Fourteen gene GBM prognostic signature identifies association of immune response pathway and mesenchymal subtype with high risk group

Background: Recent research on glioblastoma (GBM) has focused on deducing gene signatures predicting prognosis. The present study evaluated the mRNA expression of selected genes and correlated with outcome to arrive at a prognostic gene signature. Methods: Patients with GBM (n = 123) were prospectively recruited, treated with a uniform protocol and followed up. Expression of 175 genes in GBM tissue was determined using qRT-PCR. A supervised principal component analysis followed by derivation of gene signature was performed. Independent validation of the signature was done using TCGA data. Gene Ontology and KEGG pathway analysis was carried out among patients from TCGA cohort. Results: A 14 gene signature was identified that predicted outcome in GBM. A weighted gene (WG) score was found to be an independent predictor of survival in multivariate analysis in the present cohort (HR = 2.507; B = 0.919; p < 0.001) and in TCGA cohort. Risk stratification by standardized WG score classified patients into low and high risk predicting survival both in our cohort (p = <0.001) and TCGA cohort (p = 0.001). Pathway analysis using the most differentially regulated genes (n = 76) between the low and high risk groups revealed association of activated inflammatory/immune response pathways and mesenchymal subtype in the high risk group. Conclusion: We have identified a 14 gene expression signature that can predict survival in GBM patients. A network analysis revealed activation of inflammatory response pathway specifically in high risk group. These findings may have implications in understanding of gliomagenesis, development of targeted therapies and selection of high risk cancer patients for alternate adjuvant therapies.

Effect of signal peptide on stability and folding of escherichia coli thioredoxin

The signal peptide plays a key role in targeting and membrane insertion of secretory and membrane proteins in both prokaryotes and eukaryotes. In E. coli, recombinant proteins can be targeted to the periplasmic space by fusing naturally occurring signal sequences to their N-terminus. The model protein thioredoxin was fused at its N-terminus with malE and pelB signal sequences. While WT and the pelB fusion are soluble when expressed, the malE fusion was targeted to inclusion bodies and was refolded in vitro to yield a monomeric product with identical secondary structure to WT thioredoxin. The purified recombinant proteins were studied with respect to their thermodynamic stability, aggregation propensity and activity, and compared with wild type thioredoxin, without a signal sequence. The presence of signal sequences leads to thermodynamic destabilization, reduces the activity and increases the aggregation propensity, with malE having much larger effects than pelB. These studies show that besides acting as address labels, signal sequences can modulate protein stability and aggregation in a sequence dependent manner.

Phylogenetic analysis and molecular dating suggest that hemidactylus anamallensis is not a member of the hemidactylus radiation and has an ancient late cretaceous origin

Background of the Work: The phylogenetic position and evolution of Hemidactylus anamallensis (family Gekkonidae) has been much debated in recent times. In the past it has been variously assigned to genus Hoplodactylus (Diplodactylidae) as well as a monotypic genus `Dravidogecko' (Gekkonidae). Since 1995, this species has been assigned to Hemidactylus, but there is much disagreement between authors regarding its phylogenetic position within this genus. In a recent molecular study H. anamallensis was sister to Hemidactylus but appeared distinct from it in both mitochondrial and nuclear markers. However, this study did not include genera closely allied to Hemidactylus, thus a robust evaluation of this hypothesis was not undertaken. Methods: The objective of this study was to investigate the phylogenetic position of H. anamallensis within the gekkonid radiation. To this end, several nuclear and mitochondrial markers were sequenced from H. anamallensis, selected members of the Hemidactylus radiation and genera closely allied to Hemidactylus. These sequences in conjunction with published sequences were subjected to multiple phylogenetic analyses. Furthermore the nuclear dataset was also subjected to molecular dating analysis to ascertain the divergence between H. anamallensis and related genera. Results and Conclusion: Results showed that H. anamallensis lineage was indeed sister to Hemidactylus group but was separated from the rest of the Hemidactylus by a long branch. The divergence estimates supported a scenario wherein H. anamallensis dispersed across a marine barrier to the drifting peninsular Indian plate in the late Cretaceous whereas Hemidactylus arrived on the peninsular India after the Indian plate collided with the Eurasian plate. Based on these molecular evidence and biogeographical scenario we suggest that the genus Dravidogecko should be resurrected.

