Increased site 1 affinity improves biopotency of porcine growth hormone - Evidence against diffusion dependent receptor dimerization

Based on phage display optimization studies with human growth hormone (GH), it is thought that the biopotency of GH cannot be increased. This is proposed to be a result of the affinity of the first receptor for hormone far exceeding that which is required to trap the hormone long enough to allow diffusion of the second receptor to form the ternary complex, which initiates signaling. We report here that despite similar site 1 kinetics to the hGH/hGH receptor interaction, the potency of porcine GH for its receptor can be increased up to 5-fold by substituting hGH residues involved in site 1 binding into pGH. Based on extensive mutations and BIAcore studies, we show that the higher potency and site 1 affinity of hGH for the pGHR is primarily a result of a decreased off-rate associated with residues in the extended loop between helices 1 and 2 that interact with the two key tryptophans Trp(104) and Trp(169) in the receptor binding hot spot. Our mutagenic analysis has also identified a second determinant (Lys(165)), which in addition to His(169), restricts the ability of non-primate hormones to activate hGH receptor. The increased biopotency of GH that we observe can be explained by a model for GH receptor activation where subunit alignment is critical for effective signaling.

CuII chain compound showing a ferromagnetic coupling through triple N1,N2-1,2,4-triazole bridges

[Cu(hyetrz)3](CF3SO3)2·H2O [hyetrz = 4-(2′-hydroxyethyl)-1,2,4-triazole] represents the first structurally characterised ferromagnetically coupled CuII chain compound containing triple N1,N2-1,2,4-triazole bridges. catena-[μ-Tris{4-(2′-hydroxyethyl)-1,2,4-triazole-N1,N2}copper(II)] bis(trifluoromethanesulfonate) hydrate (C14H23F6S2O10CuN9) crystallises in the triclinic space group Pl, a = 13.54(3), b = 14.37(3), c = 15.61(4) Å, α = 95.9(1), β = 104.9(1), γ = 106.5(1)°, V = 2763(11) Å3, Z = 4 (CuII units). The CuII ions are linked by triple N1,N2-1,2,4-triazole bridges yielding an alternating chain with Cu1−Cu2 = 3.8842(4) Å and Cu2−Cu3 = 3.9354(4) Å. Analysis of the magnetic data according to a high-temperature series expansion gives a J value of +1.45(3) cm−1. The nature and the magnitude of the ferromagnetic exchange have been discussed on the basis of the structural features. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).

(Table 1) Dissolved Hafnium and Neodymium in the South Atlantic measured on water bottle samples during POLARSTERN cruise ANT-XXIV/3

We present the first combined dissolved hafnium (Hf) and neodymium (Nd) concentrations and isotope compositions of deep water masses from the Atlantic sector of the Southern Ocean. Eight full depth profiles were analyzed for Hf and twelve for Nd. Hafnium concentrations are generally depleted in the upper few hundred meters ranging between 0.2 pmol/kg and 0.4 pmol/kg and increase to relatively constant values of around 0.6 pmol/kg in the deeper water column. At the stations north of the Polar Front (PF), Nd concentrations increase linearly from about 10 pmol/kg at depths of ~ 200 m to up to 31 pmol/kg close to the bottom indicating particle scavenging and release. Within the Weddell Gyre (WG), however, Nd concentrations are essentially constant at 25 pmol/kg at depths greater than ~ 1000 m. The distributions of both elements show a positive correlation with dissolved silicon implying a close linkage to diatom biogeochemistry. Hafnium essentially shows invariant isotope compositions with values averaging at epsilon-Hf = +4.6, whereas Nd isotopes mark distinct differences between water masses, such as modified North Atlantic Deep Water (NADW, epsilon-Nd = -11 to -10) and Antarctic Bottom Water (AABW, epsilon-Nd = -8.6 to -9.6), but also waters locally advected via the Agulhas Current can be identified by their unradiogenic Nd isotope compositions. Mixing calculations suggest that a small fraction of Nd is removed by particle scavenging during mixing of water masses north of the PF. Nevertheless, the Nd isotope composition has apparently not been significantly affected by uptake and release of Nd from particles, as indicated by mixing calculations. A mixing envelope of an approximated North Pacific and a North Atlantic end-member shows that Nd isotope and concentration patterns in the Lower Circumpolar Deep Water (LCDW) can be fully explained by ~ 30:70 percentage contributions of these respective end-members.

