Bone mass does not correlate with the serum fibroblast growth factor 23 in hemodialysis patients

Circulating fibroblast growth factor 23 (FGF23) increases renal phosphate excretion, decreases bone mineralization and is markedly increased in hemodialysis patients. Bone cells express fibroblast growth receptor 1, suggesting that FGF23 could alter bone mineralization by means of a direct effect on the skeleton and/or secondarily due to hypophosphatemia. To distinguish between these possibilities we measured serum concentrations of FGF23, parathyroid hormone, phosphate, calcium, and markers of bone remodeling, and assessed bone mineral density in 99 hemodialysis patients. FGF23 concentrations were increased in all hemodialysis patients, even in those without hyperphosphatemia, and positively correlated with serum phosphate but not with parathyroid hormone. Hemodialysis did not decrease the serum FGF23 concentration. We found no significant correlation between serum FGF23 levels and bone mineral density. Further analysis by gender or T-score did not modify these results. Serum markers of bone remodeling significantly correlated with parathyroid hormone but not with FGF23 levels. The increase in serum FGF23 concentration in hemodialysis patients cannot be solely ascribed to hyperphosphatemia. Our study suggests that the effects of FGF23 on bone mineralization are mainly due to hypophosphatemia and not a direct effect on bone

Freshwater conservation assessments in (semi-)arid regions: testing river intermittence and buffer strategies using freshwater mussels (Bivalvia, Unionida) in Morocco

The IUCN Red List assessments are essentially based on population trends and range, namely Area of Occupancy (AOO) and Extent of Occupancy (EOO). Range estimations are based on fixed grids, but this is likely inappropriate for species living in river networks. Furthermore, AOO and EOO are measured using the whole hydrographic network, therefore disregarding temporary sections, which is particularly problematic in arid and semi-arid regions. Here we mapped the permanent hydrographic network of Morocco using satellite imagery, complemented with field surveys to collect samples for molecular analyses of the five freshwater mussel species present and assess their distribution. The phylogeographic patterns are described for each species and used to identify priority areas and evolutionary significant units for conservation. Permanent hydrographic river sections represent only 18.3% of the whole hydrographic network. A north-to-south gradient of genetic diversity, species richness and distribution range was found, being coherent with water availability and river intermittence. Isolated evolutionary units were detected in southern basins that should also receive particular attention in conservation planning. We propose the mean river width multiplied by the extent of the river network as the best and the most adequate way to estimate both EOO and AOO. Given the worldwide degradation of freshwater systems and biodiversity, an accurate (re)assessment of species conservation status supported with maps of intermittent water bodies will be essential for prioritizing and guiding conservation actions and management plans, especially in arid and semi-arid regions.This work was partially supported by the Portuguese Foundation for Science and Technology (FCT) under grant SFRH/BD/115728/2016 (MLL) and grant SFRH/BD/137935/2018 (AGS). This research was developed under ConBiomics: the missing approach for the Conservation of freshwater Bivalves Project N° NORTE-01-0145-FEDER-030286, co-financed by COMPETE 2020, Portugal 2020 and the European Union through the ERDF, and by FCT through national funds. This study was additionally conducted within the scope of project “Biodiversity and conservation of the critically endangered freshwater mussels in Morocco: ecogeographic, genetic and physiological information”, funded by Mohamed bin Zayed Species Conservation Fund (Reference 15256799) and project “Breeding the most endangered bivalve on Earth: Margaritifera marocana”, funded by IUCN SOS save our species fund (Reference 2015B-015). Official capture and sampling licenses were issued by the Université Cadi Ayyad (Faculté des Sciences, Semlalia, Marrakech, Maroc)

Microcondylaea bonellii as a new host for the European bitterling Rhodeus amarus

We report for the first time that the freshwater mussel Microcondylaea bonellii (Ferussac, 1827) functions as a suitable host for the European bitterling Rhodeus amarus (Bloch, 1782). Given the recent expansion of R. amarus in Europe, the possible physiological cost (e.g. competition for oxygen, reduction in water circulation, and consequent impairment of filter-feeding) of this interaction may further affect the already poor conservation status of M. bonellii populations.We acknowledge the two anonymous referees for the helpful suggestions that improve the clarity of our manuscript. This research was funded by FCT under project ConBiomics No NORTE-01-0145-FEDER-030286, cofinanced by COMPETE 2020, Portugal 2020 and the European Union through the ERDF

What controls the isotopic composition of Greenland surface snow?

International audienceWater stable isotopes in Greenland ice core data provide key paleoclimatic information, and have been compared with precipitation isotopic composition simulated by isotopically enabled atmospheric models. However, post-depositional processes linked with snow metamorphism remain poorly documented. For this purpose, monitoring of the isotopic composition (d18O, dD) of near-surface water vapor, precipitation and samples of the top (0.5 cm) snow surface has been conducted during two summers (2011-2012) at NEEM, NW Greenland. The samples also include a subset of 17O-excess measurements over 4 days, and the measurements span the 2012 Greenland heat wave. Our observations are consistent with calculations assuming isotopic equilibrium between surface snow and water vapor. We observe a strong correlation between near-surface vapor d18O and air temperature (0.85 ± 0.11‰ °C-1 (R = 0.76) for 2012). The correlation with air temperature is not observed in precipitation data or surface snow data. Deuterium excess (d-excess) is strongly anti-correlated with d18O with a stronger slope for vapor than for precipitation and snow surface data. During nine 1-5-day periods between precipitation events, our data demonstrate parallel changes of d18O and d-excess in surface snow and near-surface vapor. The changes in d18O of the vapor are similar or larger than those of the snow d18O. It is estimated using the CROCUS snow model that 6 to 20% of the surface snow mass is exchanged with the atmosphere. In our data, the sign of surface snow isotopic changes is not related to the sign or magnitude of sublimation or deposition. Comparisons with atmospheric models show that day-to-day variations in near-surface vapor isotopic composition are driven by synoptic variations and changes in air mass trajectories and distillation histories. We suggest that, in between precipitation events, changes in the surface snow isotopic composition are driven by these changes in near-surface vapor isotopic composition. This is consistent with an estimated 60% mass turnover of surface snow per day driven by snow recrystallization processes under NEEM summer surface snow temperature gradients. Our findings have implications for ice core data interpretation and model-data comparisons, and call for further process studies. © Author(s) 2014

Functional Interaction between CFTR and the Sodium-Phosphate Co-Transport Type 2a in Xenopus laevis Oocytes

A growing number of proteins, including ion transporters, have been shown to interact with Cystic Fibrosis Transmembrane conductance Regulator (CFTR). CFTR is an epithelial chloride channel that is involved in Cystic Fibrosis (CF) when mutated; thus a better knowledge of its functional interactome may help to understand the pathophysiology of this complex disease. In the present study, we investigated if CFTR and the sodium-phosphate co-transporter type 2a (NPT2a) functionally interact after heterologous expression of both proteins in Xenopus laevis oocytes.NPT2a was expressed alone or in combination with CFTR in X. laevis oocytes. Using the two-electrode voltage-clamp technique, the inorganic phosphate-induced current (IPi) was measured and taken as an index of NPT2a activity. The maximal IPi for NPT2a substrates was reduced when CFTR was co-expressed with NPT2a, suggesting a decrease in its expression at the oolemna. This was consistent with Western blot analysis showing reduced NPT2a plasma membrane expression in oocytes co-expressing both proteins, whereas NPT2a protein level in total cell lysate was the same in NPT2a- and NPT2a+CFTR-oocytes. In NPT2a+CFTR- but not in NPT2a-oocytes, IPi and NPT2a surface expression were increased upon PKA stimulation, whereas stimulation of Exchange Protein directly Activated by cAMP (EPAC) had no effect. When NPT2a-oocytes were injected with NEG2, a short amino-acid sequence from the CFTR regulatory domain that regulates PKA-dependent CFTR trafficking to the plasma membrane, IPi values and NPT2a membrane expression were diminished, and could be enhanced by PKA stimulation, thereby mimicking the effects of CFTR co-expression.We conclude that when both CFTR and NPT2a are expressed in X. laevis oocytes, CFTR confers to NPT2a a cAMPi-dependent trafficking to the membrane. This functional interaction raises the hypothesis that CFTR may play a role in phosphate homeostasis

Captive breeding of Margaritifera auricularia (Spengler, 1793) and its conservation importance

