Hydrochlorothiazide in CLDN16 mutation

BACKGROUND: Hydrochlorothiazide (HCT) is applied in the therapy of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) caused by claudin-16 (CLDN16) mutation. However, the short-term efficacy of HCT to reduce hypercalciuria in FHHNC has not yet been demonstrated in a clinical trial. METHODS: Four male and four female patients with FHHNC and CLDN16 mutation, under long-standing HCT therapy (0.4-1.2 mg/kg, median 0.9 mg/kg, dose according to calciuria), aged 0.7-22.4 years, were included in a clinical study to investigate the effect of HCT on calciuria. The study design consisted of three periods: continued therapy for 4 weeks, HCT withdrawal for 6 weeks and restart of therapy at the same dose for 4 weeks. Calciuria and magnesiuria were assessed weekly as Ca/creat and Mg/creat ratio, every 2 weeks in 24 h urine, and serum Mg, K and kaliuria (s-Mg, s-K and K/creat) at weeks 0, 6, 10 and 14. The data of each study period were averaged and analysed by Friedman and Wilcoxon test. RESULTS: Ca/creat was significantly reduced by HCT (median before/at/after withdrawal 0.76/1.24/0.77 mol/mol creat; n = 8, P<0.05). The reduction of Ca/24 h by HCT was not statistically significant (0.13/0.19/0.13 mmol/kg x 24 h; n = 5). Serum Mg (0.51/0.64/0.56 mmol/l; n = 8, P<0.05) and Serum K (3.65/4.35/3.65 mmol/l; n = 8, P<0.05) were significantly higher during withdrawal. However, Mg/creat (0.98/0.90/0.90 mol/mol creat; n = 8), Mg/24 h (0.14/0.12/0.18 mmol/kg x 24h; n = 5) and K/creat (6.3/8.4/6.2 mol/mol creat; n = 8) remained statistically unchanged during withdrawal. CONCLUSIONS: We demonstrated that HCT is effective in reducing hypercalciuria due to CLDN16 mutation on a short-term basis. However, the efficacy of HCT to attenuate disease progression remains to be elucidated.

From stellar to planetary composition: Galactic chemical evolution of Mg/Si mineralogical ratio

Aims. The main goal of this work is to study element ratios that are important for the formation of planets of different masses. Methods. We study potential correlations between the existence of planetary companions and the relative elemental abundances of their host stars. We use a large sample of FGK-type dwarf stars for which precise Mg, Si, and Fe abundances have been derived using HARPS high-resolution and high-quality data. Results. A first analysis of the data suggests that low-mass planet host stars show higher [Mg/Si] ratios, while giant planet hosts present [Mg/Si] that is lower than field stars. However, we found that the [Mg/Si] ratio significantly depends on metallicity through Galactic chemical evolution. After removing the Galactic evolution trend only the difference in the [Mg/Si] elemental ratio between low-mass planet hosts and non-hosts was present in a significant way. These results suggest that low-mass planets are more prevalent around stars with high [Mg/Si]. Conclusions. Our results demonstrate the importance of Galactic chemical evolution and indicate that it may play an important role in the planetary internal structure and composition. The results also show that abundance ratios may be a very relevant issue for our understanding of planet formation and evolution.

Quantitative assessment of soil parameters in Western Tajikistan using a soil spectral library approach

