Últimos itens adicionados do Acervo: Proceedings Nature

Nature é uma das mais prestigiosas e antigas revistas científicas do mundo: sua primeira edição é de 4 de novembro de 1869. Entre as inúmeras descobertas científicas publicadas na Nature estão a dos raios X, da estrutura em dupla hélice do ADN e o buraco na camada de ozônio.

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‣ ANN Based Virtual Classification Model for Discriminating Active and Inactive Withanolide E Analogs against Human Breast Cancer Cell Line MCF-7

Om Prakash; Feroz Khan; R.S. Sangwan
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
Withanolides are a group of natural C-28 steroids built on an ergostane skeleton and classified into two major groups according to their structural skeleton: (a) compounds with a beta-oriented side chain and (b) compounds with an alpha-oriented side chain. Withanolide E represents one of the members of the latter group. Classification of active compounds on the basis of pharmacophore against specific cancer cell line poses a serious concern at the primary stage of virtual screening. To overcome this problem we have developed an artificial neural network based virtual screening model for discriminating active and non-active Withanolide-E-like derivatives or analogs against human breast cancer cell line MCF-7. In the present work, a 2D chemical descriptors ensemble pharmacophore has been modelled on the basis of withanolide E structural featured molecules. The ANN structure activity based classification model could be useful for identification of active withanolide analogs as anticancer leads against MCF-7. This model can be used for predicting possible growth inhibitory concentration (logGI50) against breast cancer cell line MCF-7. The virtual screening tool “CanWithaANN” can be accessed at local network of CIMAP.

‣ QSAR studies on Withanolide analogs for anticancer activity

Dharmendra Kumar Yadav; Feroz Khan; Rajender S. Sangwan
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
Withanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one of the most important medicinal plants of Indian systems of medicine. Withanolides are basically steroidal lactones (highly oxygenated C-28 phytochemicals) and similar to ginsenosides activity. Some of the withanolides that have been reported possess immunomodulatory, and anticancer activities. In the present investigation, a quantitative structure activity relationship (QSAR) model based on forward stepwise multiple linear regression (MLR) has been developed against the MCF7, MCF7/BUS, and SK-Br-3 human solid tumor breast cancer cell lines. Relationship correlation coefficient (r2) and cross validation correlation coefficient (r2CV) of QSAR model were 0.77 and 0.73 for MCF7, 0.91 and 0.85 for MCF7/BUS, 0.93 and 0.90 for SK-Br-3 respectively. Developed QSAR model was also evaluated for prediction accuracy through internal, external and randomization validation methods. The QSAR study indicates that chemical descriptors viz., atom count (all atoms), connectivity index (order 2, standard), for MCF7, Connectivity Index (order 0, standard), Dipole Vector X (debye), Molar Refractivity...

‣ Variety in evolutionary strategies favours biodiversity in habitats of moderate productivity

Simon Pierce
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
The mechanism whereby biodiversity varies between habitats differing in productivity is a missing link between ecological and evolutionary theory with vital implications for biodiversity conservation, management and the assessment of ecosystem services. A unimodal, humped-back relationship, with biodiversity greatest at intermediate productivities, is evident when plant, animal and microbial communities are compared across productivities in nature. However, the mechanistic, evolutionary basis of this observation remains enigmatic. We show, for natural and semi-natural plant communities across a range of bioclimatic zones, that biodiversity is greatest where communities include species with widely divergent values for phenotypic traits involved in resource economics and reproductive timing, coinciding with intermediate biomass production, whilst each productivity extreme is associated with small numbers of specialised species with similar trait values. Our data demonstrate that evolution can generate a greater range of phenotypes where large, fast-growing species are prevented from attaining dominance and extreme adaptation to a harsh abiotic environment is not a prerequisite for survival.

