Association of the (CA)n repeat polymorphism of insulin-like growth factor-I and -202 A/C IGF-binding protein-3 promoter polymorphism with adult height in patients with severe growth hormone deficiency

A number of mathematical models for predicting growth and final height outcome have been proposed to enable the clinician to 'individualize' growth-promoting treatment. However, despite optimizing these models, many patients with isolated growth hormone deficiency (IGHD) do not reach their target height. The aim of this study was to analyse the impact of polymorphic genotypes [CA repeat promoter polymorphism of insulin-like growth factor-I (IGF-I) and the -202 A/C promoter polymorphism of IGF-Binding Protein-3 (IGFBP-3)] on variable growth factors as well as final height in severe IGHD following GH treatment. DESIGN, PATIENTS AND CONTROLS: One hundred seventy eight (IGF-I) and 167 (IGFBP-3) subjects with severe growth retardation because of IGHD were studied. In addition, the various genotypes were also studied in a healthy control group of 211 subjects.

Intracellular Ca(2+) operates a switch between repair and lysis of streptolysin O-perforated cells

Pore-forming (poly)peptides originating from invading pathogens cause plasma membrane damage in target cells, with consequences as diverse as proliferation or cell death. However, the factors that define the outcome remain unknown. We show that in cells maintaining an intracellular Ca(2+) concentration [Ca(2+)](i) below a critical threshold of 10 microM, repair mechanisms seal off 'hot spots' of Ca(2+) entry and shed them in the form of microparticles, leading to [Ca(2+)](i) reduction and cell recovery. Cells that are capable of preventing an elevation of [Ca(2+)](i) above the critical concentration, yet are unable to complete plasma membrane repair, enter a prolonged phase of [Ca(2+)](i) oscillations, accompanied by a continuous shedding of microparticles. When [Ca(2+)](i) exceeds the critical concentration, an irreversible formation of ceramide platforms within the plasma membrane and their internalisation drives the dying cells beyond the 'point of no return'. These findings show that the extent of [Ca(2+)](i) elevation determines the fate of targeted cells and establishes how different Ca(2+)-dependent mechanisms facilitate either cell survival or death.

Short-term response of the Ca cycle of a montane forest in Ecuador to low experimental CaCl 2 additions

The tropical montane forests of the E Andean cordillera in Ecuador receive episodic Sahara-dust inputs particularly increasing Ca deposition. We added CaCl2 to isolate the effect of Ca deposition by Sahara dust to tropical montane forest from the simultaneously occurring pH effect. We examined components of the Ca cycle at four control plots and four plots with added Ca (2 × 5 kg ha–1 Ca annually as CaCl2) in a random arrangement. Between August 2007 and December 2009 (four applications of Ca), we determined Ca concentrations and fluxes in litter leachate, mineral soil solution (0.15 and 0.30 m depths), throughfall, and fine litterfall and Al concentrations and speciation in soil solutions. After 1 y of Ca addition, we assessed fine-root biomass, leaf area, and tree growth. Only < 3% of the applied Ca leached below the acid organic layer (pH 3.5–4.8). The added CaCl2 did not change electrical conductivity in the root zone after 2 y. In the second year of fertilization, Ca retention in the canopy of the Ca treatment tended to decrease relative to the control. After 2 y, 21% of the applied Ca was recycled to soil with throughfall and litterfall. One year after the first Ca addition, fine-root biomass had decreased significantly. Decreasing fine-root biomass might be attributed to a direct or an indirect beneficial effect of Ca on the soil decomposer community. Because of almost complete association of Al with dissolved organic matter and high free Ca2+ : Al3+ activity ratios in solution of all plots, Al toxicity was unlikely. We conclude that the added Ca was retained in the system and had beneficial effects on some plants.

