Implications of the polymorphism of HLA-G on its function, regulation, evolution and disease association

The HLA-G gene displays several peculiarities that are distinct from those of classical HLA class I genes. The unique structure of the HLA-G molecule permits a restricted peptide presentation and allows the modulation of the cells of the immune system. Although polymorphic sites may potentially influence all biological functions of HLA-G, those present at the promoter and 3′ untranslated regions have been particularly studied in experimental and pathological conditions. The relatively low polymorphism observed in the MHC-G coding region both in humans and apes may represent a strong selective pressure for invariance, whereas, in regulatory regions several lines of evidence support the role of balancing selection. Since HLA-G has immunomodulatory properties, the understanding of gene regulation and the role of polymorphic sites on gene function may permit an individualized approach for the future use of HLA-G for therapeutic purposes

Sensing, measuring and modelling the mechanical properties of sandstone

We present a hybrid framework for simulating the strength and dilation characteristics of sandstone. Where possible, the grain-scale properties of sandstone are evaluated experimentally in detail. Also, using photo-stress analysis, we sense the deviator stress (/strain) distribution at the microscale and its components along the orthogonal directions on the surface of a V-notch sandstone sample under mechanical loading. Based on this measurement and applying a grain-scale model, the optical anisotropy index K0 is inferred at the grain scale. This correlated well with the grain contact stiffness ratio K evaluated using ultrasound sensors independently. Thereafter, in addition to other experimentally characterised structural and grain-scale properties of sandstone, K is fed as an input into the discrete element modelling of fracture strength and dilation of the sandstone samples. Physical bulk scale experiments are also conducted to evaluate the load-displacement relation, dilation and bulk fracture strength characteristics of sandstone samples under compression and shear. A good level of agreement is obtained between the results of the simulations and experiments. The current generic framework could be applied to understand the internal and bulk mechanical properties of such complex opaque and heterogeneous materials more realistically in future

EXPRESSION OF MITOCHONDRIAL GENOME ALTERATION AS A POTENTIAL BIOMARKER FOR COLORECTAL ADENOPOLYPS IN RELATIVE TO AGE AND RACE

Colorectal cancer (CRC) is a major cause of morbidity and mortality in the United States. The precision of an appropriate staging of colorectal polyp progression to cancer is misperceived among pathologists as well as doctors. Alternative approaches, such as identification of molecular markers associated with CRC progression, will be a useful predictive tool, to decrease the incidence colorectal cancer. The mitochondrial DNA (mtDNA) is predominantly susceptible to mutations because of high levels of reactive oxygen species (ROS) within the organelle. The cumulative frequency of mitochondrial genome mutations is age-related. Given that colorectal cancer is most frequently seen in older people, mtDNA mutations may play a vital role in CRC tumorigenesis which may inhibit oxidative phosphorylation due to increase ROS production. This study aims to identify a profile of mtDNA mutations/protein expression patterns in the early stages of colorectal tumors within and among African-American (AA) and Caucasian patients relative to age stratification. A combination of PCR-based sequencing and qRT-PCR technologies were employed to determine the mtDNA variants and different proteins expression levels in 16 CRC tissues samples obtained from the University of Alabama-Cooperative Human Tissue Network. Fifty-eight mtDNA mutations were identified out of which 93% of mutations were somatic and 7% were germline mutation. Most germline mutations were found in COIII region. Three of the mutations of COIII Adel9409, A9437G Gdel9438 were not reported previously. Additionally, the relative RNA expression in ATP6 region in the early stages CRC adenoma was higher in AA compare to Caucasian tissue samples. Our preliminary results suggest that there are certain mitochondrial mutations/expressions that may be associated with specific adenoma stages. Subsequently, our findings may aid in designing new clinical strategies for early screening and prevention in individuals with high risk

Chromatin protein HP1α interacts with the mitotic regulator borealin protein and specifies the centromere localization of the chromosomal passenger complex

Accurate mitosis requires the chromosomal passenger protein complex (CPC) containing Aurora B kinase, borealin, INCENP, and survivin, which orchestrates chromosome dynamics. However, the chromatin factors that specify the CPC to the centromere remain elusive. Here we show that borealin interacts directly with heterochromatin protein 1α (HP1α) and that this interaction is mediated by an evolutionarily conserved PXVXL motif in the C-terminal borealin with the chromo shadow domain of HP1α. This borealin-HP1α interaction recruits the CPC to the centromere and governs an activation of Aurora B kinase judged by phosphorylation of Ser-7 in CENP-A, a substrate of Aurora B. Consistently, modulation of the motif PXVXL leads to defects in CPC centromere targeting and aberrant Aurora B activity. On the other hand, the localization of the CPC in the midzone is independent of the borealin-HP1α interaction, demonstrating the spatial requirement of HP1α in CPC localization to the centromere. These findings reveal a previously unrecognized but direct link between HP1α and CPC localization in the centromere and illustrate the critical role of borealin-HP1α interaction in orchestrating an accurate cell division. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc

Rho Kinase Phosphorylation Promotes Ezrin-Mediated Metastasis in Hepatocellular Carcinoma

View looking at top level of theater core from top of escalator; Known colloquially as The Egg. The Centre, an ellipsoid dome of titanium and glass surrounded by an artificial lake, seats 5,452 people in three halls (Opera, Music and Theater) and is almost 12,000 m² in size. The exterior of the theater is a titanium accented glass dome that is completely surrounded by a man-made lake. It is said to look like an egg floating on water, or a water drop. The dome measures 212 meters in east-west direction, 144 meters in north-south direction, and is 46 meters high. Guests arrive in the building after walking through a hallway that goes underneath the lake. The titanium shell is broken by a glass curtain in north-south direction that gradually widens from top to bottom. Source: Wikipedia; http://en.wikipedia.org/wiki/Main_Page (accessed 5/11/2011