bluuebunny/crossref_metadata_2025 huggingface dataset:
CD44 variant 6 is correlated with peritoneal dissemination and poor prognosis in patients with advanced epithelial ovarian cancer
Authors: Tjhay Francisca , Motohara Takeshi , Tayama Shingo , Narantuya Dashdemberel , Fujimoto Koichi , Guo Jianying , Sakaguchi Isao , Honda Ritsuo , Tashiro Hironori , Katabuchi Hidetaka
Published: August 2015

Cancer stem cells (CSCs) drive tumor initiation and metastasis in several types of human cancer. However, the contribution of ovarian CSCs to peritoneal metastasis remains unresolved. The cell adhesion molecule CD44 has been identified as a major marker for CSCs in solid tumors, including epithelial ovarian cancer. CD44 exists as a standard form (CD44s) and also as numerous variant isoforms (CD44v) generated by alternative mRNA splicing. Here we show that disseminated ovarian tumors in the pelvic peritoneum contain highly enriched CD44v6‐positive cancer cells, which drive tumor metastasis and are responsible for tumor resistance to chemotherapy. Clinically, an increased number of CD44v6‐positive cancer cells in primary tumors was associated with a shortened overall survival in stage III–IV ovarian cancer patients. Furthermore, a subpopulation of CD44v6‐positive cancer cells manifested the ability to initiate tumor metastasis in the pelvic peritoneum in an in vivo mouse model, suggesting that CD44v6‐positive cells show the potential to serve as metastasis‐initiating cells. Thus, the peritoneal disseminated metastasis of epithelial ovarian cancer is initiated by the CD44v6‐positive subpopulation, and CD44v6 expression is a biomarker for the clinical outcome of advanced ovarian cancer patients. Given that a distinct subpopulation of CD44v6‐positive cancer cells plays a critical role in peritoneal metastasis, definitive treatment should target this subpopulation of CD44v6‐positive cells in epithelial ovarian cancer.
Preventative role of interleukin-17 producing regulatory T helper type 17 (Treg17) cells in type 1 diabetes in non-obese diabetic mice
Authors: Bellemore S M , Nikoopour E , Schwartz J A , Krougly O , Lee-Chan E , Singh B
Published: August 2015

T helper type 17 (Th17) cells have been shown to be pathogenic in autoimmune diseases; however, their role in type 1 diabetes (T1D) remains inconclusive. We have found that Th17 differentiation of CD4+ T cells from BDC2·5 T cell receptor transgenic non-obese diabetic (NOD) mice can be driven by interleukin (IL)-23 + IL-6 to produce large amounts of IL-22, and these cells induce T1D in young NOD mice upon adoptive transfer. Conversely, polarizing these cells with transforming growth factor (TGF)-β + IL-6 led to non-diabetogenic regulatory Th17 (Treg17) cells that express high levels of aryl hydrocarbon receptor (AhR) and IL-10 but produced much reduced levels of IL-22. The diabetogenic potential of these Th17 subsets was assessed by adoptive transfer studies in young NOD mice and not NOD.severe combined immunodeficient (SCID) mice to prevent possible transdifferentiation of these cells in vivo. Based upon our results, we suggest that both pathogenic Th17 cells and non-pathogenic regulatory Treg17 cells can be generated from CD4+ T cells under appropriate polarization conditions. This may explain the contradictory role of Th17 cells in T1D. The IL-17 producing Treg17 cells offer a novel regulatory T cell population for the modulation of autoimmunity.
An overview of programmes offered by shelters for street children inSouthAfrica
Authors: Mokomane Zitha , Makoae Mokhantšo
Published: August 2015

This paper reports part of the findings from a 2014 audit of shelters for street children conducted in four provinces ofSouthAfrica. The paper focuses on the assessment of the types, structure and implementation of the programmes, as well as on the adequacy of resources necessary for implementing the programmes. The overall picture that emerged from the assessment was that all shelters draw on a comprehensive and enabling legislative and policy framework to offer some elements of developmental, therapeutic and recreational programmes at the early intervention level. Overall, however, the implementation of the programmes does not effectively take into consideration the varied and interconnected factors that, within and across multiple social systems, impel children to the streets. It was thus apparent that the programmes do not adequately address the risks and opportunities of street children inSouthAfrica, specifically within the eco‐developmental framework. Recommendations are offered for social work policy and practice to further enhance the quality and impact of programmes offered in the shelters.
Scale Economies, Technical Efficiency, and the Sources of Total Factor Productivity Growth of Quebec Dairy Farms
Authors: Singbo Alphonse , Larue Bruno
Published: August 2015

Canada's average cost for milk production is among the highest in the world. This paper focuses on specific potential causes by estimating economies of scale and technical efficiency for a panel of Quebec dairy farms that spans the 2001–10 period. Additionally, this paper investigates the sources of total factor productivity growth. The stochastic frontier analysis, based on an input‐distance function, is used to estimate returns to scale relationships across dairy farms. The results show that there is significant economies scale to be exploited and that cost of production could also be reduced by improving technical efficiency. Accordingly, the paper indicates that input‐mix effect is the main source of total factor productivity growth. The results have important implications for Canada's supply management policy, and more specifically for the trading of production quota between dairy farmers, as well as for the delivery of targeted extension services.
Porphyromonas gingivalis biofilm formation in different titanium surfaces, an in vitro study
Authors: Di Giulio Mara , Traini Tonino , Sinjari Bruna , Nostro Antonia , Caputi Sergio , Cellini Luigina
Published: August 2015

Objective

The aim of this work was to evaluate the biofilm formation of Porphyromonas gingivalis on disks of titanium (Ti) grade 4 (G4) and Ti‐6Al‐4V alloy grade 5 (G5) with different surface topographies.

