Molecular mechanism of the relaxin signaling pathways: Activation of cAMP, PI3K, and PKCzeta

Relaxin is a polypeptide hormone that has diverse effects on reproductive and non-reproductive tissues. Relaxin activates the G-protein coupled receptors, LGR7 and LRG8. Early studies described increased cAMP and protein kinase A activity upon relaxin treatment, but cAMP accumulation alone could not account for all of the relaxin-mediated effects. We utilized the human monocyte cell line THP-1 to study the mechanism of relaxin-stimulated CAMP production. ^ Relaxin treatment in THP-1 cells produces a biphasic time course in cAMP accumulation, where the first peak appears as early as 1–2 minutes with a second peak at 10–20 minutes. Selective inhibitors for phosphoinositide 3-kinase (P13K), such as wortmannin and LY294002, show a dose-dependent inhibition of relaxin-stimulated cAMP accumulation, specific for the second peak of the relaxin time course. Neither the effects of relaxin nor the inhibition of relaxin by LY294002 is mediated by the activity of phosphodiesterases. Furthermore, LY294002 blocks upregulation of vascular endothelial growth factor transcript levels by relaxin. ^ To further delineate relaxin signaling pathways, we searched for downstream targets of PI3K that could activate adenylyl cyclase (AC). Protein kinase C ζ (PKCζ) was a prime candidate because it activates types II and V AC. Chelerythrine chloride (a general PKC inhibitor) inhibits relaxin-induced cAMP production to the same degree as LY294002 (∼40%). Relaxin stimulates PKCζ translocation to the plasma membrane in THP-1, MCF-7, PHM1-31, and MMC cells, as shown by immunocytochemistry. PKCζ translocation is P13K-dependent and independent of cAMP production. Antisense PKCζ oligodeoxynucleotides (PKCζ-ODNs) deplete both PKCζ transcript and protein levels in THP-1 cells. PKCζ-ODNs abolish relaxin-mediated PKCζ translocation and inhibit relaxin stimulation of cAMP by 40%, as compared to mock and random ODN controls. Treatment with LY294002 in the presence of PKCζ-ODNs results in little further inhibition. Taken together, we present a novel role for PI3K and PKCζ in relaxin stimulation of cAMP and provide the first example of the PKCζ regulation of AC in an endogenous system. Furthermore, we have identified higher order complexes of AC isoforms and PKA anchoring proteins in attempts to explain the differential coupling of relaxin to cAMP and PI3K-signaling pathways in various cell types. ^

Perceptions of institutional support of community -based participatory research within prevention research centers

The Institute of Medicine (IOM) report on the future of health care states that the focus on health needs to shift to the management and prevention of chronic illnesses and that academic health centers (AHCs) should play an active role in this process through community partnerships (IOM, 2002). Grant funding from the National Institutes of Health and the creation of the Centers for Disease Control and Prevention (CDC) Prevention Research Centers (PRC) across the county represent a transition toward more proactively seeking out community partnerships to better design and disseminate health promotion programs (Green, 2001). ^ The focus of the PRCs is to conduct rigorous, community-based, prevention research, to seek outcomes applicable to public health programs and policies. The PRCs work is to create and foster partnerships among public health and community organizations, to address health promotion and disease prevention issues (CDC, 2003). ^ The W.K. Kellogg Foundation defines CBPR as "a collaborative approach to research that equitably involves all partners in the research process and recognizes the unique strengths that each brings. CBPR begins with a research topic of importance to the community with the aim of combining knowledge and action for social change to improve community health." ^ In 1995, CDC asked the IOM to review the PRC program to examine the extent to which the program is providing the public health community with strategies to address public health problems in disease prevention and health promotion (IOM, 1997). No comprehensive evaluation n of the individual PRCs had ever been done (IOM, 1997). ^ The CDC was interested in understanding how it could better support the PRC program through improved management and oversight to influence the program's success. The CDC only represents one of the entities that influence the success of a PRC. Another key entity to consider is the support of and influence of the Schools of Public Health in which the PRCs reside. Using evaluation criteria similar to those that were developed by the IOM, this study examined how aspects of structural capacity of the Schools of Public Health in which the PRCs reside are perceived to influence PRC community-based research activities. ^

(Table 1) Species richness and diversity of tundra plants in herbivore exclosure and control plots near Barrow, Alaska