Plio-Pleistocene Mg/Ca and TEX86 sea surface temperature records of ODP Sites 184-1143 and 165-999,

The western warm pools of the Atlantic and Pacific oceans are a critical source of heat and moisture for the tropical climate system. Over the past five million years, global mean temperatures have cooled by 3-4 °C. Yet, current reconstructions of sea surface temperatures indicate that temperature in the warm pools has remained stable during this time. This stability has been used to suggest that tropical sea-surface temperatures are controlled by some sort of thermostat-like regulation. Here we reconstruct sea surface temperatures in the South China Sea, Caribbean Sea and western equatorial Pacific Ocean for the past five million years, using a combination of the Mg/Ca, TEXH86-and Uk'37 surface temperature proxies. Our data indicate that during the period of Pliocene warmth from about 5 to 2.6 million years ago, the western Pacific and western Atlantic warm pools were about 2 °C warmer than today. We suggest that the apparent lack of warming seen in the previous reconstructions was an artefact of low seawater Mg/Ca ratios in the Pliocene oceans. Taking this bias into account, our data indicate that tropical sea surface temperatures did change in conjunction with global mean temperatures. We therefore conclude that the temperature of the warm pools of the equatorial oceans during the Pliocene was not limited by a thermostat-like mechanism.

Mg/Ca ratios of Cenozoic benthic foraminifera from the Indian and South Atlantic Ocean

We investigate the evolution of Cenozoic climate and ice volume as evidenced by the oxygen isotopic composition of seawater (delta18Osw) derived from benthic foraminiferal Mg/Ca ratios to constrain the temperature effect contained in foraminiferal delta18O values. We have constructed two benthic foraminiferal Mg/Ca records from intermediate water depth sites (Ocean Drilling Program sites 757 and 689 from the subtropical Indian Ocean and the Weddell Sea, respectively). Together with the previously published composite record of Lear et al. (2002, doi:10.1126/science.287.5451.269) and the Neogene record from the Southern Ocean of Billups and Schrag (2002, doi:10.1029/2000PA000567), we obtain three, almost complete representations of the delta18Osw for the past 52 Myr. We discuss the sensitivity of early Cenozoic Mg/Ca-derived paleotemperatures (and hence the delta18Osw) to assumptions about seawater Mg/Ca ratios. We find that during the middle Eocene (~ 49-40 Ma), modern seawater ratios yield Mg/Ca-derived temperatures that are in good agreement with the oxygen isotope paleothermometer assuming ice-free conditions. Intermediate waters cooled during the middle Eocene reaching minimum temperatures by 40 Ma. The corresponding delta18Osw reconstructions support ice growth on Antarctica beginning by at least 40 Ma. At the Eocene/Oligocene boundary, Mg/Ca ratios (and hence temperatures) from Weddell Sea site 689 display a well-defined maximum. We caution against a paleoclimatic significance of this result and put forth that the partitioning coefficient of Mg in benthic foraminifera may be sensitive to factors other than temperature. Throughout the remainder of the Cenozoic, the temporal variability among delta18Osw records is similar and similar to longer-term trends in the benthic foraminiferal delta18O record. An exception occurs during the Pliocene when delta18Osw minima in two of the three records suggest reductions in global ice volume that are not apparent in foraminiferal delta18O records, which provides a new perspective to the ongoing debate about the stability of the Antarctic ice sheet. Maximum delta18Osw values recorded during the Pleistocene at Southern Ocean site 747 agree well with values derived from the geochemistry of pore waters (Schrag et al., 1996, doi:10.1126/science.272.5270.1930) further highlighting the value of the new Mg/Ca calibrations of Martin et al. (2002, doi:10.1016/S0012-821X(02)00472-7) and Lear et al. (2002, doi:10.1016/S0016-7037(02)00941-9) applied in this study. We conclude that the application of foraminiferal Mg/Ca ratios allows a refined view of Cenozoic ice volume history despite uncertainties related to the geochemical cycling of Mg and Ca on long time scales.

