Abstract: After two decades watching atmospheric oxygen levels drop, a Scripps researcher's conclusions about climate could leave one feeling light-headed.
Abstract: This video is part of CARLINK PROJECT simulation videos. It presents the performance of communications in Vehicular Ad-hoc Networks (VANETs) using the IEEE 802.11b standard in the transmission of files.- Jamal Toutouh -
Abstract: This video is part of CARLINK PROJECT simulation videos. It presents the performance of communications in Vehicular Ad-hoc Networks (VANETs) using the IEEE 802.11b standard in the transmission of files.- Jamal Toutouh -
Abstract: The longest geological cycle identified is described as about 600 million years in "Megacycles", the proceedings of a geological conference, Edited by G Williams. However Prof. S. Afanasiev of Moscow has determined the cycle very accurately to be 586.24 million years using his Nanocycles Method. It so happens that cosmologists, Broadhurst, T.J., Ellis, R.S., Koo, D.C. & Szalay (Nature 343, p 726) have observed regular mega-walls of galaxies at spacings that they describe as 128 Mpc/h, which based on the latest Hubble constant values would correspond to 588 million light years. Some cosmologists have suggested that the regularity might result from standing waves. Standing waves in space of wavelength 586 million light years would oscillate in 586 million years. In addition, if there are present harmonics of these waves as both the geological cycles and the additional peaks in the galaxy survey indicate, then powerfully energetic events would recur on Earth at these intervals. This agreement on the wave sizes actually allows a much more accurate Hubble constant to be determined from Afanasiev's accurate cycle period.
Malignant Melanoma is the most aggressive of malignant cutaneous tumours. Cases with lymphonode involvement, and distant metastases, carry a very poor prognosis, (50% and 20% respectively alive in 5 years), while those presenting without evident lymphonode involvement have a much better survival rate (60% alive in 5 years).
It is therefore extremely important to do early malignant melanoma diagnosis. There are several criteria that may lead to the diagnosis of a malignant melanoma. The most important one is the ABCD rule.
The ABCD diagnosis of Malignant Melanoma -
A = Asymmetry: Moles are commonly symmetrical and round. Very early melanomas, are asymmetrical assuming different forms. One half does not match the other half.
B = Border: Commonly moles, have even and smooth borders. Early melanomas, are usually uneven and notched borders. The edges are ragged, notched or blurred.
C = Color: Moles commonly are a single shade of brown, early malignant melanomas shows brown-tan or black color. Further, as melanomas progress, may see red, white, and blue color.
D = Diameter: Early malignant melanomas, differently from moles, tend to grow larger in diameter. First suspects in melanoma start from a 6 millimeters diameter on. Any sudden or continuing increase in size should be of special concern.
Synthesis: a mole with diameter of 6 millimeter, that it introduces alterations - irregular asymmetry, edges, color - must induce the patient to address early on dermatologist to careful clinical and dermatoscopic examination and consequently, if necessary, to surgical removal of the lesion, with successive hystological examination.
Melanoma Prevention
According to the risk factors for malignant melanoma, the following preventive measures are also recommended:
* UV exposure, should be reduced. Prolonged sunbathing, as well as the use of tanning lamps, is not recommended. Children, under three years of age, should be held in the shade.
* Sun protection, should be obtained through suitable clothing. Children should be peculiarly dressed when playing outside.
* Use adequate sunscreens.
* Sunburns should be avoided, particularly in children.
Therefore people with multiple and abnormal moles, or with a family history of malignant melanoma, should have their skin checked continuously by a doctor/dermatologist.
Abstract: Background MUC2 mucin produced by intestinal goblet cells is the major component of the intestinal mucus barrier. The inflammatory bowel disease ulcerative colitis is characterized by depleted goblet cells and a reduced mucus layer, but the aetiology remains obscure. In this study we used random mutagenesis to produce two murine models of inflammatory bowel disease, characterized the basis and nature of the inflammation in these mice, and compared the pathology with human ulcerative colitis.
Methods and Findings By murine N-ethyl-N-nitrosourea mutagenesis we identified two distinct noncomplementing missense mutations in Muc2 causing an ulcerative colitis-like phenotype. 100% of mice of both strains developed mild spontaneous distal intestinal inflammation by 6 wk (histological colitis scores versus wild-type mice, p , 0.01) and chronic diarrhea Monitoring over 300 mice of each strain demonstrated that 25% and 40% of each strain, respectively, developed severe clinical signs of colitis by age 1 y. Mutant mice showed aberrant Muc2 biosynthesis, less stored mucin in goblet cells, a diminished mucus barrier, and increased susceptibility to colitis induced by a luminal toxin. Enhanced local production of IL-1b, TNF-a, and IFN-c was seen in the distal colon, and intestinal permeability increased 2-fold. The number of leukocytes within mesenteric lymph nodes increased 5-fold and leukocytes cultured in vitro produced more Th1 and Th2 cytokines (IFN-c, TNF-a, and IL-13). This pathology was accompanied by accumulation of the Muc2 precursor and ultrastructural and biochemical evidence of endoplasmic reticulum (ER) stress in goblet cells, activation of the unfolded protein response, and altered intestinal expression of genes involved in ER stress, inflammation, apoptosis, and wound repair. Expression of mutated Muc2 oligomerisation domains in vitro demonstrated that aberrant Muc2 oligomerisation underlies the ER stress. In human ulcerative colitis we demonstrate similar accumulation of nonglycosylated MUC2 precursor in goblet cells together with ultrastructural and biochemical evidence of ER stress even in noninflamed intestinal tissue. Although our study demonstrates that mucin misfolding and ER stress initiate colitis in mice, it does not ascertain the genetic or environmental drivers of ER stress in human colitis.