Isotope measurements from ODP Hole 104-642B

The Pliocene (5.3-2.6 Ma) is often described as a relatively stable climatic period, with warm temperatures characterizing high latitudes. New suborbital resolved stable isotope records from ODP Hole 642B in the Eastern Nordic Seas document that the Pliocene was not a stable period characterized by one climate. Rather, seven distinct climate phases, each lasting between 150,000 and 400,000 years, are identified and characterized in the time interval 5.1-3.1 Ma. Four of the transitions between the defined climate phases occurred close to an eccentricity minimum and a minimum in amplitude of change for Northern Hemisphere summer insolation, while two occurred around an eccentricity maximum and a maximum in amplitude in insolation change. Hence, a low frequency response of the Nordic Seas to insolation forcing is indicated. In addition, paleogeographic and related paleoceanographic changes, expansion of the Arctic sea ice cover and onset of NHG were important factors behind the evolving Pliocene low frequency variability in the eastern Nordic Seas. It is likely that the identified climate phases and transitions are important beyond the Nordic Seas, due to their association with changes to both insolation and paleogeography. Also, a strong and variable degree of diagenetic calcite overgrowth is documented for the planktic foraminifera, especially influencing the planktic d18O results; the absolute values and amplitude of change cannot be taken at face value.

Documentation and sedimentology of core PS1021-1 from the Antarctic continental margin off Kap Norvegia

Sedimentological analyses concerning ice rafted debris, grain size distribution, biogenous components, and clay mineral composition of four sediment cores from the Antarctic continental margin off Kapp Norvegia reveal a cyclical pattern of three different sediment facies. These are classified into warm and cold types representing warm and cold climatic periods and a short transition period from cold to warm events. The sedimentological parameters reflect the variations within the cryosphere and the hydrosphere, which are directly influenced by the climatic fluctuations. The unusually high content of carbonaceous planktonic and benthonic foraminifera in these polar sediments, as well as the interfingering of terrigeneous and biogeneous-rich sediments with increasing distance from the continent, might reflect the influence of the Weddell Sea Polynya and the oscillations of polynya, pack-ice and ice shelf extent during the late Pleistocene.

Stable isotope ratios on planktonic foraminifer N. pachyderma of surface sediments from the Arctic Ocean (Table 1)

Planktic foraminifers Neogloboquadrina pachyderma (sin.) from 87 eastern and central Arctic Ocean surface sediment samples were analyzed for stable oxygen and carbon isotope composition. Additional results from 52 stations were taken from the literature. The lateral distribution of delta18O (18O/16O) values in the Arctic Ocean reveals a pattern of roughly parallel, W-E stretching zones in the Eurasian Basin, each ~0.5 per mil wide on the delta18O scale. The low horizontal and vertical temperature variability in the Arctic halocline waters (0-100 m) suggests only little influence of temperature on the oxygen isotope distribution of N. pachyderma (sin.). The zone of maximum delta18O values of up to 3.8 per mil is situated in the southern Nansen Basin and relates to the tongue of saline (> 33%.) Atlantic waters entering the Arctic Ocean through the Fram Strait. delta18O values decrease both to the Barents Shelf and to the North Pole, in accordance with the decreasing salinities of the halocline waters. In the Nansen Basin, a strong N-S delta18O gradient is in contrast with a relatively low salinity change and suggests contributions from different freshwater sources, i.e. salinity reduction from sea ice meltwater in the south and from light isotope waters (meteoric precipitation and river-runoff) in the northern part of the basin. North of the Gakkel Ridge, delta18O and salinity gradients are in good accordance and suggest less influence of sea ice melting processes. The delta13C (13C/12C) values of N. pachyderma (sin.) from Arctic Ocean surface sediment samples are generally high (0.75-0.95 per mil). Lower values in the southern Eurasian Basin appear to be related to the intrusion of Atlantic waters. The high delta13C values are evidence for well ventilated surface waters. Because the perennial Arctic sea ice cover largely prevents atmosphere-ocean gas exchange, ventilation on the seasonally open shelves must be of major importance. Lack of delta13C gradients along the main routes of the ice drift from the Siberian shelves to the Fram Strait suggests that primary production (i.e. CO2 consumption) does probably not change the CO2 budget of the Arctic Ocean significantly.

