Nature Precedings
Not a member yet
3446 research outputs found
Sort by
Genome Replikin Count Predicts Increased Lethality of Cancer
No full textThose cancers, like thyroid and pancreatic cancer, with the lowest 5-year mortality rates, have Replikin Counts of about 20; lung and brain cancers, with the highest 5-year mortality rates, have Replikin Counts of 275 and 325 respectively; the others fall in between with approximate linearity. This is the first quantitative relationship of a genomic structure, Replikins, to 5-year mortality rates
Integrating Open Lab Notebooks with Online Databases
No full textMy slides from a presentation and panel discussion on integrating open lab notebooks with online databases. A video archive of the presentation is available here: http://vimeo.com/2010063
Cancer chemopreventive action of α-(-)-bisabolol, a sesquiterpene alcohol involves inhibition of cathepsin D and ornithine decarboxylase via tramping nitric oxide
No full textTerpenoids, traditionally used for cosmetic and medicinal purposes, are currently being explored as cancer chemopreventive as well as chemotherapeutic agent in clinical trials. α-(-)-bisabolol, a naturally occurring monocyclic sesquiterpene alcohol is a major component of essential oil of chamomile (Matricaria recutita L., Chamomilla recutita L., Matricaria chamomilla; Family Asteraceae). As substantiated previously, α-(-)-bisabolol is known to have antimicrobial, anti-irritant, anti-inflammatory and anti-allergic properties. It also affects cell viability and growth of various human and murine cell lines by either inducing apoptosis or suppressing Akt activation or down regulating expression of some genes implicated in carcinogenesis. To elucidate the possible mechanism for its cancer chemopreventive action, herein we are reporting dose-dependent effect of α-(-)-bisabolol on ornithine decarboxylase (ODC, a key rate limiting enzyme in mammalian polyamine biosynthesis), cathepsin D (CATD, a lysosomal aspartyl protease) and dihydrofolate reductase (DHFR, a protein of purine biosynthetic pathway) all of these proteins get over-expressed during cell transformation, proliferation and malignancy. Our results demonstrate greater activity of α-(-)-bisabolol by exhibiting potent inhibition of ODC (99% at a concentration of 100μM with an IC50 value of 0.01μM) and CATD (22% at 10μM). The molecule did not affect DHFR activity significantly. To establish the hypothesis whether inhibition of CATD and ODC involves tramping of nitric oxide (NO), we have also investigated the scavenging potential of α-(-)-bisabolol and the results were found to be promising with an IC50 of 0.1μM. Our findings suggest that α-(-)-bisabolol not only inhibits ODC and CATD activity through scavenging of NO radicals but also exerts anti-tumour promoting properties which may perhaps be due to channeling of arginine in the NO and polyamine biosynthesis pathways. These results provide a possibility of developing α-(-)-bisabolol as a viable cancer chemopreventive agent
Inhibiton of NFκB activation and aromatase activity by vanilloids: An in vitro and in silico study
No full textTarget-specific drugs, including natural products, offer promise for the amelioration of cancer and other human ailments with reduced side-effects. Capsaicin, the pungent ingredient present in chillies (Capsicum annuum L.), and capsazepine, a synthetic analogue of capsaicin (collectively referred to as vanilloids), are known to possess a variety of pharmacological and physiological properties. In our continuous effort to discover cancer chemopreventive agents from natural products, we investigated the effect of vanilloids on NFκB activation with stably transfected 293/NFκB-Luc human embryonic kidney cells induced by treatment with tumor necrosis factor (TNFα), and aromatase activity. Capsaicin and capsazepine blocked TNFα-induced NFκB activation in a dose-dependent manner with IC50 values of 13.5 and 8.5 μM, respectively. No cytotoxicity was observed at higher test concentration (20 μg/mL). In addition, these vanilloids inhibited aromatase activity with IC50 values of 0.68 and 4.21 μM, respectively. Computer aided molecular docking studies showed acceptable docking scores indicating good binding affinity of vanilloids with aromatase and NFκB. Based on these findings, aromatase and NFκB are suggested as valid targets for these compounds; additional investigation of chemopreventive or chemotherapeutic potential is required
Bogoch Replikins Pandemic Prevention: Increase of Strain-Specific Influenza Genomic Replikin Counts, Having Predicted Outbreaks and their Location Seven Times Consecutively, Up to Two Years in Advance, Provides Time for Prevention of Pandemics
Full text linkEarlier studies have shown that the increased concentration of a new class of virus genomic peptides, Replikins, precedes and predicts virus outbreaks. We now find that the area in the genome of the highest concentration of Replikins, and the country in which this peak exists in scout viruses, have permitted in the past five years seven consecutive accurate predictions of the geographic localization of coming outbreaks, including those now realized in Mexico for H1N1, and in Cambodia for H5N1. Real-time Replikin analysis of the evolution of the virus genome identified both mutations and structural reorganization of the hemagglutinin and p B1 genes over several years before each outbreak. This information, together with the specific Replikin sequences so obtained, permitted solid-phase synthesis of Replikin vaccines in seven days, which blocked H5N1 in chickens. The information also now provides up to two years of time to thoroughly test and distribute vaccines to high risk individuals in the countries identified; thus for the first time, a quantitative genomic Replikins method to both predict initial outbreaks and to prevent the development of a pandemic