Sr/Ca, U/Ca, and stable isotope data and bimonthly records of Ogasawara coral core OGA-02-1

Instrumental climate observations provide robust records of global land and ocean temperatures during the twentieth century. Unlike for temperature, continuous salinity observations in the surface ocean are scarce prior to 1970, and the magnitude of salinity changes during the twentieth century is largely unknown. Surface ocean salinity is a major component in climate dynamics, as it influences ocean circulation and water mass formation. Here we present an annually resolved reconstruction of salinity variations in the surface waters of the western subtropical North Pacific Ocean since 1873, based on bimonthly records of d18O, Sr/Ca, and U/Ca in a coral from the Ogasawara Islands. The reconstruction indicates that an abrupt regime shift toward fresher surface ocean conditions occurred between 1905 and 1910. Observational atmospheric data suggest that the abrupt freshening was associated with a weakening of the winds that drive the Kuroshio Current system and the associated subtropical gyre circulation. We note that the abrupt early-twentieth-century freshening in the western subtropical North Pacific precedes abrupt climate change in the northern North Atlantic by a few years. The potential for abrupt regime shifts in surface ocean salinity should be considered in climate predictions for the coming decades.

Mg/Ca and stable oxygen measurement of the past 27 Ma of ODP Hole 120-747A

We explore the applicability of paired Mg/Ca and 18O/16O measurements on benthic foraminifera from Southern Ocean site 747 to paleoceanographic reconstructions on pre-Pleistocene timescales. We focus on the late Oligocene through Pleistocene (27-0 Ma) history of paleotemperatures and the evolution of the d18O values of seawater (d18Osw) at a temporal resolution of ~100-200 kyr. Absolute paleotemperature estimates depend on assumptions of how Mg/Ca ratios of seawater have changed over the past 27 Myr, but relative changes that occur on geologically brief timescales are robust. Results indicate that at the Oligocene to Miocene boundary (23.8 Ma), temperatures lag the increase in global ice-volume deduced from benthic foraminiferal d18O values, but the smaller-scale Miocene glaciations are accompanied by ocean cooling of -1°C. During the mid-Miocene phase of Antarctic ice sheet growth (~15-13 Ma), water temperatures cool by ~3°C. Unlike the benthic foraminiferal d18O values, which remain relatively constant thereafter, temperatures vary (by 3°C) and reach maxima at ~12 and ~8.5 Ma. The onset of significant Northern Hemisphere glaciation during the late Pliocene is synchronous with an ~4°C cooling at site 747. A comparison of our d18Osw curve to the Haq et al. (1987, doi:10.1126/science.235.4793.1156 ) sea level curve yields excellent agreement between sequence boundaries and times of increasing seawater 18O/16O ratios. At ~12-11 Ma in particular, when benthic foraminiferal d18O values do not support a further increase in ice volume, the d18Osw curve comes to a maximum that corresponds to a major mid-Miocene sea level regression. The agreement between the character of our Mg/Ca-based d18Osw curve and sequence stratigraphy demonstrates that benthic foramaniferal Mg/Ca ratios can be used to trace the d18Osw on pre-Pleistocene timescales despite a number of uncertainties related to poorly constrained temperature calibrations and paleoseawater Mg/Ca ratios. The Mg/Ca record also highlights that deep ocean temperatures can vary independently and unexpectedly from ice volume changes, which can lead to misinterpretations of the d18O record.

Mg/Ca ratios of Neogloboquadrina pachyderma (s) and Globigerina bulloides in Irminger Sea sediment trap time series

