A two-scale damage model for high cycle fatigue delamination in laminated composites

In this paper a model for predicting fatigue delamination growth in laminated composites under high cycle fatigue is proposed. The model uses the cohesive zone approach and a two-scale continuum damage mechanics model. The behavior of the interface material is considered quasi-brittle at the macro scale while plastic deformations are allowed at the scale of micro-defects. The validity of the proposed model is investigated through several standard tests using experimental data from literature. Good agreement between the numerical and experimental results is observed. The model is also capable of simulating fatigue under variable amplitude loading. This feature of model is shown through several sample simulations

Lysophosphatidic acid acyltransferase 3 regulates Golgi complex structure and function

Recent studies have suggested that the functional organization of the Golgi complex is dependent on phospholipid remodeling enzymes. Here, we report the identification of an integral membrane lysophosphatidic acid–specific acyltransferase, LPAAT3, which regulates Golgi membrane tubule formation, trafficking, and structure by altering phospholipids and lysophospholipids. Overexpression of LPAAT3 significantly inhibited the formation of Golgi membrane tubules in vivo and in vitro. Anterograde and retrograde protein trafficking was slower in cells overexpressing LPAAT3 and accelerated in cells with reduced expression (by siRNA). Golgi morphology was also dependent on LPAAT3 because its knockdown caused the Golgi to become fragmented. These data are the first to show a direct role for a specific phospholipid acyltransferase in regulating membrane trafficking and organelle structure

Three new chondrosarcoma cell lines: one grade III conventional central chondrosarcoma and two dedifferentiated chondrosarcomas of bone

BackgroundChondrosarcoma is the second most common primary sarcoma of bone. High-grade conventional chondrosarcoma and dedifferentiated chondrosarcoma have a poor outcome. In pre-clinical research aiming at the identification of novel treatment targets, the need for representative cell lines and model systems is high, but availability is scarce.MethodsWe developed and characterized three cell lines, derived from conventional grade III chondrosarcoma (L835), and dedifferentiated chondrosarcoma (L2975 and L3252) of bone. Proliferation and migration were studied and we used COBRA-FISH and array-CGH for karyotyping and genotyping. Immunohistochemistry for p16 and p53 was performed as well as TP53 and IDH mutation analysis. Cells were injected into nude mice to establish their tumorigenic potential.ResultsWe show that the three cell lines have distinct migrative properties, L2975 had the highest migration rate and showed tumorigenic potential in mice. All cell lines showed chromosomal rearrangements with complex karyotypes and genotypic aberrations were conserved throughout late passaging of the cell lines. All cell lines showed loss of CDKN2A, while TP53 was wild type for exons 5–8. L835 has an IDH1 R132C mutation, L2975 an IDH2 R172W mutation and L3252 is IDH wild type.ConclusionsBased on the stable culturing properties of these cell lines and their genotypic profile resembling the original tumors, these cell lines should provide useful functional models to further characterize chondrosarcoma and to evaluate new treatment strategies

Lipid phosphate phosphatase 3 participates in transport carrier formation and protein trafficking in the early secretory pathway

The inhibition of phosphatidic acid phosphatase (PAP) activity by propanolol indicates that diacylglycerol (DAG) is required for the formation of transport carriers at the Golgi and for retrograde trafficking to the ER. Here we report that the PAP2 family member lipid phosphate phosphatase 3 (LPP3, also known as PAP2b) localizes in compartments of the secretory pathway from ER export sites to the Golgi complex. The depletion of human LPP3: (i) reduces the number of tubules generated from the ER-Golgi intermediate compartment and the Golgi, with those formed from the Golgi being longer in LPP3-silenced cells than in control cells; (ii) impairs the Rab6-dependent retrograde transport of Shiga toxin subunit B from the Golgi to the ER, but not the anterograde transport of VSV-G or ssDsRed; and (iii) induces a high accumulation of Golgi-associated membrane buds. LPP3 depletion also reduces levels of de novo synthesized DAG and the Golgi-associated DAG contents. Remarkably, overexpression of a catalytically inactive form of LPP3 mimics the effects of LPP3 knockdown on Rab6-dependent retrograde transport. We conclude that LPP3 participates in the formation of retrograde transport carriers at the ER-Golgi interface, where it transitorily cycles, and during its route to the plasma membrane

Clinical practice: The care of children with Down syndrome

Down syndrome (DS) is one of the most common chromosomal abnormalities. Because of medical advances and improvements in overall medical care, the median survival of individuals with DS has increased considerably. This longer life expectancy requires giving the necessary care to the individual with DS over their total longer lifespan. DS medical guidelines are designed for the optimal care of the child in whom a diagnosis of DS has been confirmed. We present an overview of the most important issues related to children with DS based on the most relevant literature currently available

The HOG Pathway Dictates the Short-Term Translational Response after Hyperosmotic Shock

In the global osmoshock translational response in yeast, some gene products were translationally mobilized without transcriptional up-regulation. Conversely, other transcriptionally up-regulated mRNAs were translationally inhibited. Analogous changes occurred on the protein level. These translational responses were strongly dependent on Hog1 and Rck2

Galacto-Oligosaccharides : production, properties, applications, and significance as prebiotics

Galacto-oligosaccharides (GOS) have now been definitely established as prebiotic ingredients after in vitro and animal and human in vivo studies. Currently, GOS are produced by glycoside hydrolases (GH) using lactose as substrate. Converting lactose into GOS by GH results in mixtures containing GOS of different degrees of polymerization (DP), unreacted lactose, and monomeric sugars (glucose and galactose). Recent and future developments in the production of GOS aim at delivering purer and more efficient mixtures. To produce high-GOS-content mixtures, GH should not only have good ability to catalyze the transgalactosylation reaction relative to hydrolysis, but also have low affinity for the GOS formed relative to the affinity for lactose. In this article, several microbial GH, proposed for the synthesis of GOS, are hierarchized according to the referred performance indicators. In addition, strategies for process improvement are discussed. Besides the differences in purity of GOS mixtures, differences in the position of the glycosidic linkages occur, because different enzymes have different regiochemical selectivity. Depending on oligosaccharide composition, GOS products will vary in terms of prebiotic activity, as well as other physiological effects. This review focuses on GOS production from synthesis to purification processes. Physicochemical characteristics, physiological effects, and applications of these prebiotic ingredients are summarized. Regulatory aspects of GOS-containing food products are also highlighted with emphasis on the current process of health claims evaluation in Europe.Agência da Inovação-Progama IDEIA (Portugal)Fundação para a Ciência e a Tecnologia (FCT