Critical Role of Activating Transcription Factor 4 in the Anabolic Actions of Parathyroid Hormone in Bone

Parathyroid hormone (PTH) is a potent anabolic agent for the treatment of osteoporosis. However, its mechanism of action in osteoblast and bone is not well understood. In this study, we show that the anabolic actions of PTH in bone are severely impaired in both growing and adult ovariectomized mice lacking bone-related activating transcription factor 4 (ATF4). Our study demonstrates that ATF4 deficiency suppresses PTH-stimulated osteoblast proliferation and survival and abolishes PTH-induced osteoblast differentiation, which, together, compromise the anabolic response. We further demonstrate that the PTH-dependent increase in osteoblast differentiation is correlated with ATF4-dependent up-regulation of Osterix. This regulation involves interactions of ATF4 with a specific enhancer sequence in the Osterix promoter. Furthermore, actions of PTH on Osterix require this same element and are associated with increased binding of ATF4 to chromatin. Taken together these experiments establish a fundamental role for ATF4 in the anabolic actions of PTH on the skeleton

Genetic Drivers of Heterogeneity in Type 2 Diabetes Pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P \u3c 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care

Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P &lt; 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p

Comparing salinities of 0, 10 and 20 in biofloc genetically improved farmed tilapia (Oreochromis niloticus) production systems

A 150 days (150-d) experiment was carried out to investigate the production efficiency, inorganic nitrogen syndrome and bacteria community of indoor biofloc technology (BFT) systems used to rear genetically improved farmed tilapia (Oreochromis niloticus) under 0 (S-0), 10 (S-10), and 20 salinities (S-20). The start-up period for BFT was 50, 60 and 80 d for S-0, S-10 and S-20 groups, respectively. At steady state, the total ammonium nitrogen (NH4+-N) and nitrite nitrogen (NO2−-N) were lower than 3.0 mg/L and 0.34 mg/L, respectively and no nitrate-nitrogen (NO3−-N) accumulation was observed. The fish survival rate was above 95% for all the groups. The final fish biomass of the S-10 group (35.83 ± 1.08 kg/m3) was not significantly different from the S-0 (34.79 ± 1.33 kg/m3) group but was significantly higher than S-20 (32.6 ± 1.04 kg/m3). The feed conversion ratio for the tilapia in S-20 was 1.46, which was higher than the ratio in S-0 (1.40) and S-10 (1.39) tilapia. There was no significant difference in the crude protein content of the back muscle from tilapia of the three experimental groups. No significant difference in blood parameters, except for aspartate aminotransferase and alkaline phosphatase was observed between the three groups. Evaluation of microorganisms in the three BFT systems revealed that Proteobacteria, Bacteroidetes, and Fusobacteria were the top three at the phylum level in all groups. However, a significant difference was observed at the genus level in the bacteria of the three BFTs at different salinity (P < 0.05)

Exploiting a hybrid environmental design strategy in the continental climate of Beijing

The built environment in China is required to achieve a 50% reduction in carbon emissions by 2020 against the 1980 design standard. A particular challenge is how to maintain acceptable comfort conditions through the hot humid summers and cold desiccating winters of its continental climate regions. Fully air-conditioned sealed envelopes, often fully glazed, are becoming increasingly common in these regions. Remedial strategies involve technical refinements to the air-handling equipment and a contribution from renewable energy sources in an attempt to achieve the prescribed net reduction in energy use. However an alternative hybrid environmental design strategy is developed in this research project. It exploits observed temperate periods of weeks, days, even hours in duration to free-run an office and exhibition building configured to promote natural stack ventilation when ambient conditions permit and mechanical ventilation when conditions require it, the two modes delivered through the same physical infrastructure. The proposal is modelled in proprietary software and the methodology adopted is described. The challenge is compounded by its first practical application to an existing reinforced concrete frame originally designed to receive a highly glazed envelope. This original scheme is reviewed in comparison. Furthermore the practical delivery of the proposal value engineered out a proportion of the ventilation stacks. The likely consequence of this for the environmental performance of the building is investigated through a sensitivity study

Performance of feeding Artemia with bioflocs derived from two types of fish solid waste

