A Novel Atlas-Based Strategy for Understanding Cardiac Dysfunction in Patients with Congenital Heart Disease

Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease. Infants diagnosed with TOF require surgical interventions to survive into adulthood. However, as a result of postoperative structural malformations and long-term ventricular remodeling, further interventions are often required later in life. To help identify those at risk of disease progression, serial cardiac magnetic resonance (CMR) imaging is used to monitor these patients. However, most of the detailed information on cardiac shape and biomechanics contained in these large four-dimensional (4D) data sets goes unused in clinical practice for lack of efficient and comprehensive quantitative analysis tools. While current global metrics of cardiac size and function, such as indexed ventricular mass and volumes, can identify patients at risk of further complications, they are not adequate to explain the underlying mechanisms causing the postoperative malfunctions, and help cardiologists plan optimal personalized treatments. We are proposing a novel approach that uses 4D ventricular shape models derived from CMR imaging exams to generate statistical atlases of ventricular shape and finite-element models of ventricular biomechanics to identify specific features of cardiac shape and biomechanical properties that explain variations in ventricular function. This study has the potential to discover novel biomarkers that precede adverse ventricular remodeling and dysfunction.     

Allometric growth, life-history invariants and population energetics

Population and community level processes must be at least partially determined by variation in the body sizes of constituent individuals, implying quantitative scaling relations can be extended to account for variation in those processes. Here we integrate allometric growth and life‐history invariant theories, and use this approach to develop theory describing the energetics of stationary populations. Our predictions approximate, with no free parameters, the scaling of production/biomass and assimilation/biomass ratios in mammalian populations and work partially for fish populations. This approach appears to be a promising direction and suggests the need for further development of the growth and life‐history models, and extensions of those theories.     

Brazilian Tapir Density in the Pantanal: A Comparison of Systematic Camera-Trapping and Line-Transect Surveys

The density of Brazilian tapirs ( Tapirus terrestris) was studied in the northeastern part of the Pantanal wetlands of Brazil using two simultaneous and independent methods: (1) systematic camera trapping combined with capture–recapture analysis, with camera traps spaced 1 km apart and distributed over 54 km²; and (2) line-transect sampling using an array of 12 linear transects, from 3.8 to 7.2 km long, covering the principal open and forest habitat types across the entire 1063 km² SESC Pantanal Reserve. The two methods yielded conservative density estimates of 0.58 ± 0.11 tapirs/km² (camera trapping) and 0.55 (95% CI 0.30–1.01) tapirs/km² (line transects). The study suggests that certain Pantanal habitats and sites can sustain relatively high population densities of tapirs when these animals are protected from hunting. Further testing of the camera-trapping methodology as applied to tapirs is required, particularly focusing on extending the survey period. As it represents a relatively rapid method for estimating population density, in comparison to line-transect surveys, and as it generates information simultaneously on multiple species that are conservation priorities, we recommend that camera-trapping surveys be applied more widely across a variety of Pantanal habitats and land-use categories in order to confirm the value of the vast 140,000 km² wilderness region for this vulnerable species.     

Hypertrophic Gene Expression Induced by Chronic Stretch of Excised Mouse Heart Muscle

Altered mechanical stress and strain in cardiac myocytes induce modifications in gene expression that affects cardiac remodeling and myocyte contractile function. To study the mechanisms of mechanotransduction in cardiomyocytes, probing alterations in mechanics and gene expression has been an effective strategy. However, previous studies are self-limited due to the general use of isolated neonatal rodent myocytes or intact animals. The main goal of this study was to develop a novel tissue culture chamber system for mouse myocardium that facilitates loading of cardiac tissue, while measuring tissue stress and deformation within a physiological environment. Intact mouse right ventricular papillary muscles were cultured in controlled conditions with superfusate at 95% O₂/ 5% CO₂, and 34°C, such that cell to extracellular matrix adhesions as well as cell to cell adhesions were undisturbed and both passive and active mechanical properties were maintained without significant changes. The system was able to measure the induction of hypertrophic markers (BNP, ANP) in tissue after 2 hrs and 5 hrs of stretch. ANP induction was highly correlated with the diastolic load of the muscle but not with developed systolic load. Load induced ANP expression was blunted in muscles from muscle-LIM protein knockout mice, in which defective mechanotransduction pathways have been predicted.     