Conclusions Characterization of the mouse models we created and comparison with human disease suggest that ER stress-related mucin depletion could be a fundamental component of the pathogenesis of human colitis and that clinical studies combining genetics, ER stress-related pathology and relevant environmental epidemiology are warranted.
Abstract: Projects to facilitate collaboration between biologists and computer scientists. Lecture from the Women in Bioinformatics series. Fran Lewitter, Ph.D. Director of the Bioinformatics and Research Computing Department, Whitehead Institute, MIT
Abstract: Lab for the Computer-Aided Discovery Methods course taught at Baylor College of Medicine. Design of an array CGH assay. Finding recurrent aberrations in breast cancer using publicly available array CGH data. Subtracting known human structural polymorphisms. Gene annotation to identify aberrations that involve genes known to be relevant for cancer progression. Identifying aberrations relevant for cancer progression by integrating DNA dosage and gene expression information.
Abstract: CD8+ cytotoxic T-lymphocytes (CTLs) perform a critical role in the immune control of viral infections, including those caused by human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV). As a result, genetic variation at CTL epitopes is strongly influenced by host-specific selection for either escape from the immune response, or reversion due to the replicative costs of escape mutations in the absence of CTL recognition. Under strong CTL-mediated selection, codon positions within epitopes may immediately “toggle” in response to each host, such that genetic variation in the circulating virus population is shaped by rapid adaptation to immune variation in the host population. However, this hypothesis neglects the substantial genetic variation that accumulates in virus populations within hosts. Here, we evaluate this quantity for a large number of HIV-1– (n ≥ 3,000) and HCV-infected patients (n ≥ 2,600) by screening bulk RT-PCR sequences for sequencing “mixtures” (i.e., ambiguous nucleotides), which act as site-specific markers of genetic variation within each host. We find that nonsynonymous mixtures are abundant and significantly associated with codon positions under host-specific CTL selection, which should deplete within-host variation by driving the fixation of the favored variant. Using a simple model, we demonstrate that this apparently contradictory outcome can be explained by the transmission of unfavorable variants to new hosts before they are removed by selection, which occurs more frequently when selection and transmission occur on similar time scales. Consequently, the circulating virus population is shaped by the transmission rate and the disparity in selection intensities for escape or reversion as much as it is shaped by the immune diversity of the host population, with potentially serious implications for vaccine design.
Abstract: Background The ability to predict antibody binding sites (aka antigenic determinants or B-cell epitopes) for a given protein is a precursor to new vaccine design and diagnostics. Among the various methods of B-cell epitope identification X-ray crystallography is one of the most reliable methods. Using these experimental data computational methods exist for B-cell epitope prediction. As the number of structures of antibody-protein complexes grows, further interest in prediction methods using 3D structure is anticipated. This work aims to establish a benchmark for 3D structure-based epitope prediction methods.
Results Two B-cell epitope benchmark datasets inferred from the 3D structures of antibody-protein complexes were defined. The first is a dataset of 62 representative 3D structures of protein antigens with inferred structural epitopes. The second is a dataset of 82 structures of antibody-protein complexes containing different structural epitopes. Using these datasets, eight web-servers developed for antibody and protein binding sites prediction have been evaluated. In no method did performance exceed a 40% precision and 46% recall. The values of the area under the receiver operating characteristic curve for the evaluated methods were about 0.6 for ConSurf, DiscoTope, and PPI-PRED methods and above 0.65 but not exceeding 0.70 for protein-protein docking methods when the best of the top ten models for the bound docking were considered; the remaining methods performed close to random. The benchmark datasets are included as a supplement to this paper.
Conclusion It may be possible to improve epitope prediction methods through training on datasets which include only immune epitopes and through utilizing more features characterizing epitopes, for example, the evolutionary conservation score. Notwithstanding, overall poor performance may reflect the generality of antigenicity and hence the inability to decipher B-cell epitopes as an intrinsic feature of the protein. It is an open question as to whether ultimately discriminatory features can be found.
Abstract: Acetylcholinesterase (AChE) rapidly hydrolyzes acetylcholine in the neuromuscular junctions and other cholinergic synapses to terminate the neuronal signal. In physiological conditions, AChE exists as tetramers associated with the proline-rich attachment domain (PRAD) of either collagen-like Q subunit (ColQ) or proline-rich membrane-anchoring protein. Crystallographic studies have revealed that different tetramer forms may be present, and it is not clear whether one or both are relevant under physiological conditions. Recently, the crystal structure of the tryptophan amphiphilic tetramerization (WAT) domain of AChE associated with PRAD ([WAT]4PRAD), which mimics the interface between ColQ and AChE tetramer, became available. In this study we built a complete tetrameric mouse [AChET]4–ColQ atomic structure model, based on the crystal structure of the [WAT]4PRAD complex. The structure was optimized using energy minimization. Block normal mode analysis was done to investigate the low-frequency motions of the complex and to correlate the structure model with the two known crystal structures of AChE tetramer. Significant low-frequency motions among the catalytic domains of the four AChE subunits were observed, while the [WAT]4PRAD part held the complex together. Normal mode involvement analysis revealed that the two lowest frequency modes were primarily involved in the conformational changes leading to the two crystal structures. The first 30 normal modes can account for more than 75% of the conformational changes in both cases. The evidence further supports the idea of a flexible tetramer model for AChE. This model can be used to study the implications of the association of AChE with ColQ.
Abstract: JPL engineers built a futuristic robot that may one day go to the moon. For more information see: http://www.jpl.nasa.gov/videos/technology/athlete-20070806/