iven the importance of high-latitude areas in the ocean-climate system, there is need for a paleothermometer that is reliable at low temperatures. Here we assess the applicability of the Mg/Ca-temperature proxy in colder waters (5-10?°C) by comparing for the first time the seasonal Mg/Ca and d18O cycles of N. pachyderma (s) and G. bulloides using a sediment trap time-series from the northern North Atlantic. While both species show indistinguishable seasonal d18O patterns that clearly track the near surface temperature cycle, their Mg/Ca are very different. G. bulloides Mg/Ca is high (2.0-3.1 mmol/mol), but varies in concert with the seasonal temperature cycle. The Mg/Ca of N. pachyderma (s), on the other hand, is low (1.1-1.5 mmol/mol) and shows only a very weak seasonal cycle. The d18O patterns indicate that both species calcify in the same depth zone. Consequently, depth habitat differences cannot explain the contrasting Mg/Ca patterns. The elevated Mg/Ca in pristine G. bulloides might be due to the presence of high Mg phases that are not preserved in fossil shells. The contrasting absence of a seasonal trend in the Mg/Ca of N. pachyderma (s) confirms other studies where calcification temperatures were less well constrained. The reason for this absence is not fully known, but may include species-specific vital effects. The very different seasonal patterns of both species' Mg/Ca underscore the importance of parameters other than temperature in controlling planktonic foraminiferal Mg/Ca. Our results therefore lend further caution in the interpretation of Mg/Ca-temperature reconstructions from high northern latitudes.

Mg/Ca and d18O measurements of planktonic foraminifera from Sargasso Sea

Paired Mg/Ca and d18O measurements on planktonic foraminiferal species (G. ruber white, G. ruber pink, G. sacculifer, G. conglobatus, G. aequilateralis, O. universa, N. dutertrei, P. obliquiloculata, G. inflata, G. truncatulinoides, G. hirsuta, and G. crassaformis) from a 6-year sediment trap time series in the Sargasso Sea were used to define the sensitivity of foraminiferal Mg/Ca to calcification temperature. Habitat depths and calcification temperatures were estimated from comparison of d18O of foraminifera with equilibrium calcite, based on historical temperature and salinity data. When considered together, Mg/Ca (mmol/mol) of all species, except two, show a significant (r = 0.93) relationship with temperature (T °C) of the form Mg/Ca = 0.38 (±0.02) exp 0.090 (±0.003)T, equivalent to a 9.0 ± 0.3% change in Mg/Ca for a 1°C change in temperature. Small differences exist in calibrations between species and between different size fractions of the same species. O. universa and G. aequilateralis have higher Mg/Ca than other species, and in general, data can be best described with the same temperature sensitivity for all species and pre-exponential constants in the sequence O. universa > G. aequilateralis = G. bulloides > G. ruber = G. sacculifer = other species. This approach gives an accuracy of ±1.2°C in the estimation of calcification temperature. The 9% sensitivity to temperature is similar to published studies from culture and core top calibrations, but differences exist from some literature values of pre-exponential constants. Different cleaning methodologies and artefacts of core top dissolution are probably implicated, and perhaps environmental factors yet understood. Planktonic foraminiferal Mg/Ca temperature estimates can be used for reconstructing surface temperatures and mixed and thermocline temperatures (using G. ruber pink, G. ruber white, G. sacculifer, N. dutertrei, P. obliquiloculata, etc.). The existence of a single Mg thermometry equation is valuable for extinct species, although use of species-specific equations will, where statistically significant, provide more accurate evaluation of Mg/Ca paleotemperature.