Kinetic proofreading at single molecular level: aminoacylation of tRNA(Ile) and the role of water as an editor

Proofreading/editing in protein synthesis is essential for accurate translation of information from the genetic code. In this article we present a theoretical investigation of efficiency of a kinetic proofreading mechanism that employs hydrolysis of the wrong substrate as the discriminatory step in enzyme catalytic reactions. We consider aminoacylation of tRNA(Ile) which is a crucial step in protein synthesis and for which experimental results are now available. We present an augmented kinetic scheme and then employ methods of stochastic simulation algorithm to obtain time dependent concentrations of different substances involved in the reaction and their rates of formation. We obtain the rates of product formation and ATP hydrolysis for both correct and wrong substrates (isoleucine and valine in our case, respectively), in single molecular enzyme as well as ensemble enzyme kinetics. The present theoretical scheme correctly reproduces (i) the amplitude of the discrimination factor in the overall rates between isoleucine and valine which is obtained as (1.8x10(2)).(4.33x10(2)) = 7.8x10(4), (ii) the rates of ATP hydrolysis for both Ile and Val at different substrate concentrations in the aminoacylation of tRNA(Ile). The present study shows a non-michaelis type dependence of rate of reaction on tRNA(Ile) concentration in case of valine. The overall editing in steady state is found to be independent of amino acid concentration. Interestingly, the computed ATP hydrolysis rate for valine at high substrate concentration is same as the rate of formation of Ile-tRNA(Ile) whereas at intermediate substrate concentration the ATP hydrolysis rate is relatively low. We find that the presence of additional editing domain in class I editing enzyme makes the kinetic proofreading more efficient through enhanced hydrolysis of wrong product at the editing CP1 domain.

High Temperatures Result in Smaller Nurseries which Lower Reproduction of Pollinators and Parasites in a Brood Site Pollination Mutualism

In a nursery pollination mutualism, we asked whether environmental factors affected reproduction of mutualistic pollinators, non-mutualistic parasites and seed production via seasonal changes in plant traits such as inflorescence size and within-tree reproductive phenology. We examined seasonal variation in reproduction in Ficus racemosa community members that utilise enclosed inflorescences called syconia as nurseries. Temperature, relative humidity and rainfall defined four seasons: winter; hot days, cold nights; summer and wet seasons. Syconium volumes were highest in winter and lowest in summer, and affected syconium contents positively across all seasons. Greater transpiration from the nurseries was possibly responsible for smaller syconia in summer. The 3-5 degrees C increase in mean temperatures between the cooler seasons and summer reduced fig wasp reproduction and increased seed production nearly two-fold. Yet, seed and pollinator progeny production were never negatively related in any season confirming the mutualistic fig-pollinator association across seasons. Non-pollinator parasites affected seed production negatively in some seasons, but had a surprisingly positive relationship with pollinators in most seasons. While within-tree reproductive phenology did not vary across seasons, its effect on syconium inhabitants varied with season. In all seasons, within-tree reproductive asynchrony affected parasite reproduction negatively, whereas it had a positive effect on pollinator reproduction in winter and a negative effect in summer. Seasonally variable syconium volumes probably caused the differential effect of within-tree reproductive phenology on pollinator reproduction. Within-tree reproductive asynchrony itself was positively affected by intra-tree variation in syconium contents and volume, creating a unique feedback loop which varied across seasons. Therefore, nursery size affected fig wasp reproduction, seed production and within-tree reproductive phenology via the feedback cycle in this system. Climatic factors affecting plant reproductive traits cause biotic relationships between plants, mutualists and parasites to vary seasonally and must be accorded greater attention, especially in the context of climate change.

