RANKL protein is expressed at the pannus-bone interface at sites of articular bone erosion in rheumatoid arthritis

Objectives. Receptor activator of NF-kappa B ligand (RANKL) and osteoprotegerin (OPG) have been demonstrated to be critical regulators of osteoclast generation and activity. In addition, RANKL has been implicated as an important mediator of bone erosion in rheumatoid arthritis (RA). However, the expression of RANKL and OPG at sites of pannus invasion into bone has not been examined. The present study was undertaken to further elucidate the contribution of this cytokine system to osteoclastogenesis and subsequent bone erosion in RA by examining the pattern of protein expression for RANKL, OPG and the receptor activator of NF-kappa B (RANK) in RA at sites of articular bone erosion. Methods. Tissues from 20 surgical procedures from 17 patients with RA were collected as discarded materials. Six samples contained only synovium or tenosynovium remote from bone, four samples contained pannus-bone interface with adjacent synovium and 10 samples contained both synovium remote from bone and pannu-bone interface with adjacent synovium. Immunohistochemistry was used to characterize the cellular pattern of RANKL, RANK and OPG protein expression immediately adjacent to and remote from sites of bone erosion. Results. Cellular expression of RANKL protein was relatively restricted in the bone microenvironment; staining was focal and confined largely to sites of osteoclast-mediated erosion at the pannus-bone interface and at sites of subchondral bone erosion. RANK-expressing osteoclast precursor cells were also present in these sites. OPG protein expression was observed in numerous cells in synovium remote from bone but was more limited at sites of bone erosion, especially in regions associated with RANKL expression. Conclusions. The pattern of RANKL and OPG expression and the presence of RANK-expressing osteoclast precursor cells at sites of bone erosion in RA contributes to the generation of a local microenvironment that favours osteoclast differentiation and activity. These data provide further evidence implicating RANKL in the pathogenesis of arthritis-induced joint destruction.

A simple remote sensing based information system for monitoring sites of conservation importance

Monitoring is essential for conservation of sites, but capacity to undertake it in the field is often limited. Data collected by remote sensing has been identified as a partial solution to this problem, and is becoming a feasible option, since increasing quantities of satellite data in particular are becoming available to conservationists. When suitably classified, satellite imagery can be used to delineate land cover types such as forest, and to identify any changes over time. However, the conservation community lacks (a) a simple tool appropriate to the needs for monitoring change in all types of land cover (e.g. not just forest), and (b) an easily accessible information system which allows for simple land cover change analysis and data sharing to reduce duplication of effort. To meet these needs, we developed a web-based information system which allows users to assess land cover dynamics in and around protected areas (or other sites of conservation importance) from multi-temporal medium resolution satellite imagery. The system is based around an open access toolbox that pre-processes and classifies Landsat-type imagery, and then allows users to interactively verify the classification. These data are then open for others to utilize through the online information system. We first explain imagery processing and data accessibility features, and then demonstrate the toolbox and the value of user verification using a case study on Nakuru National Park, Kenya. Monitoring and detection of disturbances can support implementation of effective protection, assist the work of park managers and conservation scientists, and thus contribute to conservation planning, priority assessment and potentially to meeting monitoring needs for Aichi target 11.

Discrete time models of the term structure of interest rates and interest rate contingent claims

In this study, discrete time one-factor models of the term structure of interest rates and their application to the pricing of interest rate contingent claims are examined theoretically and empirically. The first chapter provides a discussion of the issues involved in the pricing of interest rate contingent claims and a description of the Ho and Lee (1986), Maloney and Byrne (1989), and Black, Derman, and Toy (1990) discrete time models. In the second chapter, a general discrete time model of the term structure from which the Ho and Lee, Maloney and Byrne, and Black, Derman, and Toy models can all be obtained is presented. The general model also provides for the specification of an additional model, the ExtendedMB model. The third chapter illustrates the application of the discrete time models to the pricing of a variety of interest rate contingent claims. In the final chapter, the performance of the Ho and Lee, Black, Derman, and Toy, and ExtendedMB models in the pricing of Eurodollar futures options is investigated empirically. The results indicate that the Black, Derman, and Toy and ExtendedMB models outperform the Ho and Lee model. Little difference in the performance of the Black, Derman, and Toy and ExtendedMB models is detected. ^

Globalizing governmentality: Sites of neoliberal assemblage in the Americas

This dissertation analyzes processes of globalization, through a critical examination of the dynamics of neoliberalism in the Americas. It employs and also develops a Foucauldian governmentality analytical framework, demonstrating how such a framework contributes to our understanding of world politics. This dissertation also develops the concept of a liberal political imaginary—consisting of the market, society, and the state—and utilizes this as an analytical framework for understanding the globalization of neoliberal forms of governance. The research suggests that discourses and practices of globalization, global civil society, and global governance represent a fundamental transformation in the way that contemporary social and political reality is understood, and that this has significant consequences for the kinds of political practices and relations that are possible. Moreover, the research suggests the globalization of a neoliberal form of competitive subjectivity that can be applied to a broad range of actors—from individuals to nation-states and international organizations—is reshaping contemporary world politics. The dissertation concludes by suggesting how Foucauldian IR can move forward by incorporating studies of contemporary transformations in capitalism into their analyses.