Improved development of microspore-derived embryo cultures of Brassica napus cv Topaz following changes in glutathione metabolism

Glutathione has been shown to play an important role during embryo development in both plant and animal systems. The effects of altered glutathione metabolism during microspore-derived embryos (MDEs) of Brassica napus were investigated following exogenous application of reduced glutathione (GSH), its oxidized form (GSSG) and buthionine sulfoximine (BSO), an inhibitor of glutathione de novo synthesis. Applications of BSO which lowered the cellular glutathione redox status, i.e. GSH/(GSH + GSSG), enhanced significantly the quality of the embryos and their ability to convert into viable plants. Histological analyses revealed that inclusions of BSO in the culture medium altered the pattern of storage product accumulation in the embryos and improved the architecture of the shoot apical meristems (SAMs). Compared with their control counterparts which showed severe signs of SAM deterioration, such as the formation of intercellular spaces and differentiation of the meristematic cells, BSO-treated embryos had well-organized SAMs. The improved SAM organization observed in the presence of BSO also correlated with the proper localization pattern of WUSCHEL , a SAM molecular marker gene which was miss-expressed in control embryos. The beneficial effects of BSO on embryo development and conversion were ascribed to the increasing levels of ABA. The concentration of this growth regulator in BSO-treated embryos was always higher than that of control embryos during the second half of the maturation period. Furthermore, many structural alterations induced by BSO could be reproduced in embryos cultured in the presence of ABA. Taken together, these results suggest that a lowering of the glutathione redox status during embryo development may represent a metabolic switch needed for increasing the endogenous levels of ABA, which is required for successful completion of the developmental program.     

Changing places: how the results of new field work in the Rubeho Mountains influence conservation priorities in the Eastern Arc Mountains of Tanzania

The Rubeho Mountains are a poorly studied mountain block within the Eastern Arc Mountain range of Tanzania and Kenya. We present the results of field surveys for vertebrates undertaken during the period February 2000 to December 2002. One hundred and twelve man‐days of surveys recorded 35 mammal, 107 bird, ten reptile and nine amphibian species, including eleven species endemic and seven near‐endemic to the Eastern Arc, with one species new to science. Of these, nine species are regarded as threatened with extinction. The new survey data significantly elevate the biological importance of the Rubehos within the Eastern Arc range. Further analyses highlight how the overall biological ranking of the Eastern Arc mountain blocks is correlated with survey effort. The majority of the forest habitat on the Rubehos is contained in three national (Central Government) Forest Reserves (Mang'alisa, Mafwomero and Ukwiva). Our surveys recorded high levels of disturbance to the forest habitat in all three reserves and we draw attention to the need for additional conservation investment in this area.     

Anti-inflammatory potential of human corneal stroma-derived stem cells determined by a novel in vitro corneal epithelial injury model

BACKGROUND An in vitro injury model mimicking a corneal surface injury was optimised using human corneal epithelial cells(hCEC).AIM To investigate whether corneal-stroma derived stem cells(CSSC) seeded on an amniotic membrane(AM) construct manifests an anti-inflammatory, healing response.METHODS Treatment of hCEC with ethanol and pro-inflammatory cytokines were compared in terms of viability loss, cytotoxicity, and pro-inflammatory cytokine release, in order to generate the in vitro injury. This resulted in an optimal injury of 20%(v/v) ethanol for 30 s with 1 ng/mL interleukin-1(IL-1) beta. Co-culture experiments were performed with CSSC alone and with CSSC-AM constructs.The effect of injury and co-culture on viability, cytotoxicity, IL-6 and IL-8 production, and IL1 B, TNF, IL6, and CXCL8 mRNA expression were assessed.RESULTS Co-culture with CSSC inhibited loss of hCEC viability caused by injury. Enzyme linked immunosorbent assay and polymerase chain reaction showed a significant reduction in the production of IL-6 and IL-8 pro-inflammatory cytokines, and reduction in pro-inflammatory cytokine mRNA expression during co-culture with CSSC alone and with the AM construct. These results confirmed the therapeutic potential of the CSSC and the possible use of AM as a cell carrier for application to the ocular surface.CONCLUSION CSSC were shown to have a potentially therapeutic anti-inflammatory effectwhen treating injured hCEC, demonstrating an important role in corneal regeneration and wound healing, leading to an improved knowledge of their potential use for research and therapeutic purposes.     