Materials and methods

Porphyromonas gingivalis ATCC 33277 was used to develop an in vitro mature biofilm on a total of 96 disk‐shaped specimens of laser‐treated (L), sandblasted (S), and machined (M) surfaces of Ti G4 and Ti G5. Surface roughness (Ra) and the wettability contact angle (WCA) were measured to characterize the surface of the specimens. The bacterial biofilm was evaluated by biomass quantification, bacterial viability, visualization of the biofilm extracellular matrix, and bacterial cell count. Data were analyzed using one‐way ANOVA and Holm–Sidak tests and expressed as mean ± standard deviation.

Results

The Ra for the L group was 0.10 (±0.07) μm inside the craters and 0.40 (±0.08) μm in the area surrounding the craters resulting the smoothest (P < 0.05) in respect to the S group (1.30 ± 0.61 μm) and the M group (0.75 ± 0.23 μm). The L group showed a higher WCA than S and M groups for both G4 (109.9° ± 6.6) and G5 (104.2° ± 5.9) materials (P < 0.05). The L group displayed both the less P. gingivalis bacterial biomass (0.38 ± 0.01 for G4; 0.62 ± 0.02 for G5) that was significant in respect to G4‐S (P < 0.001), G4‐M (P < 0.001), and G5‐M (P = 0.001) and the less total cell number (215 ± 18 for G4 and 244 ± 9 for G5) than S and M groups for both G4 and G5 materials (P < 0.01).

Conclusion

Within the limits of the present study, the results showed that G4‐L appears to be significantly efficient in the reduction of the P. gingivalis biofilm formation.
A new device for improving dental implants anchorage: a histological and micro‐computed tomography study in the rabbit
Authors: Barak Shlomo , Neuman Moshe , Iezzi Giovanna , Piattelli Adriano , Perrotti Vittoria , Gabet Yankel
Published: August 2015

Objective

In the present study, a new healing cap that could generate a pulsed electromagnetic field (PEMF) around titanium implants to stimulate peri‐implant osteogenesis was tested in the rabbit model.

Materials and methods

A total of 22 implants were inserted in the proximal tibial metaphysis of 22 rabbits. A healing cap containing the active device was inserted in half of the implants (11 test implants); an “empty” healing cap was inserted in the other ones (11 control implants). The animals were euthanized after 2 and 4 weeks, and the samples were processed for micro‐computed tomography and histology. The peri‐implant volume was divided into coronal (where the PEMF was the strongest) and apical regions.

Results

Most of the effects of the tested device were confined to the coronal region. Two weeks post‐implantation, test implants showed a significant 56% higher trabecular bone fraction (BV/TV), associated with enhanced trabecular number (Tb.N, +37%) and connectivity density (Conn.D, +73%) as compared to the control group; at 4 weeks, the PEMF induced a 69% increase in BV/TV and 34% increase of Tb.N. There was no difference in the trabecular thickness (Tb.Th) at either time point. Furthermore, we observed a 48% higher bone‐to‐implant contact (BIC) in the test implants vs. controls after 2 weeks; this increase tended to remain stable until the fourth week. Mature trabecular and woven bone were observed in direct contact with the implant surface with no gaps or connective tissue at the bone‐implant interface.

Conclusions

These results indicate that the PEMF device stimulated early bone formation around dental implants resulting in higher peri‐implant BIC and bone mass already after 2 weeks which suggests an acceleration of the osseointegration process by more than three times.
E‐commerce trade in invasive plants
Authors: Humair Franziska , Humair Luc , Kuhn Fabian , Kueffer Christoph
Published: August 2015

Biological invasions are a major concern in conservation, especially because global transport of species is still increasing rapidly. Conservationists hope to anticipate and thus prevent future invasions by identifying and regulating potentially invasive species through species risk assessments and international trade regulations. Among many introduction pathways of non‐native species, horticulture is a particularly important driver of plant invasions. In recent decades, the horticultural industry expanded globally and changed structurally through the emergence of new distribution channels, including internet trade (e‐commerce). Using an automated search algorithm, we surveyed, on a daily basis, e‐commerce trade on 10 major online auction sites (including eBay) of approximately three‐fifths of the world's spermatophyte flora. Many recognized invasive plant species (>500 species) (i.e., species associated with ecological or socio‐economic problems) were traded daily worldwide on the internet. A markedly higher proportion of invasive than non‐invasive species were available online. Typically, for a particular plant family, 30–80% of recognized invasive species were detected on an auction site, but only a few percentages of all species in the plant family were detected on a site. Families that were more traded had a higher proportion of invasive species than families that were less traded. For woody species, there was a significant positive relationship between the number of regions where a species was sold and the number of regions where it was invasive. Our results indicate that biosecurity is not effectively regulating online plant trade. In the future, automated monitoring of e‐commerce may help prevent the spread of invasive species, provide information on emerging trade connectivity across national borders, and be used in horizon scanning exercises for early detection of new species and their geographic source areas in international trade.
Hypoglycaemia in adults with insulin‐treated diabetes in the UK: self‐reported frequency and effects
Authors: Frier B. M. , Jensen M. M. , Chubb B. D.
Published: August 2015

Aim

Few real‐life studies of non‐severe (self‐treated) hypoglycaemic events are available. This survey quantified the self‐reported frequency of non‐severe hypoglycaemia and its effects in adults with insulin‐treated diabetes in the UK.

