Inactivation of Osteoblast PKC Signaling Reduces Cortical Bone Mass and Density and Aggravates Renal Osteodystrophy in Mice with Chronic Kidney Disease on High Phosphate Diet

Chronic kidney disease (CKD) frequently leads to hyperphosphatemia and hyperparathyroidism, mineral bone disorder (CKD-MBD), ectopic calcifications and cardiovascular mortality. PTH activates the osteoanabolic Gα_s/PKA and the Gα_q/11/PKC pathways in osteoblasts, the specific impact of the latter in CKD-MBD is unknown. We generated osteoblast specific Gα_q/11 knockout (KO) mice and established CKD-MBD by subtotal nephrectomy and dietary phosphate load. Bone morphology was assessed by micro-CT, osteoblast function by bone planar scintigraphy at week 10 and 22 and by histomorphometry. Osteoblasts isolated from Gα_q/11 KO mice increased cAMP but not IP3 in response to PTH 1-34, demonstrating the specific KO of the PKC signaling pathway. Osteoblast specific Gα_q/11 KO mice exhibited increased serum calcium and reduced bone cortical thickness and mineral density at 24 weeks. CKD Gα_q/11 KO mice had similar bone morphology compared to WT, while CKD Gα_q/11-KO on high phosphate diet developed decreased metaphyseal and diaphyseal cortical thickness and area, as well as a reduction in trabecular number. Gα_q/11-KO increased bone scintigraphic tracer uptake at week 10 and mitigated tracer uptake in CKD mice at week 22. Histological bone parameters indicated similar trends. Gα_q/11-KO in osteoblast modulates calcium homeostasis, bone formation rate, bone morphometry, and bone mineral density. In CKD and high dietary phosphate intake, osteoblast Gα_q/11/PKC KO further aggravates mineral bone disease.     

Milk fat globule membrane glycoproteins: Valuable ingredients for lactic acid bacteria encapsulation?

The membrane (Milk Fat Globule Membrane – MFGM) surrounding the milk fat globule is becoming increasingly studied for its use in food applications due to proven nutritional and technological properties. This review focuses first on current researches which have been led on the MFGM structure and composition and also on laboratory and industrial purification and isolation methods developed in the last few years. The nutritional, health benefits and techno-functional properties of the MFGM are then discussed. Finally, new techno-functional opportunities of MFGM glycoproteins as a possible ingredient for Lactic Acid Bacteria (LAB) encapsulation are detailed. The ability of MFGM to form liposomes entrapping bioactive compounds has been already demonstrated. One drawback is that liposomes are too small to be used for bacteria encapsulation. For the first time, this review points out the numerous advantages to use MFGM glycoproteins as a protecting, encapsulating matrix for bacteria and especially for LAB.     

Antioxidant activity and phenolic content of 16 raisin grape (Vitis vinifera L.) cultivars and selections

Six raisin grape cultivars and 10 new raisin grape selections were analyzed for antioxidant activity (ABTS assay) and for total and individual phenolic compounds. Samples were freeze–dried and values are reported on a dry weight basis. Antioxidant activity across the 16 samples ranged from 7.7 to 60.9 μmol Trolox/g DW, with A95-27 exhibiting the greatest activity. Total phenolic content, determined in gallic acid equivalents using the Folin–Ciocalteau assay, ranged from 316.3 to 1141.3 mg gallic acid/100 g DW and was strongly correlated (r = 0.990) with antioxidant results. Concentrations of individual phenolics were determined by HPLC. trans-Caftaric acid was the predominant compound in all samples. A95-15 contained the lowest concentration (153.5 μg/g DW) of caftaric acid, while Fiesta contained the highest concentration (598.7 μg/g DW). Selections A56-66, A95-15, and A95-27 had much higher levels of catechin (86.5–209.1 μg/g DW) and epicatechin (126.5–365.7 μg/g DW) than the other samples.     

“I think you just got mixed up”: confident peer tutors hedge to support partners’ face needs

During collaborative learning, computer-supported or otherwise, students balance task-oriented goals with the interpersonal goals of relationship-building. This means that in peer tutoring, some pedagogically beneficial behaviors may be avoided by peer tutors due to their likelihood to get in the way of relationship-building. In this paper, we explore how the interpersonal closeness between students in a peer tutoring dyad and the peer tutors’ instructional self-efficacy impacts those tutors’ delivery style of various tutoring moves, and explore the impact those tutoring move delivery styles have on their partners’ learning. We found that tutors with lower social closeness with their tutees provide more positive feedback to their tutee and use more indirect instructions and comprehension-monitoring, but this is only the case for tutors with greater tutoring self-efficacy. And in fact, those tutees solved more problems and learned more when their tutors hedged instructions and comprehension-monitoring, respectively. We found no effect of hedging for dyads with greater social closeness, on the other hand, suggesting that interpersonal closeness may reduce the face-threat of direct instructions and comprehension-monitoring, and hence reduce the need for indirectness, while tutors’ instructional self-efficacy allows tutors to use those moves without feeling threatened themselves. These results emphasize that designers of CSCL systems should understand the nature of how the interpersonal closeness between collaborating students intersects with those students’ self-efficacy to impact the use and delivery of their learning behaviors, in order to best support them in collaborating effectively.     