Summary of Precipitation and Streamflow for Potrero and San Clemente Creeks in Water-Year 2007, Santa Lucia Preserve, Monterey County, California

In March 2007 CSU-Monterey Bay began hydrologic monitoring of Santa Lucia Preserve for the Santa Lucia Conservancy. This project is a continuation of monitoring begun by Balance Hydrologics as part of the permit requirements for land development. The purpose of this annual report is to present data summaries for the 2007 water year (October 1, 2006 to September 31, 2007). Rainfall in water year 2007 was very low, representing the 15 year drought rainfall. Streamflow was relatively low as well as indicated by baseflow conditions approaching the drought conditions of water-year 1991 (Croyle and Smith, 2007). Document contains 30 pages)

Accuracy in Copy Number Calling by qPCR and PRT : A Matter of DNA

7 p.

The Metabolic Core and Catalytic Switches Are Fundamental Elements in the Self-Regulation of the Systemic Metabolic Structure of Cells

19 p.

Role of Monoubiquitylation on the Control of IκBα Degradation and NF-κB Activity

9 p.

1998 warmwater fish survey of Vancouver Lake, Clark County

The Vancouver Lake warmwater fish population was sampled during the fall of 1998. Vancouver Lake is a large lake, connected directly to the Columbia River through the Lake River to the north and the constructed flushing channel on the eastern shore. A total of 16 species of fish were encountered, mostly warmwater game fish with a few seasonal visitors. The lake has suffered from water quality problems, and during the 1970s, it was dredged, and a channel was created to aid in increasing the water turnover rate, effectively connecting both ends of the lake to the Columbia River. As there is direct access to the Columbia River, managing this lake as a closed system may prove difficult. It is of our opinion that it may be a more effective use of resources to increase the anglers access to the available resources through providing improved boat launch access, and fish habitat structure throughout the lake. Additionally, educating the public about the how-to's of common carp angling could possibly open up additional resources not commonly utilized by the public. (Document pdf contains 38 pages)

Interim report on surface water resources and quality of waters in Lee County, Florida

Report seeks to address following questions: 1. Where within Lee County are surface supplies of water located? 2. What are the variations in this supply? 3. What can be done to provide better answers to questions 1 and 2 than are available at the present time? (PDF contains 76 pages.)

Early Functional Deficit and Microglial Disturbances in a Mouse Model of Amyotrophic Lateral Sclerosis

11 p.

GFAP Isoforms in Adult Mouse Brain with a Focus on Neurogenic Astrocytes and Reactive Astrogliosis in Mouse Models of Alzheimer Disease

24 p.

Validity of Resting Energy Expenditure Predictive Equations before and after an Energy-Restricted Diet Intervention in Obese Women

11 p.

Squaring the circle. Social and environmental implications of pre-pottery neolithic building technology at Tell Qarassa (South Syria)

We present the results of the microstratigraphic, phytolith and wood charcoal study of the remains of a 10.5 ka roof. The roof is part of a building excavated at Tell Qarassa (South Syria), assigned to the Pre-Pottery Neolithic B period (PPNB). The Pre-Pottery Neolithic (PPN) period in the Levant coincides with the emergence of farming. This fundamental change in subsistence strategy implied the shift from mobile to settled aggregated life, and from tents and huts to hard buildings. As settled life spread across the Levant, a generalised transition from round to square buildings occurred, that is a trademark of the PPNB period. The study of these buildings is fundamental for the understanding of the ever-stronger reciprocal socio-ecological relationship humans developed with the local environment since the introduction of sedentism and domestication. Descriptions of buildings in PPN archaeological contexts are usually restricted to the macroscopic observation of wooden elements (posts and beams) and mineral components (daub, plaster and stone elements). Reconstructions of microscopic and organic components are frequently based on ethnographic analogy. The direct study of macroscopic and microscopic, organic and mineral, building components performed at Tell Qarassa provides new insights on building conception, maintenance, use and destruction. These elements reflect new emerging paradigms in the relationship between Neolithic societies and the environment. A square building was possibly covered here with a radial roof, providing a glance into a topologic shift in the conception and understanding of volumes, from round-based to square-based geometries. Macroscopic and microscopic roof components indicate buildings were conceived for year-round residence rather than seasonal mobility. This implied performing maintenance and restoration of partially damaged buildings, as well as their adaptation to seasonal variability