To determine the role lemmings play in structuring plant communities and their contribution to the 'greening of the Arctic', we measured plant cover and biomass in 50 + year old lemming exclosures and control plots in the coastal tundra near Barrow, Alaska. The response of plant functional types to herbivore exclusion varied among land cover types. In general, the abundance of lichens and bryophytes increased with the exclusion of lemmings, whereas graminoids decreased, although the magnitude of these responses varied among land cover types. These results suggest that sustained lemming activity promotes a higher biomass of vascular plant functional types than would be expected without their presence and highlights the importance of considering herbivory when interpreting patterns of greening in the Arctic. In light of the rapid environmental change ongoing in the Arctic and the potential regional to global implications of this change, further exploration regarding the long-term influence of arvicoline rodents on ecosystem function (e.g. carbon and energy balance) should be considered a research priority.

(Table 1) Age of Cretaceous seamounts in the Western Pacific

Dynamics of the Pacific Plate is recorded in the systematic variation of location and the 40Ar-39Ar age of seamounts in the Western Pacific from 120 to 65 Ma ago. The seamounts are grouped into three linear zones as long as 5000 km. The seamounts become younger in the southeastern direction along the strike of these zones. Correlation between age and location of seamounts allows to divide the history of their formation into three stages. Rate of seamount growth was relatively low (2-4 cm/yr) during the first and the third stages within intervals of 120-90 and 85-65 Ma, whereas during the second stage (90-85 Ma), the seamounts were growing very fast (80-100 cm/yr). In the midst of this stage, at ~87 Ma ago, magmatic activity increased abruptly. Dynamics of seamount building is in good agreement with (1) pulses in development of the Ontong Java, Manihiki, and Caribbean-Colombian oceanic plateaus; (2) age of spreading acceleration in the mid-Cretaceous; and (3) a short period when the Izanagi Plate ceased to exist and the Kula Plate was formed. Variation in seamounts' age and location are in consistence with the hypothesis of diffuse extension of the Pacific Plate in course of its motion with formation of impaired zones of decompression melting. Direction of extension (325°-340° NW) calculated from the strike of seamount zones is consistent with the path of the Pacific Plate (330° NW) in the Late Cretaceous. Immense perioceanic volcanic belts were formed at that time along the margin of the Asian continent. The Okhotsk-Chukchi Peninsula Belt extends at a right angle to the compression vector. Three stages of this belt's evolution are synchronous with the stages of seamount formation in the Pacific Plate. Delay in origination of the East Sikhote-Alin Volcanic Belt and its different orientation were caused by counterclockwise rotation of the vector of convergence of oceanic and continental plates in the mid-Cretaceous. At the same time, i.e. 95-85 Ma ago, volcanic activity embraced the entire continental margin and tin granites were emplaced everywhere in the Eastern Asia. This short episode (90+/-5 Ma) corresponds to the mid-Cretaceous maximum of compression of the continental margin, and its age fits well a culmination in extension of the Pacific Plate.

Pliocene-Plistocene deposition of carbonate and organic carbon in ODP Hole 159-959C