Soil degradation is a major problem in the agriculturally dominated country of Tajikistan, which makes it necessary to determine and monitor the state of soils. For this purpose a soil spectral library was established as it enables the determination of soil properties with relatively low costs and effort. A total of 1465 soil samples were collected from three 10x10 km test sites in western Tajikistan. The diffuse reflectance of the samples was measured with a FieldSpec PRO FR from ASD in the spectral range from 380 to 2500 nm in laboratory. 166 samples were finally selected based on their spectral information and analysed on total C and N, organic C, pH, CaCO₃, extractable P, exchangeable Ca, Mg and K, and the fractions clay, silt and sand. Multiple linear regression was used to set up the models. Two third of the chemically analysed samples were used to calibrate the models, one third was used for hold-out validation. Very good prediction accuracy was obtained for total C (R² = 0.76, RMSEP = 4.36 g kg⁻¹), total N (R² = 0.83, RMSEP = 0.30 g kg⁻¹) and organic C (R² = 0.81, RMSEP = 3.30 g kg⁻¹), good accuracy for pH (R² = 0.61, RMSEP = 0.157) and CaCO3(R² = 0.72, RMSEP = 4.63 %). No models could be developed for extractable P, exchangeable Ca, Mg and K, and the fractions clay, silt and sand. It can be concluded that the spectral library approach has a high potential to substitute standard laboratory methods where rapid and inexpensive analysis is required.

Current Regulating and Supporting Services: Nutrient Cycles

The study forest regulates nutrient cycles as a supporting ecosystem service mainly via retention in the biosphere and the soil organic layer. How tight the nutrient cycles are depends on environmental conditions. In this chapter, we focus on the roles of (1) deposition from the atmosphere, (2) soil moisture regime, and (3) conversion to pasture in the nutrient cycle. Between 1998 and 2010, there were a seasonal deposition of salpetric acid, an episodic deposition of Ca and Mg from Sahara dusts, and a continuous increase in reactive N inputs related to Amazonian forest fires, the El Niño Southern Oscillation cycle, and the economic development, respectively. Simultaneously, soils became increasingly drier enhancing nutrient release by mineralization. An increasing number of rain storms could considerably increase the export of N and base metals (K, Ca, Mg) via fast surface-near lateral transport in soil. Land-use change from forest to pasture introduces alkaline ashes and grass-derived organic matter. The resulting increases in soil pH and nutrient and substrate supply increase nutrient cycling rates because of enhanced microbial activity.

Chronostratigraphy of the 600,000 year old continental record of Lake Van

Lake Van sediment cores from the Ahlat Ridge and Northern Basin drill sites of the ICDP project PALEOVAN contain a wealth of information about past environmental processes. The sedimentary sequence was dated using climatostratigraphic alignment, varve chronology, tephrostratigraphy, argon-argon single-crystal dating, radiocarbon dating, magnetostratigraphy, and cosmogenic nuclides. Based on the lithostratigraphic framework, the different age constraints are compiled and a robust and precise chronology of the 600,000 year-old Lake Van record is constructed. Proxy records of total organic carbon content and sediment color, together with the calcium/potassium-ratios and arboreal pollen percentages of the 174-meter-long Ahlat Ridge record, mimic the Greenland isotope stratotype (NGRIP). Therefore, the proxy records are systematically aligned to the onsets of interstadials reflected in the NGRIP or synthesized Greenland ice-core stratigraphy. The chronology is constructed using 27 age control points derived from visual synchronization with the GICC05 timescale, an absolutely-dated speleothem record (e.g., Hulu, Sanbao, Linzhu cave) and the Epica Dome C timescale. In addition, the uppermost part of the sequence is complemented with four ages from Holocene varve chronology and two calibrated radiocarbon ages. Furthermore, nine argon-argon ages and a comparison of the relative paleointensity record of the magnetic field with reference curve PISO-1500 confirm the accuracy of the age model. Also the identification of the Laschamp event via measurements of 10Be in the sediment confirms the presented age model. The chronology of the Ahlat Ridge record is transferred to the 79-meter-long event-corrected composite record from the Northern Basin and supplemented by additional radiocarbon dating on organic marco-remains. The basal age of the Northern Basin record is estimated at ~90 ka. The variations of the time series of total organic carbon content, the Ca/K ratio, and the arboreal pollen percentages illustrate that the presented chronology and paleoclimate data are suited for reconstructions and modeling of the Quaternary and Pleistocene climate evolution in the Near East at millennial timescales. Furthermore, the chronology of the last 250 kyr can be used to test other dating techniques.

