Structure-activity relationships of cryptopleurine analogs with E-ring modifications as anti-hepatitis C virus agents

The tylophorine analog rac-cryptopleurine exhibited potent anti-hepatitis C virus (HCV) activity through allosteric regulation of ATPase activity of heat shock cognate protein 70 (Hsc70). We evaluated the impact of modifications on the E-ring of rac-cryptopleurine to the inhibitory activity against HCV replication and regulation of ATPase activity of Hsc70. Cryptopleurine analog YXM-110 with a 13α-hydroxyl group maintained activity against HCV and promoted ATP/ADP turnover of Hsc70; however, compounds with hydroxyl groups at other positions or with other orientations (YXM-109, YXM-139, and YXM-140) did not exhibit similar activities. Size modification or heteroatom incorporation of the E-ring led to loss of anti-HCV activity. Promotion of the chaperone activity of Hsc70 with carboxyl terminus Hsc70 interacting protein (CHIP) further enhanced the anti-HCV activity of rac-cryptopleurine and XYM-110. This structure-activity relationship (SAR) study refined structural design and optimization for developing rac-crytopleurine analogs as potent anti-HCV agents targeted against the host factor involved in HCV replication.     

Effects of Sarcoptic Mange on Coyotes at Wind Cave National Park

Abstract: Home-range size and population abundance indices of coyotes (Canis latrans) have not been documented in Wind Cave National Park, South Dakota, USA. In 2003 and 2004, we captured a total of 26 coyotes and radiocollared 22 adults (12 F, 10 M). In 2003 and 2004, 2 of 17 (12%) and 5 of 9 (56%) coyotes, respectively, were infected with sarcoptic mange (Sarcoptes scabiei) at the time of capture. Thus, objectives were modified to document effects of the mange epizootic on the coyote population. In 2003, home-range (adaptive-kernel) sizes for male coyotes with mange and those considered healthy were 8.26 ± 1.63 (SE) km² and 9.67 ± 2.80 km², respectively. In 2004, home-range sizes for those male coyotes with and without mange were 22.69 ± 9.06 km² and 12.51 ± 2.73 km², respectively. Male home-range size did not differ between years (P = 0.14) or by status (with or without mange; P = 0.84). Survival of collared coyotes was 60% at the end of 2003. Results from fecal line transects, an index of relative abundance, indicated that the coyote population decreased by 48% from 2003 to 2004. Continued monitoring of sarcoptic mange epizootics will enable managers to assess the effects of mange on coyote populations.     

Spatial mismatches between plant biodiversity facets and evolutionary legacy in the vicinity of a major Mediterranean city

The analyses of congruencies among biodiversity components address the issue of conservation priorities, but previously they have been done at coarse scales with limited relevance for conservation actions. Moreover, these former studies consider only the species level components of biodiversity and not the intra-specific evolutionary legacy that influences future biodiversity. This study represents the first assessment of congruencies between various components of plant biodiversity and the evolutionary legacy of a narrow endemic taxon (Arenaria provincialis, Caryophyllaceae). Assessment is conducted in the vicinity of a Mediterranean big city (Marseille, S.E. France) where habitats and flora are threatened by mass tourism and urban sprawl. Our analyses reveal that the different plant biodiversity facets assessed are spatially mismatched and unequally protected. Moreover, by using only species-level components of biodiversity as conservation targets we ignore crucial areas for the evolutionary legacy of this narrow endemic plant. Our results highlight the crucial role of phylogeography as a criterion to target the genetic precursors of future biodiversity in conservation planning.     

The impact of science and technology on the civilization

The rapid increase of available scientific knowledge is largely due to the introduction of novel research strategies. The application of these strategies, both in fundamental and in translational scientific research, leads to bursts of technological innovations. In order to fulfill the justified public request for sustainability of technological innovations that contribute to the shaping of the future, increasing attention should be given to science-based technology and policy assessment. These requests are illustrated by benefit/risk evaluations of relevance for the use of genetic engineering as an efficient and effective research strategy. Expected benefits of a responsibly planned introduction of GM crops are outlined as a prospective example for the guiding theme “Biotechnology for sustainability of human society”.     

Factors in Pinus ponderosa and Calocedrus decurrens mortality in Yosemite Valley,USA

Management practices over the past 100 years, especially fire exclusion and suppression, in Yosemite Valley, Yosemite National Park, CA resulted in forest stands with basal areas in excess of 110 m² ha^-1. Accelerated attack by several species of bark beetles (Scolytidae) followed a severe drought in 1976–77. Pinus ponderosa, already under attack by root rot (Heterobasidion annosus) was affected severely, and mortality exceeded 70%. Calocedrus decurrens did not suffer comparable mortality and has replaced P. ponderosa as the dominant species. Size class distributions as well as comparisons of relative density and relative basal area from 1961, 1976 and 1983–85 also demonstrate a major change in forest composition. This change is most pronounced on alluvial landforms.     

Behavior of vanadate and vanadyl ion in canine blood

Radiolabeled vanadium as either vanadyl ion or vanadate ion was injected intravenously into adult beagle dogs, and blood samples were collected at various times up to 48 hr post injection. For each sample, the distribution of vanadium between the cells and the plasma was determined, and the plasma was analyzed by electrophoresis to identify specific vanadium-binding proteins. Initially, vanadyl ion left the bloodstream more rapidly than vanadate, but the rates equalized after about 5 hr. A significant fraction of the vanadium in blood was associated with the cellular component following injection of both forms of vanadium. About 77% of the plasma vanadium was eventually bound by the serum iron transport protein transferrin, regardless of the vanadium species initially injected. For both vanadyl and vanadate, about 30 hr were required to reach the maximum degree of transferrin binding.     

Environmental vulnerability assessment of eco-development zone of Great Himalayan National Park,Himachal Pradesh,India

The Great Himalayan National Park (GHNP), located in western Himalaya, is a key mountainous ecosystem prone to environmental vulnerability because of anthropogenic stress and the natural disasters, viz., landslide and forest fire. We assessed the environmental vulnerability of the eco-development zone of GHNP using remote sensing (RS) and geographic information system (GIS) technologies. To quantify the environmental vulnerability, a numerical model using spatial principal component analysis (SPCA) was developed. This model considered five factors: land use/land cover, forest canopy density, forest fire risk, landslide susceptibility and human population density. The environmental vulnerability integrated index (EVSI) calculated for the 1990, 2000 and 2010 periods was found to be 2.00, 2.72, and 3.40, respectively. The results showed temporal increase in the environmental vulnerability in the zone. Based on the numerical outputs, the vulnerability of the region was categorized into five classes: potential, slight, medium, high, and severe. The primary factor responsible for the increase in vulnerability overtime was land use/land cover change in the study area due to hydro-electric power projects, construction of roads, and other infrastructure developments. Forest fire and decreased forest canopy density are other major contributing factors responsible for the increase in the environmental vulnerability. Our results indicated that integration of RS, GIS and SPCA can effectively quantify and assess environmental vulnerability.     

Multiomic Analysis Reveals Disruption of Cholesterol Homeostasis by Cannabidiol in Human Cell Lines

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