(Appendix A) Pigment content, microbial biomass and activity, and grain size characteristics in caged and control sites of the Arctic long-term observatory HAUSGARTEN

Present theories of deep-sea community organization recognize the importance of small-scale biological disturbances, originated partly from the activities of epibenthic megafaunal organisms, in maintaining high benthic biodiversity in the deep sea. However, due to technical difficulties, in situ experimental studies to test hypotheses in the deep sea are lacking. The objective of the present study was to evaluate the potential of cages as tools for studying the importance of epibenthic megafauna for deep-sea benthic communities. Using the deep-diving Remotely Operated Vehicle (ROV) "VICTOR 6000", six experimental cages were deployed at the sea floor at 2500 m water depth and sampled after 2 years (2y) and 4 years (4y) for a variety of sediment parameters in order to test for caging artefacts. Photo and video footage from both experiments showed that the cages were efficient at excluding the targeted fauna. The cage also proved to be appropriate to deep-sea studies considering the fact that there was no fouling on the cages and no evidence of any organism establishing residence on or adjacent to it. Environmental changes inside the cages were dependent on the experimental period analysed. In the 4y experiment, chlorophyll a concentrations were higher in the uppermost centimeter of sediment inside cages whereas in the 2y experiment, it did not differ between inside and outside. Although the cages caused some changes to the sedimentary regime, they are relatively minor compared to similar studies in shallow water. The only parameter that was significantly higher under cages at both experiments was the concentration of phaeopigments. Since the epibenthic megafauna at our study site can potentially affect phytodetritus distribution and availability at the seafloor (e.g. via consumption, disaggregation and burial), we suggest that their exclusion was, at least in part, responsible for the increases in pigment concentrations. Cages might be suitable tools to study the long-term effects of disturbances caused by megafaunal organisms on the diversity and community structure of smaller-sized organisms in the deep sea, although further work employing partial cage controls, greater replication, and evaluating faunal components will be essential to unequivocally establish their utility.

Middle Eocene Fe and Ca counts, Ca/Fe ratios, revised splices and astronomical age models form different Sites of IODP Exp342

Accurate age models are a tool of utmost important in paleoclimatology. Constraining the rate and pace of past climate change are at the core of paleoclimate research, as such knowledge is crucial to our understanding of the climate system. Indeed, it allows for the disentanglement of the various drivers of climate change. The scarcity of highly resolved sedimentary records from the middle Eocene (Bartonian - Lutetian Stages; 47.8 - 37.8 Ma) has led to the existence of the "Eocene astronomical time scale gap" and hindered the establishment of a comprehensive astronomical time scale (ATS) for the entire Cenozoic. Sediments from the Newfoundland Ridge drilled during Integrated Ocean Drilling Program (IODP) Expedition 342 span the Eocene gap at an unprecedented stratigraphic resolution with carbonate bearing sediments. Moreover, these sediments exhibit cyclic lithological changes that allow for an astronomical calibration of geologic time. In this study, we use the dominant obliquity imprint in XRF-derived calcium-iron ratio series (Ca/Fe) from three sites drilled during IODP Expedition 342 (U1408, U1409, U1410) to construct a floating astrochronology. We then anchor this chronology to numerical geological time by tuning 173-kyr cycles in the amplitude modulation pattern of obliquity to an astronomical solution. This study is one of the first to use the 173-kyr obliquity amplitude cycle for astrochronologic purposes, as previous studies primarily use the 405-kyr long eccentricity cycle as a tuning target to calibrate the Paleogene geologic time scale. We demonstrate that the 173-kyr cycles in obliquity's amplitude are stable between 40 and 50 Ma, which means that one can use the 173-kyr cycle for astrochronologic calibration in the Eocene. Our tuning provides new age estimates for magnetochron reversals C18n.1n - C21r and a stratigraphic framework for key sites from Expedition 342 for the Eocene. Some disagreements emerge when we compare our tuning for the interval between C19r and C20r with previous tuning attempts from the South Atlantic. We therefore present a revision of the original astronomical interpretations for the latter records, so that the various astrochronologic age models for the middle Eocene in the North- and South-Atlantic are consistent.

