MV-mimicking micelles loaded with PEG-serine-ACP nanoparticles to achieve biomimetic intra/extra fibrillar mineralization of collagen in vitro

Since their discovery, matrix vesicles (MVs) containing minerals have received considerable attention for their role in the mineralization of bone, dentin and calcified cartilage. Additionally, MVs' association with collagen fibrils, which serve as the scaffold for calcification in the organic matrix, has been repeatedly highlighted. The primary purpose of the present study was to establish a MVs–mimicking model (PEG-S-ACP/micelle) in vitro for studying the exact mechanism of MVs-mediated extra/intra fibrillar mineralization of collagen in vivo. In this study, high-concentration serine was used to stabilize the amorphous calcium phosphate (S-ACP), which was subsequently mixed with polyethylene glycol (PEG) to form PEG-S-ACP nanoparticles. The nanoparticles were loaded in the polysorbate 80 micelle through a micelle self-assembly process in an aqueous environment. This MVs–mimicking model is referred to as the PEG-S-ACP/micelle model. By adjusting the pH and surface tension of the PEG-S-ACP/micelle, two forms of minerals (crystalline mineral nodules and ACP nanoparticles) were released to achieve the extrafibrillar and intrafibrillar mineralization, respectively. This in vitro mineralization process reproduced the mineral nodules mediating in vivo extrafibrillar mineralization and provided key insights into a possible mechanism of biomineralization by which in vivo intrafibrillar mineralization could be induced by ACP nanoparticles released from MVs. Also, the PEG-S-ACP/micelle model provides a promising methodology to prepare mineralized collagen scaffolds for repairing bone defects in bone tissue engineering.     

Enhancement of the repair of carcinogen-induced DNA damage in the hamster pancreas by dietary selenium

We measured single strand breaks (SSB) in pancreas DNA produced by N-nitrosobis(2-oxopropyl)amine (BOP) in hamsters fed purified diets containing added sodium selenite (Se) at 0.0, 0.1 and 5.0 ppm. There were fewer SSB in those given the 5.0 ppm Se diet throughout the experiment. One hour after dosing with BOP (20 mg/kg), there were 2.26 ± 0.47, 2.83 ± 0.43 and 1.74 ± 0.43 SSB per 10⁸ daltons (mean ± S.E.M.) respectively in the three groups. The SSB were repaired faster in the 5.0 ppm Se-fed group. The approximate half-lives of the SSB were 33, 30 and 8 days, respectively. In the hamsters fed 5.0 ppm Se there was a small, statistically significant increase in pancreatic DNA synthesis. Autoradiographic analysis indicated that this was repair synthesis. In a second experiment, hamsters were fed one of the three diets prior to and for 2 days after administration of a single dose of BOP (20 mg/kg). They were then fed the 5.0 ppm Se diet for 5 days. The number of SSB was compared with those in hamsters fed their original diet for 7 days after BOP dosing. There was a statistically significant difference in the number of SSB in the hamsters fed 0.1 ppm Se before and for 2 days after BOP. In these hamsters there were 1.21 ± 0.24 SSB per 10⁸ daltons compared with 3.19 ± 0.4 (mean ± S.E.M.). These results suggest high levels of dietary Se stimulate the repair of carcinogen-induced DNA damage.     

Testing different 3D techniques using geometric morphometrics: Implications for cranial fluctuating asymmetry in humans

This study aimed to test the performance of 3D digitizer, CT scanner, and surface scanner in detecting cranial fluctuating asymmetry. Sets of 32 landmarks (6 in the midline and 13 bilateral) were acquired from 14 archeological crania using a 3D digitizer, and from 3D models generated from a CT scanner and surface scanner using Viewbox 4. Levels of shape variation were analyzed in MorphoJ using Procrustes analysis of variance and Principal component analysis. Intra-observer error accounted for 1.7%, 1.8%, and 4.5% of total shape variation for 3D digitizer, CT scanner, and surface scanner respectively. Fluctuating asymmetry accounted for 15%–16% of total shape variation. Variation between techniques accounted for 18% of total shape variation. We found a higher level of missing landmarks in our surface scan data than for both 3D digitizer and CT scanner data, and both 3D model-based techniques sometimes obscured taphonomic damage. All three 3D techniques are appropriate for measuring cranial fluctuating asymmetry. We advise against combining data collected with different techniques.     

