Morphology and Hemodynamics during Vascular Regeneration in Critically Ischemic Murine Skin Studied by Intravital Microscopy Techniques

With the understanding of angiogenesis and arteriogenesis, new theories about the orchestration of these processes have emerged. The aim of this study was to develop an in vivo model that enables visualization of vascular regenerating mechanisms by intravital microscopy techniques in collateral arteriolar flap vascularity.

A phase IIa randomized controlled clinical and histological pilot study evaluating rhGDF-5/?-TCP for periodontal regeneration

The primary objective of this study was to clinically and histologically evaluate periodontal wound healing/regeneration following surgical implantation of recombinant human growth/differentiation factor-5 (rhGDF-5) adsorbed onto a particulate ?-tricalcium phosphate (?-TCP) carrier rhGDF-5/?-TCP into periodontal defects in man.

Life history, ecology and the biogeography of strong genetic breaks among 15 species of PaciWc rockWsh, Sebastes

Strong genetic change over short spatial scales is surprising among marine species with high dispersal potential. Concordant breaks among several species signals a role for geographic barriers to dispersal. Along the coast of California, such breaks have not been seen across the biogeographic barrier of Point Conception, but other potential geographic boundaries have been surveyed less often.;We tested for strong-population structure in 11 species of Sebastes sampled across two regions containing potential dispersal barriers, and conducted a meta-analysis including four additional species. We show two strong breaks north of Monterey Bay, spanning an oceanographic gradient and an upwelling jet. Moderate genetic structure is just as common in the north as it is in the south, across the biogeographic break at Point Conception. Gene Xow is generally higher among deep-water species, but these conclusions are confounded by phylogeny. Species in the subgenus Sebastosomus have higher structure than those in the subgenus;Pteropodus, despite having larvae with longer pelagic phases. DiVerences in settlement behavior in the face of ocean currents might help explain these diVerences. Across similar species across the same coastal environment, we document a wide variety of patterns in gene Xow, suggesting that interaction of individual species traits such as settlement behavior with environmental factors such as;oceanography can strongly impact population structure

Recruitment dynamics of the grove-dominant tree Microberlinia bisulcata in African rain forest: extending the light response versus adult longevity trade-off concept

In groves of ectomycorrhizal caesalpiniaceous species in the Atlantic coastal forest of Central Africa the dominant tree Microberlinia bisulcata, which is shade-intolerant as a seedling but highly light-responding as a sapling, shows very limited regeneration. M. bisulcata saplings were mapped in an 82.5-ha plot at Korup and found to be located significantly far (>40 m) away from adults, a result confirmed by direct testing in a second 56-ha plot. Sapling growth over 6 years, the distribution of newly emerging seedlings around adults, recruitment of saplings in a large opening and the outward extent of seedlings at the grove edge were also investigated. Two processes appear to have been operating: (1) a very strong and consistent restriction of the very numerous seedlings establishing after masting close to adults, and (2) a strong but highly spatially variable promotion of distant survivors by increased light from the deaths of large trees of species other than M. bisulcata (which itself has very low mortality rate). This leads to an apparent escape-from-adults effect. To maintain saplings in the shade between multiple short periods of release ectomycorrhizal connections to other co-occurring caesalp species may enable a rachet-type mechanism. The recorded sapling dynamics currently contribute an essential part of the long-term cycling of the groves. M. bisulcata is an interesting example of an important group of tropical trees, particularly in Africa, which are both highly light-demanding when young yet capable also of forming very large forest emergents. To more comprehensively explain tropical tree responses, the case is made for adding a new dimension to the trade-off concept of early tree light-response versus adult longevity.

Do fungal pathogens drive density-dependent mortality in established seedlings of two dominant African rain forest trees?

Where one or a few tree species reach local high abundance, different ecological factors may variously facilitate or hinder their regeneration. Plant pathogens are thought to be one of those possible agents which drive intraspecific density-dependent mortality of tree seedlings in tropical forests. Experimental evidence for this is scarce, however. In an African rain forest at Korup, we manipulated the density of recently established seedlings (~5–8 wk old; low vs. high-density) of two dominant species of contrasting recruitment potential, and altered their exposure to pathogens using a broad-spectrum fungicide. Seedling mortality of the abundantly recruiting subcanopy tree Oubanguia alata was strongly density-dependent after 7 mo, yet fungicide-treated seedlings had slightly higher mortality than controls. By contrast, seedling mortality of the poorly recruiting large canopy-emergent tree Microberlinia bisulcata was unaffected by density or fungicide. Ectomycorrhizal colonization of M. bisulcata was not affected by density or fungicide either. For O. alata, adverse effects of fungicide on its vesicular arbuscular mycorrhizas may have offset any possible benefit of pathogen removal. We tentatively conclude that fungal pathogens are not a likely major cause of density dependence in O. alata, or of early post-establishment mortality in M. bisulcata. They do not explain the latter's currently very low recruitment rate at Korup.

