Age-Progressive and Gender-Dependent Bone Phenotype in Mice Lacking Both Ebf1 and Ebf2 in Prrx1-Expressing Mesenchymal Cells

Ebfs are a family of transcription factors regulating the differentiation of multiple cell types of mesenchymal origin, including osteoblasts. Global deletion of Ebf1 results in increased bone formation and bone mass, while global loss of Ebf2 leads to enhanced bone resorption and decreased bone mass. Targeted deletion of Ebf1 in early committed osteoblasts leads to increased bone formation, whereas deletion in mature osteoblasts has no effect. To study the effects of Ebf2 specifically on long bone development, we created a limb bud mesenchyme targeted Ebf2 knockout mouse model by using paired related homeobox gene 1 (Prrx1) Cre. To investigate the possible interplay between Ebf1 and Ebf2, we deleted both Ebf1 and Ebf2 in the cells expressing Prrx1. Mice with Prrx1-targeted deletion of Ebf2 had a very mild bone phenotype. However, deletion of both Ebf1 and Ebf2 in mesenchymal lineage cells lead to significant, age progressive increase in bone volume. The phenotype was to some extent gender dependent, leading to an increase in both trabecular and cortical bone in females, while in males a mild cortical bone phenotype and a growth plate defect was observed. The phenotype was observed at both 6 and 12 weeks of age, but it was more pronounced in older female mice. Our data suggest that Ebfs modulate bone homeostasis and they are likely able to compensate for the lack of each other. The roles of Ebfs in bone formation appear to be complex and affected by multiple factors, such as age and gender

Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch

Silver birch (Betula pendula) is a pioneer boreal tree that can be induced to flower within 1 year. Its rapid life cycle, small (440-Mb) genome, and advanced germplasm resources make birch an attractive model for forest biotechnology. We assembled and chromosomally anchored the nuclear genome of an inbred B. pendula individual. Gene duplicates from the paleohexaploid event were enriched for transcriptional regulation, whereas tandem duplicates were overrepresented by environmental responses. Population resequencing of 80 individuals showed effective population size crashes at major points of climatic upheaval. Selective sweeps were enriched among polyploid duplicates encoding key developmental and physiological triggering functions, suggesting that local adaptation has tuned the timing of and cross-talk between fundamental plant processes. Variation around the tightly-linked light response genes PHYC and FRS10 correlated with latitude and longitude and temperature, and with precipitation for PHYC. Similar associations characterized the growth-promoting cytokinin response regulator ARR1, and the wood development genes KAK and MED5A.Peer reviewe

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Author Correction: Genome sequencing and population genomic analyses provide insights into the adaptive landscape of silver birch.

In the version of this article initially published, there was a mistake in the calculation of the nucleotide mutation rate per site per generation: 1 × 10−9 mutations per site per generation was used, whereas 9.5 × 10−9 was correct. This error affects the interpretation of population-size changes over time and their possible correspondence with known geological events, as shown in the original Fig. 4 and supporting discussion in the text, as well as details in the Supplementary Note. Neither the data themselves nor any other results are affected. Figure 4 has been revised accordingly. Images of the original and corrected figure panels are shown in the correction notice

Design parameters for nitrogen removal by constructed wetlands treating mine waters and municipal wastewater under Nordic conditions

Abstract Nitrogen (N) loads from municipal and mine wastewater discharges typically increase N concentrations in recipient water bodies which should get more attention especially in cold-climate regions. This study compared N removal efficiency of six constructed wetlands (CWs) treating mine waters and three CWs polishing municipal wastewater. There were clear impacts of point source N loading to recipient water bodies in all cases studied and &gt;300-fold increase in N was seen in some cases. First-order N removal coefficient was determined for seven of these CWs. All CWs studied were observed to remove N efficiently during the warm growing season but the amount of N released increased significantly during the cold season. Although some year-round purification was achieved by both peat-based and pond-type CWs, removal of nitrate + nitrite-N ((NO3− + NO2−)-N) was low during winter. The first-order N removal coefficient varied from 4.9 · 10−6 to 1.9 · 10−3 d−1 and showed that peat-based CWs were slightly more efficient in N removal than pond-type CWs. However, purification efficiency was steadier and higher for pond-type CWs, as lower hydraulic load or longer water residence time compensated for purification performance. Pond-type CWs showed mean removal efficiency of 59% and 46% for ammonium-N (NH4+-N) and (NO3− + NO2−)-N, respectively, whereas peatland-type CWs had lower removal efficiency for NH4+-N (mean of 26%) and in many cases negative removal for (NO3− + NO2−)-N. Correlation analysis revealed no clear, systematic relationship between temperature and N removal. However, in some CWs the highest correlation was between temperature and (NO3− + NO2−)-N, reflecting lower denitrification rate at lower temperature. More than 50% removal was found to require a hydraulic load below 10 mm d−1. In order to achieve 70% of NH4+-N removal, Ntot load lower than 75 g m−2 year−1 and a residence time longer than 80 d are needed in CWs in cold-climate regions

Arsenic, antimony, and nickel leaching from northern peatlands treating mining influenced water in cold climate

Abstract Increased metal mining in the Arctic region has caused elevated loads of arsenic (As), antimony (Sb), nickel (Ni), and sulfate (SO42−) to recipient surface or groundwater systems. The need for cost-effective active and passive mine water treatment methods has also increased. Natural peatlands are commonly used as a final step for treatment of mining influenced water. However, their permanent retention of harmful substances is affected by influent concentrations and environmental conditions. The effects of dilution, pH, temperature, oxygen availability, and contaminant accumulation on retention and leaching of As, Sb, Ni, and sulfate from mine process water and drainage water obtained from treatment peatlands in Finnish Lapland were studied in batch sorption experiments, and discussed in context of field data and environmental impacts. The results, while demonstrating effectiveness of peat to remove the target contaminants from mine water, revealed the risk of leaching of As, Sb, and SO42− from treatment peatlands when diluted mine water was introduced. Sb was more readily leached compared to As while leaching of both was supported by higher pH of 9. No straightforward effect of temperature and oxygen availability in controlling removal and leaching was evident from the results. The results also showed that contaminant accumulation in treatment peatlands after long-term use can lead to decreased removal and escalated leaching of contaminants, with the effect being more pronounced for As and Ni