During Ocean Drilling Program (ODP) Leg 159, four sites (Sites 959-962) were drilled along a depth transect on the Côte d'Ivoire/Ghana Transform Margin. In this study, the Pliocene-Pleistocene history of carbonate and organic carbon accumulation at Hole 959C is reconstructed for the eastern equatorial Atlantic off the Ivory Coast/Ghana based on bulk carbonate, sand fraction, organic carbon, and other organic geochemical records (d13Corg, marine organic matter percentages derived from organic petrology, hydrogen index, C/N). Pliocene-Pleistocene sedimentation off the Ivory Coast/Ghana was strongly affected by low mean sedimentation rates, which are attributed to persistently enhanced bottom-water velocities related to the steep topography of the transform margin. Sand fraction and bulk carbonate records reveal typical glacial/interglacial cycles, preserved, however, with low time resolution. Intermediate carbonate accumulation rates observed throughout the Pliocene-Pleistocene suggest intense winnowing and sediment redistribution superimposed by terrigenous dilution. 'Atlantic-type' sand and carbonate cycles, consistent with records from pelagic areas of the eastern equatorial Atlantic, are encountered at Hole 959C prior to about 0.9 Ma. Total organic carbon (TOC) records are frequently inversely correlated to carbonate contents, indicating mainly productivity-driven carbonate dissolution related to changes in paleoproductivity. During Stages 22-24, 20, 16, 12, 8, and 4, sand and carbonate records reveal a 'Pacific-type' pattern, showing elevated contents during glacials commonly in conjunction with enhanced TOC records. Formation of 'Pacific-type' patterns off the Ivory Coast/Ghana is attributed to drastically increased bottom-water intensities along the transform margin in accordance with results reported from the Walvis Ridge area. Short-term glacial/interglacial changes in paleoproductivity off the Ivory Coast/Ghana are to some extend recognizable during glacials prior to 1.7 Ma and interglacial Stages 21, 19, 13, 9, and 1. Enhanced coastal upwelling during interglacials is attributed to local paleoclimatic and oceanographic conditions off the Ivory Coast/Ghana. Quantitative estimates of marine organic carbon based on organic petrologic and d13Corg records reveal an offset in concentration ranging from 15% to 60%. Highest variabilities of both records are recorded since ~0.9 Ma. Discrepancies between the isotopic and microscopic records are attributed to an admixture of C4 plant debris approaching the eastern equatorial Atlantic via atmospheric dust. Terrestrial organic material likely originated from the grass-savannah-covered Sahel zone in central Africa. Estimated C4 plant concentrations and accumulation rates range from 10% to 37% and from almost zero to 0.006 g/cm**2/k.y., respectively. The strongest eolian supply to the northern Gulf of Guinea is indicated between 1.9 and 1.68 Ma and during glacial isotopic Stages 22-24, 20, 14, and 12. The presence of grass-type plant debris is further supported by organic petrologic studies, which reveal well-preserved cell tissues of vascular plants or tube-shaped, elongated terrestrial macerals showing different levels of oxidation.

Flower and seed biomass, and germination rate of arctic tundra plants in response to long term experimental warming

We provide new information on changes in tundra plant sexual reproduction in response to long-term (12 years) experimental warming in the High Arctic. Open-top chambers (OTCs) were used to increase growing season temperatures by 1-2 °C across a range of vascular plant communities. The warming enhanced reproductive effort and success in most species; shrubs and graminoids appeared to be more responsive than forbs. We found that the measured effects of warming on sexual reproduction were more consistently positive and to a greater degree in polar oasis compared with polar semidesert vascular plant communities. Our findings support predictions that long-term warming in the High Arctic will likely enhance sexual reproduction in tundra plants, which could lead to an increase in plant cover. Greater abundance of vegetation has implications for primary consumers - via increased forage availability, and the global carbon budget - as a function of changes in permafrost and vegetation acting as a carbon sink. Enhanced sexual reproduction in Arctic vascular plants may lead to increased genetic variability of offspring, and consequently improved chances of survival in a changing environment. Our findings also indicate that with future warming, polar oases may play an important role as a seed source to the surrounding polar desert landscape.

Observations of muskoxen and caribou in the high Arctic

Summary: Summer daily activity and movement patterns and habitat selectivity by Peary caribou (Rangifer tarandus pearyi) and muskoxen (Ovibos moschatus) were studied at two sites in Canada's High Arctic. Caribou showed a greater mobility and broader selection of habitat than muskoxen. Muskoxen fed more than they rested in contrast to the greater amount of time spent resting than feeding by caribou. The sedge-producing hydric-meadow vegetalion type was highly selected for by muskoxen at both study areas; caribou selected against the hydric-meadow type and preferred the polar desert and mesic-meadow types. Caribou displayed a greater variety in plant species selection than muskoxen, favouring willow (Salix arctica), grasses, forbs, and the flowers of vascular plants- Muskoxen feci extensively on sedges in the hydric-meadow. It is suggested the abundance and distribution of sedge-producing meadows may control the regional abundance and distribution of muskoxen. Winter climate is probably the ultimate factor controlling densities of muskoxen and caribou in the High Arctic.

