Proteoliposomes as matrix vesicles' biomimetics to study the initiation of skeletal mineralization

During the process of endochondral bone formation, chondrocytes and osteoblasts mineralize their extracellular matrix by promoting the formation of hydroxyapatite (HA) seed crystals in the sheltered interior of membrane-limited matrix vesicles (MVs). Ion transporters control the availability of phosphate and calcium needed for HA deposition. The lipidic microenvironment in which MV-associated enzymes and transporters function plays a crucial physiological role and must be taken into account when attempting to elucidate their interplay during the initiation of biomineralization. In this short mini-review, we discuss the potential use of proteoliposome systems as chondrocyte- and osteoblast-derived MVs biomimetics, as a means of reconstituting a phospholipid microenvironment in a manner that recapitulates the native functional MV microenvironment. Such a system can be used to elucidate the interplay of MV enzymes during catalysis of biomineralization substrates and in modulating in vitro calcification. As such, the enzymatic defects associated with disease-causing mutations in MV enzymes could be studied in an artificial vesicular environment that better mimics their in vivo biological milieu. These artificial systems could also be used for the screening of small molecule compounds able to modulate the activity of MV enzymes for potential therapeutic uses. Such a nanovesicular system could also prove useful for the repair/treatment of craniofacial and other skeletal defects and to facilitate the mineralization of titanium-based tooth implants

Solvable K-essence Cosmologies and Modified Chaplygin Gas Unified Models of Dark Energy and Dark Matter

This paper is devoted to the investigation of modified Chaplygin gas model in the context of solvable k-essence cosmologies. For this purpose, we construct equations of state parameter of this model for some particular values of the parameter $n$. The graphical behavior of these equations are also discussed by using power law form of potential. The relationship between k-essence and modified Chaplygin gas model shows viable results in the dark energy scenario. We conclude that the universe behaves as a cosmological constant, quintessence phase or phantom phase depending upon $n$.Comment: 14 pages, 6 figure

Dissipative Future Universe without Big Rip

The present study deals with dissipative future universe without big rip in context of Eckart formalism. The generalized chaplygin gas, characterized by equation of state $p=-\frac{A}{\rho^\frac{1}{\alpha}}$, has been considered as a model for dark energy due to its dark-energy-like evolution at late time. It is demonstrated that, if the cosmic dark energy behaves like a fluid with equation of state $p=\omega\rho$; $\omega < -1$, as well as chaplygin gas simultaneously then the big rip problem does not arises and the scale factor is found to be regular for all time.Comment: 6 pages, 2 figures, To appear in Int. J. Theor. Phy

Modified gravity in a viscous and non-isotropic background

We study the dynamical evolution of an $f(R)$ model of gravity in a viscous and anisotropic background which is given by a Bianchi type-I model of the Universe. We find viable forms of $f(R)$ gravity in which one is exactly the Einsteinian model of gravity with a cosmological constant and other two are power law $f(R)$ models. We show that these two power law models are stable with a suitable choice of parameters. We also examine three potentials which exhibit the potential effect of $f(R)$ models in the context of scalar tensor theory. By solving different aspects of the model and finding the physical quantities in the Jordan frame, we show that the equation of state parameter satisfy the dominant energy condition. At last we show that the two power law $f(R)$ models behave like quintessence model at late times and also the shear coefficient viscosity tends to zero at late times.Comment: 7 pages, 2 figure

Identification of new susceptibility loci for osteoarthritis (arcOGEN):a genome-wide association study

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Osteoarthritis is the most common form of arthritis worldwide and is a major cause of pain and disability in elderly people. The health economic burden of osteoarthritis is increasing commensurate with obesity prevalence and longevity. Osteoarthritis has a strong genetic component but the success of previous genetic studies has been restricted due to insufficient sample sizes and phenotype heterogeneity. We undertook a large genome-wide association study (GWAS) in 7410 unrelated and retrospectively and prospectively selected patients with severe osteoarthritis in the arcOGEN study, 80% of whom had undergone total joint replacement, and 11,009 unrelated controls from the UK. We replicated the most promising signals in an independent set of up to 7473 cases and 42,938 controls, from studies in Iceland, Estonia, the Netherlands, and the UK. All patients and controls were of European descent. We identified five genome-wide significant loci (binomial test p≤5·0×10(-8)) for association with osteoarthritis and three loci just below this threshold. The strongest association was on chromosome 3 with rs6976 (odds ratio 1·12 [95% CI 1·08-1·16]; p=7·24×10(-11)), which is in perfect linkage disequilibrium with rs11177. This SNP encodes a missense polymorphism within the nucleostemin-encoding gene GNL3. Levels of nucleostemin were raised in chondrocytes from patients with osteoarthritis in functional studies. Other significant loci were on chromosome 9 close to ASTN2, chromosome 6 between FILIP1 and SENP6, chromosome 12 close to KLHDC5 and PTHLH, and in another region of chromosome 12 close to CHST11. One of the signals close to genome-wide significance was within the FTO gene, which is involved in regulation of bodyweight-a strong risk factor for osteoarthritis. All risk variants were common in frequency and exerted small effects. Our findings provide insight into the genetics of arthritis and identify new pathways that might be amenable to future therapeutic intervention.Arthritis Research UK 1803

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10−8, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers