Biotic and abiotic controls on carbon storage in aggregates in calcareous alpine and prealpine grassland soils

Alpine and prealpine grasslands provide various ecosystem services and are hotspots for the storage of soil organic C (SOC) in Central Europe. Yet, information about aggregate-related SOC storage and its controlling factors in alpine and prealpine grassland soils is limited. In this study, the SOC distribution according to the aggregate size classes large macroaggregates (> 2000 μm), small macroaggregates (250–2000 μm), microaggregates (63–250 μm), and silt-/clay-sized particles (< 63 μm) was studied in grassland soils along an elevation gradient in the Northern Limestone Alps of Germany. This was accompanied by an analysis of earthworm abundance and biomass according to different ecological niches. The SOC and N stocks increased with elevation and were associated with relatively high proportions of water-stable macroaggregates due to high contents of exchangeable Ca$^{2+}$ and Mg$^{2+}$. At lower elevations, earthworms appeared to act as catalyzers for a higher microaggregate formation. Thus, SOC stabilization by aggregate formation in the studied soils is a result of a joined interaction of organic matter and Ca$^{2+}$ as binding agents for soil aggregates (higher elevations), and the earthworms that act as promoters of aggregate formation through the secretion of biogenic carbonates (low elevation). Our study highlights the importance of aggregate-related factors as potential indices to evaluate the SOC storage potential in other mountainous grassland soils

Protocol for the Collection of Cross-cultural Comparative Data on Local Indicators of Climate Change Impacts

Unidad de excelencia María de Maeztu CEX2019-000940-MThis protocol has been designed to collect local perceptions of climate change impacts on climatic (e.g. rainfall patterns change), physical (e.g., shrinking glaciers), biological (e.g., phenological changes), and socioeconomic systems (e.g., crop failure due to rainfall patterns change), but also adaptations to those impacts, local agricultural calendars and local narratives to allow the reconstruction of historical and relevant events using a combination of quantitative and qualitative methodologies

Machine learning based prediction of squamous cell carcinoma in ex vivo confocal laser scanning microscopy

Image classification with convolutional neural networks (CNN) offers an unprecedented opportunity to medical imaging. Regulatory agencies in the USA and Europe have already cleared numerous deep learning/machine learning based medical devices and algorithms. While the field of radiology is on the forefront of artificial intelligence (AI) revolution, conventional pathology, which commonly relies on examination of tissue samples on a glass slide, is falling behind in leveraging this technology. On the other hand, ex vivo confocal laser scanning microscopy (ex vivo CLSM), owing to its digital workflow features, has a high potential to benefit from integrating AI tools into the assessment and decision-making process. Aim of this work was to explore a preliminary application of CNN in digitally stained ex vivo CLSM images of cutaneous squamous cell carcinoma (cSCC) for automated detection of tumor tissue. Thirty-four freshly excised tissue samples were prospectively collected and examined immediately after resection. After the histologically confirmed ex vivo CLSM diagnosis, the tumor tissue was annotated for segmentation by experts, in order to train the MobileNet CNN. The model was then trained and evaluated using cross validation. The overall sensitivity and specificity of the deep neural network for detecting cSCC and tumor free areas on ex vivo CLSM slides compared to expert evaluation were 0.76 and 0.91, respectively. The area under the ROC curve was equal to 0.90 and the area under the precision-recall curve was 0.85. The results demonstrate a high potential of deep learning models to detect cSCC regions on digitally stained ex vivo CLSM slides and to distinguish them from tumor-free skin

Discordant Clinical Course of Vitamin-D-Hydroxylase (CYP24A1) Associated Hypercalcemia in Two Adult Brothers With Nephrocalcinosis

Background/Aims: Hypercalcemia can result in nephrocalcinosis/nephrolithiasis and may lead to renal failure. Idiopathic infantile hypercalcemia is caused by mutations of the CYP24A1 gene, which regulates vitamin D activity. Classically infants present with hypercalcemia. Recently, a number of individuals have been reported with late onset clinical manifestation or late diagnosis in adulthood. All these patients are believed to show hypercalciuria. Methods: We report a 24 year old patient of healthy consanguine parents. Genetic analysis was performed by Sanger sequencing of the CYP24A1 gene in the index patient and targeted exon 2 analysis of all other family members. Results: The patient was hospitalized with severe malaise during an acute EBV-infection. He showed hypercalcemia > 3mmol/l and acute, hypovolemic renal failure with profound nephrocalcinosis, but no hypercalciuria. Genetic workup revealed a homozygous loss-of-function mutation p.E143del in the CYP24A1 gene. His clinically asymptomatic brother showed nephrocalcinosis of lesser degree. Repeatedly, low parathyroid hormone levels were detected in both brothers. Conclusion: This family displays the highly variable phenotype of CYP24A1 biallelic mutation carriers. CYP24A1 associated disease is an important differential diagnosis for the workup and counseling of infants as well as adults with hypercalcemia since a proper genetic diagnosis may result in therapeutic consequences

A collaborative approach to bring insights from local observations of climate change impacts into global climate change research

Bringing insights from Indigenous and local knowledge into climate change research requires addressing the transferability, integration, and scalability of this knowledge. Using a review of research on place-based observations of climate change impacts, we explore ways to address these challenges. Our search mostly captured scientist-led qualitative research, which - while facilitating place-based knowledge transferability to global research - did not include locally led efforts documenting climate change impacts. We classified and organized qualitative multi-site place-based information into a hierarchical system that fosters dialogue with global research, providing an enriched picture of climate change impacts on local social-ecological systems. A network coordinating the scalability of place-based research on climate change impacts is needed to bring Indigenous and local knowledge into global research and policy agendas.Peer reviewe

Consistency in climate change impact reports among indigenous peoples and local communities depends on site contexts

Unidad de excelencia María de Maeztu CEX2019-000940-MIndigenous Peoples and local communities are heavily affected by climatic changes. Investigating local understandings of climate change impacts, and their patterned distribution, is essential to effectively support monitoring and adaptation strategies. In this study, we aimed to understand the consistency in climate change impact reports and factors influencing consistency at site and individual levels. We conducted cross-cultural research among iTaukei (Fiji), Dagomba (Ghana), fisherfolks (Tanzania), Tsimane' (Bolivia), Bassari (Senegal), ribeirinhos (Brazil), Mapuche (Chile), Mongolian (China), Tibetan (China) and Daasanach (Kenya) communities using semi-structured interviews, focus groups, and surveys among 1860 individuals. We found that cross-culturally more than two-thirds of individual reports of climate change impacts match site-confirmed reports. Consistency in reports is higher for changes related to pastoralism than crop production and wild plant gathering. Individual's experience with nature, Indigenous and local knowledge, and local family roots are not significantly associated with consistency across sites, but site-specific associations are prevalent. Despite high average consistency among sites, there is considerable variation caused by site-specific factors, including livelihood activities, socio-cultural settings, and environmental conditions. Site contexts and related consistency in climate change impact reports need to be taken into account for climate change monitoring and adaptation planning

Refining Kidney Survival in 383 Genetically Characterized Patients With Nephronophthisis

Introduction: Nephronophthisis (NPH) comprises a group of rare disorders accounting for up to 10% of end-stage kidney disease (ESKD) in children. Prediction of kidney prognosis poses a major challenge. We assessed differences in kidney survival, impact of variant type, and the association of clinical characteristics with declining kidney function. Methods: Data was obtained from 3 independent sources, namely the network for early onset cystic kidney diseases clinical registry (n = 105), an online survey sent out to the European Reference Network for Rare Kidney Diseases (n = 60), and a literature search (n = 218). Results: A total of 383 individuals were available for analysis: 116 NPHP1, 101 NPHP3, 81 NPHP4 and 85 NPHP11/TMEM67 patients. Kidney survival differed between the 4 cohorts with a highly variable median age at onset of ESKD as follows: NPHP3, 4.0 years (interquartile range 0.3–12.0); NPHP1, 13.5 years (interquartile range 10.5–16.5); NPHP4, 16.0 years (interquartile range 11.0–25.0); and NPHP11/TMEM67, 19.0 years (interquartile range 8.7–28.0). Kidney survival was significantly associated with the underlying variant type for NPHP1, NPHP3, and NPHP4. Multivariate analysis for the NPHP1 cohort revealed growth retardation (hazard ratio 3.5) and angiotensin-converting enzyme inhibitor (ACEI) treatment (hazard ratio 2.8) as 2 independent factors associated with an earlier onset of ESKD, whereas arterial hypertension was linked to an accelerated glomerular filtration rate (GFR) decline. Conclusion: The presented data will enable clinicians to better estimate kidney prognosis of distinct patients with NPH and thereby allow personalized counseling

Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using ∼2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5×10−8) or suggestive associations (p<4×10−7) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4×10−7. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels

Reductions in External Divalent Cations Evoke Novel Voltage-Gated Currents in Sensory Neurons

It has long been recognized that divalent cations modulate cell excitability. Sensory nerve excitability is of critical importance to peripheral diseases associated with pain, sensory dysfunction and evoked reflexes. Thus we have studied the role these cations play on dissociated sensory nerve activity. Withdrawal of both Mg2+ and Ca2+ from external solutions activates over 90% of dissociated mouse sensory neurons. Imaging studies demonstrate a Na+ influx that then causes depolarization-mediated activation of voltage-gated Ca2+ channels (CaV), which allows Ca2+ influx upon divalent re-introduction. Inhibition of CaV (ω-conotoxin, nifedipine) or NaV (tetrodotoxin, lidocaine) fails to reduce the Na+ influx. The Ca2+ influx is inhibited by CaV inhibitors but not by TRPM7 inhibition (spermine) or store-operated channel inhibition (SKF96365). Withdrawal of either Mg2+ or Ca2+ alone fails to evoke cation influxes in vagal sensory neurons. In electrophysiological studies of dissociated mouse vagal sensory neurons, withdrawal of both Mg2+ and Ca2+ from external solutions evokes a large slowly-inactivating voltage-gated current (IDF) that cannot be accounted for by an increased negative surface potential. Withdrawal of Ca2+ alone fails to evoke IDF. Evidence suggests IDF is a non-selective cation current. The IDF is not reduced by inhibition of NaV (lidocaine, riluzole), CaV (cilnidipine, nifedipine), KV (tetraethylammonium, 4-aminopyridine) or TRPM7 channels (spermine). In summary, sensory neurons express a novel voltage-gated cation channel that is inhibited by external Ca2+ (IC50∼0.5 µM) or Mg2+ (IC50∼3 µM). Activation of this putative channel evokes substantial cation fluxes in sensory neurons