‣ Identification of Unique proteins of Candida albicans as Antifungal Drug Targets

Himanshu Tripathi; Abha Meena; Feroz Khan; Suaib Luqman
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
There are growing examples of drug resistance in the fungal pathogens to evade antifungal drugs by developing mutation in the key targeted enzymes and high expression of drug transporter genes including ABC transporters and MFS transporters. This led to the urgent need to identify novel (unique or essential to fungus) targets that can be used in development of potential antifungal drugs. We have used a comparative genomics approach to find out novel targets in opportunistic fungus, Candida albicans responsible for severe infection in immunocompromised humans. To identify novel targets we have analyzed available total 14,633 protein sequences (proteome) of C. albicans [SC5314] retrieved through RefSeq, an experimentally curated reference sequence database at NCBI, USA. To explore the unique proteins, proteome of C. albicans was first compared against human proteome and then with Saccharomyces cerevisiae (Yeast) through BLAST program (NCBI). Results showed that out of the available 14,633 protein sequences of C. albicans, 4,568 were identified unique when compared against human, while 2,955 were identified unique when compared against S. cerevisiae. Further work is ongoing to explore functionally known and unknown, unique or essential proteins/genes of C. albicans. Predicted as well as experimental data has been compiled in the form of a database namely...

‣ QSAR and Docking Studies of Gallic Acid Derivatives for Anticancer and Immunomodulatory Activity

Dharmendra Kumar Yadav; Feroz Khan; Arvind Singh Negi
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
Immuno-modulation is the process of alteration in immune response due to foreign intrusion of molecules inside the body. In the present communication QSAR and molecular docking studies for immuno-modulatory activity of derivatives of gallic acid were performed. Molecular docking studies showed higher binding affinity with INFα-2, IL-6, and IL-4 receptors. Binding site residues indicate hydrogen bonds formation with gallic acid derivative compounds G-3, G-4, G-5, G-6, G-7 and G-10. Further screening through quantitative structure activity relationship model establishes the immuno-modulatory activity of the compounds G-4, G-7, G-9, G-10, G-12 and G-13. Activity was predicted through a robust statistical model, developed by forward feed multiple linear regression method with leave-one-out approach. Relationship correlating measure (r2) and prediction accuracy (rCV2) of QSAR model were 0.99 and 0.96, respectively. QSAR studies indicate that dipole moment, steric energy, amide group count, λ max (UV-visible) and molar refractivity correlate well with their activities, while decrease in dipole moment, steric energy and molar refractivity have negative correlation. Moreover, on the basis of bioavailability, in-silico ADME and toxicity risk assessment screening...

‣ Productivity and forage quality of a phytodiverse semi-natural grassland under various management regimes

Tatiana From; Ute K. Petersen; Johannes Isselstein
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
Grassland management experiment (GrassMan) was set up in 2008 on a permanent semi-natural grassland in the Solling uplands, Germany. The main research focus is on the ecosystem functioning of the phytodiverse grassland (e.g. productivity and forage quality, water and nutrient fluxes). The aim of our study was to analyse the effects of vegetation composition and functional diversity on productivity and forage quality of the semi-natural permanent grassland. Variation in sward composition was achieved by herbicide application and resulted in three sward types: control sward type (without herbicide application), monocot-reduced and dicot-reduced. Further management factors included different nutrient input levels (without fertilizer and 180-30-100 kg/ha of N-P-K per year) and use intensity (cut once or three times a year). Functional diversity was determined by estimation of the yield shares for each species in the species composition and their specific functional characteristics. Forage quality was analysed by near infrared spectroscopy (NIRS). While sward type influenced the forage quality, yield variation was explained mainly by the management regime.

‣ Artificial Neural Network

Smrita Singh
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Conferência ou Objeto de Conferência
Português
In the postgenomic era, computational methods are being used in diverse areas like drug discovery, robotics, weather forecasting etc. Computational methods are incorporated with various programmes that are further instructed with complex algorithms based on different logistic approaches. Artificial neural network is one of them to be utilized in various molecular dynamics and simulation studies. Therefore, it is essential to understand the basic logic while programming in order to troubleshoot the computational methods.