The 'consciousness' of the living state: Extending the Baars global broadcast model across physiological subsystems
No full textFor the broad spectrum of cognitive biological phenomena having 'dual' information sources, isolation from crosstalk between them requires more metabolic free energy than permitting correlation. This allows an evolutionary exaptation leading to dynamic global broadcasts at multiple scales, similar to the well-studied exaptation of noise to trigger stochastic resonance amplification in physiological systems. Entropy gradient models adapted from nonequilibrium thermodynamics lead to an index theorem in which analytic solutions of empirical equations describe different possible topological modes. Not only is the living state characterized by cognition at every scale and level of organization, but by multiple, shifting, tunable, cooperative broadcasts that link selected subsets of those structures to address problems. As for animal consciousness, the 'stream' of cognitive physiological broadcast is constrained by the riverbanks of embedding context, expressed in terms of systematic regularities of an enveloping environmental information source and the limitations imposed by developmental trajectory
A database of orthologous exons in primates for comparative analysis of RNA-seq data
Full text linkRNA-seq technology facilitates the study of gene expression at the level of individual exons and transcripts. Moreover, RNA-seq enables unbiased comparative analysis of expression levels across species. Such analyses typically start by mapping sequenced reads to the appropriate reference genome before comparing expression levels across species. However, this comparison requires prior knowledge of orthology at the exon level. With this in mind, I constructed a database of orthologous exons across three primate species (human, chimpanzee, and rhesus macaque). The database facilitates cross-species comparative analysis of exon- and transcript-level regulation. A web application allowing for an easy database query: http://giladlab.uchicago.edu/orthoExon
Antidiabetic, Anti-hyperlipidemic & Hepatoprotective effect of a Polyherbal Unani formulation “Qurs Tabasheer” in STZ-diabetic wistar rats
No full textThe present study was undertaken to evaluate the antihyperglycemic, antihyperlipidemic and hepatoprotective effect of a traditional unani formulation “Qurs Tabasheer” in streptozotocin (STZ) induced diabetic wistar rats. Up until now, no study was undertaken to appraise the efficacy of “Qurs Tabasheer” in the diabetic rats. Qurs Tabasheer is a unani formulation restraining preparations from six various herbs namely Tukhme Khurfa (Portulaca oleracea seed), Gule Surkh (Rosa damascena flower), Gile armani (Arminium bole), Gulnar (Punica granatum flower), Tabasheer (Bambusa arundinasia dried exudate on node), Tukhme Kahu (Lactuca sativa Linn seed). The effect of Qurs Tabasheer was assessed in STZ (60 mg/kg, i.p single shot) induced diabetic wistar rats. STZ produced a marked increase in the serum glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, triglycerides and trimmed down the HDL level. We have weighed the effect of Qurs Tabasheer on hepatic activity through estimating levels of various liver enzymes viz. Hexokinase, Glucose-6-Phosphatase and Fructose-1-6-biphosphatase in STZ diabetic wistar rats. In STZ-induced diabetic wistar rats the level of Hexokinase, and Glucose-6-Phosphatase was decreased to a significant level while the level of fructose-1-6-biphophatase was augmented. Therapy with Qurs Tabasheer for 30 days to STZ-induced diabetic rats significantly reduces the level of serum glucose, total cholesterol, triglycerides, glucose-6-phosphatase and fructose-1-6-biphosphatase, while magnitude of HDL cholesterol and hexokinase was amplified. Antihyperglycemic, antihyperlipidemic activity of Qurs Tabasheer suspension in STZ- induced wistar rats was found to be more effective than oral hypoglycemic drug Glimepiride
"Dark Mediators" of Proteins as Revealed by NMR in Water: Residue-selective Anion Bindings that are Masked by Pre-existing Buffer
No full textIons are commonly believed to impose their effects on proteins by unspecific electrostatic screening. Here, by NMR we reveal that in water sulfate, chloride and thiocyanate are able to bind a well-folded WW domain at distinctive residues and affinities, which is surprisingly masked by the pre-existing buffer. Our study reveals that the specific anion binding is so ubiquitous and consequently no longer negligible in establishing "postreductionist framework" for protein biochemistry
Medicine beyond magic bullets: a formal case for multilevel interventions
Full text linkWestern medicine's paradigmatic search for 'magic bullet' interventions is facing increasing difficulty: Between 1950 and 2010 the inflation-adjusted cost per USFDA-approved drug has increased exponentially in time, a draconian inverse of the famous Moore's Law of computing. A sequence of empirically-oriented statistical models suggests that carefully designed synergistic multifactorial and multiscale strategies might evade this relationship