O-GlcNAc transferase integrates metabolic pathways to regulate the stability of c-MYC in human prostate cancer cells

Metabolic disruptions that occur widely in cancers offer an attractive focus for generalized treatment strategies. The hexosamine biosynthetic pathway (HBP) senses metabolic status and produces an essential substrate for O-linked β-N-acetylglucosamine transferase (OGT), which glycosylates and thereby modulates the function of its target proteins. Here, we report that the HBP is activated in prostate cancer cells and that OGT is a central regulator of c-Myc stability in this setting. HBP genes were overexpressed in human prostate cancers and androgen regulated in cultured human cancer cell lines. Immunohistochemical analysis of human specimens (n = 1987) established that OGT is upregulated at the protein level and that its expression correlates with high Gleason score, pT and pN stages, and biochemical recurrence. RNA interference-mediated siliencing or pharmacologic inhibition of OGT was sufficient to decrease prostate cancer cell growth. Microarray profiling showed that the principal effects of OGT inhibition in prostate cancer cells were related to cell-cycle progression and DNA replication. In particular, c-MYC was identified as a candidate upstream regulator of OGT target genes and OGT inhibition elicited a dose-dependent decrease in the levels of c-MYC protein but not c-MYC mRNA in cell lines. Supporting this relationship, expression of c-MYC and OGT was tightly correlated in human prostate cancer samples (n = 1306). Our findings identify HBP as a modulator of prostate cancer growth and c-MYC as a key target of OGT function in prostate cancer cells.

The stability of alcohol consumption between age 16 and 26: Evidence from a National Birth Cohort Study

This study examined the association between moderate drinking at age 16 (adolescence) and alcohol consumption at age 26 (young adulthood), whilst controlling for possible confounding effects at the individual and family level (assessed at birth and age 10). Using the British Cohort Study (BCS70), 6515 respondents provided data on their adolescent alcohol consumption and other behaviours. Of these, 4392 also completed the survey at age 26. Consumption patterns established in adolescence persisted, to a large degree, into early adulthood. Those adolescents who drank moderately in adolescence drank significantly less in adulthood than those adolescents who drank to heavy or hazardous levels. Implications for health promotion strategies and guidance are discussed.

Evolving techniques for characterising and monitoring the stability of infrastructure slopes

Landslides and debris flows, commonly triggered by rainfall, pose a geotechnical risk causing disruption to transport routes and incur significant financial expenditure. With infrastructure maintenance budgets becoming ever more constrained, this paper provides an overview of some of the developing methods being implemented by Queen’s University, Belfast in collaboration with the Department for Regional Development to monitor the stability of two distinctly different infrastructure slopes in Northern Ireland. In addition to the traditional, intrusive ground investigative and laboratory testing methods, aerial LiDAR, terrestrial LiDAR, geophysical techniques and differential Global Positioning Systems have been used to monitor slope stability. Finally, a comparison between terrestrial LiDAR, pore water pressure and soil moisture deficit (SMD) is presented to outline the processes for a more informed management regime and to highlight the season relationship between landslide activity and the aforementioned parameters.

Impact of long-term storage at ambient temperatures on the total quality and stability of high-pressure processed tomato juice

High-pressure processing (HPP) can produce tomato juice of high quality and safety with a short shelf life under refrigeration temperatures. Long-term higher temperature storage studies are rare and temperature tolerant products are challenging to develop. The effect of high-pressure processing (HPP) on the total quality (colour, microbial counts, phytochemical levels, antioxidant and enzymatic activities) and stability (retention over time) of tomato juice during long-term storage was investigated. Thermal processing (TP) was used as a control treatment, and overall, two different ambient conditions (20 °C and 28 °C) were tested. Immediately after processing, HPP products proved superior to TP ones (enhanced redness, total carotenoids and lycopene, stable total phenols and inactivation of pectin methyl esterase). During initial storage (30 d) most quality attributes of HPP juice remained stable. Prolonged storage, however, led to losses of most quality attributes, although HPP (20 °C) showed lower quality degradation rate constants comparison to TP and HPP (28 °C). Industrial Relevance: There is a demand for ambient stable tomato products, especially in some parts of the world, and current industrial practices (canning, pasteurisation) either compromise in product quality or require refrigeration conditions. High-pressure processing has been investigated as milder technology, with a potential to deliver superior quality. The drawback is that is also requires chill storage. The results of this study show how quality parameters behave in a high-pressured tomato product and pave the way for further development that could optimise this technology. This could be of economic importance for the tomato juice industry to develop new products stable in ambient temperatures and perhaps beneficial for cutting down the refrigeration costs under specific conditions.