Methods

Adults aged > 15 years with Type 1 diabetes or insulin‐treated Type 2 diabetes completed ≤ 4 weekly questionnaires (7–day recall). Respondents with Type 2 diabetes were grouped by insulin regimen: basal‐only, basal–bolus and ‘other’.

Results

Overall, 1038 respondents (466 with Type 1 diabetes, 572 with Type 2 diabetes) completed 3528 questionnaires. Mean numbers of non‐severe events per week were 2.4 (Type 1 diabetes; median = 2) and 0.8 (Type 2 diabetes; median = 0); 23% and 26% of non‐severe events occurred at night, respectively. Fatigue and reduced alertness were the commonest issues following events (78% and 51% of respondents, respectively). The effects of nocturnal events persisted longer than those of daytime events: Type 1 diabetes = 10.6 vs. 4.9 h (P = 0.0002); Type 2 diabetes = 15.3 vs. 5.1 h (P < 0.0001). In the week following an event, respondents’ blood glucose measurements increased by 4.3 (Type 1 diabetes; 12% increment) and 4.2 (Type 2 diabetes; 21% increment) tests/week. In employed respondents, 20% of events caused work‐time loss, more so following nocturnal (vs. daytime) hypoglycaemia: Type 1 diabetes = 2.7 vs. 1.1 h (P = 0.0184); Type 2 diabetes = 2.5 vs. 1.6 h (P = 0.1340). Most respondents rarely/never informed healthcare professionals about events (Type 1 diabetes = 82%, Type 2 diabetes = 69%).

Conclusions

Non‐severe hypoglycaemia is common in adults with insulin‐treated diabetes in the UK, with consequent health‐related/economic effects. Communication about non‐severe hypoglycaemia is limited and the burden of hypoglycaemia may be underestimated.
Effectiveness of the Kids in Control of Food (KICk–OFF) structured education course for 11–16 year olds with Type 1 diabetes
Authors: Price K. J. , Knowles J. A. , Fox M. , Wales J. K. H. , Heller S. , Eiser C. , Freeman J. V. ,   the KICk–OFF Study group
Published: August 2015

Aim

To assess the effect of a 5–day structured education course (Kids in Control of Food; KICk–OFF) on biomedical and psychological outcomes in young people with Type 1 diabetes.

Methods

This was a cluster‐randomized trial involving 31 UK paediatric centres. Participants were recruited prior to stratified centre randomization. Intervention centres delivered KICk–OFF courses, whereas control centres delivered usual care. Participants were 11–16 years of age and had Type 1 diabetes for at least one year. The KICk–OFF course was delivered by trained educators to eight participants per course. Glycaemic control and quality of life were measured at baseline, 6, 12 and 24 months. Secondary outcomes were hypoglycaemia, ketoacidosis, fear of hypoglycaemia and diabetes self‐efficacy.

Results

Three hundred and ninety‐six participants provided baseline data (199 intervention and 197 control). At 6 and 12 months the intervention group showed significantly improved total generic quality of life scores compared with controls (baseline: 80 vs. 82; 6 months: 82 vs. 82; P = 0.04). Across the whole intervention group mean HbA1c levels were not significantly different from controls; baseline HbA1c mean (95% confidence interval), 78 mmol/mol (75–81) vs. 76 mmol/mol (74–79) [9.3% (9–9.6%) vs. 9.1% (8.9–9.4%); 24 months: 77 mmol/mol (74–79) vs. 78 mmol/mol (75–81) (9.2% (8.9–9.4%) vs. 9.3% (9–9.6%)], adjusted mean difference, –2.0 mmol/mol (6.5–2.5) [2.3% (–2.7% to 2.4%)], P = 0.38.

Conclusions

Attending a KICk–OFF course was associated with significantly improved total quality of life scores within 6 months. Glycaemic control, as measured by HbA1c, was no different at 24 months. (Clinical Trial Registry No: ISRCTN3704268)
An Augmented Static Olley–Pakes Productivity Decomposition with Entry and Exit: Measurement and Interpretation
Authors: Maliranta Mika , Määttänen Niku
Published: August 2015

We develop an augmented Olley–Pakes (OP) decomposition that allows us to examine how entering and exiting firms contribute to the popular OP covariance measure of allocative efficiency. Applying the decomposition to a comprehensive micro‐level data, we find that a large part of the OP covariance component can be attributed to entrants and exiting firms. We also build a model of firm dynamics that is consistent with our main empirical results. In the model economy, the standard OP covariance component tends to increase with certain type of distortions because of endogenous changes in firm entry and exit.
Reproducibility of Echocardiograph‐Derived Multilevel Left Ventricular Apical Twist Mechanics
Authors: Stewart Glenn M. , Yamada Akira , Kavanagh Justin J. , Haseler Luke J. , Chan Jonathan , Sabapathy Surendran
Published: August 2015