Telomeres: Linking stress and survival, ecology and evolution.

Telomeres are protective structures at the ends of eukaryotic chromosomes. The loss of telomeres through cell division and oxidative stress is related to cellular aging, organismal growth and disease. In this way, telomeres link molecular and cellular mechanisms with organismal processes, and may explain variation in a number of important life-history traits. Here, we discuss how telomere biology relates to the study of physiological ecology and life history evolution. We emphasize current knowledge on how telomeres may relate to growth, survival and lifespan in natural populations. We finish by examining interesting new connections between telomeres and the glucocorticoid stress response. Glucocorticoids are often employed as indices of physiological condition, and there is evidence that the glucocorticoid stress response is adaptive. We suggest that one way that glucocorticoids impact organismal survival is through elevated oxidative stress and telomere loss. Future work needs to establish and explore the link between the glucocorticoid stress response and telomere shortening in natural populations. If a link is found, it provides an explanatory mechanism by which environmental perturbation impacts life history trajectories.

Effect of sorafenib on murine liver regeneration

Hepatocellular carcinoma (HCC) is a common cause of cancer-related death. Sorafenib prolongs survival of patients with advanced disease and is approved for the systemic treatment of unresectable HCC. It possesses antiangiogenic and antiproliferative properties by way of inhibition of the receptor tyrosine kinases vascular endothelial growth factor receptor 2 (VEGFR-2) and platelet-derived growth factor receptor-beta 1/2 (PDGFR-β) and the kinase RAF. Sorafenib represents a candidate compound for adjuvant therapy in HCC patients. The aim of our study was to investigate whether sorafenib affects liver regeneration. C57BL6 mice received sorafenib orally at 30 mg/kg/day or its vehicle either for 14 days until the day before hepatectomy or starting the day after surgery or both. Animals were sacrificed 24, 72, and 120 hours after hepatectomy. Liver regeneration was calculated as a percent of initial liver weight. Bromodeoxyuridine (BrdU) incorporation and phospho-extracellular signal-regulated kinase (pERK1/2) were determined by immunohistochemistry on liver sections. VEGF-A, PDGF-BB, and hepatocyte growth factor (HGF) levels were measured in liver tissue homogenates. Histological analysis of scar tissue was performed. Treatment stopped 1 day before surgery had no impact on liver regeneration. Continuous sorafenib treatment and treatment started 1 day after surgery had statistically significant effects on liver regeneration at 120 hours compared to vehicle-treated control animals (72% ± 12 versus control 88% ± 15 and 70% ± 13 versus control 86% ± 5 at 120 hours, both P ≤ 0.02). BrdU incorporation showed decreased numbers of positive nuclei in both groups receiving sorafenib after surgery. Phospho-ERK levels were reduced in sorafenib-treated animals. An increase of VEGF-A levels was observed in mice receiving sorafenib. Wound-healing complications were observed in animals receiving sorafenib after surgery and confirmed on histological sections. CONCLUSION: This preclinical study shows that sorafenib did not impact on liver regeneration when ceased before surgery; however, administration after hepatectomy affected late liver regeneration.

Paracrine effects of mesenchymal stem cells enhance vascular regeneration in ischemic murine skin

New theories on the regeneration of ischemic vasculature have emerged indicating a pivotal role of adult stem cells. The aim of this study was to investigate homing and hemodynamic effects of circulating bone marrow-derived mesenchymal stem cells (MSCs) in a critically ischemic murine skin flap model. Bone marrow-derived mesenchymal stem cells (Lin(-)CD105(+)) were harvested from GFP(+)-donor mice and transferred to wildtype C57BL/6 mice. Animals receiving GFP(+)-fibroblasts served as a control group. Laser scanning confocal microscopy and intravital fluorescence microscopy were used for morphological analysis, monitoring and quantitative assessment of the stem cell homing and microhemodynamics over two weeks. Immunohistochemical staining was performed for GFP, eNOS, iNOS, VEGF. Tissue viability was analyzed by TUNEL-assay. We were able to visualize perivascular homing of MSCs in vivo. After 4 days, MSCs aligned along the vascular wall without undergoing endothelial or smooth muscle cell differentiation during the observation period. The gradual increase in arterial vascular resistance observed in the control group was abolished after MSC administration (P<0.01). At capillary level, a strong angiogenic response was found from day 7 onwards. Functional capillary density was raised in the MSC group to 197% compared to 132% in the control group (P<0.01). Paracrine expression of VEGF and iNOS, but not eNOS could be shown in the MSC group but not in the controls. In conclusion, we demonstrated that circulating bone marrow-derived MSCs home to perivascular sites in critically ischemic tissue, exhibits paracrine function and augment microhemodynamics. These effects were mediated through arteriogenesis and angiogenesis, which contributed to vascular regeneration.