‣ Structural requirements for the binding affinity of some small, non–peptide C5a receptor antagonists

Haiying Xie; Weiming Wang; Ziqiang Xie; Hong Chen; Kexian Chen
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Complement anaphylatoxin 5a (C5a) has been recognized as a potent therapeutic target for anti-inflammatory therapy, thus, blocking the action of C5a on its binding receptors may provide an effective treatment of a variety of inflammatory diseases. However, there have been few clinically available non-peptide C5a receptor antagonists disclosed at present. In pursuit of better anti-inflammatory drugs, quantitative structure–activity relationship studies were carried out in a series of non-peptide C5a receptor antagonists with binding activity using different physicochemical descriptors. The conventional best 2D-QSAR models were developed using a training set of 35 molecules and an external test set of 8 molecules by genetic function approximation (GFA) and stepwise multiple linear regression (Stepwise-MLR) with acceptable r^2^ of 0.773 and 0.863, r^2^~CV~ of 0.752 and 0.775, and r^2^~pred~ of 0.801 and 0.888, respectively, indicating binding activity strongly depends on thermodynamic properties as expressed by the hydrophobicity of molecules.

‣ Consortium Building For PEM MFC Using Synthetic Media As Substrate

Muralidharan Ayyappan; Dimpal Parida; Arti Yadav; Ramya Mohandass
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Microbial production of electricity is an important form of bioenergy since Microbial Fuel cells (MFC) offer the possibility of extracting electric current from a wide range of organic wastes and renewable biomass. Factors affecting the MFC operational effectiveness are the MFC design and the bacterial metabolism and electron transfer. The purpose of this study is to identify species which are responsible for electricity generation so as to build a suitable consortium and to investigate the relative efficiencies between the microbial consortiums. Enrichment by repeated transfer of a bacterial consortium harvested from the anode compartment of a MFC with synthetic media as a substrate increased the output from an initial level of 34 mA to a maximal level of 363 mA. Scanning electron microscope image indicated the enhanced microbial biofilm deposition over the electrode which were not initially detected in the community.

‣ Identification of a highly polymorphic tetranucleotide repeat locus (DXpS) at Xp and development of a DXpS/HUMARA biplex methylation-based PCR assay that enhances detection of X-chromosome inactivation

Filipe B. Machado; Ester S. Ramos; Pamela C. Radic; Carlos D. de Brasi; Enrique Medina-Acosta
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
The methylation-based PCR assay at the polymorphic (CAG)n repeat in exon 1 of the human androgen receptor _AR_ gene (HUMARA) is a standard method for determination of the methylation state of alleles in active X (Xa) and inactive X (Xi) chromosomes. HUMARA assay is endowed with heterozygosity rates ~85% worldwide. This means that in a proportion of females it is uninformative. The HUMARA genotype is not neutral, being linked to Kennedy´s disease. Moreover, allele designation and quantification from trinucleotide repeats demand normalizing for minor (stutter) products differing from the original template by multiples of the repeat unit. Here, we report on the identification of a highly polymorphic tetranucleotide repeat (named DXpS) mapping to within a CpG island on Xp. This island is 191 bp downstream from the start of the repeat element, and contains sites for the HhaI, HpaII and BstUI methyl-sensitive restriction enzymes. We developed the DXpS and the HUMARA markers into a biplex methylation-based quantitative fluorescent PCR assay. For DXpS we observed twelve alleles with negligible stuttering. DXpS exhibited a heterozygosity rate of 87% (n = 60), matching that of HUMARA. The combined informativeness of the biplex assay was 98%. Random and nonrandom X-inactivation patterns inferred with DXpS in phenotypically normal females and haemophiliac females carrying a defective F8 gene were highly concordant (r^2^ = 0.96) with HUMARA patterns. DXpS represents a notable advancement in detecting X-chromosome inactivation due to the observed high rate of heterozygosity...

