bluuebunny/crossref_metadata_2025 huggingface dataset:
The Synthesis and Characterization of New, Robust Titanium (IV) Scorpionate Complexes
Authors: Gerschler-Zia Jared , Dunne James , Sadow Aaron
Published: October 2010

Titanium complexes possessing sterically encumbered ligands have allowed for the preparation of reactive moieties (imido, alkylidene and alkylidyne species) relevant to reactions such as olefin polymerization and alkyne hydroamination. For this reason, we have targeted robust scorpionate ancillary ligands to support reactive titanium centers. Thus, a series of titanium complexes were synthesized using an achiral oxazoline-based scorpionate ligand, tris(4,4-dimethyl-2-oxazolinyl)phenyl borate [To^M^]^-^ as well as the related chiral ligand, tris(4-isopropyl-2-oxazolinyl)phenyl borate [To^P^]^-^. The complex [Ti(κ^3^- To^M^)Cl~3~] was prepared in moderate yield (43%) by the rapid (<1 min at room temperature) reaction of Li[To^M^] and TiCl~4~ in methylene chloride; this new compound was characterized by ^1^H NMR spectroscopy as the expected C~3v~-symmetric species. One route to Ti (IV) alkyls involves salt metathesis; accordingly, syntheses of [To^M^]Ti alkyl complexes by interaction of [Ti(κ^3^-To^M^)Cl~3~] and one or three equivalents of alkylating agents, such as benzyl potassium (KCH~2~C~6~H~5~), trimethylsilylmethyllithium (LiCH~2~Si(CH~3~) ~3~), or neopentyl lithium (LiCH~2~C(CH~3~)~3~) are currently under investigation. The complexes [Ti(=NBut) (κ~3~-To^M^)(Cl)(Bu^t^py)] (Bu^t^py=4 tert-butylpyridine) and [Ti(=NBu^t^) (κ~3~-To^P^)(Cl)(Bu^t^py)] were synthesized by reaction of the known Ti imido [Ti(=NBu^t^)(Cl)~2~(Bu^t^py)~2~] with Li[To^M^] or Li[To^P^], respectively, by stirring overnight in methylene chloride at ambient temperature. The complexes were identified using ^1^H NMR spectroscopy, ^1^H-^13^C HMQC and ^1^H-^15^N HMBC correlation experiments.
The human genome is composed of viral DNA: Viral homologues of the protein products cause Alzheimer's disease and others via autoimmune mechanisms.
Authors: Carter Christopher
Published: October 2010

The human genome is composed of millions of fragmented contiguous viral DNA sequences, dating from the dawn of evolution and reflecting retroviral insertions over millions of years of coexistence. Herpes and other viral insertion points correspond to the locations of over 120 Alzheimer's disease susceptibility genes and to linkage hotspots. The greater the number of pathogen matches, the more important the gene. These DNA sequences are translated into short contiguous 5-12 amino acid stretches (vatches), identical in viruses and man, and in other pathogens implicated in Alzheimer's disease (Borrelia, Chlamydia, Helicobacter, C. Neoformans , P. Gingivalis). C. Neoformans, which has been associated with a rare but curable form of dementia, expresses the most number of hits to Alzheimer's disease proteins. Vatches are often immunogenic and antibodies to viral proteins may knock down their human counterparts or activate immune responses killing the cells containing their human homologues. This is supported by the presence of the complement membrane attack complex in Alzheimer's disease neurones and by the ability of tau antigens (homologous to pathogen proteins) to promote the formation of neurofibrillary tangles and Alzheimer's disease pathology in mice. Vatches may act as dummy ligands or decoy receptors and interfere with the interactome of their human counterparts. Alzheimer's disease is thus a "pathogenetic" disorder caused by pathogens but dependent on the genes that create these matching sequences. This scenario is relevant to many other, and perhaps most human disorders, given the massive genomic extent of viral coverage. The vatches in the human proteome, dictated by polymorphisms and mutations, may predict, from birth, the spectrum of pathogens that match our proteins and which pathogenetic disease we are likely to develop. These may all be preventable by vaccination, pathogen detection and elimination and curable by immunosuppressant approaches, perhaps with a unique, safe, and effective immunosuppressant panacea.
Dicroidium: no more a Triassic Gondwana index fossil
Authors: Srivastava Ashwini , Srivastava Rashmi , Agnihotri Deepa
Published: October 2010

A large number of Dicroidium-frond, considered as the marker of Early Triassic Gondwana flora, are discovered for the first time with well preserved cuticle from Early Permian (Lower Gondwana) sequence of Barakar Formation, Satpura Gondwana Basin, India. The presence of Dicroidium in Late Permian mixed floral zone of Jordan has been viewed as its possible origin in paleotropics but the evidence in hand exhibits its Gondwanic derivation and threatens the recognition of Dicroidium flora for Middle Gondwana in association with Lower Gondwana Glossopteris and Upper Gondwana Ptilophyllun flora.
Microstructural Correlates of Resilience against Major Depressive Disorder: Epigenetic Mechanisms?
Authors: Frodl Thomas , Ferguson Yolande , Fagan Andrew , Lisiecka Danusia , Carballedo Angela , Daly Ian , Meaney James , Kelleher Dermot
Published: October 2010