High temperature thermal stability of the HfO2/Ge (100) interface as a function of surface preparation studied by synchrotron radiation core level photo emission

High resolution soft x-ray photoemission spectroscopy (SXPS) have been used to study the high temperature thermal stability of ultra-thin atomic layer deposited (ALD) HfO2 layers (∼1 nm) on sulphur passivated and hydrofluoric acid (HF) treated germanium surfaces. The interfacial oxides which are detected for both surface preparations following HfO2 deposition can be effectively removed by annealing upto 700 °C without any evidence of chemical interaction at the HfO2/Ge interface. The estimated valence and conduction band offsets for the HfO2/Ge abrupt interface indicated that effective barriers exist to inhibit carrier injection.

Structural stability of adenylate kinase from the sulfate-reducing bacteria Desulfovibrio gigas

Biophysical Chemistry 110 (2004) 83–92

Metal ions modulate the folding and stability of the tumor suppressor protein S100A2

Febs Journal (2009)276:1776-1786

Isolation and characterization of genomic DNA sequences that enhance the stability of plasmid DNA in mammalian cells /

The ease of production and manipulation has made plasmid DNA a prime target for its use in gene transfer technologies such as gene therapy and DNA vaccines. The major drawback of plasmid however is its stability within mammalian cells. Plasmid DNA is usually lost by cellular mechanisms or as a result of mitosis by simple dilution. This study set out to search for mammalian genomic DNA sequences that would enhance the stability of plasmid DNA in mammalian cells.Creating a plasmid based genomic DNA library, we were able to screen the human genome by transfecting the library into Human Embryonic Kidney (HEK 293) Cells. Cells that contained plasmid DNA were selected, using G418 for 14 days. The resulting population was then screened for the presence of biologically active plasmid DNA using the process of transformation as a detector.A commercially available plasmid DNA isolation kit was modified to extract plasmid DNA from mammalian cells. The standardized protocol had a detection limit of -0.6 plasmids per cell in one million cells. This allowed for the detection of 45 plasmids that were maintained for 32 days in the HEK 293 cells. Sequencing of selected inserts revealed a significantly higher thymine content in comparison to the human genome. Sequences with high A/T content have been associated with Scaffold/Matrix Attachment Region (S/MAR) sequences in mammalian cells. Therefore, association with the nuclear matrix might be required for the stability of plasmids in mammalian cells.

Information Sharing and the Stability of Cooperation in Research Joint Ventures.

The model studies information sharing and the stability of cooperation in cost reducing Research Joint Ventures (RJVs). In a four-stage game-theoretic framework, firms decide on participation in a RJV, information sharing, R&D expenditures, and output. An important feature of the model is that voluntary information sharing between cooperating firms increases information leakage from the RJV to outsiders. It is found that it is the spillover from the RJV to outsiders which determines the decision of insiders whether to share information, while it is the spillover affecting all firms which determines the level of information sharing within the RJV. RJVs representing a larger portion of firms in the industry are more likely to share information. It is also found that when sharing information is costless, firms never choose intermediate levels of information sharing : they share all the information or none at all. The size of the RJV is found to depend on three effects : a coordination effect, an information sharing effect, and a competition effect. Depending on the relative magnitudes of these effects, the size of the RJV may increase or decrease with spillovers. The effect of information sharing on the profitability of firms as well as on welfare is studied.

Stability of Random Sums and Extremes

This study is about the stability of random sums and extremes.The difficulty in finding exact sampling distributions resulted in considerable problems of computing probabilities concerning the sums that involve a large number of terms.Functions of sample observations that are natural interest other than the sum,are the extremes,that is , the minimum and the maximum of the observations.Extreme value distributions also arise in problems like the study of size effect on material strengths,the reliability of parallel and series systems made up of large number of components,record values and assessing the levels of air pollution.It may be noticed that the theories of sums and extremes are mutually connected.For instance,in the search for asymptotic normality of sums ,it is assumed that at least the variance of the population is finite.In such cases the contributions of the extremes to the sum of independent and identically distributed(i.i.d) r.vs is negligible.

