bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractMental 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

AbstractThe 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

AbstractHIV/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

AbstractOriental 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

AbstractThe 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

AbstractLet 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

AbstractGas 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

AbstractIn 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

AbstractBisphosphonates (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

AbstractThe 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

AbstractAntigens 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

AbstractPIM3 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

AbstractThe 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

AbstractProtein 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

AbstractAs 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

AbstractThere 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.