Mental disorders are a major cause of long-term disability and are a direct cause of mortality, with approximately 800.000 individuals dying from suicide every year worldwide - a high proportion of them related to major depressive disorder (MDD)^1^. Healthy relatives of patients with major depressive disorder (MDD) are at risk to develop the disease. This higher vulnerability is associated with structural^2-4^ and functional brain changes^5^. However, we found using high angular resolution diffusion imaging (HARDI) with 61 diffusion directions that neuron tracts between frontal cortices and limbic as well as temporal and parietal brain regions are characterized by better diffusion coefficients in unaffected relatives (UHR), who managed to stay healthy, compared to healthy volunteers without any family history for a psychiatric disease (HC). Moreover, those UHR with stronger fibre connections better managed incidences of adversity in early life without later developing depression, while in HC axonal connections were found to be decreased when they had early-life adversity. Altogether these findings indicate the presence of stronger neural fibre connections in UHR, which seem to be associated with resilience against environmental stressors, which we suggest occur through epigenetic mechanisms.
Young and Early Career Investigators: Report from a Global HIV Vaccine Enterprise Working Group
Authors: Frahm Nicole , Rabadan Raul , Fuchs Jonathan , Leslie Alasdair , Liu Yong , Barouch Dan , Ndung’u Thumbi , Alter Galit , Cardozo Timothy , Chohan Bhavna , Moore Penny , Fellay Jacques
Published: October 2010

The scientific challenges facing HIV-1 vaccine development are unprecedented in the history of vaccinology. As a result, investigators, funders, and other stakeholders generally agree that “game-changing” ideas are required. While innovation can certainly arise from investigators at all career stages, young and early-career investigators, defined as those under 40 years of age or within 10 years of their final degree or clinical training, are especially key contributors of novel and transformative ideas. Young and early-career investigators bring energy, enthusiasm, and fresh perspectives that are unbiased by prevailing dogma and that are essential to scientific progress.
The 2010 Scientific Strategic Plan of the Global HIV Vaccine Enterprise: A Roadmap for the Future
Authors: Bernstein Alan , Piot Peter
Published: October 2010

HIV/AIDS is arguably the most significant health challenge facing the world today. The 2008 numbers tell the story: 33.4 million were living with HIV, 2 million people died of AIDS and 2.7 million people were newly infected. Despite impressive scientific advances in developing over two dozen drugs to treat HIV infections, there is still no cure. In addition, only about one-third of those who need drugs have access to therapy.In 2003, recognizing the enormity of the scientific and humanitarian challenge of HIV/AIDS, two-dozen leading investigators and major funding organizations formed the Global HIV Vaccine Enterprise, a voluntary alliance of independent organizations committed to working together to accelerate the development of an HIV vaccine.At the center of the Enterprise vision is a global research agenda,the Scientific Strategic Plan, a high level framework that represents the collective perspectives and shared accountability of the Enterprise Council, the Enterprise’s senior advisory body to work toward aligning their strategies and activities to help realize a shared vision for the field.
Crossing Lilium Orientals of different ploidy creates Fusarium-resistant hybrid
Authors: Sixiang Zheng , Hongzhi Wu , Yan Zhao , Feihu Liu
Published: October 2010

Oriental hybrid lily is of great commercial value, but it is susceptible to Fusarium disease that causes a significant loss to the production. A diploid Oriental hybrid resistant to Fusarium, Cai-74, was diploidized from triploid obtained from the offspring of tetraploid (from ‘Star Fighter’) and diploid (‘Con Amore’, ‘Acapulco’) by screening the hybrids of different cross combinations following inoculating Fusarium oxysporum to the tissue cultured plantlets in a greenhouse. By analyzing saponins content in bulbs of a number of lily genotypes with a known Fusarium resistance, it was found that the mutant Cai-74 had a much higher content of saponin than its parents. Highly resistant wild L. dauricum had the highest level (4.59mg/g), followed by the resistant Cai-74 with 4.01mg/g. The resistant OT cultivars ‘Conca d’or’ and ‘Robina’ had a higher saponins content (3.70 mg/g) and 2.83 mg/g, than the susceptible Oriental lily cultivars ‘Sorbonne’, ‘Siberia’ and ‘Tiber’. The hybrid Cai-74 had a different karyotype compared with the normal Lilium Oriental hybrid cultivars. The results suggested that Cai-74 carries a chromosomal variation correlated to Fusarium resistance. Cai-74 might be used as a genetic resource for breeding of Fusarium resistant cultivars of Oriental hybrid lilies.
Ecological correlates of wildlife diseases
Authors: Watve Milind , Jog Maithili
Published: October 2010

The parasite loads appear to differ widely within and between species of free ranging wild mammals. Using data on fecal propagule densities of 29 species of wild mammals from 20 wild life parks in India we tried to identify the ecological factors that are best predictors of parasite loads. Parasite loads were consistently negatively correlated with predatory pressures at both interspecific and intraspecific levels. Carnivores had higher mean parasite loads and the effect of diet and that of predatory pressure appeared to be independent of each other. No other ecological factors were significantly and consistently associated with fecal parasite loads.
Protein and DNA evolution: Statistics and combinatorics are the rules of the game
Authors: Goswami Arunava , Duttagupta Srimoyee , Chakraborty Chirantan , Pal Amita , Pal Choudhury Pabitra , Hassan Sk Sarif
Published: October 2010