Mid-Pliocene deep-sea bottom water temperatures based on ostracode Mg/Ca ratios

We studied magnesium:calcium (Mg/Ca) ratios in shells of the deep-sea ostracode genus Krithe from a short interval in the middle Pliocene between 3.29 and 2.97 Ma using deep-sea drilling sites in the North and South Atlantic in order to estimate bottom water temperatures (BWT) during a period of climatic warmth. Results from DSDP and ODP Sites 552A, 610A, 607, 658A, 659A, 661A and 704 for the period Ma reveal both depth and latitudinal gradients of mean Mg/Ca values. Shallower sites (552A, 610A and 607) have higher mean Mg/Ca ratios (10.3, 9.7, 10.1 mmol/mol) than deeper sites (661A, 6.3 mmol/mol), and high latitude North Atlantic sites (552A, 610 and 607) have higher Mg/Ca ratios than low latitude (658A: 9.8 mmol/mol, 659A: 7.7 mmol/mol, 661A: 6.3 mmol/mol) and Southern Ocean (704: 8.0 mmol/mol) sites. Converting Mg/Ca ratios into estimated temperatures using the calibration of Dwyer et al. (1995) [Dwyer, G.S., Cronin, T.M., Baker, P.A., Raymo, M.E., Buzas, J.S., Corrège, T., 1995. North Atlantic deepwater temperature change during late Pliocene and late Quaternary climatic cycles. Science 270, 1347-1351] suggests that mean middle Pliocene bottom water temperatures at the study sites in the deep Atlantic were about the same as modern temperatures. However, brief pulses of elevated BWT occurred several times between 3.29 and 2.97 Ma in both the North and South Atlantic Ocean suggesting short-term changes in deep ocean circulation.

Short-term response of the Ca cycle of a montane forest in Ecuador to low experimental CaCl2 additions

The tropical montane forests of the E Andean cordillera in Ecuador receive episodic Sahara- dust inputs particularly increasing Ca deposition. We added CaCl2 to isolate the effect of Ca deposition by Sahara dust to tropical montane forest from the simultaneously occurring pH effect. We examined components of the Ca cycle at four control plots and four plots with added Ca (2 × 5 kg ha?1 Ca annually as CaCl2) in a random arrangement. Between August 2007 and December 2009 (four applications of Ca), we determined Ca concentrations and fluxes in litter leachate, mineral soil solution (0.15 and 0.30 m depths), throughfall, and fine litterfall and Al con- centrations and speciation in soil solutions. After 1 y of Ca addition, we assessed fine-root bio- mass, leaf area, and tree growth. Only < 3% of the applied Ca leached below the acid organic layer (pH 3.5?4.8). The added CaCl2 did not change electrical conductivity in the root zone after 2 y. In the second year of fertilization, Ca retention in the canopy of the Ca treatment tended to decrease relative to the control. After 2 y, 21% of the applied Ca was recycled to soil with throughfall and litterfall. One year after the first Ca addition, fine-root biomass had decreased significantly. Decreasing fine-root biomass might be attributed to a direct or an indirect beneficial effect of Ca on the soil decomposer community. Because of almost complete association of Al with dissolved organic matter and high free Ca2+ : Al3+ activity ratios in solution of all plots, Al toxicity was unlikely. We conclude that the added Ca was retained in the system and had benefi- cial effects on some plants.

Ca-amendement and tillage: medium term synergies for improving key soil properties of acid soils. Soil and tillage research, 134: 195-206

Ca-amendments are routinely applied to improve acid soils, whilst no-tillage (NT) has been widely recommended in soils where traditional tillage (TT) has led to losses of organic matter. However, the potential interactions between the two treatments are only partially known. Our study was conducted on an annual forage crop agrosystem with a degraded Palexerult soil located in SW Spain, in order to assess if the combination of NT plus a Ca-amendment provides additional benefits to those of their separate use. To this end we analysed the effects of four different combinations of tillage and Ca-amendment on selected key soil properties, focusing on their relationships. The experimental design was a split-plot with four replicates. The main factor was tillage (NT versus TT) and the second factor was the application or not of a Ca-amendment, consisting of a mixture of sugar foam (SF) and red gypsum (RG). Soil samples were collected from 3 soil layers down to 50 cm after four years of treatment (2009). The use of the Ca-amendment improved pH and Al-toxicity down to 25 cm and increased exchangeable Ca2+ down to 50 cm, even under NT due to the combined effect of SF and RG. Both NT and the Ca-amendment had a beneficial effect on total organic carbon (TOC), especially on particulate organic carbon (POC), in the 0–5 cm layer, with the highest contents observed when both practices were combined. Unlike NT, the Ca-amendment failed to improve soil aggregation in spite of the carbon supplied. This carbon was not protected within the stable aggregates in the medium term, making it more susceptible to mineralization. We suggest that the fraction of Al extracted by oxalate from solid phase (AlOxa-Cu-K) and the glomalin-related soil proteins (GRSPs) are involved in the accumulation of carbon within water stable aggregates, probably through the formation of non-toxic stable Al-OM compounds, including those formed with GRSPs. NT alone decreased AlK in the 0–5 cm soil layer, possibly by increasing POC, TOC and GRSPs, which were observed to play a role in reducing Al toxicity. From our findings, the combination of NT and Ca-amendment appears to be the best management practice to improve chemical and physical characteristics of acid soils degraded by tillage.

