Temporal Profile of Astrocytes and Changes of Oligodendrocyte-Based Myelin Following Middle Cerebral Artery Occlusion in Diabetic and Non-diabetic Rats

The long-term impacts of cerebral ischemia and diabetic ischemia on astrocytes and oligodendrocytes have not been defined. The objective of this study is to define profile of astrocyte and changes of myelin in diabetic and non-diabetic rats subjected to focal ischemia.Focal cerebral ischemia of 30-min duration was induced in streptozotocin-induced diabetic and vehicle-injected normoglycemic rats. The brains were harvested for immunohistochemistry of glial fibrillary acidic protein (GFAP) and 2'', 3''-cyclic nucleotide 3''-phosphodiesterase (CNPase) at various reperfusion endpoints ranging from 30 min up to 28 days. The results showed that activate astrocytes were observed after 30 min and peaked at 3 h to 1 day after reperfusion in ischemic penumbra, and peaked at 7 days of reperfusion in ischemic core. Diabetes inhibited the activation of astrocytes in ischemic hemisphere. Demyelination occurred after 30 min of reperfusion in ischemic core and peaked at 1 day. Diabetes caused more severe demyelination compared with non-diabetic rats. Remyelination started at 7 days and completed at 14 and 28 days in ischemic region. Diabetes inhibited the remyelination processes. It is concluded that ischemia activates astrocytes and induces demyelination. Diabetes inhibits the activation of astrocytes, exacerbates the demyelination and delays the remyelination processes. These may contribute to the detrimental effects of hyperglycemia on ischemic brain damage.     

Good Manufacturing Practices (GMP) manufacturing of advanced therapy medicinal products: a novel tailored model for optimizing performance and estimating costs

Background aimsAdvanced therapy medicinal products (ATMP) have gained considerable attention in academia due to their therapeutic potential. Good Manufacturing Practice (GMP) principles ensure the quality and sterility of manufacturing these products. We developed a model for estimating the manufacturing costs of cell therapy products and optimizing the performance of academic GMP-facilities.MethodsThe “Clean-Room Technology Assessment Technique” (CTAT) was tested prospectively in the GMP facility of BCRT, Berlin, Germany, then retrospectively in the GMP facility of the University of California-Davis, California, USA. CTAT is a two-level model: level one identifies operational (core) processes and measures their fixed costs; level two identifies production (supporting) processes and measures their variable costs. The model comprises several tools to measure and optimize performance of these processes. Manufacturing costs were itemized using adjusted micro-costing system.ResultsCTAT identified GMP activities with strong correlation to the manufacturing process of cell-based products. Building best practice standards allowed for performance improvement and elimination of human errors. The model also demonstrated the unidirectional dependencies that may exist among the core GMP activities. When compared to traditional business models, the CTAT assessment resulted in a more accurate allocation of annual expenses. The estimated expenses were used to set a fee structure for both GMP facilities. A mathematical equation was also developed to provide the final product cost.ConclusionsCTAT can be a useful tool in estimating accurate costs for the ATMPs manufactured in an optimized GMP process. These estimates are useful when analyzing the cost-effectiveness of these novel interventions.     

Comparative Efficacy of Lamivudine and Emtricitabine: A Systematic Review and Meta-Analysis of Randomized Trials

Introduction

Lamivudine and emtricitabine are considered equivalent by several guidelines, but evidence of comparable efficacy is conflicting.

Methods

We searched two databases up to June 30 2013 to identify randomized and quasi-randomized trials in which lamivudine and emtricitabine were used as part of combination antiretroviral therapy for treatment-naïve or experienced HIV-positive adult patients. We only included trials where partner drugs in the regimen were identical or could be considered to be comparable. We allowed for comparisons between tenofovir and abacavir provided the study population did not begin treatment with a viral load >100,000 copies/ml.

Results

12 trials contributed 15 different randomized comparisons providing data on 2251 patients receiving lamivudine and 2662 patients receiving emtricitabine. Treatment success was not significantly different in any of the 12 trials. In the three trials that directly compared lamivudine and emtricitabine, the relative risk for achieving treatment success was non-significant (RR 1.03 95%CI 0.96-1.10). For all trials combined, the pooled relative risk for treatment success was not significantly different (RR 1.00, 95%CI 0.97–1.02). No heterogeneity was observed (I ² = 0). Similarly, there was no difference in the pooled relative risk for treatment failure (RR 1.08, 95%CI 0.94–1.22, I ² = 3.4%).