Let us assume AVMAYDRYVAIC or MAYDRYVAICCP, most important signature domain of olfactory receptor (OR) gene family assembled in evolution following simplest possible laws of statistics which says the addition of V after A in AVMAYDRYVAIC or addition of A after M are independent events. There are 20 amino acids present in nature so the probability of joint occurrence of such events is 1/400. Therefore for making a contiguous string of AVMAYDRYVAIC or MAYDRYVAICCP, the probability would be 1 out of 2012. Over millions of years of evolution this has certainly happened and that is why we see such a signature sequence in OR1D2, OR1D subfamily member 2 as per "HORDE database":https://senselab.med.yale.edu/ORDB/files/humanorseqanal.html. Now let us assume that another hypothetical protein domain, AKHNARDRIINY has formed in the aforesaid method. In this paper, using rules of combinatorics we show that how genomes and proteomes of distantly related organisms have formed and this is the general rule.
Accuracy of computational solvation free energies for neutral and ionic compounds: Dependence on level of theory and solvent model
Authors: Rayne Sierra , Forest Kaya
Published: October 2010

Gas to aqueous phase standard state (1 atm to 1 mol/L; 298.15 K) free energies of solvation ([DELTA]G^o^~solv~) were calculated for a range of neutral and ionic inorganic and organic compounds using various levels and combinations of Hartree-Fock and density functional theory (DFT) and composite methods (CBS-Q//B3, G4MP2, and G4) with the IEFPCM-UFF, CPCM, and SMD solvation models in Gaussian 09 (G09). For a subset of highly polar and generally polyfunctional neutral organic compounds previously identified as problematic for prior solvation models, we find significantly reduced [DELTA]G^o^~solv~ errors using the revised solvent models in G09. The use of composite methods for these compounds also substantially reduces their apparent [DELTA]G^o^~solv~ errors. In contrast, no general level of theory effects between the B3LYP/6-31+G** and G4 methods were observed on a suite of simpler neutral, anionic, and cationic molecules commonly used to benchmark solvation models. Further investigations on mono- and polyhalogenated short chain alkanes and alkenes and other possibly difficult functional groups also revealed significant [DELTA]G^o^~solv~ error reductions by increasing the level of theory from DFT to G4. Future solvent model benchmarking efforts should include high level composite method calculations to allow better discrimination of potential error sources between the levels of theory and the solvation models.
Using combined XRD-XRF analysis to identify meteorite ablation debris
Authors: Kayani Saheeb
Published: October 2010

In this research paper, X-ray diffraction (XRD) and X-ray fluorescence (XRF) spectrometry has been used to determine the mineralogical and elemental composition of a stone sample recovered from a location near village Lehri in district Jhelum, Pakistan. The test data is compared with previous findings (as reported in literature and included in references) to identify this sample stone as part of a meteorite ablation debris.
Density functional theory calculation of interaction between bisphosphate and farnesyl pyrophosphate synthase
Authors: Ohno Kazuki , Mori Kenichi , Hagiwara Yohsuke , Orita Masaya , Takeuchi Makoto
Published: October 2010

Bisphosphonates (BPs) are the most widely used and effective treatment for osteoporosis and Pagets disease of the bone. To date, a number of BPs-namely alendronate, risedronate, and minodronate-have been launched to market. Nitrogen-BPs (N-BPs) act by inhibiting the enzyme farnesyl pyrophosphate synthase (FPPS), and several crystal structures of complexes between FPPS and N-BPs have been identified. Understanding the physical basis of the binding between proteins and small molecules is an important goal in both medicinal chemistry and structural biology. Here, we conducted density functional theory calculations for BPs and their surrounding residues and were able to successfully reproduce experimental results qualitatively. In addition, we found that both the side chain and backbone of Phe 99 are important for binding between minodronate and FPPS, suggesting that the strong activity of minodronate comes from its interaction with Phe 99, which alendronate and risedronate lack.
ABO and Rh Blood Group Distribution Among Kunbis (Maratha) population of Amravati District, Maharashtra
Authors: WARGHAT NANDKISHOR , SHARMA NAVIN , BAIG MUMTAZ , Yadav A. , Sharma S. , Pachalore G.
Published: October 2010

The present study reports the distribution of ABO and Rh blood groups among the Kunbis (Maratha) population of Amravati district. The phenotypic frequency of blood group B is observed highest (33.06) percent, O (31.04), A (27.02) and AB is lowest (08.33) percent. The phenotypic frequency of Rh negative is (04.26) percent. TheKunbis (Maratha) population shows close genetic relationship with the Gujratis.
Trypsin digest of cancer cells surface stimulates anti-tumor immune response better than cancer cells themselves
Authors: Lokhov Petr , Elena Balashova
Published: October 2010

Antigens expressed on the surface of cancer cells are accessible targets for both humoral and cell-mediated immune responses, and are therefore potential candidates for vaccine development. Treating surface of live human breast adenocarcinoma cells (MCF-7) with trypsin yields a digest that contains 0.7% of total cell protein. Despite this difference, the trypsin digest stimulates in cytotoxicity assays anti-tumor response which kills 10-40% more cancer cells than those stimulated with cells themselves. From these results, we concluded that trypsin digest obtained from live cancer cells contains the essential antigens to induce an immune-mediated anti-tumor effect, and therefore, is candidate for anti-tumor vaccine development.
In Silico Analysis and Identification of Potent Inhibitors for Human Serine/Threonine Protein Kinase PIM-3 Involved in Hepatic Cancer
Authors: Guttala Prasanna Kumar , Pradhan Dibyabhaba , Umamaheswari Amineni
Published: October 2010

