Molecular architecture of the ribosome‐bound Hepatitis C Virus internal ribosomal entry site RNA

Internal ribosomal entry sites (IRESs) are structured cis‐acting RNAs that drive an alternative, cap‐independent translation initiation pathway. They are used by many viruses to hijack the translational machinery of the host cell. IRESs facilitate translation initiation by recruiting and actively manipulating the eukaryotic ribosome using only a subset of canonical initiation factor and IRES transacting factors. Here we present cryo‐EM reconstructions of the ribosome 80S‐ and 40S‐bound Hepatitis C Virus (HCV) IRES. The presence of four subpopulations for the 80S•HCV IRES complex reveals dynamic conformational modes of the complex. At a global resolution of 3.9 Å for the most stable complex, a derived atomic model reveals a complex fold of the IRES RNA and molecular details of its interaction with the ribosome. The comparison of obtained structures explains how a modular architecture facilitates mRNA loading and tRNA binding to the P‐site. This information provides the structural foundation for understanding the mechanism of HCV IRES RNA‐driven translation initiation.     

Hormone-regulated expression and distribution of versican in mouse uterine tissues

Background  

Remodeling of the extracellular matrix is one of the most striking features observed in the uterus during the estrous cycle and after hormone replacement. Versican (VER) is a hyaluronan-binding proteoglycan that undergoes RNA alternative splicing, generating four distinct isoforms. This study analyzed the synthesis and distribution of VER in mouse uterine tissues during the estrous cycle, in ovariectomized (OVX) animals and after 17beta-estradiol (E2) and medroxyprogesterone (MPA) treatments, either alone or in combination.     

Defining winter trophic habitat of juvenile Gulf Sturgeon in the Suwannee and Apalachicola rivermouth estuaries, acoustic telemetry investigations

Three automated listening post‐telemetry studies were undertaken in the Suwannee and Apalachicola estuaries to gain knowledge of habitats use by juvenile Gulf Sturgeons (Acipenser oxyrinchus desotoi) on winter feeding grounds. A simple and reliable method for external attachment of small acoustic tags to the dorsal fin base was developed using shrink‐tubing. Suspending receivers on masts below anchored buoys improved reception and facilitated downloading; a detection range of 500–2500 m was realized. In the Apalachicola estuary, juvenile GS stayed in shallow water (< 2 m) within the estuarine transition zone all winter in the vicinity of the Apalachicola River mouth. Juvenile GS high‐use areas did not coincide with high density benthic macrofauna areas from the most recent (1999) benthos survey. In the Suwannee estuary, juveniles ranged widely and individually throughout oligohaline to mesohaline subareas of the estuary, preferentially using mesohaline subareas seaward of Suwannee Reef (52% of acoustic detections). The river mouth subarea was important only in early and late winter, during the times of adult Gulf Sturgeon migrations (41% of detections). Preferred winter feeding subareas coincided spatially with known areas of dense macrofaunal benthos concentrations. Following a dramatic drop in air and water temperatures, juvenile GS left the river mouth and estuary, subsequently being detected 8 km offshore in polyhaline open Gulf of Mexico waters, before returning to the estuary. Cold‐event offshore excursions demonstrate that they can tolerate full‐salinity polyhaline waters in the open Gulf of Mexico, for at least several days at a time. For juvenile sturgeons, the stress and metabolic cost of enduring high salinity ( Jarvis et al., 2001 ; McKenzie et al., 2001 ; Singer and Ballantyne, 2002 ) for short periods in deep offshore waters seems adaptively advantageous relative to the risk of cold‐event mortality in shallow inshore waters of lower salinity. Thus, while juveniles can tolerate high salinities for days to weeks to escape cold events, they appear to make only infrequent use of open polyhaline waters. Throughout the winter foraging period, juvenile GS stayed primarily within the core area of Suwannee River mouth influence, extending about 12 km north and south of the river mouth, and somewhat seaward of Suwannee Reef (< 5 km offshore). None were detected departing the core area past either of the northern or southern acoustic gates, located 66 and 52 km distant from the river mouth, respectively.     