Analysis and mapping of CACNB4, CHRNA1, KCNJ3, SCN2A and SPG4, physiological candidate genes for porcine congenital progressive ataxia and spastic paresis

The cause of porcine congenital progressive ataxia and spastic paresis (CPA) is unknown. This severe neuropathy manifests shortly after birth and is lethal. The disease is inherited as a single autosomal recessive allele, designated cpa. In a previous study, we demonstrated close linkage of cpa to microsatellite SW902 on porcine chromosome 3 (SSC3), which corresponds syntenically to human chromosome 2. This latter chromosome contains ion channel genes (Ca(2+), K(+) and Na(+)), a cholinergic receptor gene and the spastin (SPG4) gene, which cause human epilepsy and ataxia when mutated. We mapped porcine CACNB4, KCNJ3, SCN2A and CHRNA1 to SSC15 and SPG4 to SSC3 with the INRA-Minnesota porcine radiation hybrid panel (IMpRH) and we sequenced the entire open reading frames of CACNB4 and SPG4 without finding any differences between healthy and affected piglets. An anti-epileptic drug treatment with ethosuximide did not change the severity of the disease, and pigs with CPA did not exhibit the corticospinal tract axonal degeneration found in humans suffering from hereditary spastic paraplegia, which is associated with mutations in SPG4. For all these reasons, the hypothesis that CACNB4, CHRNA1, KCNJ3, SCN2A or SPG4 are identical with the CPA gene was rejected.

A multi-tracer study of groundwater origin and transit-time in the aquifers of the Venice region (Italy)

Located in the northeastern region of Italy, the Venetian Plain (VP) is a sedimentary basin containing an extensively exploited groundwater system. The northern part is characterised by a large undifferentiated phreatic aquifer constituted by coarse grain alluvial deposits and recharged by local rainfalls and discharges from the rivers Brenta and Piave. The southern plain is characterised by a series of aquitards and sandy aquifers forming a well-defined artesian multi-aquifer system. In order to determine origins, transit times and mixing proportions of different components in groundwater (GW), a multi tracer study (H, He/He, C, CFC, SF, Kr, Ar, Sr/Sr, O, H, cations, and anions) has been carried out in VP between the rivers Brenta and Piave. The geochemical pattern of GW allows a distinction of the different water origins in the system, in particular based on View the MathML source HCO3-,SO42-,Ca/Mg,NO3-, O, H. A radiogenic Sr signature clearly marks GW originated from the Brenta and Tertiary catchments. End-member analysis and geochemical modelling highlight the existence of a mixing process involving waters recharged from the Brenta and Piave rivers, from the phreatic aquifer and from another GW reservoirs characterised by very low mineralization. Noble gas excesses in respect to atmospheric equilibrium occur in all samples, particularly in the deeper aquifers of the Piave river, but also in phreatic water of the undifferentiated aquifers. He–H ages in the phreatic aquifer and in the shallower level of the multi-aquifer system indicate recharge times in the years 1970–2008. The progression of H–He ages with the distance from the recharge areas together with initial tritium concentration (H + Hetrit) imply an infiltration rate of about 1 km/y and the absence of older components in these GW. SF and Kr data corroborate these conclusions. H − He ages in the deeper artesian aquifers suggest a dilution process with older, tritium free waters. C Fontes–Garnier model ages of the old GW components range from 1 to 12 ka, yielding an apparent GW velocity of about 1–10 m/y. Increase of radiogenic He follows the progression of C ages. Ar, radiogenic He and C tracers yield model-dependent age-ranges in overall good agreement once diffusion of C from aquitards, GW dispersion, lithogenic Ar production, and He production-rate heterogeneities are taken into account. The rate of radiogenic He increase with time, deduced by comparison with C model ages, is however very low compared to other studies. Comparison with C and C data obtained 40 years ago on the same aquifer system shows that exploitation of GW caused a significant loss of the old groundwater reservoir during this time.