PIM3 belongs to a family of proto oncogenes that encode serine/threonine protein kinases in human. Pim-3 is involved in cell cycle progression, suppression of apoptosis and proliferation of human hepatoma cell lines. During normal cell cycle progression, Bcl-2 associated death promoter (BAD protein) inactivates Bcl-2 and Bcl-xL there by promoting apoptosis. However, phosphorylation of BAD protein by Pim-3 leaves Bcl-2 free to inhibit Bax-triggered apoptosis. Thus, designing inhibitors against Pim-3 would stop BAD phosphorylation, hence would be highly useful for development of novel means of cancer therapeutics. Computer aided drug designing approach was followed here to explore lead molecules targeting human Pim-3. For this, proteomic nature and phylogeny of human Pim-3 was studied. A homology model of human Pim-3 was generated based on crystal structure of human Pim-1 (PDB ID: 1XWS) using Modeller9v7. Pim-1 inhibitor ‘BI1’ was incorporated into the 3D model and further energy minimized by applying OPLS force field in Maestro v9.0. The stereochemistry assessment of the model had revealed a highly reliable model with 94.8% of residues in the most favored region and no residues in disallowed region of Ramachandran plot. The human Pim-3 3D model inhibitor (BI1) complex was analyzed to locate active site residues such as Leu44, Gly45, Phe49, Val52, Ala65, Lys67, Glu89, Ile104, Leu120, Glu121, Arg122, Pro123, Glu171, Leu174, Ile185 and Asp186. These active site residues were further confirmed using SiteMap. BI1 and two published Pim family inhibitors (Imidazo[1,2-b]pyridazine, SGI-1776) structural analogs were searched from more than one million entries of Ligand.Info Metadatabase and an in house library of 1171 compounds was prepared. Maestro 9.0 virtual screening protocol was used to check binding affinity of 1171 compounds into Pim-3 active site through sequential application of flexible Glide HTVS (Virtual High Throughput Screening), SP and XP method respectively. Fifteen lead molecules identified in the present study were proposed as potential drug molecules against human Pim-3. Lead‘1’ was observed to have higher binding affinity towards human Pim-3 with lowest XP Gscore (-11.90 kcal/mol). The docking complex was observed to be highly stabilized through formation of hydrogen bond with Glu124 and Van der Waal interactions with active site residues. From the present study, it can be concluded that the generated model of human Pim-3 can be used for further studies and lead ‘1’ structure would be highly useful for designing novel inhibitors against hepatic cancer.
Ligand Based Virtual Screening to Design Novel Human MEK1 Protein Inhibitors for Potential Development of Drugs Against Melanoma
Authors: Potluri Vijayasree , Pradhan Dibyabhaba , Umamaheswari Amineni
Published: October 2010

The Ras-dependent Raf/MEK/ERK signaling pathway is a major regulator of cell proliferation and survival. Hyper activation of the pathway is frequently observed in human malignancies as a result of aberrant activation of receptor tyrosine kinases or mutations in RAF (V600E). MEK1 is dual-specificity tyrosine/threonine protein kinases found in the pathway. The RAF mutation (present in 50% of melanomas) have been shown to be highly dependent on MEK1 activity and also MEK1 is the only acknowledged activator of ERK, making them attractive targets for therapeutic intervention. In view of its importance, identification of potent inhibitor against MEK1 may be valuable to design effective drugs against melanoma. Inhibitors for human MEK1 reported till dates have poor pharmacokinetic properties and some are under clinical trials. Therefore, with an objective to identify potent MEK1 inhibitors with good pharmacokinetic properties, computer assisted virtual screening method was accomplished. The X-ray crystallographic structure of human MEK1 was investigated to adjudge unique inhibitor binding pocket (Lys97, Leu118, Val127, Ile141, Met143, Asp208, Phe209 and Ser212) flanking to ATP binding site. Four inhibitors (Crystal structure inhibitor: BBM; inhibitors under clinical trial: AZD6244; AZD8330; RDEA119) of MEK1 were attained from the literature to search geometrically closely related chemical entities through Ligand.Info high throughput screening tool. 1549 structural analogues were prepared using LigPrep applying flexible filter to generate fully customized ligand libraries that were optimized for further computational analysis. Glide v5.5 flexible docking procedures were applied to the customized ligand library for screening ligands with good binding affinity towards the inhibitor binding pocket of human MEK1 and nine lead molecules were proposed. Pharmacokinetic and toxicity predictions for these molecules gauged their ADME and safety profile. The lead molecules were ranked based on XP Gscore and binding orientations were correlated with the four existing inhibitors. Lead ‘1’ (Catechin) was noticed to have highest binding affinity among all (XP Gscore: -10.98 Kcal/mol; Five hydrogen bonds: two with Asp208 and one with each of Phe209, Ser212 and W1105) with a well complementing binding mode with the crystallographic data of human MEK1-BBM complex. The docking result endeavors potency of Catechin as a promising inhibitor for Melanoma. However, all the nine lead molecules obtained would open up new avenues for designing of potent MEK1 inhibitors.
Designing Novel Lead Molecules For Human Ribosomal Protein S6 Kinase Beta-1 Involved In Cancers: Ligand Based Virtual Screening Approach
Authors: Ganesh Nainaru , Pradhan Dibyabhaba , Umamaheswari Amineni
Published: October 2010