Margaritifera auricularia is one of the most endangered freshwater mussels (Bivalvia, Unionida) in the world. Since 2013, the abundance of this species in the Ebro River basin (Spain) has sharply declined, driving the species to the verge of regional extinction. Therefore, any management measures that might facilitate the recovery of this species would be essential for its conservation. During 2014–2016, captive breeding of M. auricularia allowed the production of >106 juveniles, out of which 95% were released into the natural environment, and 5% were grown in the laboratory under controlled conditions. The aim of this experimental work was to establish the best culture conditions for the survival and growth of M. auricularia juveniles in the laboratory. The experiment was divided into two phases: phase I, in which juveniles recently detached from fish gills were cultured in detritus boxes until they reached a shell length of 1 mm; and phase II, in which these specimens were transferred to larger aquaria to grow up to 3–4 mm. The best experimental conditions for juvenile survival and growth corresponded to treatments in glass containers at a density of 0.2 ind. L−1, using river water, with added substrate and detritus, enriched with phytoplankton, and avoiding extra aeration. The highest survival and growth rates attained, respectively, values of c. 60% at 100 days and 2.56 mm in shell length at 30–32 weeks. This is the first study to report on the long‐term survival and growth of juvenile M. auricularia in the laboratory, providing essential information in order to implement future conservation measures addressed at reinforcing the natural populations of this highly threatened species in European water bodies.This project was funded by the Government of Aragón, Department of Rural Development and Sustainability and carried out by the Environmental Service Department of SARGA. Special thanks go to Manuel Alcántara, Miguel Ángel Muñoz, Ester Ginés, Carlos Catalá, and Juan Pablo de la Roche, who were involved in the project. The authors appreciate the work of the reviewer and editor who improved the quality of the manuscript. The Aragón's forest rangers are thanked for their assistance during fieldwork

Race-free estimated glomerular filtration rate equation in kidney transplant recipients:development and validation study

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P 30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m 2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m 2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P 30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P 30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys.TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.</p

Biology and conservation of freshwater bivalves : past, present and future perspectives

Freshwater bivalves have been highly threatened by human activities, and recently their global decline has been causing conservational and social concern. In this paper, we review the most important research events in freshwater bivalve biology calling attention to the main scientific achievements. A great bias exists in the research effort, with much more information available for bivalve species belonging to the Unionida in comparison to other groups. The same is true for the origin of these studies, since the publishing pattern does not always correspond to the hotspots of biodiversity but is concentrated in the northern hemisphere mainly in North America, Europe and Russia, with regions such as Africa and Southeast Asia being quite understudied. We also summarize information about past, present and future perspectives concerning the most important research topics that include taxonomy, systematics, anatomy, physiology, ecology and conservation of freshwater bivalves. Finally, we introduce the articles published in this Hydrobiologia special issue related with the International Meeting on Biology and Conservation of Freshwater Bivalves held in 2012 in Braganc¸a, Portugal.We would like to express our gratitude to our sponsors and institutions, especially to the Polytechnic Institute of Braganca for all the logistic support. We acknowledge all keynote speakers, authors, session chairpersons and especially to all attendees whose contributions were fundamental for the success of this meeting. We would also like to thank all referees of this special issue and to Koen Martens, Editor-in-Chief of Hydrobiologia, for all the valuable comments and suggestions. The chronogram was built with the help of the expert opinion of fellow colleagues Rafael Araujo, Arthur Bogan, Kevin Cummings, Dan Graf, Wendell Haag, Karl-Otto Nagel and David Strayer to whom we are very grateful. The authors acknowledge the support provided by Portuguese Foundation for Science and Technology (FCT) and COMPETE funds-projects CONBI (Contract: PTDC/AAC-AMB/117688/2010) and ECO-IAS (Contract: PTDC/AAC-AMB/116685/2010), and by the European Regional Development Fund (ERDF) through the COMPETE, under the project "PEst-C/MAR/LA0015/2011"

A Genome-Wide Association Study of Nephrolithiasis in the Japanese Population Identifies Novel Susceptible Loci at 5q35.3, 7p14.3, and 13q14.1

Nephrolithiasis is a common nephrologic disorder with complex etiology. To identify the genetic factor(s) for nephrolithiasis, we conducted a three-stage genome-wide association study (GWAS) using a total of 5,892 nephrolithiasis cases and 17,809 controls of Japanese origin. Here we found three novel loci for nephrolithiasis: RGS14-SLC34A1-PFN3-F12 on 5q35.3 (rs11746443; P = 8.51×10−12, odds ratio (OR) = 1.19), INMT-FAM188B-AQP1 on 7p14.3 (rs1000597; P = 2.16×10−14, OR = 1.22), and DGKH on 13q14.1 (rs4142110; P = 4.62×10−9, OR = 1.14). Subsequent analyses in 21,842 Japanese subjects revealed the association of SNP rs11746443 with the reduction of estimated glomerular filtration rate (eGFR) (P = 6.54×10−8), suggesting a crucial role for this variation in renal function. Our findings elucidated the significance of genetic variations for the pathogenesis of nephrolithiasis