‣ Preventing hereditary cancers caused by opportunistic carcinogens

Bernard Friedenson
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Objectives Previous studies reported inherited BRCA1/2 deficits appear to cause cancer by impairing normal protective responses to some carcinogens. Opportunistic carcinogens can exploit these deficits by causing chronic inflammation, constant cell death and replacement in a mutagenic environment, DNA crosslinking or double strand breaks. Some of the resulting cancers may be prevented if BRCA1/2 specific carcinogens are identified. Methods The literature was systematically searched for carcinogens capable of exploiting deficits in BRCA1/2 pathways. Search criteria were common exposure, available information, required BRCA1/2 pathway repairs, increased risks for any cancer, and effects on stem cells. Results Formaldehyde and acetaldehyde are closely related carcinogens and common pollutants that are everywhere. Alcohol metabolism also produces acetaldehyde. High levels of either carcinogen overwhelm normal detoxification systems, cause inflammation, inhibit DNA repair and produce DNA cross links as critical carcinogenic lesions. Searching model system studies revealed both carcinogens activate stem cells, BRCA1/2 pathways and connected BRCA1/2 pathways to myeloid leukemia. For example, the BRCA1-BARD1 complex is required for proper nucleophosmin functions. Nucleophosmin prevents a major subset of acute myeloid leukemia (AML). Next...

‣ The use of DCEEG to estimate functional and metabolic state of nervous tissue of the brain at hyper- and hypoventilation

Sergey Murik
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
A pilot study has been made of the simultaneous DC potential and total slow electrical activity changes during modeling various metabolic and functional states of the human brain. The multi-electrode DCEEG recordings have been performed during the hyperventilation (frequent deep one-minute long breathing motions) and the hypoventilation (voluntary breath holding). It has been shown that the ischemic state occurring in hyperventilation is accompanied by the negative shift of DC potential and increase in the EEG rhythms amplitude. A distention of brain vessels during hypoventilation (voluntary breath-hold) and an improvement of blood supply and thus improvement of vital and functional state of neurons gave rise to an increase in the EEG rhythm amplitude too, though against a background of a positive DC-potential shift. Obtained results are considered in context of the generation of the qualitatively different functional states of brain cells during hyper- and hypoventilation which is reflected in their resting potential and activity. The conducted study shows the prospects for DCEEG and the method we used for DCEEG data processing to understand the character of functional and metabolic changes in the nervous tissue.

‣ Pramipexole protective effect on rotenone induced neurotoxicity in mice

Mohamed M. Salama; Dina El-Tantawy; Sahar A. El-Dakroury; Hasan Abd-Elghaffar; Sara El-Dosouky; Abdelaziz A. Ghanem; Seham A. Gad-Elhak
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Introduction: Pramipexole is a new dopaminergic drug which has been approved for PD treatment. However, we tried to find a new capacity for this drug rather than symptomatic effect. Materials and Methods: A chronic rotenone model with daily oral dose of 30mg/kg was induced in mice. Pramipexole was tried in a new approach where the treatment began in the middle of rotenone course with oral dose 1mg/kg/day of pramipexole. Results: Further analysis of behavioral tests and immunohistochemistry revealed success of pramipexole in improving the rotenone intoxicated mice. Conclusion: These results showed possible beneficial effects of pramipexole against rotenone-induced neurotoxicity.

‣ Corticofugal projections from the anterior olfactory nucleus target olfactory bulb principal cells

Kurt R. Illig
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
The anterior olfactory nucleus (AON) is a cortical structure reciprocally connected with the olfactory bulb (OB) and the piriform cortex. Here, using small extracellular and intracellular injections to trace the terminal projections in the OB from individual cells in the rat AON, and examining the morphology and distribution of these projections, I report that these projections appear to preferentially target and directly synapses with mitral cells. These findings suggests that the AON acts to modulate incoming olfactory information based on ongoing processing, perhaps in a way that tunes the OB to signal the presence of particular odors.

