Targeting the glycoprotein 130 receptor subunit to control pain and inflammation

The glycoprotein 130 (gp130) is a shared signal-transducing-membrane-associated receptor for several hematopoietic cytokines. Its activation is implicated in pain and in a variety of diseases via signaling of proinflammatory cytokines. These include interleukin-6 (IL-6) subfamily cytokines, many of which play important roles in the pathogenesis of diseases such as rheumatoid arthritis, Castleman's disease, and Kaposi's sarcoma. Several strategies have been developed to block gp130-receptor-mediated signaling. These include the application of monoclonal antibodies, the creation of mutant form(s) of the gp130 with increased binding affinity for such ligands as IL-6/sIL-6R complex, and the generation of antagonists by selective mutagenesis of the specific cytokine/gp130 receptor binding site(s). Other strategies include targeting gp130-mediated signaling pathways such as that involving signal transducer and activator of transcription-3. This review provides a summary of the latest research pertaining to the role of gp130 in the pathogenesis of inflammatory and other diseases in which the gp130 receptor is implicated. An overview of antagonists targeting the gp130 receptor is included with particular emphasis on their mechanism of action and their limitations and potential for therapeutic application.

Response of diatom assemblages to 130 years of environmental change in Florida Bay (USA)

Coastal ecosystems around the world are constantly changing in response to interacting shifts in climate and land and water use by expanding human populations. The development of agricultural and urban areas in South Florida significantly modified its hydrologic regime and influenced rates of environmental change in wetlands and adjacent estuaries. This study describes changes in diatom species composition through time from four sediment cores collected across Florida Bay, for the purposes of detecting periods of major shifts in assemblage structure and identifying major drivers of those changes. We examined the magnitude of diatom assemblage change in consecutive 2-cm samples of the 210Pb-dated cores, producing a record of the past ~130 years. Average assemblage dissimilarity among successive core samples was ~30%, while larger inter-sample and persistent differences suggest perturbations or directional shifts. The earliest significant compositional changes occurred in the late 1800s at Russell Bank, Bob Allen Bank and Ninemile Bank in the central and southwestern Bay, and in the early 1900s at Trout Cove in the northeast. These changes coincided with the initial westward redirection of water from Lake Okeechobee between 1881 and 1894, construction of several canals between 1910 and 1915, and building the Florida Overseas Railroad between 1906 and 1916. Later significant assemblage restructurings occurred in the northeastern and central Bay in the late 1950s, early 1960s and early 1970s, and in the southwestern Bay in the 1980s. These changes coincide with climate cycles driving increased hurricane frequency in the 1960s, followed by a prolonged dry period in the 1970s to late 1980s that exacerbated the effects of drainage operations in the Everglades interior. Changes in the diatom assemblage structure at Trout Cove and Ninemile Bank in the 1980s correspond to documented eutrophication and a large seagrass die-off. A gradual decrease in the abundance of freshwater to brackish water taxa in the cores over ~130 years implies that freshwater deliveries to Florida Bay were much greater prior to major developments on the mainland. Salinity, which was quantitatively reconstructed at these sites, had the greatest effect on diatom communities in Florida Bay, but other factors—often short-lived, natural and anthropogenic in nature—also played important roles in that process. Studying the changes in subfossil diatom communities over time revealed important environmental information that would have been undetected if reconstructing only one water quality variable.

Paleoceanographic and paleoclimatic evolution of the Aegean Sea since the last interglacial (~130 ka BP) with special emphasis on sapropel formation