The genuine epistles of the Apostolical fathers,

Mode of access: Internet.

Modulation of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase activity and oxidative modification during the development of adjuvant arthritis

Adjuvant arthritis (AA) was induced by intradermal administration of Mycobacterium butyricum to the tail of Lewis rats. In sarcoplasmic reticulum (SR) of skeletal muscles, we investigated the development of AA. SR Ca(2+)-ATPase (SERCA) activity decreased on day 21, suggesting possible conformational changes in the transmembrane part of the enzyme, especially at the site of the calcium binding transmembrane part. These events were associated with an increased level of protein carbonyls, a decrease in cysteine SH groups, and alterations in SR membrane fluidity. There was no alteration in the nucleotide binding site at any time point of AA, as detected by a FITC fluorescence marker. Some changes observed on day 21 appeared to be reversible, as indicated by SERCA activity, cysteine SH groups, SR membrane fluidity, protein carbonyl content and fluorescence of an NCD-4 marker specific for the calcium binding site. The reversibility may represent adaptive mechanisms of AA, induced by higher relative expression of SERCA, oxidation of cysteine, nitration of tyrosine and presence of acidic phospholipids such as phosphatidic acid. Nitric oxide may regulate cytoplasmic Ca(2+) level through conformational alterations of SERCA, and decreasing levels of calsequestrin in SR may also play regulatory role in SERCA activity and expression.

Stable isotopes and Mg/Ca ratios on foraminifera and Ba/Ca ratios of sediment core SK168/GC-1

The past variability of the South Asian Monsoon is mostly known from records of wind strength over the Arabian Sea while high-resolution paleorecords from regions of strong monsoon precipitation are still lacking. Here, we present records of past monsoon variability obtained from sediment core SK 168/GC-1, which was collected at the Alcock Seamount complex in the Andaman Sea. We utilize the ecological habitats of different planktic foraminiferal species to reconstruct freshwater-induced stratification based on paired Mg/Ca and d18O analyses and to estimate seawater d18O (d18Osw). The difference between surface and thermocline temperatures (delta T) and d18Osw (delta d18Osw) is used to investigate changes in upper ocean stratification. Additionally, Ba/Ca in G. sacculifer tests is used as a direct proxy for riverine runoff and sea surface salinity (SSS) changes related to monsoon precipitation on land. Our delta d18Osw time series reveals that upper ocean salinity stratification did not change significantly throughout the last glacial suggesting little influence of NH insolation changes. The strongest increase in temperature gradients between the mixed layer and the thermocline is recorded for the mid-Holocene and indicate the presence of a significantly shallower thermocline. In line with previous work, the d18Osw and Ba/Ca records demonstrate that monsoon climate during the LGM was characterized by a significantly weaker southwest monsoon circulation and strongly reduced runoff. Based on our data the South Asian Summer Monsoon (SAM) over the Irrawaddyy strengthened gradually after the LGM beginning at ~18 ka. This is some 3 kyrs before an increase of the Ba/Ca record from the Arabian Sea and indicates that South Asian Monsoon climate dynamics are more complex than the simple N-S displacement of the ITCZ as generally described for other regions. Minimum d18Osw values recorded during the mid-Holocene are in phase with Ba/Ca marking a stronger monsoon precipitation, which is consistent with model simulations.