Protein kinases are clinically relevant and attractive drug targets for most of the cancerous diseases. Ribosomal protein s6 kinase (P70s6 kinase) is a mitogen activated Ser/Thr protein kinase, essential for cell growth, G1 cell cycle progression and cell survival. Human P70s6 kinase is involved in different signaling pathways and phosphorylates the downstream S6 protein of the 40S ribosomal subunit there by controlling the translational activity. Over expression of human P70s6 or rapid amplification of gene (RPS6KB1) leads to rapid cell proliferation causing cancer in various organs of humans like colon, breast, ovary, etc. The over expression is principally due to activation of some phosphorylating sites or ATP binding sites in the domain regions. In the present study, we identified new leads that can show inhibitory activity against cancer causing human P70s6 kinase through ligand based virtual screening. Proteomic analysis of human P70s6 kinase was performed by using Prosite, Pfam, BLOCKS databases to know the functional aspects like patterns, domains, and motifs; simultaneously, phylogeny of the protein was analyzed to delineate its relationship with other protein kinases involved in cancer. The initial virtual screening was performed to search structural analogs for published inhibitors (Staurosporine; 4-(Benzimidazol-2-yl)-1, 2, 5-oxadiazol-3-ylamine derivative; 4-{4-[4-(3-Trifluoromethyl-phenyl)-1H-imidazol-2-yl]-1H-pyrazolo-[3, 4-d] pyrimidine hydrochloride) from Ligand.Info database. Consequently, an initial ligand dataset of 1171 compounds were compiled and prepared using LigPrep. Human P70s6 kinase crystal structure was explored using Glide to set grid around centroid of catalytic domain residues. Flexible Glide computational docking methods of Maestro9.0 were applied subsequently to put forward 9 lead molecules with strong binding affinity towards human P70s6 kinase catalytic domain. Binding affinity and orientation of the proposed 10 leads were better or par with the existing inhibitors and had no ADME violation or reactive functional group. The top ranked compounds (lead 1) had shown XP Gscore of -12.99 kcal/mol and three hydrogen bonds with human P70s6 kinase catalytic domain residues Gly100, Glu173 and Leu175. Comparative analysis of the published inhibitors and Lead 1 had revealed that the binding mode of the docking complexes corroborating well, at the same time, Lead 1 interaction was stronger with less XP Gscore, more number of hydrogen bonds and good Van der Waals contacts. In view of the analysis Lead 1 would be considered for designing potential inhibitor for cancer therapy.
Apellicon: a web-based tool for constructing and curating Textpresso databases.
Authors: Urbanski William , Condie Brian
Published: October 2010

As more research literature in the biological sciences is made available in electronic format, text mining systems are increasingly being used to improve the ability of investigators to retrieve relevant information. Through the use of advanced indexing techniques that utilize biological ontologies, semantic databases, and other formal representations of biological concepts text mining systems have been able to effectively parse biological literature. While text mining systems are increasingly effective at creating the linkages required to provide context-specific search results, the systems themselves are difficult to set up and use by novice computer users due to the highly technical nature of the applications. Because most researchers in the biological sciences do not have a strong computer science background we have focused on improving the quality of existing, proven text mining systems by implementing a web-based GUI that greatly improves the workflow of these systems. Textpresso in particular has an excellent web-based interface for searching literature but does not have an easy to use administrative interface. We developed the Apellicon interface to enable a wide range of users to build and manage a Textpresso database. An important feature of Apellicon is that it can enable groups to collaborate in building a Textpresso database.
DNA SEQUENCE PATTERNS
Authors: Kannan Sriram
Published: October 2010

There is significance in the molecular weight derived sequence patterns of adenosine, guanosine, cytosine, thymine, methyl cytosine and hydroxyl methyl cytosine if one has to consider the molecular events holistically by including single nucleotide polymorphisms, tumor suppressor gene activity like that of ten eleven translocation gene, CpG methylation, miRNA SNP patterns and SNPs neighboring CpGs. This research article focuses on observing simulation results of validated SNPs in a sequence using substitution patterns of molecular weight of A, G, C, T, 5OHC, 5MC. The outcome helped to bring out positions in a DNA sequence where in validated bi allelic SNPs were never found to occur and SNPs neighboring methylated CpGs do show disconcordance and a simulated effect of gene function like that of ten eleven translocation do show disconcordance with other SNP occurrence patterns. Further the occurrence position of miRNA SNPs do differ from other SNPs. Hence molecular weight based recognition of sequences might play a role in genome evolution, cancer related methylation and variation.
The eDAL Suite: Tools and Concepts for Primary Data Citation
Authors: Lange Matthias , Colmsee Christian , Flemming Steffen , Chen Jinbo , Klapperstück Matthias , Scholz Uwe
Published: October 2010