The production of bioflocs with the solid waste from recirculating aquaculture systems (RAS) and feeding Artemia results in additional nutrient retention and lowers waste discharged from RAS. The solid waste from the drum-filters of two RAS, which stocked European eel (Anguilla anguilla) and Nile tilapia (Oreochromis niloticus), was used as substrate to produce bioflocs in suspended growth reactors, referred to as E-flocs and T-flocs, respectively. Mono-diets consisting of 100% E-flocs and 100% T-flocs were added to culture Artemia, referred as E-Artemia and T-Artemia, respectively, in a laboratory scale test. The efficiency of this feeding regime was investigated. A significant difference was observed in terms of crude protein content (35.59 ± 0.2%) for E-flocs, (29.29 ± 0.95)% for T-flocs, (70.01 ± 0.92)% for E-Artemia and (65.63 ± 0.89)% for T-Artemia. 134 out of the total operational taxonomic units (OTUs) were present in E-flocs and T-flocs from the analysis of high-throughput sequencing data. Most of the shared OTUs belonged to cyanobacteria. C18:1n7 of T-flocs was higher than that of E-flocs (P 0.05). The survival rate of E-Artemia was (22 ± 0.02) %, significantly higher than that of T-Artemia (16% ± 0.02%) (P 0.05). The EPA of Artemia fed with E-flocs was (3.00 ± 0.46)%, significantly higher than that of T-Artemia (1.57 ± 0.19%) (P < 0.05). This study offers a method for reusing the aquaculture waste, which will be helpful to achieve a zero-pollution discharge for aquaculture systems. Keywords: Bioflocs, Fish waste, Artemia, Recirculating aquaculture system, Suspended growth reactor

Caprolactam-Based Brønsted Acidic Ionic Liquids for Biodiesel Production from Jatropha Oil

Caprolactam-based ionic liquids show many advantages, such as the lower toxicity, lower cost, and a simple preparation process. In this work, caprolactam-based ionic liquids were prepared and adopted as catalysts for the transesterification of Jatropha oil with methanol. The results demonstrated that the SO3H-functional caprolactam‐based ionic liquids have higher catalytic activity than those of the caprolactam-based ionic liquids without sulfonic group or the SO3H-functional pyridine-based ionic liquids, attributed to their stronger Brønsted acidity. By optimizing the reaction parameter, the biodiesel yield catalyzed by 1-(4-sulfonic group) butylcaprolactamium hydrogen sulfate ([HSO3-bCPL][HSO4]) could reach above 95% at 140 °C for 3 h. Furthermore, the ionic liquid had a good reusability

Effect of seeding biofloc on the nitrification establishment in moving bed biofilm reactor (MBBR)

In recirculating aquaculture systems, nitrification is usually accelerated by inoculating nitrifier or mature biocarriers. In this study, the performance of the establishment of nitrification in the MBBR according to three different strategies: conventional method (Control group A), inoculation with biofloc recovered from a tilapia biofloc culture system (Group B), and addition with extra nitrite (Group C) in the Moving bed biofilm reactor (MBBR) was compared. Among them, the biofloc-inoculated group considerably accelerated the nitrification process in the MBBR (38 d), which is roughly 18 d faster than the control group (A) (56 d) and 21 d faster than group C (59 d). Less ammonia (8 mg/L NH4+-N, 10 mg/L in other groups) and external nitrite (2 mg/L NO2−-N) in the influent caused effluent ammonia to drop more slowly (5 d slower than the control group, 8 d slower than the B group), which is detrimental to the nitrification process' development. Notably, the influent's hydraulic retention time (HRT) was reduced from 12 h to 6 h following the successful establishment of nitrification. During the adaptation to reduced HRT, the MBBR inoculated with biofloc experienced short-term changes in the water quality index of the effluent water, whereas the other groups did not. The biofilm seeded with biofloc had the highest mean gray value ratio (1.42) of live/dead cell fluorescence, which grew better and could cover the entire groove under multiple microscope observations. However, the other groups did not demonstrate a similar trend. In summary, the research found that seeding biofloc use as nitrification bioaugmentation into the MBBR of the recirculating aquaculture system (RAS) to greatly speed up the nitrification process

Quality of life profiles and their associations with depressive symptoms and cognitive impairment of community-dwelling older adults in Hong Kong

BackgroundThis study aimed to (1) explore the quality of life (QoL) profiles of older adults in Hong Kong and (2) examine their association with predictors (age, sex, body mass index, and depressive symptoms) and distal outcome (cognitive impairment) using a person-centered approach.MethodsA total number of 328 community-dwelling older adults in Hong Kong were invited to participate in this study. Data from 259 older adults were identified as valid for the primary analysis. Latent profile analysis was used to explore QoL profiles. Multinomial logistic regression using the R3STEP function in Mplus was used to explore the predictive role of age, sex, body mass index, and depressive symptoms in profile membership. The Bolck-Croon-Hagenaars approach was used to examine how the distal outcome of cognitive impairment differs as a function of QoL profiles.ResultsThree QoL profiles emerged from the latent profile analysis (Low, Moderate and High QoL). It was found that depression, but not age, sex, or body mass index, significantly predicted QoL profile membership. The results of the Bolck-Croon-Hagenaars analysis revealed no significant differences in cognitive impairment across the three QoL profiles.ConclusionThis is the first study that examined the relationship between QoL, depressive symptoms and cognitive impairment of older adults using a person-centered approach. The findings provide additional information for the evidence obtained from variable-centered approach on the associations among variables abovementioned. Our additional focus on the antecedents of emergent QoL profiles also provide practical knowledge regarding timely treatment for or prevention of depressive symptoms, which we submit will be crucial for enhancing the QoL of older adults