Pedogeomorphology, geochronology and paleobotany of soil profiles obtained in the Nagqu area, central Tibet

Vast areas on the Tibetan Plateau are covered by alpine sedge mats consisting of different species of the genus Kobresia. These mats have topsoil horizons rich in rhizogenic organic matter which creates turfs. As the turfs have recently been affected by a complex destruction process, knowledge concerning their soil properties, age and pedogenesis are needed. In the core area of Kobresia pygmaea mats around Nagqu (central Tibetan Plateau, ca. 4500 m a.s.l.), four profiles were subjected to pedological, paleobotanical and geochronological analyses concentrating on soil properties, phytogenic composition and dating of the turf. The turf of both dry K. pygmaea sites and wet Kobresia schoenoides sites is characterised by an enrichment of living (dominant portion) and dead root biomass. In terms of humus forms, K. pygmaea turfs can be classified as Rhizomulls mainly developed from Cambisols. Wet-site K. schoenoides turfs, however, can be classified as Rhizo-Hydromors developed from Histic Gleysols. At the dry sites studied, the turnover of soil organic matter is controlled by a non-permafrost cold thermal regime. Below-ground remains from sedges are the most frequent macroremains in the turf. Only a few pollen types of vascular plants occur, predominantly originating from sedges and grasses. Large amounts of microscopic charcoal (indeterminate) are present. Macroremains and pollen extracted from the turfs predominantly have negative AMS 14C ages, giving evidence of a modern turf genesis. Bulk-soil datings from the lowermost part of the turfs have a Late Holocene age comprising the last ca. 2000 years. The development of K. pygmaea turfs was most probably caused by an anthropo(zoo)-genetically initiated growth of sedge mats replacing former grass-dominated vegetation ('steppe'). Thus the turfs result from the transformation of pre-existing topsoils comprising a secondary penetration and accumulation of roots. K. schoenoides turfs, however, are characterised by a combined process of peat formation and penetration/accumulation of roots probably representing a (quasi) natural wetland vegetation.

Age models, organic analyses and major-element analyses of sediment cores on a transect of the tropical African rainbelt

The distribution of rainfall in tropical Africa is controlled by the African rainbelt**1, which oscillates on a seasonal basis. The rainbelt has varied on centennial to millennial timescales along with changes in Northern Hemisphere high-latitude climate**2, 3, 4, 5, the Atlantic meridional overturning circulation**6 and low-latitude insolation**7 over the past glacial-interglacial cycle. However, the overall dynamics of the African rainbelt remain poorly constrained and are not always consistent with a latitudinal migration**2, 4, 5, 6, as has been proposed for other regions**8, 9. Here we use terrestrially derived organic and sedimentary markers from marine sediment cores to reconstruct the distribution of vegetation, and hence rainfall, in tropical Africa during extreme climate states over the past 23,000 years. Our data indicate that rather than migrating latitudinally, the rainbelt contracted and expanded symmetrically in both hemispheres in response to changes in climate. During the Last Glacial Maximum and Heinrich Stadial 1, the rainbelt contracted relative to the late Holocene, which we attribute to a latitudinal compression of atmospheric circulation associated with lower global mean temperatures**10. Conversely, during the mid-Holocene climatic optimum, the rainbelt expanded across tropical Africa. In light of our findings, it is not clear whether the tropical rainbelt has migrated latitudinally on a global scale, as has been suggested**8,9.

Fly-through movie for the reconstructed folds in the onset region of the Petermann Glacier, North Greenland

The increasing catalogue of high-quality ice-penetrating radar data provides a unique insight in the internal layering architecture of the Greenland ice sheet. The stratigraphy, an indicator of past deformation, highlights irregularities in ice flow and reveals large perturbations without obvious links to bedrock shape. In this work, to establish a new conceptual model for the formation process, we analysed the radar data at the onset of the Petermann Glacier, North Greenland, and created a three-dimensional model of several distinct stratigraphic layers. We demonstrate that the dominant structures are cylindrical folds sub-parallel to the ice flow. By numerical modelling, we show that these folds can be formed by lateral compression of mechanically anisotropic ice, while a general viscosity contrast between layers would not lead to folding for the same boundary conditions. We conclude that the folds primarily form by converging flow as the mechanically anisotropic ice is channelled towards the glacier.

Histological structure of the facial skin in the bald uakari (Cacajao calvus), compared to other non-red Neotropical primates

In social species, such as primates, facial appearances transmit a variety of social signals. Although it is suggested that the intense red colour of the face of the bald uakari monkey might be an indicator of health, this hypothesis still has not been verified. This study describes the histological structure of the skin of the face in the bald uakari, compared with other non-red neotropical primates, to better understand the maintenance of its colour. The facial skin of the bald uakari monkey is characterized by a thinner epidermis, absence of melanin pigments and a high density of vascular capillaries that spread below the epidermis. These vascular capillaries are larger and more tortuous than in other neotropical primates. The skin of the face of the bald uakari monkey allows a direct external assessment of haematological status, suggesting that the colour of the face would be an honest indicator of health, but could also signal sexual or behavioural states.