Biochemical Investigations on the Stability of Biological Membranes

In this project, an attempt has been made to study the stability of erythrocyte and lysosomal membranes biochemically. Erythrocytes were chosen for the study because of their ready availability and relative simplicity. Biological membranes forming closed boundaries between compartments of varying composition consist mainly of proteins and lipids. They are asymmetric, fluid structures that are thermodynamically stable and metabolically active. Normal cellular function begins with normal membrane structure and any variation in it may upset the normal functions. The degree of fluidity of a membrane depends on the chain length of its lipids and degree of unsaturation of constituent fatty acids. In response to environmental changes, many cells can regulate composition of their membranes to maintain the overall semi fluid environment necessary for many membrane associated functions. The assembly and Maintenance of membrane structures in cells is a dynamic process. The components are not only synthesized and inserted into a growing membrane but are also continuously degraded at a slower rate. This turnover process varies with each individual molecule.Lysosomes are important in the catabolic processes occurring in the cell. Lysosomes contain hydrolytic enzymes and are stable under normal conditions. In certain pathological conditions, the lysosomal membrane may rupture, releasing the hydrolytic enzymes into the cell and digestion of cell takes place as a whole. This is very dangerous. In normal life processes of multi cellular organisms, lysosomes rupture following the death of a cell and it may have some value as a built in mechanism for selfremoval of dead cells.An attempt has also been made in this project towards developing lysosome membrane stability as an index of fish spoilage during storage. Different membranes within the cell and between cells have different compositions as reflected in the ratio of protein to lipid. The difference is not surprising given the very different functions of membranes

Influence of Processing Variables on Protein Quality and Frozen Storage Stability of Two Commercially Important Species of Squid (Loligo duvaucelii and Doryteuthis sibogae )

Cephalopods are utilized as an important food item in various countries because of its delicacy as raw consumed food. Mainly sepia and loligo are consumed raw by Japanese and Russians. The freshness of the products is very important when the product is consumed raw. The major species that dominate our squid catch are Loligo duvaucelii and Doryteuthis sibogae. There is a noticeable difference in the quality of both the species. The needle squid (Doryteuthis sibogae ) contributes about 35% of the total squid landing. Due to the fast deterioration , a major portion of the needle squid, which is caught during the first few hauls, is thrown back to sea. The catch in the last hauls only are taken to the landing centers. At present the needle squid is processed as blanched rings and the desired quality is not obtained if it is processed as whole, whole cleaned or as tubes. In this study an attempt is made to investigate the biochemical characteristics in both the species of squid in relation to their quality and, the process control measures to be adopted. The effect of various treatments on their quality and the changes in proteolytic and lysosomal enzymes under various processing conditions are also studied in detail.Thus this study can provide the seafood industry with relevant suggestions and solutions for effective utilization of both the species of squid with emphasis on needle squid.

Acid activated montmorillonite: an efficient immobilization support for improving reusability, storage stability and operational stability of enzymes

Three enzymes, α-amylase, glucoamylase and invertase, were immobilized on acid activated montmorillonite K 10 via two independent techniques, adsorption and covalent binding. The immobilized enzymes were characterized by XRD, N2 adsorption measurements and 27Al MAS-NMR spectroscopy. The XRD patterns showed that all enzymes were intercalated into the clay inter-layer space. The entire protein backbone was situated at the periphery of the clay matrix. Intercalation occurred through the side chains of the amino acid residues. A decrease in surface area and pore volume upon immobilization supported this observation. The extent of intercalation was greater for the covalently bound systems. NMR data showed that tetrahedral Al species were involved during enzyme adsorption whereas octahedral Al was involved during covalent binding. The immobilized enzymes demonstrated enhanced storage stability. While the free enzymes lost all activity within a period of 10 days, the immobilized forms retained appreciable activity even after 30 days of storage. Reusability also improved upon immobilization. Here again, covalently bound enzymes exhibited better characteristics than their adsorbed counterparts. The immobilized enzymes could be successfully used continuously in the packed bed reactor for about 96 hours without much loss in activity. Immobilized glucoamylase demonstrated the best results.