Analysis by Live Imaging of Effects of the Adenovirus E4orf4 Protein on Passage through Mitosis of H1299 Tumor Cells

The adenovirus E4orf4 protein expressed at high levels kills cancer cells but not normal human primary cells. Previous studies suggested that disruption of processes that regulate mitosis may underlie E4orf4 toxicity. Here we have used live imaging to show that E4orf4 induces a slowed defective transit through mitosis, exhibiting a delay or often failure in cytokinesis that may account for an accumulation of G₁ tetraploids in the population of dying E4orf4-expressing cells.     

Polysubstituted Isochroman Derivatives with Plant Growth Regulating Properties on Wheat (Triticum aestivum L. cv Klein Escorpion)

The synthesis of isochroman derivatives 4–9 from α-hydroxylactone 3 is reported. These heterocycles, carrying different substituents on C-3, C-4, and C-8, exhibited different degrees of inhibition of the vegetative growth of wheat (Triticum aestivum cv Klein Escorpion) plants, whereas plant developmental patterns such as their protein profile, carotenes/chlorophylls ratio, and weight/length relationship were not significantly affected. Microscopic observation of transverse sections of shoots and roots showed morphological changes in the treated plants, consistent with delayed development. The results suggest that among these isochromans the C-3 carbonyl moiety of the lactone and the C-4 free hydroxyl group are important but not essential for activity, and that a short side chain appended to C-3 is tolerated. However, cleavage of the C-8 methyl ether group to the related free phenol causes a drastic reduction in the growth inhibitory activity.     

Discovery of novel intracellular receptor modulating drugs

Utilizing the co-transfection assay as a guide to determining structure activity relationships, we have been pursuing the discovery of non-steroidal hPR modulators. Small molecule, non-steroidal lead structures have been identified. Optimization of these structures has yielded more potent hPR modulators. Improved cross-reactivity profiles with other intracellular receptors are a feature of these compounds owing to their non-steroidal nature.     

Berberine reverts hepatic mitochondrial dysfunction in high-fat fed rats: A possible role for SirT3 activation

Berberine is an isoquinoline alkaloid with anti-diabetic properties. Despite the central role of liver and thus hepatic mitochondria in whole-body metabolism, berberine effects on hepatic mitochondrial function in an obesity model are still unknown. Here, we demonstrate that berberine treatment recovers mitochondrial efficiency when altered by a high-fat feeding. Mitochondria isolated from the liver of high-fat fed rats exhibited decreased capacity to accumulate calcium and impaired oxidative phosphorylation (OXPHOS) capacity, as shown by impaired mitochondrial membrane potential, oxygen consumption and cellular ATP levels. Interestingly, the recovery of mitochondrial function by berberine was associated with an increased activity of the mitochondrial sirtuin 3 (SirT3). In conclusion, berberine potent protective effects against metabolic syndrome may rely on increasing mitochondrial SirT3 activity, normalizing mitochondrial function and preventing a state of energetic deficit caused by impaired OXPHOS.     

Human and non-human determinants of forest composition in southern Spain: evidence of shifts towards cork oak dominance as a result of management over the past century

Aims Both human and non‐human determinants have shaped Mediterranean forest structure over the last few millennia. The effects of recent human activities on forest composition, however, remain poorly understood. We quantified changes in forest composition during the past century in the mixed forests of Quercus suber (cork oak) and Q. canariensis (Algerian oak), and explored the effects of forest management and environmental (climate, topography) factors on forest structure at various spatial and temporal scales. Location Mountains north of the Strait of Gibraltar (southern Spain). Methods First, we quantified 20th‐century changes in species composition from a series of inventories in nine mixed forests (c. 40,000 ha), and examined them in terms of the management practices and environmental conditions. Second, we analysed present‐day Q. suber and Q. canariensis stand structure along environmental gradients at two spatial scales: (1) that of the forest landscape (c. 284 ha), combining local inventories and topographic variables and using a digital elevation model; and (2) regional (c. 87,600 km²), combining data from the Spanish Forest Inventory for the Andalusia region and estimates of climatic variables. Results Historical data indicate anthropogenic changes in stand composition, revealing a sharp increase in the density of cork oaks over the last century. Forest management has favoured this species (for cork production) at the expense of Q. canariensis. The impact of management is imprinted on the present‐day forest structure. The abundance of both species increases with annual mean precipitation, and they coexist above 800 mm (the minimum threshold for Q. canariensis). Quercus suber dominates in most of the stands, and species segregation in the landscape is associated with the drainage network, Q. canariensis being clearly associated with moister habitats near streams. Main conclusions Our study quantitatively exemplifies a recent human‐mediated shift in forest composition. As a result of forest management, the realized niche of the cork oak has been enlarged at the expense of that of Q. canariensis, providing further evidence for humans as major drivers of oak forest composition across the Mediterranean. Recent regeneration problems detected in Q. suber stands, a reduced demand for wood products, conservation policies, and climate change augur new large‐scale shifts in forest composition.     

Geobotany in a fault in the world’s largest continuous wetland in central South America

Wetlands Ecology and Management - The Pantanal is located in the center of South America in a tectonically active sedimentary basin of Quaternary age. Even though the relief is flat and the...