Five long piston cores collected from different subbasins of the Aegean Sea constitute the primary source of data for this PhD thesis. This study is the first to document a continuous paleoceanographic and paleoclimatic record of the Aegean Sea since the last interglacial. The chronostratigraphic reconstructions of the cored sediments based on organic carbon contents, stratigraphic position of known ash layers and oxygen isotopic curve matching collectively demonstrate the presence of sapropel S1 and MISS sapropels S3, S4 and S5 in the Aegean Sea subbasins. Generally, the organic carbon (TOC wt%) contents in sapropels range between 0.8% and 2% with highest concentrations of 9-13% in sapropels S4 and S5. Average sedimentation rates range between 4.7 and 11.8 cmlka with highest rates being observed in Euboea and North Ikaria basins (9.8 and 11.8 cm lka, respectively). The timing of the onset of sapropels S4 and S5 mostly predate those in the eastern Mediterranean with ages ranging from 106.4-105.6 and 128.6-128.4 ka BP, respectively. On the other hand, the initiation of the onset of sapropel S3 (i.e., 83.2-80.4 ka BP) seems to agree with its Mediterranean counterparts, which highlights the heterogeneity of the Aegean Sea subbasins in terms of rapid vs. lagged response to changing climatic conditions. The sapropel initiations appear to be synchronous across the Aegean Sea; whereas, the terminations display a wider temporal variability implying that the cessation of sapropels is controlled both by the amplitude of paleoclimatic changes and the physiography/location ofthe subbasins. Quantitative variations in the planktonic faunal assemblages exhibit a sequence of bioevents during the last -130,000 years which allow identification of four major biozones. The distributional patterns of the most significant taxa demonstrate similar trends among all core localities suggesting that the major changes in the planktonic foraminifera assemblages have taken place rather synchronously in the Aegean Sea. Sapropels S3, S4 and S5 were deposited under similar hydrographic conditions during which a distinct deep chlorophyll maximum (DCM) layer was established. This situation points to a stratified water column and increased export productivity during times of sapropel formation. On the other hand, the faunal contrast between Sl and older sapropels indicates that the former was developed in the absence of a DCM layer, lacking a deep phytoplankton assemblage. Under such conditions, oxygen advection via intermediate water flow must have been significantly reduced which implies significant stagnation. Sapropels are interpreted to have been deposited under normal marine conditions with temporary establishment of semi-euxinic bottom water conditions. Both marine and terrestrial organic matter contributed equally to MISS sapropels. In addition, organic carbon isotopic values across sapropels are more depleted than those in the eastern Mediterranean which, in tum, suggests enhanced riverine input during their deposition. Primary productivity calculations show that, particularly for sapropels with very high TOC values, both preservation and increased productivity are imperative in order to deposit sapropels with very high organic carbon contents (i.e., up to 13%).

d11B and metal/Ca ratios versus size fractions in the Surface and deep dwelling species, ODP Holes 130-806B and 108-664C

We have assessed the reliability of several foraminifer-hosted proxies of the ocean carbonate system (d11B, B/Ca, and U/Ca) using Holocene samples from the Atlantic and Pacific oceans. We examined chemical variability over a range of test sizes for two surface-dwelling foraminifers (Globigerinoides sacculifer and Globigerinoides ruber). Measurements of d11B in G. ruber show no significant relationship with test size in either Atlantic or Pacific sites and appear to provide a robust proxy of surface seawater pH. Likewise there is no significant variability in the d11B of our Atlantic core top G. sacculifer, but we find that d11B increases with increasing test size for G. sacculifer in the Pacific. These systematic differences in d11B are inferred to be a consequence of isotopically light gametogenic calcite in G. sacculifer and its preferential preservation during postdepositional dissolution. The trace element ratio proxies of ocean carbonate equilibria, U/Ca and B/Ca, show systematic increases in both G. ruber and G. sacculifer with increasing test size, possibly as a result of changing growth rates. This behavior complicates their use in paleoceanographic reconstructions. In keeping with several previous studies we find that Mg/Ca ratios increase with increasing size fraction in our well-preserved Atlantic G. sacculifer but not in G. ruber. In contrast to previous interpretations we suggest that these observations reflect a proportionally larger influence of compositionally distinct gametogenic calcite in small individuals compared to larger ones. As with d11B this influences G. sacculifer but not G. ruber, which has negligible gametogenic calcite.

Mg/Ca ratio of Globorotalia tumida and subsurface temperature reconstruction for ODP Site 130-806

The tropical Pacific thermocline strength, depth, and tilt are critical to tropical mean state and variability. During the early Pliocene (~3.5 to 4.5 Ma), the Eastern Equatorial Pacific (EEP) thermocline was deeper and the cold tongue was warmer than today, which resulted in an mean state with a reduced zonal sea surface temperature gradient, or El Padre. However, it is unclear whether the deep thermocline was a local feature of the EEP or a basin-wide condition with global implications. Our measurements of Mg/Ca of Globorotalia tumida in a western equatorial Pacific site indicate Pliocene subsurface temperatures warmer than today; thus, El Padre included a basin-wide thermocline that was relatively warm, deep, and weakly tilted. At ~4 Ma, thermocline steepening was coupled to cooling of the cold tongue. Since ~4 Ma, the basin-wide thermocline cooled/shoaled gradually, with implications for thermocline feedbacks in tropical dynamics and the interpretation of TEX86-derived temperatures.

Can I still qualify for Medicaid nursing facility eligibility if my income is more than the allowed $2,130 per month? September 19, 2013

A Miller Trust is an irrevocable trust established on or before August 10, 1993, for the benefit of an individual and is used to help pay the cost of nursing facility care. The person residing in the nursing facility is designated as the beneficiary, and after the beneficiary’s death, all remaining amounts, up to the amount of Medicaid paid for the beneficiary, are paid to the State, the residuary beneficiary. Once a trust is established, a bank account for monies associated with the trust can be opened. Only certain funds, including the beneficiary’s earned and unearned income, can be deposited into the Miller Trust account. A trustee, usually a spouse or family member, is the person who administers the trust and pays out money.

Mallard Investigations W-130-R-4 Quarterly Federal Aid Performance Report

W-130-R-4 Quarterly Federal Aid Performance Report