , Feng Changyong , Dewhurst Stephen
Published: May 2014

Objectives

HIV‐1 infection of the CNS is associated with impairment of CBF and neurocognitive function, and accelerated signs of aging. As normal aging is associated with rarefaction of the cerebral vasculature, we set out to examine chronic viral effects on the cerebral vasculature.

Methods

DOX‐inducible HIV‐1 Tat‐tg and WT control mice were used. Animals were treated with DOX for three weeks or five to seven months. Cerebral vessel density and capillary segment length were determined from quantitative image analyses of sectioned cortical tissue. In addition, movement of red blood cells in individual capillaries was imaged in vivo using multiphoton microscopy, to determine RBCV and flux.

Results

Mean RBCV was not different between Tat‐tg mice and age‐matched WT controls. However, cortical capillaries from Tat‐tg mice showed a significant loss of RBCV heterogeneity and increased RBCF that was attributed to a marked decrease in total cortical capillary length (35–40%) compared to WT mice.

Conclusions

Cerebrovascular rarefaction is accelerated in HIV‐1 Tat‐transgenic mice, and this is associated with alterations in red cell blood velocity. These changes may have relevance to the pathogenesis of HIV‐associated neurocognitive disorders in an aging HIV‐positive population.
Heat shock protein 70 is necessary for Rice stripe virus infection in plants
Authors: Jiang Shanshan , Lu Yuwen , Li Kunfeng , Lin Lin , Zheng Hongying , Yan Fei , Chen Jianping
Published: May 2014

Heat shock proteins 70 (HSP70s) are a highly conserved family of genes in eukaryotes, and are involved in a remarkable variety of cellular processes. In many plant positive‐stranded RNA viruses, HSP70 participates in the construction of a viral replication complex and plays various roles during viral infection. Here, we found increased expression of HSP70 following infection by Rice stripe virus (RSV), a negative‐stranded RNA virus, in both rice (the natural host) and Nicotiana benthamiana (an experimental host). Heat treatment of N. benthamiana (Nb) plants enhanced viral infection, whereas RSV infection was retarded and viral RNAs accumulated at a low level when HSP70 was silenced. In both bimolecular fluorescence complement and in vitro pull‐down assays, the N‐terminus of RSV RNA‐dependent RNA polymerase (RdRp) interacted and co‐localized with the HSP70s of both plants (OsHSP70 and NbHSP70). The localization of the N‐terminus of RdRp when expressed alone was not obviously different from when it was co‐expressed with OsHSP or NbHSP, and vice versa. RSV infection also had no effect on the localization of host HSP70. These results demonstrate that host HSP70 is necessary for RSV infection and probably plays a role in viral replication by interacting with viral RdRp, which provides the first evidence of an interacting host protein related to RSV replication, which has been little studied to date.
Forests trapped in nitrogen limitation – an ecological market perspective on ectomycorrhizal symbiosis
Authors: Franklin Oskar , Näsholm Torgny , Högberg Peter , Högberg Mona N.
Published: May 2014

Ectomycorrhizal symbiosis is omnipresent in boreal forests, where it is assumed to benefit plant growth. However, experiments show inconsistent benefits for plants and volatility of individual partnerships, which calls for a re‐evaluation of the presumed role of this symbiosis.

We reconcile these inconsistencies by developing a model that demonstrates how mycorrhizal networking and market mechanisms shape the strategies of individual plants and fungi to promote symbiotic stability at the ecosystem level.

The model predicts that plants switch abruptly from a mixed strategy with both mycorrhizal and nonmycorrhizal roots to a purely mycorrhizal strategy as soil nitrogen availability declines, in agreement with the frequency distribution of ectomycorrhizal colonization intensity across a wide‐ranging data set. In line with observations in field‐scale isotope labeling experiments, the model explains why ectomycorrhizal symbiosis does not alleviate plant nitrogen limitation. Instead, market mechanisms may generate self‐stabilization of the mycorrhizal strategy via nitrogen depletion feedback, even if plant growth is ultimately reduced.