Left ventricular (LV) twist mechanics are routinely assessed via echocardiography in clinical and research trials investigating the function of obliquely oriented myocardial fibers. However, echocardiograph‐derived measures of LV twist may be compromised by nonstandardized acquisition of the apical image. This study examined the reproducibility of echocardiograph‐derived parameters of apical twist mechanics at multiple levels of the apical myocardium. Two sets of 2D LV parasternal short‐axis images were obtained in 30 healthy subjects (24 men; 19–57 year) via echocardiography. Images were acquired immediately distal to the papillary muscles (apical image 1), immediately above the point of LV cavity obliteration at end systole (apical image 3), and midway between apical image 1 and apical image 3 (apical image 2). Repeat scans were performed within 1 hour, and twist mechanics (rotation and rotation rate) were calculated via frame‐by‐frame tracking of natural acoustic echocardiographic markers (speckle tracking). The magnitude of apical rotation increased progressively toward the apex (apical image 1: 4.2 ± 2.1°, apical image 2: 7.2 ± 3.9°, apical image 3: 11.8 ± 4.6°). apical images 1, 2, and 3 each had moderate to good correlations between repeat scans (ICC: 0.531–0.856). When apical images 1, 2, and 3 were averaged, rotation was 7.7 ± 2.7° and between‐scan correlation was excellent (ICC: 0.910). Similar results were observed for systolic and diastolic rotation rates. Averaging multiple standardized apical images, tending progressively toward the apex, generated the most reproducible rotation indices and may be optimal for the assessment of LV twist mechanics across therapeutic, interventional, and research studies; however, care should be taken given the influence of acquisition level on the magnitude of apical rotation.
Inter‐individual variation promotes ecological success of populations and species: evidence from experimental and comparative studies
Authors: Forsman Anders , Wennersten Lena
Published: August 2015

Biological diversity is threatened by exploitation, fragmentation of natural habitats, pollution, climate change, and anthropogenic spread of species. The question of how among‐individual variation influences the performance of populations and species is a poorly explored but currently growing field of research. Here, we review 31 experimental and 14 comparative studies and first investigate whether there is empirical support for the propositions that higher levels of among‐individual phenotypic and genetic variation promote the ecological and evolutionary success of populations and species in the face of environmental change. Next, we examine whether and how the effect of diversity depends on environmental conditions. Finally, we explore whether the relationship linking population fitness to diversity is typically linear, asymptotic, or whether the benefits peak at intermediate diversity. The reviewed studies provide strong, almost invariable, evidence that more variable populations are less vulnerable to environmental changes, show decreased fluctuations in population size, have superior establishment success, larger distribution ranges, and are less extinction prone, compared with less variable populations or species. Given the overwhelming evidence that variation promotes population performance, it is important to identify conditions when increased variation does not have the theoretically expected effect, a question of considerable importance in biodiversity management, where there are many other practical constraints. We find that experimental outcomes generally support the notion that genetic and phenotypic variation is of greater importance under more stressful than under benign conditions. Finally, population performance increased linearly with increasing diversity in the majority (10 of 12) of manipulation studies that included four or more diversity levels; only two experiments detected curvilinear relationships.
Responses of nectar‐feeding birds to floral resources at multiple spatial scales
Authors: Schmid B. , Nottebrock H. , Esler K. J. , Pagel J. , Pauw A. , Böhning‐Gaese K. , Schurr F. M. , Schleuning M.
Published: August 2015

The responses of animal pollinators to the spatially heterogeneous distribution of floral resources are important for plant reproduction, especially in species‐rich plant communities. We explore how responses of pollinators to floral resources varied across multiple spatial scales and studied the responses of two nectarivorous bird species (Cape sugarbird Promerops cafer, orange‐breasted sunbird Anthobaphes violacea) to resource distributions provided by communities of co‐flowering Protea species (Proteaceae) in South African fynbos. We used highly resolved maps of about 125 000 Protea plants at 27 sites and estimated the seasonal dynamics of standing crop of nectar sugar for each plant to describe the spatiotemporal distribution of floral resources. We recorded avian population sizes and the rates of bird visits to > 1300 focal plants to assess the responses of nectarivorous birds to floral resources at different spatial scales. The population sizes of the two bird species responded positively to the amount of sugar resources at the site scale. Within sites, the effects of floral resources on pollinator visits to plants varied across scales and depended on the resources provided by individual plants. At large scales (radii > 25 m around focal plants), high sugar density decreased per‐plant visitation rates, i.e. plants competed for animal pollinators. At small scales (radii < 5 m around focal plants), we observed either competition or facilitation for pollinators between plants, depending on the sugar amount offered by individual focal plants. In plants with copious sugar, per‐plant visitation rates increased with increasing local sugar density, but visitation rates decreased in plants with little sugar. Our study underlines the importance of scale‐dependent responses of pollinators to floral resources and reveals that pollinators’ responses depend on the interplay between individual floral resources and local resource neighbourhood.
Contrasting patterns of lichen functional diversity and species richness across an elevation gradient
Authors: Bässler Claus , Cadotte Marc W. , Beudert Burkhard , Heibl Christoph , Blaschke Markus , Bradtka Johannes Heribert , Langbehn Thomas , Werth Silke , Müller Jörg
Published: August 2015