Index properties, consolidation characteristics and sediment rebound of ODP Sites 167-1020 and 167-1021 sediments

Drilling during Leg 167 at the California margin was scheduled to recover continuous sedimentary sections. Multiple advanced piston core (APC) holes drilled at different depth offsets provided core overlap in successive APCs. Correlation of high-resolution laboratory physical properties data from adjacent APC holes was used to compile composite depth sections for each site. The composite depth sections were used to confirm continuous recovery and enable high-resolution sampling. The meters composite depth (mcd) scale differs from the shipboard meters below seafloor (mbsf) scale because of (1) core expansion following recovery (MacKillop et al., 1995, doi:10.2973/odp.proc.sr.138.118.1995), (2) coring gaps, and (3) stretching/compression of sediment during coring (Lyle, Koizumi, Richter, et al., 1997, doi:10.2973/odp.proc.ir.167.1997). Moran (1997, doi:10.2973/odp.proc.sr.154.132.1997) calculated that sediment expansion accounted for 90%-95% of the Leg 154 depth offset between shipboard mbsf and the mcd scales. Terzaghi's one-dimensional theory of consolidation (Terzaghi, 1943) describes the response of sediments to stress loading and release. Mechanical loading in marine environments is provided by the buoyant weight of the overlying sediments. The load increases with depth below seabed, resulting in sediment volume reduction as water is "squeezed" out of the voids in the sediment. Stress release during core recovery results in expansion of the sediment and volume increase as water returns to the sediment. The sediment expansion or rebound defines the elastic properties of the sediment. In this study we examine the elastic deformation properties of sediments recovered from Sites 1020 and 1021. These results are used to (1) correct the laboratory index properties measurements to in situ values and (2) determine the contribution of sediment rebound to the depth offset between the mbsf and mcd scales.

Appendix 7: List of species with their distribution ranges restricted to the corresponding phytogeographical region

Understanding species distribution patterns and the corresponding environmental determinants is a crucial step in the development of effective strategies for the conservation and management of plant communities and ecosystems. Therefore, a central prerequisite is the biogeographical and macroecological analysis of factors and processes that determine contemporary, potential, as well as future geographic distribution of species. This thesis has been conducted in the framework of the BIOMAPS-BIOTA project at the Nees Institute of Biodiversity of Plants, which was funded by the German Federal Ministry of Education and Research (BMBF). The study investigated patterns of plants species richness and phytogeographic regions under contemporary environmental conditions and forecasted future climate change in the area of West Africa covering five countries: Benin, Burkina Faso, Côte d'Ivoire, Ghana and Togo. Firstly, geographic patterns of vascular plant species richness have been depicted at a relatively fine spatial resolution based on the potential distribution of 3,393 species. Species richness is closely related to the steep climatic gradient existing in the region with a high concentration of species in the most humid areas in the south and decreases towards the northern drier areas. The investigation of the effectiveness of the existing network of protected areas shows an overall good coverage of species in the study area. However, the proportion of covered species is considerably lower at national extent for some countries, thus calling for more protected areas in order to cover adequately a maximum number of plants species in these countries. Secondly, based on the potential distribution range of vascular plant species, seven phytogeographic regions have been delineated that broadly reflect the vegetation zones as defined by White (1983). However notable differences to the delineation of White (1983) occur at the margins of some regions. Corresponding to a general southward shifted of all regions. And expansion of the Sahel vegetation zone is observed in the north, while the rainforest zone is decreased in the very south.This is alarming since the rainforest shelters a high number of species and a high proportion of range-restricted or endemic species, despite their relatively small extent compared to the other regions. Finally, the evaluation of the potential impact of climate change on plant species richness in the study area, results in a severe loss of future suitable habitat for up to 50% of species per grid cell, particularly in the rainforest region. Moreover, the analysis of the possible shift of phytogeographic regions shows in general a strong deterioration of the West African rainforest. In contrast the drier areas are expanding continuously, although a slight gain in species number can be observed in some particular regions. The overall lesson to retain from the results of this study is that the West African rainforest should be fixed as a high priority area for the conservation of biodiversity of plants, since it is subject to severe contemporary and projected future threats.