We suggest that this feedback mechanism maintains the strong nitrogen limitation ubiquitous in boreal forests. The mechanism may also have the capacity to eliminate or even reverse the expected positive effect of rising CO2 on tree growth in strongly nitrogen‐limited boreal forests.
Spatial structure of an individual‐based plant–pollinator network
Authors: Dupont Yoko L. , Trøjelsgaard Kristian , Hagen Melanie , Henriksen Marie V. , Olesen Jens M. , Pedersen Nanna M. E. , Kissling W. Daniel
Published: May 2014

The influence of space on the structure (e.g. modularity) of complex ecological networks remains largely unknown. Here, we sampled an individual‐based plant–pollinator network by following the movements and flower visits of marked bumblebee individuals within a population of thistle plants for which the identities and spatial locations of stems were mapped in a 50 × 50 m study plot. The plant–pollinator network was dominated by parasitic male bumblebees and had a significantly modular structure, with four identified modules being clearly separated in space. This indicated that individual flower visitors opted for the fine‐scale division of resources, even within a local site. However, spatial mapping of network modules and movements of bumblebee individuals also showed an overlap in the dense center of the plant patch. Model selection based on Akaike information criterion with traits as predictor variables revealed that thistle stems with high numbers of flower heads and many close neighbours were particularly important for connecting individuals within the modules. In contrast, tall plants and those near the patch center were crucial for connecting the different modules to each other. This demonstrated that individual‐based plant–pollinator networks are influenced by both the spatial structure of plant populations and individual‐specific plant traits. Additionally, bumblebee individuals with long observation times were important for both the connectivity between and within modules. The latter suggests that bumblebee individuals will still show locally restricted movements within sub‐patches of plant populations even if they are observed over a prolonged time period. Our individual‐based and animal‐centered approach of sampling ecological networks opens up new avenues for incorporating foraging behaviour and intra‐specific trait variation into analyses of plant–animal interactions across space.
A novel balanced isotonic sodium solution vs normal saline during major surgery in children up to 36 months: a multicenter RCT
Authors: Disma Nicola , Mameli Leila , Pistorio Angela , Davidson Andrew , Barabino Paola , Locatelli Bruno Guido , Sonzogni Valter , Montobbio Giovanni
Published: May 2014

Background

The use of isotonic electrolytic solutions for the intraoperative fluid management in children is largely recognized, but the exact composition still needs to be defined.

Objectives

The primary objective of this randomized controlled open trial was to compare the changes in chloride plasma concentration using two intraoperative isotonic fluid regimens (Sterofundin vs normal saline, both added with 1% of glucose) in children undergoing major surgery. Secondary objectives were to compare changes in other electrolytes, renal function, and the occurrence of hypoglycemia.

Methods

Children aged between 1 and 36 months, scheduled for major surgery, were randomized to receive Sterofundin or saline during the intraoperative time. Children with preoperative electrolyte abnormalities, hemodynamic instability, and severe renal or hepatic dysfunction were excluded. The primary outcome was the Δ of Cl− (Δ = change in plasma concentration between post‐ and pre‐infusion), and secondary outcomes included Δ of other electrolytes and intraoperative hypoglycemia.

Results

A total of 240 patients were included in the two study sites and randomized to receive Sterofundin plus 1% glucose or normal saline plus 1% glucose, in a open fashion (229 were finally analyzed). Δ of Cl− and Mg++ was statistically less relevant in patients who received intraoperative Sterofundin, and Δ of the other electrolytes was comparable between the two study groups. Relative risk of hyperchloremia was significantly higher when large volumes were infused (over than 46.7 ml·kg−1), regardless of type of crystalloid infused. Hypoglycemia occurred in two of 229 patients.

Conclusions

Sterofundin is safer than normal saline in protecting young children undergoing major surgery against the risk of increasing plasma chlorides and the subsequent metabolic acidosis.
Pheomelanin‐induced oxidative stress: bright and dark chemistry bridging red hair phenotype and melanoma
Authors: Napolitano Alessandra , Panzella Lucia , Monfrecola Giuseppe , d'Ischia Marco
Published: May 2014

The complex interplay of genetic and epigenetic factors linking sun exposure to melanoma in the red hair phenotype hinges on the peculiar physical and chemical properties of pheomelanins and the underlying biosynthetic pathway, which is switched on by the effects of inactivating polymorphisms in the melanocortin 1 receptor gene. In addition to the long recognized UV‐dependent pathways of toxicity and cell damage, a UV‐independent pro‐oxidant state induced by pheomelanin within the genetically determined background of the red hair phenotype has recently been disclosed. This review provides a detailed discussion of the possible UV‐dependent and UV‐independent chemical mechanisms underlying pheomelanin‐mediated oxidative stress, with special reference to the oxygen‐dependent depletion of glutathione and other cell antioxidants. The new concept of pheomelanin as a ‘living’ polymer and biocatalyst that may grow by exposure to monomer building blocks and may trigger autooxidative processes is also discussed. As a corollary, treatment of inflammatory skin diseases in RHP patients is briefly commented. Finally, possible concerted strategies for melanoma prevention in the red hair phenotype are proposed.