Niche breadth explains the range size of European-centred butterflies,but dispersal ability does not

Aim

The breadth of ecological niches and dispersal abilities have long been discussed as important determinants of species' range sizes. However, studies directly comparing the relative effects of both factors are rare, taxonomically biased and revealed inconsistent results.

Location

Europe.

Time Period

Cenozoic.

Major Taxa

Butterflies, Lepidoptera.

Methods

We relate climate, diet and habitat niche breadth and two indicators of dispersal ability, wingspan and a dispersal tendency index, to the global range size of 369 European-centred butterfly species. The relative effects of these five predictors and their variation across the butterfly phylogeny were assessed by means of phylogenetic generalized least squares models and phylogenetically weighted regressions respectively.

Results

Climate niche breadth was the most important single predictor, followed by habitat and diet niche breadth, while dispersal tendency and wingspan showed no relation to species' range size. All predictors together explained 59% of the variation in butterfly range size. However, the effects of each predictor varied considerably across families and genera.

Main Conclusions

Range sizes of European-centred butterflies are strongly correlated with ecological niche breadth but apparently independent of dispersal ability. The magnitude of range size–niche breadth relationships is not stationary across the phylogeny and is often negatively correlated across the different dimensions of the ecological niche. This variation limits the generalizability of range size–trait relationships across broad taxonomic groups.     

微生境对黄梅秤锤树野生种群叶片功能性状的影响

植物功能性状可以反映植物应对环境变化的适应策略。本文以黄梅秤锤树(Sinojackia huangmeiensis)当前唯一野生种群为对象, 比较了3种微生境(湖边、种群中心、耕地边)中该物种的叶片功能性状均值、种内变异和叶片生态化学计量特征的差异, 分析了黄梅秤锤树对湖岸带微生境变化的响应及其适应策略。结果表明: (1) 3种微生境中土壤C、N、P含量没有显著性差异(P > 0.05), 但土壤C∶N和C∶P具有显著性差异(P < 0.05), 土壤类型和养分条件有所不同。(2)黄梅秤锤树叶片功能性状的比较用单因素方差分析和贝叶斯方差分析得出的结果一致, 均为叶长、叶面积和比叶面积在中心区域显著高于湖边(P < 0.05), 而耕地边与湖边和中心区域均没有显著差异(P > 0.05); 叶N含量在湖边显著高于中心区域和耕地边(P < 0.05), 而中心区域和耕地边间没有显著差异(P > 0.05); 叶宽、叶长/叶宽、叶干物质含量、叶C和叶P含量在3种微生境间都没有显著性差异(P > 0.05)。(3)黄梅秤锤树叶片的N∶P在湖边显著高于中心区域和耕地边(P < 0.05), C∶N在湖边显著小于中心区域和耕地边(P < 0.05), N∶P和C∶N在中心区域和耕地边没有显著性差异(P > 0.05), C∶P在3种微生境间都没有显著性差异(P > 0.05)。(4)黄梅秤锤树叶片功能性状的总体变异程度在0.02-0.28之间, 其中叶片C和N含量在湖边和中心区域的种内变异程度显著较低, 表明3种生境中湖边和中心区域黄梅秤锤树种群的稳定性相对较差。(5)湖边黄梅秤锤树主要通过增加叶N含量促进生长; 中心区域黄梅秤锤树主要通过增加叶面积和比叶面积以及提高叶N的利用效率来提高光捕获能力促进生长; 耕地边黄梅秤锤树的叶N含量和叶面积、比叶面积都处于中等水平, 通过性状之间的共同作用使植株生长达到最佳水平。以上结果表明, 由于微地形、水位波动和土壤环境条件的差异, 黄梅秤锤树对3种生境中的适应策略有所不同, 并且不是通过单一性状调整来适应环境的变化, 而是通过多种性状之间的权衡达到更好的适应效果。     

Understanding the Reduced Efficiencies of Organic Solar Cells Employing Fullerene Multiadducts as Acceptors