Patterns of Fish Use and Piscivore Abundance within a Reconnected Saltmarsh Impoundment in the Northern Indian River Lagoon, Florida

Nearly all saltmarshes in east-central, Florida were impounded for mosquito control during the 1960s. The majority of these marshes have since been reconnected to the estuary by culverts, providing an opportunity to effectively measure exchange of aquatic organisms. A multi-gear approach was used monthly to simultaneously estimate fish standing stock (cast net), fish exchange with the estuary (culvert traps), and piscivore abundance (gill nets and bird counts) to document patterns of fish use in a reconnected saltmarsh impoundment. Changes in saltmarsh fish abundance, and exchange of fish with the estuary reflected the seasonal pattern of marsh flooding in the northern Indian River Lagoon system. During a 6-month period of marsh flooding, resident fish had continuous access to the marsh surface. Large piscivorous fish regularly entered the impoundment via creeks and ditches to prey upon small resident fish, and piscivorous birds aggregated following major fish movements to the marsh surface or to deep habitats. As water levels receded in winter, saltmarsh fish concentrated into deep habitats and emigration to the estuary ensued (200% greater biomass left the impoundment than entered). Fish abundance and community structure along the estuary shoreline (although fringed with marsh vegetation) were not analogous to marsh creeks and ditches. Perimeter ditches provided deep-water habitat for large estuarine predators, and shallow creeks served as an alternative habitat for resident fish when the marsh surface was dry. Use of the impoundment as nursery by transients was limited to Mugil cephalus Linnaeus, but large juvenile and adult piscivorous fish used the impoundment for feeding. In conclusion, the saltmarsh impoundment was a feeding site for piscivorous fish and birds, and functioned as a net exporter of forage fish to adjacent estuarine waters.     

Treatment with apolipoprotein A-1 mimetic peptide reduces lupus-like manifestations in a murine lupus model of accelerated atherosclerosis

Introduction

The purpose of this study was to evaluate the effects of L-4F, an apolipoprotein A-1 mimetic peptide, alone or with pravastatin, in apoE^-/-Fas^-/-C57BL/6 mice that spontaneously develop immunoglobulin G (IgG) autoantibodies, glomerulonephritis, osteopenia, and atherosclerotic lesions on a normal chow diet.

Methods

Female mice, starting at eight to nine weeks of age, were treated for 27 weeks with 1) pravastatin, 2) L-4F, 3) L-4F plus pravastatin, or 4) vehicle control, followed by disease phenotype assessment.

Results

In preliminary studies, dysfunctional, proinflammatory high-density lipoproteins (piHDL) were decreased six hours after a single L-4F, but not scrambled L-4F, injection in eight- to nine-week old mice. After 35 weeks, L-4F-treated mice, in the absence/presence of pravastatin, had significantly smaller lymph nodes and glomerular tufts (P_{L, LP} < 0.05), lower serum levels of IgG antibodies to double stranded DNA (dsDNA) (P_L < 0.05) and oxidized phospholipids (oxPLs) (P_{L, LP} < 0.005), and elevated total and vertebral bone mineral density (P_{L, LP} < 0.01) compared to vehicle controls. Although all treatment groups presented larger aortic root lesions compared to vehicle controls, enlarged atheromas in combination treatment mice had significantly less infiltrated CD68⁺ macrophages (P_LP < 0.01), significantly increased mean α-actin stained area (P_LP < 0.05), and significantly lower levels of circulating markers for atherosclerosis progression, CCL19 (P_{L, LP} < 0.0005) and VCAM-1 (P_L < 0.0002).

Conclusions

L-4F treatment, alone or with pravastatin, significantly reduced IgG anti-dsDNA and IgG anti-oxPLs, proteinuria, glomerulonephritis, and osteopenia in a murine lupus model of accelerated atherosclerosis. Despite enlarged aortic lesions, increased smooth muscle content, decreased macrophage infiltration, and decreased pro-atherogenic chemokines in L-4F plus pravastatin treated mice suggest protective mechanisms not only on lupus-like disease, but also on potential plaque remodeling in a murine model of systemic lupus erythematosus (SLE) and accelerated atherosclerosis.     

Morphology of umbilical vessels in human fetuses: a quantitative light microscope study

OBJECTIVE: To investigate the development of the intra-abdominal part of the umbilical vessels in human fetuses by light microscopy. MATERIALS AND METHODS: The location of the umbilicus and umbilical vessels in the abdominal cavity of 90 human fetuses of gestational ages 10-40 weeks was determined. The external vessel diameter, lumen diameter, wall thickness, tunica adventitia thickness, tunica media thickness and the number of vasa vasorum were recorded from cross-sectlons of the intra-abdominal part of the umbilical vessels. 1985). 1985). RESULTS: Umbilical artery agenesis was observed on the left side in two cases and on the right in one case. There was a positive correlation between gestational age and umbilical vessel measurements. There were differences between the vessel and lumen diameters, tunica media thicknesses of the vessels of the second and third trimesters, and the full-term period. There were also predictable differences between the vessel and lumen diameters, tunica media and tunica adventitia thicknesses of the umbilical vein and umbilical arteries. CONCLUSION: Detailed information on quantitative parameters of umbilical vessels at each gestational age may prove helpful in determining pathologies of umbilical vessels and illuminating certain syndromes.