Conclusions

The findings of this systematic review suggest that lamivudine and emtricitabine are clinically equivalent.     

The Influence of Variable Rainfall Frequency on Germination and Early Growth of Shade-Tolerant Dipterocarp Seedlings in Borneo

Climate change induced alterations to rainfall patterns have the potential to affect the regeneration dynamics of plant species, especially in historically everwet tropical rainforest. Differential species response to infrequent rainfall may influence seed germination and seedling establishment in turn affecting species distributions. We tested the role of watering frequency intervals (from daily to six-day watering) on the germination and the early growth of Dipterocarpaceae seedlings in Borneo. We used seeds that ranged in size from 500 to 20,000 mg in order to test the role of seed mass in mediating the effects of infrequent watering. With frequent rainfall, germination and seedling development traits bore no relationship to seed mass, but all metrics of seedling growth increased with increasing seed mass. Cumulative germination declined by 39.4% on average for all species when plants were watered at six-day intervals, and days to germination increased by 76.5% on average for all species from daily to six-day intervals. Final height and biomass declined on average in the six-day interval by 16% and 30%, respectively, but the percentage decrease in final size was greater for large-seeded species. Rooting depth per leaf area also significantly declined with seed mass indicating large-seeded species allocate relatively more biomass for leaf production. This difference in allocation provided an establishment advantage to large-seeded species when water was non-limiting but inhibited their growth under infrequent rainfall. The observed reduction in the growth of large-seeded species under infrequent rainfall would likely restrict their establishment in drier microsites associated with coarse sandy soils and ridge tops. In total, these species differences in germination and initial seedling growth indicates a possible niche axis that may help explain both current species distributions and future responses to climate change.     

Monitoring of Pb Exposure in Waterfowl Ten Years after a Mine Spill through the Use of Noninvasive Sampling

Lead exposure in waterfowl was studied using noninvasive fecal sampling in the Guadalquivir Marshes in Spain, an area affected by the 1998 Aznalcóllar mine disaster. Feces of greylag geese (Anser anser, n = 191) and purple gallinule (Porphyrio porphyrio, n = 91) were collected from three different impacted sites (Entremuros, Caracoles and Cerro de los Ánsares) during the winters of 2004 to 2008. Lead and aluminium (an indicator of sediment ingestion) and Pb isotope signatures (to discriminate between sources of Pb exposure) were analyzed in freeze-dried, acid digested samples. The concentrations of fecal porphyrins and biliverdin were determined as noninvasive biomarkers to study Pb exposure effects. Results showed a decrease in Pb exposure over time in wintering greylag geese. In contrast, for purple gallinule resident in the Entremuros a clear trend was not evident. For both species, sediment ingestion appeared to be the main source of exposure to Pb. In the Entremuros, some samples from purple gallinule were detected with higher Pb levels than expected for simple soil ingestion, and these had Pb isotopic profiles compatible with mining sludge or Pb shot. Whilst fecal Pb isotopic profiles were effective in differentiating between samples from sites with different levels and sources of pollution, the combined use of element ratios (such as Pb/Al) and other non-traditional stable isotope signatures may also prove worthwhile. Overall, the fecal Pb levels detected were below those described in feces for waterfowl from other uncontaminated areas(<10 µg/g d.w.). Despite this, for both species fecal Pb levels were positively correlated with porphyrin excretion, and for purple gallinule, with the coproporphyrin III/I ratio, suggesting some subtle effects on heme synthesis in birds. Ten years after the mine spill, Pb contamination in birds by this pollution source was still detectable and subtlethal effects may persist.     