Major environmental gradients co‐vary with elevation and have been a longstanding natural tool allowing ecologists to study global diversity patterns at smaller scales, and to make predictions about the consequences of climate change. These analyses have traditionally studied taxonomic diversity, but new functional diversity approaches may provide a deeper understanding of the ecological mechanisms driving species assembly. We examined lichen taxonomic and functional diversity patterns on 195 plots (200 m²) together with forest structure along an elevational gradient of 1000 m in a temperate low mountain range (Bohemian Forest, Germany). Along this elevation gradient temperature decreased and precipitation increased, two macroclimatic variables critical for lichens. Elevation was more important than forest structure in driving taxonomic and functional diversity. While species richness increased with elevation, functional diversity decreased and revealed that community patterns shift with elevation from random to clustered, reflecting selection for key shared traits. Higher elevations favored species with a complex growth form (which takes advantage of high moisture) and asexual reproductive mode (facilitating establishment under low temperature conditions). Our analysis highlights the need to examine alternative forms of diversity and opens the avenue for community predictions about climate change. For a regional scenario with increasing temperature and decreasing availability of moisture, we expect a loss of specialized species with a complex growth form and those with vegetative organs at higher elevations in low mountain ranges in Europe.
Is Education the Pathway to Success? A Comparison of Second Generation Turkish Professionals in Sweden, France, Germany and The Netherlands
Authors: Crul Maurice
Published: August 2015

Education is often seen as the most important mobility channel for children of immigrants. To what extent is this true? In this article, we look at successful second generation Turkish professionals in Sweden, France, Germany and The Netherlands. What kind of pathways did they take to become a professional? Based on the large quantitative international TIES survey, I reconstruct the pathways to a professional position in the four countries. We see how the open, comprehensive school systems in Sweden and France provide the main paths to a professional job. In Germany, however, it is the apprenticeship system. The Netherlands is a case in between. I describe how different educational institutional arrangements and the different ways the transition to the labour market is organised in the four countries also result in different routes to a professional career. I use new qualitative material from the ELITES project that was gathered in the four countries to illustrate the pathways to success in greater depth.
On the study of plant defence and herbivory using comparative approaches: how important are secondary plant compounds
Authors: Agrawal Anurag A. , Weber Marjorie G.
Published: August 2015

Species comparisons are a cornerstone of biology and there is a long tradition of using the comparative framework to study the ecology and evolution of plant defensive traits. Early comparative studies led to the hypothesis that plant chemistry plays a central role in plant defence, and the evolution of plant secondary chemistry in response to insect herbivory remains a classic example of coevolution. However, recent comparative work has disagreed with this paradigm, reporting little connection between plant secondary chemicals and herbivory across distantly related plant taxa. One conclusion of this new work is that the importance of secondary chemistry in plant defence may have been generally overstated in earlier research. Here, we attempt to reconcile these contradicting viewpoints on the role of plant chemistry in defence by critically evaluating the use and interpretation of species correlations as a means to study defence–herbivory relationships. We conclude that the notion that plant primary metabolites (e.g. leaf nitrogen content) are the principal determinants of herbivory (or the target of natural selection by herbivores) is not likely to be correct. Despite the inference of recent community‐wide studies of herbivory, strong evidence remains for a prime role of secondary compounds in plant defence against herbivores.
Mainstem‐tributary linkages by mayfly migration help sustain salmonids in a warming river network
Authors: Uno Hiromi , Power Mary E.
Published: August 2015

Animal migrations can link ecosystems across space. We discovered an aquatic insect that migrates between a river mainstem and its tributaries, and provides an important trophic subsidy for tributary predators. A mayfly, Ephemerella maculata, rears in a warm, sunlit productive river mainstem, then migrates as adults to cool, shaded unproductive tributaries where they oviposit and die. This migration tripled insect flux into a tributary for 1 month in summer. A manipulative field experiment showed that this E. maculata subsidy nearly tripled the growth of the young of the year steelhead trout (Oncorhynchus mykiss) in the recipient tributary over the summer months, and was more important than terrestrial invertebrate subsidies, which have been considered the primary food source for predators in small, forested creeks. By delivering food subsidies from productive but warming river mainstems to cool but food‐limited tributaries, aquatic insect migrations could enhance resilience to cool‐water predators in warming river networks.
Phosphatase inhibition prevents the activity‐dependent trafficking of GABAA receptors during status epilepticus in the young animal
Authors: Joshi Suchitra , Rajasekaran Karthik , Hawk Kyle M. , Brar Jasmit , Ross Brittany M. , Tran Christine A. , Chester Stephen J. , Goodkin Howard P.
Published: August 2015

Objectives

To determine if the activity‐dependent trafficking of γ2 subunit–containing γ‐aminobutyric acid type A receptors (GABAARs) that has been observed in older animals and posited to contribute to benzodiazepine pharmacoresistance during status epilepticus (SE) is age‐dependent, and to evaluate whether blockade of protein phosphatases can inhibit or reverse the activity‐dependent plasticity of these receptors.