Retrieval and citation of primary data is the important factor in the approaching age of “data science”. Digital data are easily shared, and just as easily wiped or lost. The problem of keeping on-line data accessible and retrievable is especially difficult for SME like plant breeders plant biotech companies as well as research projects in this domain.Intension of eDAL is the provisioning of an information retrieval and data citation infrastructure that meets the requirements of the “data science” age and implements a re-usable platform for data retrieval, data citation, and data publication. Like a shopping cart, the idea is to combine a search engine and a data cart, which retrieves, rank and collect query relevant data from crop plant data centers.
The biotechnological perspective of Beta-Glucosidases
Authors: Khan Israr , Akhtar Muhammad waheed
Published: October 2010

Biotechnology is the art and science of making and technology to process biological materials for the welfare of human being. This discussion includes the beta glucosidase classification, its structure, application, and recent research interests in relation to its significance and comparison with eukaryotic Beta glucosidases including plant, animal and yeast as well. The study also comprise of the various stress factors and modifications thereby the organism to cope it. The focus of the study is on the various kinetics principles and their full potential exploitation to increase the activity of the enzyme. As such making the enzyme a potent vehicle for various industrial, pharmaceutical and research purposes. It also include the various glycosylhydrolases of families 1 and 3 that include beta-glucosidases.
Historical Trends in Annual Water Yields for the Okanagan Basin, British Columbia, Canada
Authors: Rayne Sierra , Forest Kaya
Published: October 2010

The Okanagan Basin in south-central British Columbia, Canada, includes the Okanagan River watershed upstream from the outlet of Osoyoos Lake, with a total area of 8,046 km^2^. Over the past century, the population of the Basin has grown rapidly, and this trend is expected to continue. Water management issues attract significant attention in the region, given projected declines in supply and increases in demand. Historical streamflow data was obtained for three hydrometric stations on the Okanagan River between the outlet of Okanagan Lake at Penticton and near the U.S. border at Oliver. Collectively, the historical data series indicate no temporal changes in regional annual water yields for the Okanagan Basin over the past century, despite large increases in population and agricultural activity over this time. Although rapid and extensive human settlement and development of the region, along with possible climate change signatures during the 20th century, has potentially altered the inflow hydrographs to tributary streams in the Basin, the overall water yield of the region appears to be stable and possibly increasing.
Reading the Secrets of Biological Fluctuations
Authors: Boettiger Carl
Published: October 2010

I explore tools and applications of the van Kampen expansion of the stochastic master equation in several areas of population biology. I highlight fluctuation-dissipation and fluctuation-enhancement regimes, using information from noise to help model choice, and examples where noise changes the macroscopic dynamics of a system.
Metagenomic Analysis of the Structure and Function of the Human Gut Microbiota in Crohn's Disease
Authors: Fraser-Liggett Claire
Published: October 2010

Inflammatory bowel diseases (IBD), such as Crohn’s disease, are chronic, immunologically mediated disorders that have severe medical consequences. The current hypothesis is that these diseases are due to an overly aggressive immune response to a subset of commensal enteric bacteria. Studies to date on IBD have suggested that the disorder may be caused by a combination of bacteria and host susceptibility; however the etiologies of these diseases remain an enigma. In this application, we propose to develop and demonstrate the ability to profile Crohn’s disease at an unprecedented molecular level by elucidation of specific biomarkers (bacterial strains, genes, or proteins) that correlate to disease symptoms. To achieve this goal, we will employ a multidisciplinary approach based on metagenomic and metaproteomic molecular tools to elucidate the composition of the commensal microbiota in monozygotic twins that are either healthy or exhibit Crohn’s disease (for concordant, both are diseased; for discordant, one is healthy and one is diseased). The central hypotheses of this proposal are (1) that specific members and/or functional activities of the gastrointestinal (GI) microbiota differ in patients with Crohn’s disease as compared to healthy individuals, and (2) that it will be possible to elucidate microbial signatures which correlate with the occurrence and progression of this disease by integration of data obtained from 16S rRNA based molecular fingerprinting, metagenomics, and metaproteomics approaches. To address these hypotheses, three specific aims are proposed: 1) Obtain data on community gene content (metagenome) in a subset of healthy twins and twins with Crohn’s Disease to assess potential differences in the metabolic capabilities of the gut microbiota associated with CD, 2) Obtain data on community protein content (metaproteome) in a subset of healthy twins and twins with Crohn’s Disease to assess the state of expressed proteins associated with CD, 3) Apply various statistical clustering and classification methods to correlate/associate microbial community composition, gene and protein content with patient metadata, including metabolite profiles and clinical phenotype. The ultimate goal of these efforts is to identify novel biomarkers for non-invasive diagnostics of CD and to eventually identify drug targets (i.e. bacterial strains) for cure or suppression of disease symptoms.
jlibSEDML - a Java library for working with SED-ML
Authors: Adams Richard , Moraru Ion , Lakshminaryana Anuradha
Published: October 2010

jlibSEDML is an open-source Java library to support the emerging SED-ML standard to record the operations needed to run simulations and other operations on biochemical models. It is compatible with level 1 version 1 of the specification and is available from http://sourceforge.net/projects/jlibsedml
BioPAX: next steps for Semantic Web / CV workgroup
Authors: Splendiani Andrea
Published: October 2010

Outline of the next steps which will be proposed as actions in the Semantic Web/ Linking/ CV workgroup of BioPAX.One main focus will be to clean the RDF representation and adopt some basic relations, in order to address use cases in data-integration, pathway analysis and simple ontology/pathway integration.
Workspaces, exposures, and multiscale modelling
Authors: Nickerson David
Published: October 2010