Numerical simulation of gasless combustion taking into account the heterogeneity of the structure and the temperature dependence of diffusion

This paper presents the results of numerical simulation of self-propagating high-temperature synthesis based on a model that takes into account the heterogeneity of the mixture of the reacting powders and the temperature-dependent mutual diffusion. Dependences of the velocity of the combustion front on the size of the averaged element of the heterogeneous structure are obtained for different diffusion activation energies. It is found that as the activation energy of diffusion increases, an oscillatory regime of propagation of the combustion front is established. The boundary of the transition from the steady-state propagation of the combustion front to the oscillatory regime is determined.     

Oleuropein Prevents Neuronal Death,Mitigates Mitochondrial Superoxide Production and Modulates Autophagy in a Dopaminergic Cellular Model

Parkinson’s disease (PD) is a progressive neurodegenerative disorder, primarily affecting dopaminergic neurons in the substantia nigra. There is currently no cure for PD and present medications aim to alleviate clinical symptoms, thus prevention remains the ideal strategy to reduce the prevalence of this disease. The goal of this study was to investigate whether oleuropein (OLE), the major phenolic compound in olive derivatives, may prevent neuronal degeneration in a cellular dopaminergic model of PD, differentiated PC12 cells exposed to the potent parkinsonian toxin 6-hydroxydopamine (6-OHDA). We also investigated OLE’s ability to mitigate mitochondrial oxidative stress and modulate the autophagic flux. Our results obtained by measuring cytotoxicity and apoptotic events demonstrate that OLE significantly decreases neuronal death. OLE could also reduce mitochondrial production of reactive oxygen species resulting from blocking superoxide dismutase activity. Moreover, quantification of autophagic and acidic vesicles in the cytoplasm alongside expression of specific autophagic markers uncovered a regulatory role for OLE against autophagic flux impairment induced by bafilomycin A1. Altogether, our results define OLE as a neuroprotective, anti-oxidative and autophagy-regulating molecule, in a neuronal dopaminergic cellular model.     

Citywide multi-grid urban flood modelling: the July 2012 flood in Beijing

Global flood management is a major issue for most cities which have to deal with worsening factors such as climate change and fast urban growth. Computer models have been used to model and understand urban flooding on a local scale in cities (25–50 km²). It has been practically impossible to model bigger cities in one go in sufficiently high resolution due to the heavy computations involved.

The present paper describes a new modelling approach for urban flooding which allows modelling on large city scale (1000 km²) while keeping sufficient resolution, e.g. 5 m or 10 m grid. The multicell approach is applied for the city of Beijing for July 21st, 2012 flood event. Model results are compared to testimonials from the 2012 event. Comparison to traditional 2D urban flood computations shows that the multicell approach is much faster than standard detailed models while keeping a suitable level of precision.     

Major Ampullate Spider Silk with Indistinguishable Spidroin Dope Conformations Leads to Different Fiber Molecular Structures

To plentifully benefit from its properties (mechanical, optical, biological) and its potential to manufacture green materials, the structure of spider silk has to be known accurately. To this aim, the major ampullate (MA) silk of Araneus diadematus (AD) and Nephila clavipes (NC) has been compared quantitatively in the liquid and fiber states using Raman spectromicroscopy. The data show that the spidroin conformations of the two dopes are indistinguishable despite their specific amino acid composition. This result suggests that GlyGlyX and GlyProGlyXX amino acid motifs (X = Leu, Glu, Tyr, Ser, etc.) are conformationally equivalent due to the chain flexibility in the aqueous environment. Species-related sequence specificity is expressed more extensively in the fiber: the β-sheet content is lower and width of the orientation distribution of the carbonyl groups is broader for AD (29% and 58°, respectively) as compared to NC (37% and 51°, respectively). β-Sheet content values are close to the proportion of polyalanine segments, suggesting that β-sheet formation is mainly dictated by the spidroin sequence. The extent of molecular alignment seems to be related to the presence of proline (Pro) that may decrease conformational flexibility and inhibit chain extension and alignment upon drawing. It appears that besides the presence of Pro, secondary structure and molecular orientation contribute to the different mechanical properties of MA threads.     

Spheroid model study comparing the biocompatibility of Biodentine and MTA

The primary objective of this study was to assess the biological effects of a new dentine substitute based on Ca₃SiO₅ (Biodentine?) for use in pulp-capping treatment, on pseudo-odontoblastic (MDPC-23) and pulp (Od-21) cells. The secondary objective was to evaluate the effects of Biodentine and mineral trioxide aggregate (MTA) on gene expression in cultured spheroids. We used the acid phosphatase assay to compare the biocompatibility of Biodentine and MTA. Cell differentiation was investigated by RT-qPCR. We investigated the expression of genes involved in odontogenic differentiation (Runx2), matrix secretion (Col1a1, Spp1) and mineralisation (Alp). ANOVA and PLSD tests were used for data analysis. MDPC-23 cells cultured in the presence of MTA had higher levels of viability than those cultured in the presence of Biodentine and control cells on day 7 (P = 0.0065 and P = 0.0126, respectively). For Od-21 cells, proliferation rates on day 7 were significantly lower in the presence of Biodentine or MTA than for control (P < 0.0001). Col1a1 expression levels were slightly lower in cells cultured in the presence of MTA than in those cultured in the presence of Biodentine and in control cells. Biodentine and MTA may modify the proliferation of pulp cell lines. Their effects may fluctuate over time, depending on the cell line considered. The observed similarity between Biodentine and MTA validates the indication for direct pulp-capping claimed by the manufacturers.