‣ The Olfactory Nervous System Of Terrestrial And Aquatic Vertebrates

Ashiq Hussain
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
Animals in their natural milieu are surrounded by odors. These odors are rich source of information, and are perceived by sophisticated olfactory systems, that have evolved over time. The sense of smell helps species to localize prey, evade predators, explore food and recognize viable mates. In humans, memoirs, thoughts, emotions, and associations are more readily reached through the sense of smell than through any other channel. This suggests that olfactory processing is imperative and may differ fundamentally from processing in other sensory modalities. The molecular age in olfaction initiated in 1991 with the significant discovery of a large, multigene family of olfactory receptors in rat by Linda Buck and Richard Axel (Buck and Axel, 1991). The first cloned olfactory receptors consisted of a diverse repertoire of G-protein coupled receptors (GPCRs) with seven-trans membrane topology, and they were sparsely expressed in the olfactory epithelium. This Nobel Prize worthy pioneering discovery, together with availability of modern techniques and numerous completely sequenced genomes opened the way to characterize the gene families of olfactory receptors through exhaustive computational data mining in different species genome as well as by in vitro biology. In this review...

‣ Ornithine decarboxylase activity, a clinical biomarker for evaluating cancer chemopreventive efficacy of phytomolecules

Nusrat Masood; Vijaya Dubey; Suaib Luqman
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
Biomarkers of cancer have made a strong traipse in predicting the disease pattern and contributed significantly to the understanding of tumour state, progression, characteristics and response to therapies. Polyamines such as putrescine, spermine and spermidine are cationic biomolecules essential for the cell cycle function and serve as excellent biomarkers of tumour progression. The polyamine biosynthesis is tightly regulated by ornithine decarboxylase, a highly inducible enzyme specific to pH, temperature, time and substrate concentration. The expression of this enzyme is very high during cell transformation and tumour progression leading to elevated level of polyamines. To measure the activity of ornithine decarboxylase an improved, easy, simple, reliable and cost-effective method has been developed utilizing small quantity of chemicals. The methodology is based on the cognizance that enzyme transforms L-ornithine hydrochloride substrate to a yellow coloured product putrescine soluble in pentanol, the absorbance of which was measured spectrophotometrically. The procedure is being utilized for evaluating cancer chemopreventive efficacy of phytomolecules. We have analyzed hundreds of molecules belonging to flavonoid, terpenes and alkaloid groups and very few were found to inhibit enzyme activity in a concentration dependent manner (0.4-50µg/mL). In addition...

‣ Anticancer efficacy of phenolics based structurally related compounds and their radical scavenging action

Vijaya Dubey; Nusrat Masood; Suaib Luqman; Arvind S. Negi
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
Cancer, one of the leading causes of death worldwide, is an abnormal cell proliferation that fails to respond to the normal signals. In an effort to eradicate the growing menace of cancer, a clear understanding of fundamental biology and molecular mechanism of carcinogenesis is essential for targeted therapies. Among the devised strategies in use for cancer treatment, the one that is of immense interest is the development of plant based novel anticancer agents. Due to their tremendous availability, biological activity and efficacy, the phytochemicals deemed a gibbous future in chemoprevention. In the present study, several phenolics based structurally related compounds of steroidal and non-steroidal skeleton were synthesized and tested for their modulatory effect on ornithine decarboxylase activity, an enzyme highly upregulated in cancer. Additionally, these compounds were also examined for radical scavenging extent to establish a correlation with the anticancer property. Our result suggests that the tested compounds possessed radical scavenging activity, for being the inherent property of the phenolics. 3-(3’,4’5’-trimethoxyphenyl)-4,5,6-trimethoxyindan-1-one oxime exhibited highest inhibition of enzyme activity (91%) followed by 1-(2...