Methods

The efficacy and potency of diazepam 0.2–10 mg/kg administered 3 or 60 min after the onset of a lithium/pilocarpine‐induced seizure in postnatal day 15–16 rats was evaluated using video–electroencephalography (EEG) recordings. The surface expression of γ2 subunit–containing GABAARs was assessed using a biotinylation assay, and GABAAR‐mediated miniature inhibitory postsynaptic currents (mIPSCs) were recorded using whole‐cell patch‐clamp recording techniques from dentate granule cells in hippocampal slices acutely obtained 60 min after seizure onset (SE‐treated). The effect of the protein phosphatase inhibitors FK506 and okadaic acid (OA) on the surface expression of these receptors was determined in organotypic slice cultures exposed to high potassium and N‐methyl‐d‐aspartate (NMDA) or in SE‐treated slices.

Results

Diazepam terminated seizures of 3 min but not 60 min duration, even at the highest dose. In the SE‐treated slices, the surface expression of γ2 subunit–containing GABAARs was reduced and the amplitude of the mIPSCs was diminished. Inhibition of protein phosphatases prevented the activity‐induced reduction of the γ2 subunit–containing GABAARs in organotypic slice cultures. Furthermore, treatment of SE‐treated slices with FK506 or OA restored the surface expression of the γ2 subunit–containing GABAARs and the mIPSC amplitude.

Significance

This study demonstrates that the plasticity of γ2 subunit–containing GABAARs associated with the development of benzodiazepine resistance in young and adult animals is similar. The findings of this study suggest that the mechanisms regulating the activity‐dependent trafficking of GABAARs during SE can be targeted to develop novel adjunctive therapy for the treatment of benzodiazepine‐refractory SE.
Electronic brachytherapy used for the successful treatment of three different types of equine tumours
Authors: Bradley W. M. , Schilpp D. , Khatibzadeh S. M.
Published: August 2015

An electronic form of interstitial brachytherapy was used to treat tumours on 3 different horses. One horse was treated for an ocular lymphoma, the second for a sarcoid, and the third for melanoma. This form of brachytherapy contains inherent advantages over previously used forms of brachytherapy and provides another treatment option for equine tumours that cannot be treated with, or do not respond to, conventional tumour therapies.
Influence of artificial and casting defects on fatigue strength of moulded components in Ti‐6Al‐4V alloy
Authors: Léopold G. , Nadot Y. , Billaudeau T. , Mendez J.
Published: August 2015

The influence of defects on the fatigue strength of a cast Ti‐6Al‐4V alloy has been investigated. An experimental programme has been defined with different castings. On a first stage, a flat fatigue specimen has been developed to be representative of the real aircraft component. Then, reference fatigue properties have been determined and reduction of the fatigue strength has been quantified for artificial and natural defects. It is shown that an artificial defect with a chemically milled surface is representative of an in‐service component surface machining: surface pinholes have similar influence on the fatigue behaviour. Furthermore, the experimental results have shown that the geometrical morphology is not the major parameter that governs the fatigue life reduction: the defect type has a major influence. It is also shown that the initiation stage is not negligible in the total fatigue life about 105 cycles. Kitagawa diagrams were built to determine critical defect sizes.
Resident‐immigrant dichotomy matters for classifying wetland site groups and metacommunities
Authors: Bried Jason T. , McIntyre Nancy E. , Dzialowski Andrew R. , Davis Craig A.
Published: August 2015

The fact that species have resident (autochthonous) or immigrant (allochthonous) status at any given locality may have strong implications for ecological analysis.

We used wetlands and adult odonates as a model system to evaluate the resident‐immigrant dichotomy for two modes of community analysis: (1) grouping sites based on species compositional variation and (2) identifying metacommunity structure. We tested a hypothesis of gradient‐structured (non‐random) resident occurrence versus unstructured (random) immigrant occurrence in the metacommunity context and predicted the resident occurrence would more effectively partition community variation and produce stronger site groupings than total (resident + immigrant) occurrence.

Site group classification after fractioning out resident occurrence consistently and in some cases dramatically outperformed total occurrence. Resident damselflies produced the strongest classifications, which we attribute to greater dispersal limitation, environmental sorting or both.

As predicted only the resident occurrence led to identifiable metacommunity structures, primarily Clementsian‐style turnover. This suggests the resident occurrence is gradient‐driven with species responding similarly to abiotic filters, whereas immigrant occurrence is more opportunistic and random.

The resident‐immigrant dichotomy appears to have strong influence on quantitative classification of sites and metacommunities, and species composition of resident adult damselflies is potentially useful for differentiating and indicating site groups of non‐forested freshwater wetlands.
Phytoplankton lipid content influences freshwater lake methanogenesis
Authors: West William E. , McCarthy Shayna M. , Jones Stuart E.
Published: August 2015

Rates of methanogenesis in freshwater sediments have been shown to increase with inputs of phytoplankton biomass. Although many studies have shown the importance of resource quality for decomposition, little is known of the importance of substrate quality on rates of methanogenesis.

Here, we studied the effects of lipid content and taxonomic affiliation of phytoplankton biomass on rates of methanogenesis in lake sediment slurries from five lakes differing in trophic status.