Here I present technical details on the software package PMR2, which is the software running the CellML and Physiome Project model repositories. In particular, the use of mercurial repositories to define workspaces for collaborative model development, creating modular hierarchies of embedded workspaces, and defining exposures as a means to provide permanent links to specific revisions of model workspaces. I also briefly mention the use of OpenCMISS to link CellML models into large scale, spatially distributed field modeling and simulation.
SBGN-ED - a tool for editing, validating, and translating of SBGN maps
Authors: Czauderna Tobias , Klukas Christian , Junker Astrid , Schreiber Falk
Published: October 2010

The recently proposed Systems Biology Graphical Notation (SBGN) provides a standard for the visual representation of biochemical and cellular processes. SBGN helps to communicate biological knowledge more efficient and accurate between different research communities in the life sciences. However, to support SBGN, methods and tools for editing, validating, and translating of SBGN maps are necessary.We present methods for these tasks, the tool SBGN-ED, and an application example. SBGN-ED allows to create all three types of SBGN maps from scratch, to validate these maps for syntactical and semantical correctness, to translate maps from the KEGG and MetaCrop databases into SBGN, and to export SBGN maps into several file and image formats.
Effect of Crohn's Disease Risk Alleles on Enteric Microbiota Marker Paper
Authors: Pace Norman , Mayer Lloyd , Zhu Wei , Dietz David , Boedeker Edgar , Sartor R. Balfour , Li Ellen , Sodergren Erica , Weinstock George , Stappenbeck Thaddeus , Frank Daniel , Tarr Phillip , Robertson Charles
Published: October 2010

This UH2/UH3 demonstration project entitled “Effects of Crohn’s disease risk alleles on enteric microbiota” is focused on characterizing intestinal associated microbiota in patients with ileal Crohn’s disease (ileal CD), ulcerative colitis (UC) and control patients without inflammatory bowel diseases (non-IBD). We hypothesize that genetic factors that affect Paneth cell function, contribute to compositional changes in intestinal microbiota. These changes in microbiota may lead to reduction of protective commensal organisms and increased numbers of aggressive organisms that incite intestinal inflammation. This hypothesis is being tested by high throughput 16S rRNA sequence analysis of de-identified ileal and colonic tissues that have been archived at Washington University St. Louis, University of North Carolina, Mount Sinai Hospital and the Cleveland Clinic. Multivariate analysis of the metagenomic data will be conducted with genotyping metadata (highly reproducible CD risk alleles, including NOD2 and ATG16L1) and phenotyping metadata (e.g. age, gender, race, body mass index, medications and smoking). Shotgun sequencing will be performed on selected fecal specimens linked to ileal tissues to identify additional, or auxiliary, or synergistic pathogenic factors or other functional changes in the microbiome. Because members of this research team have observed that a chronic viral infection is required for the Paneth cell defect in Atg16l1 hypomorphic mice, a major focus of these studies will be towards identifying potential viral triggers for the defective Paneth cell phenotype in individuals harboring the ATG16L1 risk allele. Novel genetic probes for protective and aggressive organisms will be developed by mining bacterial genome and shotgun sequencing data. Genomic sequences will be produced for candidate protective and aggressive strains (e.g. adherent-invasive strains of E. coli) isolated from human intestinal tissues where there is limited existing genome information. Quantitative qPCR assays using the novel as well as established genetic probes will be conducted to test the hypothesis that an imbalance between protective and aggressive organisms is associated with genetic factors that affect Paneth cell function.Our combined expertise in multiple disciplines across multiple institutions, our demonstrated ability to collect a large number of well-phenotyped samples with longitudinal clinical information that will be linked to host response and morphologic studies, and our consortium’s capacity for high-throughput sequencing will be used to investigate how alterations in human microbiome relate to CD risk alleles and CD pathogenesis.
The Physiome languages: CellML and FieldML
Authors: Hunter Peter
Published: October 2010

Discussion of the markup languages being defined by the VPH/Physiome project for multiscale, multiphysics modeling.
Transcriptional complex assembly represented in SBGN PD
Authors: Mazein Alexander , Watterson Steven , Ghazal Peter
Published: October 2010

This poster shows how transcriptional complex assembly can be represented in SBGN Process Description language. Example: LPS-induced TNF-alpha enhancer complex formation.
Implementation of SBML Level 3 Support within iBioSim
Authors: Myers Chris
Published: October 2010

This presentation gives details about our experiences when adding SBML Level 3 support to our iBioSim tool.
TreeRipper: towards a fully automated optical tree recognition software
Authors: Hughes Joseph
Published: October 2010

Relationships between species, genes and genomes have been printed as trees for over a century. Whilst this may have been the best format for exchanging and sharing phylogenetic hypotheses during the 20th century, the worldwide web now provides faster and automated ways of transferring and sharing phylogenetic knowledge. However, novel software is needed to defrost these published phylogenies for the 21st century.TreeRipper is a command line c++ program for the fully-automated recognition of multifurcating phylogenetic trees. The program accepts a range of input image formats (PNG, JPG/JPEG, GIF, TIFF or PDF ). Then follows a number of cleaning steps to detect lines, remove node labels, patch-up broken lines and corners and detect line edges. The edge contour is then determined to detect the branch length, tip label positions and the topology of the tree. Optical Character Recognition (OCR) is used to convert the tip labels into text with the freely available tesseract-ocr software. 32% of images meeting the prerequisites for TreeRipper were successfully recognised, the largest tree had 115 leaves.Despite the diversity of ways phylogenies have been illustrated making the design of a fully automated tree recognition software difficult, TreeRipper is a step towards automating the digitization of past phylogenies. We also provide a dataset of 100 tree images and associated tree files for training and/or benchmarking future software.
Recent trends in US patent grants and issues to be considered
Authors: Garrity George , Parker Charles
Published: October 2010