‣ Detection of BCR-ABL kinase domain mutations in CD34+ cells from newly diagnosed chronic phase CML patients and their association with imatinib resistance

Zafar Iqbal; Ijaz Shah; Aamer Aleem; Mubashar Naqvi; Ammara Tahir; Tariq Gill; Abid Taj; Abdul Qayyum; Najeeb ur-Rehman; Muhammad Ferhan; Mudassar Iqbal; Muhammad Khalid; Weng Qin; Ahmad Khalid; Mahwish Khan; Shahid Baig; Abid Jamil; Tanveer Akhtar; Muham
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
BCR-ABL kinase domain (KD) mutations, the most common cause of imatinib resistance, are infrequently detected in newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML) patients. Recent studies indicate pre-existing mutations (PEMs) can be detected in a higher percentage of CML patients using CD34+ stem/progenitor cells, and these mutations may correlate with imatinib resistance. We investigated KD mutations in CD34+ stem cells from 100 CP-CML patients by multiplex ASO-PCR and sequencing ASO-PCR products at the time of diagnosis. PEMs were detected in 32/100 patients and included F311L, M351T, and T315I. After a median follow-up of 30 months (range 8-48), all patients with PEMs exhibited imatinib resistance. Of 68 patients without PEMs, 24 developed imatinib resistance. Mutations were detected in 21 of these patients by ASO-PCR and KD sequencing. All 32 patients with PEMs had the same mutations. In imatinib-resistant patients without PEMs, we detected F311L, M351T, Y253F, and T315I mutations. All imatinib-resistant patients without T315I and Y253F mutations responded to imatinib dose escalation. In conclusion, BCR-ABL PEMs can be detected in a substantial number of CP-CML patients when investigated using CD34+ stem/progenitor cells. These mutations are associated with imatinib resistance...

‣ Endothelial Massive Calcium Accumulation Death (MCAD): Mechanism, Target, and Predictive Biomarker for Anti-Angiogenic Therapy

Larry Weisenthal
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Poster
Português
We cultured human umbilical vein endothelial cells with bevacizumab, with tyrosine kinase inhibitors known to be AA, and with traditional cytotoxic drugs. The images below show that, in the presence of physiological saline and non-favorable culture conditions, the vast majority of the endothelial cells undergo a "non-specific" type of cell death (NSCD), not associated with calcium accumulation, but with loss of cell membrane integrity, allowing uptake of the Fast Green dye, staining these dead dells a pale blue green. In the presence of known AA agents (e.g. bevacizumab, some TK inhibitors) a large percentage of the endothelial cells undergo death associated with massive calcium accumulation (MCAD), with these cells staining hyperchromatic, refractile, blue-black, precisely as reported in http://www.ncbi.nlm.nih.gov/pubmed/18793333 and http://meeting.ascopubs.org/cgi/content/abstract/ 28/15_suppl/e13617 and http://tinyurl.com/weisenthal-breast-lapatinib. MCAD is strikingly demonstrated by Fast Green/Alizarin staining as reported in http://precedings.nature.com/documents/4499/version/1. Traditional cytotoxic drugs (e.g. cisplatin) produce only NSCD and inhibit MCAD. We propose that MCAD is a cell death mechanism unique to endothelial cells and provides a practical biomarker to predict for AA activity in clinical oncology and drug development...

‣ Benchmarking the SPARC software program for estimating solubilities of naphthalene and anthracene in organic solvents

Sierra Rayne; Kaya Forest
Fonte: Nature Preceedings Publicador: Nature Preceedings
Tipo: Manuscript
Português
The SPARC software program was benchmarked for calculating the solubilities of two representative polyaromatic hydrocarbons (PAHs), naphthalene and anthracene, in a range of organic solvents at various temperatures. Although SPARC was able to reasonably approximate the solubilities of naphthalene in some organic solvents, gross errors were obtained for other solvents. For anthracene, poor prediction performance was observed in all solvents considered. Overall, the results suggest that SPARC is currently not suitable for accurately predicting the solubilities of representative PAHs relevant for the petroleum sector in various organic solvents.