Toward a stoichiometric framework for evolutionary biology

Ecological stoichiometry, the study of the balance of energy and materials in living systems, may serve as a useful synthetic framework for evolutionary biology. Here, we review recent work that illustrates the power of a stoichiometric approach to evolution across multiple scales, and then point to important open questions that may chart the way forward in this new field. At the molecular level, stoichiometry links hereditary changes in the molecular composition of organisms to key phenotypic functions. At the level of evolutionary ecology, a simultaneous focus on the energetic and material underpinnings of evolutionary tradeoffs and transactions highlights the relationship between the cost of resource acquisition and the functional consequences of biochemical composition. At the macroevolutionary level, a stoichiometric perspective can better operationalize models of adaptive radiation and escalation, and elucidate links between evolutionary innovation and the development of global biogeochemical cycles. Because ecological stoichiometry focuses on the interaction of energetic and multiple material currencies, it should provide new opportunities for coupling evolutionary dynamics across scales from genomes to the biosphere.     

Population synchrony within and among Lepidoptera species in relation to weather, phylogeny, and larval phenology

Abstract.  1. The population dynamics of native herbivore species in central Appalachian deciduous forests were studied by analysing patterns of synchrony among intra- and interspecific populations and weather.
2. Spatial synchrony of 10 Lepidoptera species and three weather variables (minimum temperature, maximum temperature, precipitation) from 12 sites was measured using cross-correlation functions relating levels of synchrony to the distance separating each set of populations. Based on both the pattern of synchrony and the region-wide cross-correlation coefficients, Lepidoptera species appear to be synchronised, at least in part, by local weather conditions.
3. Interspecific cross-correlations were calculated for all sympatric species pairs and trends in interspecific synchrony were related to phylogenetic relatedness, life-history timing, and weather. Interspecific synchrony was highest among species whose larvae were present during the same time of the season, but there was no relationship between interspecific synchrony and phylogenetic affinity.
4. Spatial synchrony of weather variables was significantly related to both species of some interspecific pairs, indicating weather as a potential mechanism involved in synchronising populations of different species.     

Brevinin-2R1 semi-selectively kills cancer cells by a distinct mechanism, which involves the lysosomal-mitochondrial death pathway

Brevinin-2R is a novel non-hemolytic defensin that was isolated from the skin of the frog Rana ridibunda . It exhibits preferential cytotoxicity towards malignant cells, including Jurkat (T-cell leukemia), BJAB (B-cell lymphoma), HT29/219, SW742 (colon carcinomas), L929 (fibrosarcoma), MCF-7 (breast adenocarcinoma), A549 (lung carcinoma), as compared to primary cells including peripheral blood mononuclear cells (PBMC), T cells and human lung fibroblasts. Jurkat and MCF-7 cells overexpressing Bcl2, and L929 and MCF-7 over-expressing a dominant-negative mutant of a pro-apoptotic BNIP3 (ΔTM-BNIP3) were largely resistant towards Brevinin-2R treatment. The decrease in mitochondrial membrane potential (ΔΨm), or total cellular ATP levels, and increased reactive oxygen species (ROS) production, but not caspase activation or the release of apoptosis-inducing factor (AIF) or endonuclease G (Endo G), were early indicators of Brevinin-2R-triggered death. Brevinin-2R interacts with both early and late endosomes. Lysosomal membrane permeabilization inhibitors and inhibitors of cathepsin-B and cathepsin-L prevented Brevinin-2R-induced cell death. Autophagosomes have been detected upon Brevinin-2R treatment. Our results show that Brevinin-2R activates the lysosomalmitochondrial death pathway, and involves autophagy-like cell death.