Measuring the long-term success of small-scale marine protected areas in a Philippine reef fishery

Tropical coral reefs are subject to multiple pressures from both natural and anthropogenic sources. These pressures have caused widespread declines in reef health, resulting in the increased use of spatial management tools such as marine protected areas (MPAs). MPAs have proven generally effective if well designed and enforced, but there are limited long-term studies investigating how the presence of small-scale MPAs affects fish populations and reef communities. Using a 12-year time series, we found that small-scale (10–50 ha) community-managed MPAs along the Danajon Bank of the Philippines preserved average fish biomass within their boundaries over time relative to surrounding fished reefs. Unprotected areas are, however, showing significant long-term biomass decline. MPAs were also found to preserve more key trophic groups and larger-bodied commercially targeted reef fish families. Fish biomass of piscivore, scavenger and invertivore trophic groups inside individual MPAs is, however, still declining at a similar rate as outside. Surprisingly, long-term benthic cover and growth form composition were not significantly affected overall by MPA presence, despite the sporadic use of highly destructive dynamite fishing in this region. Coral cover has remained historically low (21–28%) throughout the study, following widespread bleaching mortality. While management tempered overall abundance declines, we found that irrespective of MPA presence, there was a generalised decline of both large- and small-bodied fish size groups across the study region, most steeply within the 20–30 cm length fish, and a shift towards proportionally higher abundances of small (5–10 cm) fish. This indicates a combination of over-exploitation, inadequate MPA size and coverage for larger fish, and the lingering effects of the 1998 bleaching event. Generalised shifts in body size and trophic structure reported here could lead to future reductions in fishery productivity and stability and will be further exacerbated unless broader fishery regulations and enforcement is instated.

     

Ant–scale mutualism increases scale infestation,decreases folivory,and disrupts biological control in restored tropical forests

Ant–hemipteran mutualisms can have positive and negative effects on host plants depending on the level of hemipteran infestation and plant protection conferred by ants against folivory. Differential effects of such mutualisms on plant survival are well documented in undisturbed and ant-invaded systems, but few have explored how anthropogenic disturbance affects interactions between hemipterans and native ant species and what the consequences may be for recovering ecosystems. Within a fragmented landscape in Costa Rica, restored tropical forests harbor a mutualism between the native ant Wasmannia auropunctata and the scale insect Alecanochiton marquesi on the abundant, early-successional tree Conostegia xalapensis. I added A. marquesi scales to C. xalapensis seedlings and either allowed or excluded W. auropunctata to investigate if this mutualism leads to increased scale infestation, decreased scale mortality, and decreased folivory. I also examined whether these effects are mediated by the percentage of remnant forest cover in the landscape. I found that seedlings with ants excluded had fewer scale insects and higher herbivory than plants with ants present. I also found evidence that scale mortality due to fungal attack and parasitism was higher on ant-excluded versus ant-allowed seedlings but only at sites with high surrounding landscape forest cover. Together, these results suggest that mutualisms between scale insects and native ants can promote scale infestation, reduce folivory on native plant species, and potentially disrupt biological control of scale insects in recovering tropical forests. Further, my experiment underscores the importance of remnant tropical forests as sources of biological control in anthropogenically disturbed landscapes. Abstract in Spanish is available with online material.     

The intertidal mudflats of Barr Al Hikman,Sultanate of Oman,as feeding,reproduction and nursery grounds for brachyuran crabs

Brachyuran crabs are an important ecological and economical, yet often unstudied aspect of intertidal mudflats of the Arabian Peninsula. Here we provide baseline density estimates of crabs at the relatively pristine intertidal mudflats of Barr Al Hikman (Sultanate of Oman) and provide information on their life cycle and habitat preference. Across the winters of 2012–2015 crabs were sampled on a grid covering the entire intertidal depth gradient. 29 species were found and average densities varied between 12 and 54 crabs/m². Deposit-feeding and herbivorous crabs were the most abundant species across all winters. Size frequency data and the presence of ovigerous females show that most crabs species reproduce in the intertidal area. P. segnis, the most important crab for local fisheries, was found to use the intertidal area as a nursery ground. We analysed the relationships between the two most abundant crab species, Macrophthalmus sulcatus and Thalamita poissonii and the environmental variables: seagrass density, tidal elevation, median grain size and sediment depth using Random Forest models. The predictive capacity of the models and the relative importance of the environmental predictors varied between years, but crab densities in general were positively associated with seagrass density, presumably because seagrass offers feeding habitat.