Substrate quantity had a positive effect on methanogenesis despite differing trophic status. Furthermore, we observed that phytoplankton biomass quality, in terms of lipid content, enhanced methanogenesis rates. However, rates of methanogenesis between lake sediments treated with Scenedemus obliquus or Microcystis aeruginosa did not differ when lipid content was held constant.

Phytoplankton lipid content has been shown to increase when nutrients are limiting, which may result in an increase in substrate quality for methanogenesis with eutrophication. However, our study revealed that responses of substrate quantity to nutrient enrichment likely outpace the effects of resource quality and may result in a net increase in CH4 emissions from eutrophied lakes. Interestingly, the resource quality feedback may at least partially reduce the potential effect of eutrophication on lake methanogenesis.
Mapping the spatial distribution of the biomass and filter‐feeding effect of invasive dreissenid mussels on the winter‐spring phytoplankton bloom in Lake Michigan
Authors: Rowe Mark D. , Obenour Daniel R. , Nalepa Thomas F. , Vanderploeg Henry A. , Yousef Foad , Kerfoot W. Charles
Published: August 2015

The effects of the invasive bivalves Dreissena polymorpha (zebra mussel) and Dreissena rostriformis bugensis (quagga mussel) on aquatic ecosystems, including Lake Michigan, are a topic of current interest to scientists and resource managers. We hypothesised that the winter–spring phytoplankton bloom in Lake Michigan is reduced at locations where the fraction of the water column cleared per day by Dreissena filter feeding approached the net growth rate of phytoplankton, when the water column was not stratified. To test this hypothesis, we compared the spatial distribution of Dreissena filter‐feeding intensity (determined from geostatistical modelling) to the spatial distribution of chlorophyll (determined from satellite remote sensing).

To map the spatial distribution of Dreissena biomass and filter‐feeding intensity, we developed a geostatistical model based on point observations of mussel biomass measured in Lake Michigan in 1994/1995, 2000, 2005 and 2010. The model provided fine‐scale estimates of the spatial distribution of biomass for the survey years and provided estimates, with their uncertainty, of total biomass lakewide and within subregions. The approach outlined could be applied more generally to map the distribution of benthic biota in lakes from point observations.

Total biomass of Dreissena in Lake Michigan, estimated from the geostatistical model, increased significantly over each five‐year period. The total biomass in units of 106 kg ash‐free dry mass (AFDM) (with 90% confidence interval) was 6 (4–8) in 1994/1995, 18 (14–23) in 2000, 408 (338–485) in 2005 and 610 (547–680) in 2010. From 1994/1995 to 2005, increases were observed in all regions of the lake (northern, central and southern) and in all depth zones (<30, 30–50, 50–90 and >90). However, from 2005 to 2010, for depths of <50 m, biomass declined in the northern region, remained constant in the central region and increased in the southern region; biomass continued to increase in all three lake regions for depths >50 m.

The filter‐feeding intensity of Dreissena exceeded the benchmark spring phytoplankton growth rate of 0.06 day−1 in 2005 for depths <50 m (lakewide). In 2010, the filter‐feeding impact exceeded 0.06 day−1 within depths <90 m (lakewide), which greatly increased the spatial area affected relative to 2005. A regression analysis indicated a significant relationship between the reduction in satellite‐derived chlorophyll concentration (pre‐D. r. bugensis period to post‐D. r. bugensis period) and spatially co‐located filter‐feeding intensity (fraction of water column cleared per day) during periods when the water column was not stratified (December to April).
Alluvial ground water influences dissolved organic matter biogeochemistry of pools within intermittent dryland streams
Authors: Siebers Andre R. , Pettit Neil E. , Skrzypek Grzegorz , Fellman Jason B. , Dogramaci Shawan , Grierson Pauline F.
Published: August 2015

The dissolved organic matter (DOM) biogeochemistry of intermittent rivers is affected by periods of disconnection and drying after cessation of surface flow, with a pronounced concentration of solutes as pools evaporate and contract. However, inputs of alluvial ground water to stream pools may offset the effects of evaporation and influence the quantity and composition of DOM.

We used δ18O and δ2H values of surface water and alluvial ground water (AW) together with DOM fluorescence excitation–emission spectroscopy to investigate changes in DOM biogeochemistry of pools from four intermittent streams in semi‐arid north‐west Australia. Our objective was to determine whether the fluorescence characteristics of DOM in pools are driven by their connectivity to alluvial ground water.

Pool water δ18O values ranged from −8 to 13.1 ‰ and showed progressive enrichment as pools became disconnected from AW and subsequently evaporated. Parallel factor analysis of DOM fluorescence revealed that DOM in pools was generally dominated by humic‐like components, with lesser contributions from tryptophan‐like and tyrosine‐like components.

DOC concentrations were higher in more evaporated pools. Humic‐like and tryptophan‐like DOM were also highest in pools isolated from AW, suggesting that inputs of AW had a dilution effect while also moderating evaporative concentration of solutes. In contrast, tyrosine‐like DOM was only weakly correlated with the hydrological status of pools.

The proportion that each component contributed to total DOM fluorescence remained mostly consistent across both AW‐connected and evaporating pools. However, some pools with AW throughflow had higher contributions from tyrosine‐like fluorescence and lower contributions from humic‐like fluorescence.

