Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating peptide (PACAP) receptor specific peptide analogues for PET imaging of breast cancer: In vitro/in vivo evaluation

Vasoactive intestinal peptide and pituitary adenylate cyclase activating peptide have high affinity for VPAC1, VPAC2 and PAC1 receptors overexpressed on human cancer cells. Four potent analogues of these peptides, TP3939, TP3982, TP4200 and TP3805 were labeled with (64)Cu and evaluated ex vivo and in vivo to asses their biological activity and receptor specificity. The ultimate goal is to utilize (64)Cu analogues for positron emission tomography (PET) imaging of breast cancers in humans. Radiochemical purity of each analogue was >92%. The muscle relaxivity assay revealed IC(50) to be 5.3x10(-8) M, 4.4x10(-8) M, 8.1x10(-8) M, 8.1x10(-9) M and Kd values determined by receptor specific cell binding assays were 3.3 nM, 0.33 nM, 0.2 nM and 0.72 nM for TP3805, TP3939, TP3982, and TP4200 respectively. The receptor affinity, using human breast cancer tissues, was 10.93 times greater than normal breast tissues. RT-PCR confirmed increased VPAC1 receptor expression on human breast tumor cells over normal cells and corroborated with autoradiography data. The blood clearance was rapid and in vivo translocation of (64)Cu to plasma protein was <15%. Data demonstrate that these analogues are potent, have uncompromised biological activity and are worthy of further evaluation for accurate PET imaging of human breast cancers and in determining malignant and benign lesions.     

Unraveling the epigenetic code of cancer for therapy

Alterations in the genome and the epigenome are common in most cancers. Changes in epigenetic signatures, including aberrant DNA methylation and histone deacetylation, are among the most prevalent modifications in cancer and lead to dramatic changes in gene expression patterns. Because DNA methylation and histone deacetylation are reversible processes, they have become attractive as targets for cancer epigenetic therapy, both as single agents and as 'enhancing' agents for other treatment strategies. In this review we discuss our current view of the mammalian epigenome, this view has changed over the years because of the availability of novel technologies. We further demonstrate how the profound understanding of epigenetic alterations in cancer will help develop novel strategies for epigenetic therapies.     

Changes in the spatial variation of soil properties following shifting cultivation in a Mexican tropical dry forest

The role of secondary vegetation in restoring soil fertility during shifting cultivation in the tropics is well known. Yet the effect of secondary succession on the spatial patterns of soil properties has received little attention. To determine whether changes in the plant community as a result of shifting cultivation affect the scale of spatial dependence for biologically important soil nutrients, we sampled three dry tropical forest stands in Campeche, Mexico. These stands represented a gradient of cultivation history: one mature forest stand, a forest fallow that had undergone one cultivation-fallow cycle, and a forest fallow that had undergone two cultivation-fallow cycles. We used an analysis of semivariance to quantify the scale and magnitude of spatial dependence for organic matter content (OM), phosphorus (P), potassium (K), and aluminum (Al) in each stand. The scale of spatial dependence varied with cultivation history, but the degree of spatial dependence did not differ among stands. In the mature forest P and K were autocorrelated over distances >7.5 m. In the forest fallows 48–88% of the variation in soil P and K was autocorrelated over distances up to 1.1–5.1 m. In contrast, the range of autocorrelation for Al (∼2.5 m) did not differ among stands. We conclude that shifting cultivation changes the range of autocorrelation for biologically important soil nutrients at a scale that may influence plant growth. The finer scaled pattern of soil nutrients in forest fallows is likely to persist with continued shifting cultivation, since fallows are cleared every 3–15 years.     

Regional ecosystem structure and function: ecological insights from remote sensing of tropical forests

Ecological studies in tropical forests have long been plagued by difficulties associated with sampling the crowns of large canopy trees and large inaccessible regions, such as the Amazon basin. Recent advances in remote sensing have overcome some of these obstacles, enabling progress towards tackling difficult ecological problems. Breakthroughs have helped transform the dialog between ecology and remote sensing, generating new regional perspectives on key environmental gradients and species assemblages with ecologically relevant measures such as canopy nutrient and moisture content, crown area, leaf-level drought responses, woody tissue and surface litter abundance, phenological patterns, and land-cover transitions. Issues that we address here include forest response to altered precipitation regimes, regional disturbance and land-use patterns, invasive species and landscape carbon balance.     

Water deficits accelerate ripening and induce changes in gene expression regulating flavonoid biosynthesis in grape berries

Water deficits consistently promote higher concentrations of anthocyanins in red winegrapes and their wines. However, controversy remains as to whether there is any direct effect on berry metabolism other than inhibition of growth. Early (ED) and late (LD) season water deficits, applied before or after the onset of ripening (veraison), were imposed on field grown Vitis vinifera “Cabernet Sauvignon”, and the responses of gene expression in the flavonoid pathway and their corresponding metabolites were determined. ED accelerated sugar accumulation and the onset of anthocyanin synthesis. Both ED and LD increased anthocyanin accumulation after veraison. Expression profiling revealed that the increased anthocyanin accumulation resulted from earlier and greater expression of the genes controlling flux through the anthocyanin biosynthetic pathway, including F3H, DFR, UFGT and GST. Increases in total anthocyanins resulted predominantly from an increase of 3′4′5′-hydroxylated forms through the differential regulation of F3′H and F3′5′H. There were limited effects on proanthocyanidin, other flavonols, and on expression of genes committed to their synthesis. These results demonstrate that manipulation of abiotic stress through applied water deficits not only modulates compositional changes during berry ripening, but also alters the timing of particular aspects of the ripening process.     

Lip reconstruction

Lip reconstruction remains challenging. Accurate analysis of the defect and a thorough understanding of the anatomy and options for reconstruction will maintain the functional and aesthetic quality of this sensitive area.     

Metabolic stress suppresses humoral immune function in long-day,but not short-day,Siberian hamsters (<Emphasis Type="Italic">Phodopus sungorus</Emphasis>)

Individuals of many species experience marked seasonal variation in environmental conditions and must adapt to potentially large fluctuations in energy availability and expenditure. Seasonal changes in immunity have likely evolved as an adaptive mechanism to cope with seasonal stressors. In addition, these changes may be constrained by seasonal fluctuations in energy availability. The goal of this study was to assess the role of energetic trade-offs associated with seasonal variation in immunity. In addition to body fat stores, metabolic fuels (e.g., glucose) may affect immune function in seasonally breeding rodents. In this study we experimentally reduced energy availability via injections of the metabolic inhibitor 2-deoxy-d-glucose (2-DG) in long- and short-day housed Siberian hamsters (Phodopus sungorus) and then examined antigen-specific antibody production. Metabolic stress decreased antibody response compared with control animals in long days. In contrast, no difference was observed between treatment groups in short days. These data suggest that reductions in energy availability suppress immunity and short days buffer organisms against glucoprivation-induced immunosuppression.