Functional polymorphisms in the TERT promoter are associated with risk of serous epithelial ovarian and breast cancers

Genetic variation at the TERT-CLPTM1L locus at 5p15.33 is associated with susceptibility to several cancers, including epithelial ovarian cancer (EOC). We have carried out fine-mapping of this region in EOC which implicates an association with a single nucleotide polymorphism (SNP) within the TERT promoter. We demonstrate that the minor alleles at rs2736109, and at an additional TERT promoter SNP, rs2736108, are associated with decreased breast cancer risk, and that the combination of both SNPs substantially reduces TERT promoter activity.     

Thyroid hormones induce unique and potentially beneficial changes in cardiac myocyte shape in hypertensive rats near heart failure

We examined the effects of thyroid hormones (THs) on left ventricular (LV) function and myocyte remodeling in rats with spontaneously hypertensive heart failure (SHHF). SHHF rats were treated with three different TH doses from 20-21 mo of age. In terminal experiments, LV function (as determined by echocardiography and catheterization) and isolated myocyte shape were examined in SHHF rat groups and age-matched Wistar-Furth control animals. Compared with Wistar-Furth rats, the ratio of alpha- to beta-myosin was reduced in untreated SHHF rats. The alpha-to-beta-myosin ratio increased in all TH groups, which suggests a reversal of the fetal gene program. Low-dose TH produced no changes in LV myocyte size or function, but high-dose TH produced signs of hyperthyroidism (e.g., increased heart weight, tachycardia). The chamber diameter-to-wall thickness ratio declined with increasing dose due to reduced chamber diameter and increased wall thickness. This resulted in a 38% reduction in LV systolic wall stress in the middle- and high-dose groups despite sustained hypertension. Isolated myocyte data indicated that chamber remodeling and reduced wall stress were due to a unique alteration in myocyte transverse shape (e.g., reduced major diameter and increased minor diameter). Based on our present understanding of ventricular remodeling and wall stress, we believe these changes are likely beneficial. Results suggest that TH may be an important regulator of myocyte transverse shape in heart disease.     

Proteasome inhibition by lactacystin in primary neuronal cells induces both potentially neuroprotective and pro-apoptotic transcriptional responses: a microarray analysis

Although inhibition of the ubiquitin proteasome system has been postulated to play a key role in the pathogenesis of neurodegenerative diseases, studies have also shown that proteasome inhibition can induce increased expression of neuroprotective heat-shock proteins (HSPs). The global gene expression of primary neurons in response to treatment with the proteasome inhibitor lactacystin was studied to identify the widest range of possible pathways affected. Our results showed changes in mRNA abundance, both at different time points after lactacystin treatment and at different lactacystin concentrations. Genes that were differentially up-regulated at the early time point but not when most cells were undergoing apoptosis might be involved in an attempt to reverse proteasome inhibitor-mediated apoptosis and include HSP70, HSP22 and cell cycle inhibitors. The up-regulation of HSP70 and HSP22 appeared specific towards proteasome inhibitor-mediated cell death. Overexpression of HSP22 was found to protect against proteasome inhibitor-mediated loss of viability by up to 25%. Genes involved in oxidative stress and the inflammatory response were also up-regulated. These data suggest an initial neuroprotective pathway involving HSPs, antioxidants and cell cycle inhibitors, followed by a pro-apoptotic response possibly mediated by inflammation, oxidative stress and aberrant activation of cell cycle proteins.     

Enhanced cytotoxicity without internuclear spread of adenovirus upon cell fusion by measles virus glycoproteins

The efficiency of viruses in cancer therapy is enhanced by proteins that mediate the fusion of infected cells with their neighbors. It was reported that replication-competent adenovirus particles can spread between nuclei within fusion-generated syncytia. To assess this conjecture, we generated fusogenic adenoviruses that express a balanced ratio of the F and H glycoproteins of measles virus. The viruses displayed enhanced cytotoxicity but largely unchanged replication efficiencies compared to a nonfusogenic virus. Most notably, the virus genomes did not spread through fusion-generated multinuclear cells. Hence, adenovirus replication in syncytia remains largely restricted to initially transduced nuclei.     

Fractional order viscoelasticity of the aortic valve cusp: an alternative to quasilinear viscoelasticity

BACKGROUND: Quasilinear viscoelasticity (QLV) theory has been widely and successfully used to describe the time-dependent response of connective tissues. Difficulties remain, however, particularly in material parameter estimation and sensitivities. In this study, we introduce a new alternative: the fractional order viscoelasticity (FOV) theory, which uses a fractional order integral to describe the relaxation response. FOV implies a fractal-like tissue structure, reflecting the hierarchical arrangement of collagenous tissues. METHOD OF APPROACH: A one-dimensional (I-D) FOV reduced relaxation function was developed, replacing the QLV "box-spectrum" function with a fractional relaxation function. A direct-fit, global optimization method was used to estimate material parameters from stress relaxation tests on aortic valve tissue. RESULTS: We found that for the aortic heart valve, FOV had similar accuracy and better parameter sensitivity than QLV, particularly for the long time constant (tau2). The mean (n = 5) fractional order was 0.29, indicating that the viscoelastic response of the tissue was strongly fractal-like. RESULTS SUMMARY: mean QLV parameters were C = 0.079, tau1 = 0.004, tau2 = 76, and mean FOV parameters were beta = 0.29, tau = 0.076, and rho = 1.84. CONCLUSIONS: FOV can provide valuable new insights into tissue viscoelastic behavior Determining the fractional order can provide a new and sensitive quantitative measure for tissue comparison.     