The use of fullerenes with two or more adducts as acceptors has been recently shown to enhance the performance of bulk‐heterojunction solar cells using poly(3‐hexylthiophene) (P3HT) as the donor. The enhancement is caused by a substantial increase in the open‐circuit voltage due to a rise in the fullerene lowest unoccupied molecular orbital (LUMO) level when going from monoadducts to multiadducts. While the increase in the open‐circuit voltage is obtained with many different polymers, most polymers other than P3HT show a substantially reduced photocurrent when blended with fullerene multiadducts like bis‐PCBM (bis adduct of Phenyl‐C₆₁‐butyric acid methyl ester) or the indene C₆₀ bis‐adduct ICBA. Here we investigate the reasons for this decrease in photocurrent. We find that it can be attributed partly to a loss in charge generation efficiency that may be related to the LUMO‐LUMO and HOMO‐HOMO (highest occupied molecular orbital) offsets at the donor‐acceptor heterojunction, and partly to reduced charge carrier collection efficiencies. We show that the P3HT exhibits efficient collection due to high hole and electron mobilities with mono‐ and multiadduct fullerenes. In contrast the less crystalline polymer Poly[[9‐(1‐octylnonyl)‐9H‐carbazole‐2,7‐diyl]‐2,5‐thiophenediyl‐2,1,3‐benzothiadiazole‐4,7‐diyl‐2,5‐thiophenediyl (PCDTBT) shows inefficient charge carrier collection, assigned to low hole mobility in the polymer and low electron mobility when blended with multiadduct fullerenes.     

Distance-based analysis of variance for brain connectivity

The field of neuroimaging dedicated to mapping connections in the brain is increasingly being recognized as key for understanding neurodevelopment and pathology. Networks of these connections are quantitatively represented using complex structures, including matrices, functions, and graphs, which require specialized statistical techniques for estimation and inference about developmental and disorder-related changes. Unfortunately, classical statistical testing procedures are not well suited to high-dimensional testing problems. In the context of global or regional tests for differences in neuroimaging data, traditional analysis of variance (ANOVA) is not directly applicable without first summarizing the data into univariate or low-dimensional features, a process that might mask the salient features of high-dimensional distributions. In this work, we consider a general framework for two-sample testing of complex structures by studying generalized within-group and between-group variances based on distances between complex and potentially high-dimensional observations. We derive an asymptotic approximation to the null distribution of the ANOVA test statistic, and conduct simulation studies with scalar and graph outcomes to study finite sample properties of the test. Finally, we apply our test to our motivating study of structural connectivity in autism spectrum disorder.     

Honokiol: A non-adipogenic PPARγ agonist from nature

Background

Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are clinically used to counteract hyperglycemia. However, so far experienced unwanted side effects, such as weight gain, promote the search for new PPARγ activators.

Methods

We used a combination of in silico, in vitro, cell-based and in vivo models to identify and validate natural products as promising leads for partial novel PPARγ agonists.

Results

The natural product honokiol from the traditional Chinese herbal drug Magnolia bark was in silico predicted to bind into the PPARγ ligand binding pocket as dimer. Honokiol indeed directly bound to purified PPARγ ligand-binding domain (LBD) and acted as partial agonist in a PPARγ-mediated luciferase reporter assay. Honokiol was then directly compared to the clinically used full agonist pioglitazone with regard to stimulation of glucose uptake in adipocytes as well as adipogenic differentiation in 3T3-L1 pre-adipocytes and mouse embryonic fibroblasts. While honokiol stimulated basal glucose uptake to a similar extent as pioglitazone, it did not induce adipogenesis in contrast to pioglitazone. In diabetic KKAy mice oral application of honokiol prevented hyperglycemia and suppressed weight gain.

Conclusion

We identified honokiol as a partial non-adipogenic PPARγ agonist in vitro which prevented hyperglycemia and weight gain in vivo.

General significance

This observed activity profile suggests honokiol as promising new pharmaceutical lead or dietary supplement to combat metabolic disease, and provides a molecular explanation for the use of Magnolia in traditional medicine.     

Identification of glyoxalase 1 polymorphisms associated with enzyme activity

The glyoxalase system and its main enzyme, glyoxalase 1 (GLO1), protect cells from advanced glycation end products (AGEs), such as methylglyoxal (MG) and other reactive dicarbonyls, the formation of which is increased in diabetes patients as a result of excessive glycolysis. MG is partly responsible for harmful protein alterations in living cells, notably in neurons, leading to their dysfunction, and recent studies have shown a negative correlation between GLO1 expression and tissue damage. Neuronal dysfunction is a common diabetes complication due to elevated blood sugar levels, leading to high levels of AGEs. The aim of our study was to determine whether single nucleotide polymorphisms (SNPs) in the GLO1 gene influence activity of the enzyme. In total, 125 healthy controls, 101 type 1 diabetes, and 100 type 2 diabetes patients were genotyped for three common SNPs, rs2736654 (A111E), rs1130534 (G124G), and rs1049346 (5′-UTR), in GLO1. GLO1 activity was determined in whole blood lysates for all participants of the study.