The life sciences have changed radically since the Convention on Biological Diversity first opened for signatures in 1992. Traditional organism-based approaches to discovery and use of genetic resources have been supplanted by molecular approaches. Biodiversity prospecting is more likely to be a programmatic bioinformatics activity rather than an activity conducted by field scientists. Access to genetic resources is no longer centered on a hunt for novel species. Rather, the hunt is for novel genes and metabolic pathways that can be cloned into well-understood expression systems and readily scaled-up for industrial production. Information about contemporary research, development, and manufacturing practices needs to be addressed, especially when those genes do not need to be associated with their native host at the time of discovery. Information about the research organizations participating in all phases of the discovery and development process also needs to be considered, especially when it involves partnerships between academic and industrial organizations.We present a high-level view of recent trends in the issuance of US patent grants to commercial and non-commercial research organizations, and introduce a technology that is already in place which can be applied to monitoring the use of genetic materials by various stakeholders in an open and transparent manner, as intended under the International Regime for Access and Benefit Sharing (ABS).
The SBML Level 3 Annotation package: an initial proposal
Authors: Swainston Neil
Published: October 2010

The SBML Level 3 Annotation package proposal intends to extend the current Level 3 Core annotations by increasing the range of RDF features supported.Such an extension will support RDF Reification, annotation of SBML attributes, specification of relationships between annotations, negation of annotations and cross-references and cross-element annotations.
Essay: On the close relationship between speciation, inbreeding and recessive mutations.
Authors: Joly Etienne
Published: October 2010

Whilst the principle of adaptive evolution is unanimously recognised as being caused by the process of natural selection favouring the survival and/or reproduction of individuals having acquired new advantageous traits, a consensus has proven much harder to find regarding the actual origin of species. Indeed, since speciation corresponds to the establishment of reproductive barriers, it is difficult to see how it could bring a selective advantage because it amounts to a restriction in the opportunities to breed with as many and/or as diverse partners as possible. In this regard, Darwin himself did not believe that reproductive barriers could be selected for, and today most evolutionary biologists still believe that speciation can only occur through a process of separation allowing two populations to diverge sufficiently to become infertile with one another. I do, however, take the view that, if so much speciation has occurred, and still occurs around us, it cannot be a consequence of passive drift but must result from a selection process, whereby it is advantageous for groups of individuals to reproduce preferentially with one another and reduce their breeding with the rest of the population.In this essay, I propose a model whereby new species arise by “budding” from an ancestral stock, via a process of inbreeding among small numbers of individuals, driven by the occurrence of advantageous recessive mutations. Since the phenotypes associated to such mutations can only be retained in the context of inbreeding, it is the pressure of the ancestral stock which will promote additional reproductive barriers, and ultimately result in complete separation of a new species. I thus contend that the phenomenon of speciation would be driven by mutations resulting in the advantageous loss of certain functions, whilst adaptive evolution would correspond to gains of function that would, most of the time be dominant.A very important further advantage of inbreeding is that it reduces the accumulation of recessive mutations in genomes. A consequence of the model proposed is that the existence of species would correspond to a metastable equilibrium between inbreeding and outbreeding, with excessive inbreeding promoting speciation, and excessive outbreeding resulting in irreversible accumulation of recessive mutations that could ultimately only lead to the species extinction.
The C-terminal basic residues contribute to the chemical- and voltage-dependent activation of TRPA1
Authors: Samad Abdul , Sura Lucie , Benedikt Jan , Ettrich Rudiger , Minofar Babak , Teisinger Jan , Vlachova Viktorie
Published: October 2010

The ankyrin transient receptor potential channel TRPA1 is a non-selective cationic channel that is expressed by sensory neurons, where it can be activated by pungent chemicals, such as AITC (allyl isothiocyanate), cinnamon or allicin, by deep cooling (<18 °C) or highly depolarizing voltages (>+100 mV). From the cytoplasmic side, this channel can be regulated by negatively charged ligands such as phosphoinositides or inorganic polyphosphates, most likely through an interaction with as yet unidentified positively charged domain(s). In the present study, we mutated 27 basic residues along the C-terminal tail of TRPA1, trying to explore their role in AITC- and voltage-dependent gating. In the proximal part of the C-terminus, the function-affecting mutations were at Lys969, Arg975, Lys988 and Lys989. A second significant region was found in the predicted helix, centred around Lys1048 and Lys1052, in which single alanine mutations completely abolished AITC- and voltage-dependent activation. In the distal portion of the C-terminus, the charge neutralizations K1092A and R1099A reduced the AITC sensitivity, and, in the latter mutant, increased the voltage-induced steady-state responses. Taken together, our findings identify basic residues in the C-terminus that are strongly involved in TRPA1 voltage and chemical sensitivity, and some of them may represent possible interaction sites for negatively charged molecules that are generally considered to modulate TRPA1.