Benthic foraminiferal abundances from eight sites of the Northwest Australian shelf

Foraminiferal analysis of Miocene to recent strata of the Northwest Shelf of Australia is used to chart West Pacific Warm Pool (WPWP) influence. The assemblage is typified by "larger" foraminifera with ingressions of the Indo-Pacific "smaller" taxa Asterorotalia and Pseudorotalia at around 4 Ma and from 1.6 to 0.8 Ma. A review of recent and fossil biogeography of these taxa suggests their stratigraphic distribution can be used to document WPWP evolution. From 10 to 4.4 Ma a lack of biogeographic connectivity between the Pacific and Indian Ocean suggests Indonesian Throughflow (ITF) restriction. During this period, the collision of Australia and Asia trapped warmer waters in the Pacific, creating a central WPWP biogeographic province from the equator to 26°N. By 3 Ma Indo-Pacific species migrated to Japan with the initiation of the "modern" Kuroshio Current coinciding with the intensification of the North Pacific Gyre and Northern Hemisphere ice sheet expansion. Indo-Pacific taxa migrated to the northwest Australia from 4.4 to 4 Ma possibly because of limited ITF. The absence of Indo-Pacific taxa in northwest Australia indicates possible ITF restriction from 4 to 1.6 Ma. Full northwest Australian biogeographic connectivity with the WPWP from 1.6 to 0.8 Ma suggests an unrestricted stronger ITF (compared to today) and the initiation of the modern Leeuwin Current. The extinction of some Indo-Pacific species in northwest Australia after 0.8 Ma may be related to the effects of large glacial/interglacial oscillations and uplift of the Indonesian Archipelago causing Indonesian seaway restriction.

THE HERPESVIRUS NUCLEAR EGRESS COMPLEX COMPONENT, UL31, IS RECRUITED TO SITES OF DNA DAMAGE THROUGH POLY(ADP-RIBOSE) BINDING

The herpes simplex virus (HSV) UL31 gene encodes a conserved member of the herpesvirus nuclear egress complex that not only functions in the egress of DNA-containing capsids from the nucleus, but is also required for optimal viral genome expression, replication and packaging into capsids. Here, we report that the UL31 protein from HSV-2 and the orthologous protein, ORF69, from Kaposi's sarcoma-associated herpesvirus (KSHV) are recruited to sites of DNA damage. Recruitment of UL31 to sites of DNA damage occurred in HSV-2 infected cells, but did not require other viral proteins. The N-terminus of UL31 contains sequences resembling a poly(ADP-ribose) (PAR) binding motif. As protein poly-ADP ribosylation (PARylation) is a hallmark of the DNA damage response we examined the relationship between PARylation and UL31 recruitment to DNA damage. While the PAR polymerase (PARP)1/2 inhibitor, olaparib, prevented UL31 recruitment to damaged DNA, KU55933 inhibition of signaling through the ataxia telangiectasia mutated (ATM) DNA damage response pathway had no effect. These findings were further supported by experiments demonstrating direct and specific interaction between HSV-2 UL31 and PAR using purified components. Co-transfection with the viral kinase Us3, known to phosphorylate UL31, inhibited UL31 recruitment to DNA damage but also prevented the recruitment of other proteins recruited to DNA damage sites. The viral E3 ubiquitin ligase ICP0 was observed to co-localize with UL31 in transfected cells in a manner that is independent of the PAR-binding ability of UL31. However, inhibition of PARP1/2/3 did not reduce the ability of HSV-2 to replicate and we observed reduced PAR levels in the nuclei of infected cells. This study reveals a previously unrecognized function for UL31 orthologs and may suggest that the recognition of PAR by UL31 is coupled to the nuclear egress of herpesvirus capsids, influences viral DNA replication and packaging, or possibly modulates the DNA damage response mounted by virally infected cells.

Sites of Excavation and Construction

For his first solo show in Belgium, British artist Neal White presents a range of recent and new work – some of them in collaboration with artist Tina O’Connell – that reflect his ongoing preoccupations with deep time and the spaces of art. OBJECTIF EXHIBITIONS is a not-for-profit institution devoted to the presentation of contemporary art, supported by the Flemish Community. Curated by Antony Hudek

Seasonal variation of n-alkanes and polycyclic aromatic hydrocarbon concentrations in PMsub(10) samples collected at urban sites of São Paulo state, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)