(Table 1) Radiocarbon dates of core JM05-085-GC, South-Barents Sea

The Late Weichselian-Early Holocene variability of the North Atlantic Current has been studied with focus on the zonal component of this meridional transport during the transition from glacial to interglacial conditions. The investigated sediment core is from 409 m water depth in the SW Barents Sea. Eight Accelerator mass spectrometry (AMS) 14C dates show that the core covers the last 20,000 cal yr B.P. with a centennial scale resolution during Late Weichselian-Early Holocene. Planktic foraminiferal assemblages were analyzed using the >100 ?m size fraction and foraminiferal planktic and benthic d13C and d18O isotopes were measured. Furthermore, a range of physical and chemical analyses has been carried out on the bulk sediment samples. Four time periods have been identified which represent the varying oceanographic conditions in Ingøydjupet, a glacial trough located off the north coast of Norway in the SW Barents Sea. 1) The late glacial (before ca 15,000 cal yr B.P.) influenced by the nearby ice sheets with high amounts of sea ice- or iceberg-transported detritus. 2) The late Oldest Dryas stadial and the Bølling-Allerød interstadial (ca 15,000-12,700 cal yr B.P.) with cold surface water conditions influenced by the collapse of the nearby ice sheets, high amounts of sea ice- or iceberg-transported detritus and melt water and weak subsurface inflow of Atlantic Water. 3) The Younger Dryas cold stadial (12,700-11,650 cal yr B.P.) with low primary productivity and extensive sea ice cover and 4) The Preboreal and Early Holocene (11,650-6800 cal yr B.P. cal yr B.P.) with strong influx of Atlantic Water into the area, near absence of ice rafted debris and generally ameliorated conditions in both surface and bottom water masses as seen from a high flux of foraminifera and increased marine primary production.

(Table 1) Core top Globorotalia truncatulinoides d18O ratios of Atlantic Ocean samples

We investigate whether the oxygen isotope ratio in the test of Globorotalia truncatulinoides can serve as a proxy for intermediate depth (200-500 m) density. Since intermediate depth horizontal density gradients are associated with the vertical shear of upper ocean flows, this proxy could provide a tool for reconstructing past ocean circulation. The spatial pattern of core top Gr. truncatulinoides d18O in the Atlantic Ocean mimics the upper ocean density gradients associated with the major ocean currents. To better constrain the controls on the calcification depth(s) of Gr. truncatulinoides, we attempt to simulate the surface sediment data set using water column temperature and salinity conditions above the core sites. We predicted foraminiferal d18O for each core site assuming (1) the calcification occurs at a single depth and (2) the initial calcification is at the surface and the subsequent calcification is at 800 m water depth. The predicted d18O best resembles measured d18O of Gr. truncatulinoides when using (1) a single depth calcification at 350 m or (2) a two-depth approximation with 30% surface and 70% 800-m calcification. This result gives us confidence in the ability of d18O in Gr. truncatulinoides to proxy lateral density gradients at the intermediate depths associated with upper ocean flow.

(Table 1) Chemical composition of a sample contaiting native aluminium, Core DM9-647, Northeast Pacific

Composition, structure and occurrence of native aluminium in bottom sediments of the Northeast Pacific at Station DM9-647 are reported.

(Table 1) Cadmium and nutrient concentration of surface waters sampled during POLARSTERN cruise ANT-XXIV/III

The High Nutrient Low Chlorophyll (HNLC) Southern Ocean plays a key role in regulating the biological pump and the global carbon cycle. Here we examine the efficacy of stable cadmium (Cd) isotope fractionation for detecting differences in biological productivity between regions. Our results show strong meridional Cd isotope and concentration gradients modulated by the Antarctic Fronts, with a clear biogeochemical divide located near 56°S. The coincidence of the Cd isotope divide with the Southern Boundary of the Antarctic Circumpolar Current (ACC),together with evidence for northward advection of the Cd signal in the ACC, demonstrate that Cd isotopes trace surface ocean circulation regimes. The relationships between Cd isotope ratios and concentrations display two negative correlations, separating the ACC and Weddell Gyre into two distinct Cd isoscapes. These arrays are consistent with Rayleigh fractionation and imply a doubling of the isotope effect due to biological consumption of Cd during water transport from the Weddell Gyre into the ACC. The increase in magnitude of Cd isotope fractionation can be accounted for by differences in the phytoplankton biomass, community composition, and their physiological uptake mechanisms in the Weddell Gyre and ACC, thus linking Cd isotope fractionation to primary production and the global carbon cycle.

(Table 1) Low molecular weight hydrocarbon concentrations and organic carbon contents at DSDP Hole 71-511

C2-C8 hydrocarbons (36 compounds identified) from 56 shipboard sealed, deep-frozen core samples of DSDP Leg 71, Site 511, Falkland Plateau, South Atlantic, were analyzed by a combined hydrogen stripping-thermovaporization method. Concentrations, which represent hydrocarbons dissolved in the pore water and adsorbed to the mineral surfaces of the sediment, vary from 24 ng/g of dry weight sediment in Lithologic Unit 4 to 17,400 ng/g in Lithologic Unit 6 ("black shale" unit). Likewise, the organic carbon normalized C2-C8 hydrocarbon concentrations range from 104 to 3.5 x 105 ng/g Corg. The latter value is more than one order of magnitude lower than expected for petroleum source beds in the main phase of oil generation. The low maturity at 600 meters depth is further supported by light hydrocarbon concentration ratios. The change of the kerogen type from Lithologic Unit 5 (Type III) to 6 (Type II) is evidenced by changes in the C6 and C7 hydrocarbon composition. Redistribution phenomena are observed close to the Tertiary-Cretaceous unconformity and at the contact between the "black shale" unit and the overlying Cretaceous chalks and claystones. Otherwise, the low molecular weight hydrocarbons in Hole 511 are formed in situ and remain at their place of formation. The core samples turned out to be contaminated by large quantities of acetone, which is routinely used as a solvent during sampling procedures onboard Glomar Challenger.

