Pliocene-Pleistocene distribution of benthic foraminifers from ODP Hole 110-672A (Table 2)

Site 672 is located on the Atlantic abyssal plain to the east of the Lesser Antilles forearc region. It serves as a stratigraphic reference section for sediments entering the Barbados accretionary prism. A relatively complete Pliocene through lower Pleistocene section was recovered from Site 672 that contains a moderately well-preserved population of benthic foraminifers. Q-mode factor analysis of the benthic population data identified three Pliocene-Pleistocene assemblages that inhabited this site. The Factor 1 fauna, characterized by Nuttallides umboniferus, is commonly associated with the presence of Antarctic Bottom Water (AABW). The Factor 2 assemblage is characterized by Globocassidulina subglobosa, Epistominella exigua, and a combined category of unilocular species. The Factor 3 assemblage is characterized by Epistominella exigua, and Planulina wuellerstorfi. The Factor 2 and 3 faunas are associated with bottom water significantly warmer than that preferred by the Factor 1 assemblage. The distribution of these assemblages has been used to distinguish three climatic intervals in the abyssal environment during the Pliocene-Pleistocene. An early Pliocene warm interval occurred from the Ceratolithus rugosus Subzone to the middle of the Discoaster tamalis Subzone. The upper Pliocene is characterized by oscillations between the Factor 1 and Factor 2 assemblages, which suggests climatic deterioration and increased pulses of AABW flow. The persistence of an essentially modern (Factor 1) fauna throughout the early Pleistocene suggests full glacial development at both poles and a substantial volume of AABW production.

Attenuation of depression of muscle protein synthesis induced by lipopolysaccharide, tumor necrosis factor, and angiotensin II by beta-hydroxy-beta-methylbutyrate

beta-Hydroxy-beta-methylbutyrate (HMB; 50 microM) has been shown to attenuate the depression in protein synthesis in murine myotubes in response to lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) with or without interferon-gamma (IFN-gamma), and angiotensin II (ANG II). The mechanism for the depression of protein synthesis by all three agents was the same and was attributed to activation of double-stranded RNA-dependent protein kinase (PKR) with the subsequent phosphorylation of eukaryotic initiation factor 2 (eIF2) on the alpha-subunit as well as increased phosphorylation of the elongation factor (eEF2). Myotubes expressing a catalytically inactive PKR variant, PKRDelta6, showed no depression of protein synthesis in response to either LPS or TNF-alpha, confirming the importance of PKR in this process. There was no effect of any of the agents on phosphorylation of mammalian target of rapamycin (mTOR) or initiation factor 4E-binding protein (4E-BP1), and thus no change in the amount of eIF4E bound to 4E-BP1 or the concentration of the active eIF4E.eIF4G complex. HMB attenuated phosphorylation of eEF2, possibly by increasing phosphorylation of mTOR, and also attenuated phosphorylation of eIF2alpha by preventing activation of PKR. These results suggest that HMB may be effective in attenuating muscle atrophy in a range of catabolic conditions.

Attenuation of skeletal muscle atrophy in cancer cachexia by d-myo-inositol 1,2,6-triphosphate

PURPOSE: To determine the effectiveness of the polyanionic, metal binding agent D-myo-inositol-1,2,6-triphosphate (alpha trinositol, AT), and its hexanoyl ester (HAT), in tissue wasting in cancer cachexia. METHODS: The anti-cachexic effect was evaluated in the MAC16 tumour model. RESULTS: Both AT and HAT attenuated the loss of body weight through an increase in the nonfat carcass mass due to an increase in protein synthesis and a decrease in protein degradation in skeletal muscle. The decrease in protein degradation was associated with a decrease in activity of the ubiquitin-proteasome proteolytic pathway and caspase-3 and -8. Protein synthesis was increased due to attenuation of the elevated autophosphorylation of double-stranded RNA-dependent protein kinase, and of eukaryotic initiation factor 2alpha together with hyperphosphorylation of eIF4E-binding protein 1 and decreased phosphorylation of eukaryotic elongation factor 2. In vitro, AT completely attenuated the protein degradation in murine myotubes induced by both proteolysis-inducing factor and angiotensin II. CONCLUSION: These results show that AT is a novel therapeutic agent with the potential to alleviate muscle wasting in cancer patients.