Disconnection from AW and subsequent evaporative concentration of solutes is an important control on DOM fluorescence characteristics in these intermittent streams. However, production and removal of DOM were only rarely influenced by AW connectivity, likely reflecting the high hydrological variability of intermittent rivers, even following cessation of surface flow.
Antidepressant‐like effects and basal immobility depend on age and serotonin transporter genotype
Authors: Mitchell N. C. , Koek W. , Daws L. C.
Published: August 2015

Monoamine uptake inhibitors are common treatments for depression; however, the therapeutic efficacy of these drugs varies widely. Two factors that are commonly linked to clinical outcome are age and serotonin transporter (SERT) genotype. Mouse models provide powerful tools to study consequences of age and genotype on antidepressant‐like efficacy; however, to date, systematic studies of this nature are lacking. Here, we used the tail suspension test (TST), a preclinical assay for antidepressant efficacy, to gain insight into age and SERT genotype dependency of immobility time in the TST under control conditions (saline injection) and in response to the tricyclic antidepressant, desipramine (DMI). Immobility after saline injection in juvenile, adolescent, adult, mature adult and middle‐aged mice (postnatal days 21, 28, 90, 210 and 300, respectively) significantly increased with age; however, the rate of increase was slower for SERT null (−/−) mice than for wild‐type (+/+) or heterozygote (+/−) mice. Desipramine reduced immobility across ages and SERT genotypes. Middle‐aged, but not adult, SERT−/− mice were significantly more sensitive to DMI than age‐matched SERT+/+ or SERT+/− mice. Desipramine was less potent in middle‐aged SERT+/+ and SERT+/− mice than in adult SERT+/+ or SERT+/− mice. Regardless of age, DMI's maximal effects were greater in SERT−/− mice than in SERT+/+ or SERT+/− mice. These results show that immobility time in the TST varies as a function of age and SERT genotype, underscoring the utility of the TST as a potential model to examine age‐ and SERT genotype‐dependent influences on antidepressant response.
The general dynamic model: towards a unified theory of island biogeography?
Authors: Borregaard Michael K. , Matthews Thomas J. , Whittaker Robert J.
Published: August 2015

Aim

Island biogeography focuses on understanding the processes that underlie a set of well‐described patterns on islands, but it lacks a unified theoretical framework for integrating these processes. The recently proposed general dynamic model (GDM) of oceanic island biogeography offers a step towards this goal. Here, we present an analysis of causality within the GDM and investigate its potential for the further development of island biogeographical theory. Further, we extend the GDM to include subduction‐based island arcs and continental fragment islands.

Location

A conceptual analysis and a simulation of oceanic islands.

Methods

We describe the causal relationships between evolutionary and ecological processes implied by the GDM, implement them as a computer simulation and use this to simulate two alternative geological scenarios.

Results

The dynamics of species richness and rates of evolutionary processes in simulations derived from the mechanistic assumptions of the GDM corresponded broadly to those initially suggested, with the exception of trends in extinction rates. Expanding the model to incorporate different scenarios of island ontogeny and isolation revealed a sensitivity of evolutionary dynamics to attributes of island geology.

Main conclusions

We argue that the GDM of oceanic island biogeography has the potential to provide a unified framework for island biogeography, integrating geological, ecological and evolutionary processes. Our simulations highlight how the geological dynamics of distinct island types are predicted to lead to markedly different evolutionary dynamics. This sets the stage for a more predictive theory incorporating the processes governing temporal dynamics of species diversity on islands.
Outcome of intravenous recombinant tissue plasminogen activator for acute ischemic stroke in patients aged over 80 years
Authors: Mione Gioia , Ducrocq Xavier , Thilly Nathalie , Lacour Jean‐Christophe , Vespignani Hervé , Richard Sébastien
Published: August 2015

Aim

Practitioners are faced with a substantial challenge when considering recombinant tissue plasminogen activator (rt‐PA) therapy for older patients with ischemic stroke. Patients aged over 80 years suffer from the most severe cerebral infarcts. The benefit of rt‐PA treatment compared with single standard care only in stroke units remains to be clearly assessed.

Methods

We collected data from 321 patients aged over 80 years admitted for acute cerebral infarction to the stroke unit of Nancy University Hospital in France between 1 January 2009 and 31 December 2012. Patients were stratified into two groups: treated or not with rt‐PA. Baseline characteristics and outcome were collected and compared between both groups. Good outcome at 3 months was defined as modified Rankin Scale score ≤2.

Results

The 55 patients treated with rt‐PA had a higher National Institute of Health Stroke Scale score on admission than those without (15 vs 5; P < 0.001). They were more likely to have intracranial haemorrhage (20 vs 5%; P < 0.001) without an increased mortality rate (28 vs 27%; P = 0.95). Multivariate analysis showed a more favorable outcome (odds ratio 7, 95% confidence interval 3–16.5; P < 0.001). Slightly higher percentages of patients with modified Rankin Scale ≤2 were found after intention‐to‐treat analysis (49 vs 45%) and after exclusion of patients with baseline modified Rankin Scale >2 (57 vs 54 %), but without reaching significance (P > 0.05).

Conclusions

Rt‐PA therapy would appear to improve prognosis in the elderly with ischemic stroke. This suggests that age alone should no longer be a barrier to rt‐PA therapy. Geriatr Gerontol Int 2016; 16: 843–849.