Descriptions of 104 gravity and piston sediment cores from POLARSTERN expedition ARK-VIII/3 to the Arctic Ocean

Sediment descriptions and lithostratigraphy (chapter 6.4) NANSEN BASIN The upperrnost 20-50 cm of sedirnents in the Nansen Basin norrnally cornprise soft dark brown, brown-grayish and brown clay. Except for the toprnost clay, the four piston cores retrieved, contained quite different lithologies: a rnuddy diarnicton with outsized clasts (PS2157-6), sandy-silt beds alternating with clay beds (PS2159-6), and silty clay beds of brownish and grayish colours (PS2161-3). Core PS2208-3 was retrieved frorn a plateau on a searnount. The plateau was serni-encircled by hills. The upper 250 cm of this core cornprise brown and olive brown clays. Below these are several sandlayers and a 74 cm thick unit of a sandy mud with rnud-clasts up to 20 cm in diameter. GAKKEL RIDGE The uppermost 20-50 cm of sediments on the Gakkel Ridge comprise soft dark brown, brown, grayish brown clay. In most of the cores there are two horizons of brown clay separated by olive brown clay. The upper horizon is darker. The older stratigraphy is rather varied. Core PS2165-1 contains several thin gray sandlsilt layers, probably distal turbidites. The sarne is found in Core PS2167-1. This core also has a thick (approx. 2 rn) coarse grained turbidite containing large rnud clasts and basaltic rock fragrnents. The color of the turbiditic layers is dark gray. There are several horizons of hernipelagic sandylsilty clays with quite a variety in colours; black, gray, olive, brown, yellowish brown and reddish. The colour variation rnay be due to hydrotherrnal activity or provenance or a shift in redox potential. Cores PS2168-2 and PS2169-1 have typical sequences of very dark gray sandy mud with sharp lower boundaries grading upwards into olive brown clay. Below the lower boundary is often a thin (1-2 cm) gray clay layer. AMUNDSEN BASIN The giant box cores (GKG) provided in most cases excellently preserved sedirnent surfaces which consisted in the entire Amundsen Basin of dark brown to dark grayish brown silty clay with few dropstones and common calcareous microfossils (foraminifers and calcareous nannofossils). The brown and grayish brown color of the sediment surface is a result of the oxidizing conditions at the seafloor due to the rapid renewal of the bottom water rnasses. Planktic forarninifers and calcareous nannofossils are relatively frequent and well preserved despite the rernote location of the basin and its water depths of >4000 rn. Srnear slide descriptions have shown that the surface sedirnents consist dorninantly of clays to silty rnuds with clay rninerals and quartz as the rnost important constituents. The coarse fractions contained besides planktic and benthic forarninifers and coarse clastic rnaterials, rare bivalves, dropstones and mud clasts. The Station PS2190 at the North Pole is a particular good exarnple of the type of sedirnents deposited at the sea floor surface of the Arnundsen Basin, with hornogenous dark brown soft clay covering a sedirnent sequence of highly variable cornposition. Nurnerous giant box cores also provide insight into the detailed lithostratigraphy of the upperrnost sedirnent layers. Twelve box cores have been collected frorn the Arnundsen Basin. Below the youngest unit of 5-20 crn thick silty clays deposits of variable stratigraphies have been found, rnostly consisting of clays or silty clays. In a few instances turbidites have been observed. Benthic forarninifers have not been found in the surface sedirnents. Other fossils were extrernely rare. Bioturbation is weakly developed on all stations. Benthic anirnals seern to live only in and on the upperrnost 2 cm of the uppermost sediment layer. They cornprise amphipods (on all stations) and holothurians, bryozoans, polychaetes, and porifers at one station each. LOMONOSOV RIDGE Sediments from the Lomonosov Ridge show a variety of colors and textures. Following smear slide analyses they are composed mostly of clay minerals and quartz with mica and feldspars, especially in the siltier and sandier parts. Volcanic glass, microcrystalline carbonate, opaque minerals and green amphibole are occasional accessories. The sediments from the Lomonosov Ridge show a noticeable difference from sediments collected from the surrounding basins. Lomonosov Ridge sediments are richer in silt and sand than basin sediments. Occasional turbidites occur in ridge sediments but these must be of entirely local origin. The ridge sediments include frequent layers of "cottage cheese" texture made up of what appear to be small, angular mud clasts of a variety of colors.