Diversity of mesophilic clostridia in Costa Rican soils

Costa Rica is located in the Tropic, one of the most biologically diverse regions of the world; its soil is an important epicenter of biodiversity and Clostridium spp. are among the most frequent bacteria. The diversity of clostridia in Costa Rican soils and its possible association with geographic zone, pH or type of soil was studied in 117 soil samples: 18 from the Atlantic Zone, 30 from the Central Plateau, 30 from the Dry Pacific, 13 from the North Zone, and 26 from the South Pacific. The pH and the mesophilic clostridia species were determined for each sample. For bacterial isolation, a selective methodology for spores and pre-reduced anaerobically sterilized media were used. A total of 1945 strains of clostridia were isolated, 98% were identified and corresponded to 54 species; the most frequent species were C. subterminale (56%), C. oceanicum (51%), C. bifermentans and C. glycolicum (50%, each), C. sporogenes (49%), and C. sordellii (42%). An average of 7.1 species per sample was obtained; the Atlantic Zone showed the greatest diversity: 8.6 species per sample and a total of 45 species. Except for C. chauvoei, all described toxigenic clostridia species were isolated; C. sordellii (42%) and C. perfringens (38%) were the most frequent. No statistical relation could be established between geographic zone or type of soil and any species, showing that clostridia had a high adaptation capability to grow in different soil conditions; only some clostridia were isolated from very acidic samples while others from soils with a wide range of pH. In general, a uniform distribution of most species and a high variety of clostridia in Costa Rican soils were observed, in agreement with the high biodiversity described for other living beings in this country.     

Do you do text?

Retrieving information from text has become an important areain bioinformatics, and not too surprisingly, this journal haspublished more than 30 papers on this topic since the firstarticle published by the journal in 1998. In addition, ISCB(International Society for Computational Biology) (www.iscb.org)has organized special sessions in the ISMB conferences (IntelligentSystems for Molecular Biology, see www.iscb.org/ismb2005) anda specialized interest group (www.pdg.cnb.uam.es/BioLink/) forthe last five years. In parallel, major computer science conferencesin related areas have begun     

The influence of different yeasts on the fermentation,composition and sensory quality of cachaça

Summary Cachaça (sugarcane wine) was produced using different yeast strains, six being strains of Saccharomyces cerevisiae and one each of Candida apicola, Hanseniaspora occidentalis, Pichia subpelliculosa and Schizosaccharomyces pombe. The ethanol yields (%) of the non-Saccharomyces strains were similar to those of the Saccharomyces strains. The following determinations were carried out on the cachaça: acetaldehyde, ethyl acetate, propanol, isobutyl alcohol, isoamyl alcohol, volatile acidity. The cachaças showed variations in the levels of secondary compounds, but these variations did not result in differences (P ≤ 0.05) in the sensory attributes of aroma and flavour and overall impression. Of the volatile compounds quantified in the cachaças, only propanol showed a positive correlation (P ≤ 0.05) with the flavour attributes and overall impression. The S. pombe strain was considered inadequate for the production of cachaça. The cachaças were classified into five groups in an exploratory Hierarchical Cluster Analysis as a function of the volatile compounds. Principal Component Analysis showed that 93% of the variation (PC 1) occurred among the samples, and was explained by the individual volatile compounds and the total secondary compounds, with the exception of isoamyl alcohol only 7% (PC 2) was associated with the volatile acidity. The negative correlations shown between the volatile compounds of the cachaças and the ethanol content of the sugarcane wine, with the exception of acetaldehyde, showed that the variation in ethanol content of the sugarcane wine is an important factor for standardization of the ethanol/volatiles ratio and the beverage quality.     

Arum- and Paris-type arbuscular mycorrhizas in a mixed pine forest on sand dune soil in Niigata Prefecture, central Honshu, Japan

Arbuscular mycorrhizas (AM) are the most widespread mycorrhiza in nature and form two morphologies, Arum- and Paris-type. The determining factors defining the two different morphologies are not well understood. In this study, the distribution of Arum- and Paris-type AM was determined in a mixed pine forest. A total of 35 plant species belonging to 20 families and 32 genera were identified and examined for AM colonization and morphological types. AM morphological types in 14 families were confirmed as follows: Arum-type in Rosaceae, Oleaceae, Lauraceae, Vitaceae and Compositae, Paris-type in Aquifoliaceae, Ulmaceae, Araliaceae, Theaceae, Magnoliaceae, Rubiaceae and Dioscoraceae, and both and/or intermediate types in Caprifoliaceae and Gramineae. Plant families whose AM morphological status was previously unknown were clarified as follows: Polygonaceae and Commelinaceae showed Arum-type morphology; Celastraceae, Menispermaceae and Elaeagnaceae had typical Paris-type morphology. The proportion of Arum-type to Paris-type species decreased in the following order: annuals > perennials > deciduous species > evergreen species, and pioneer group > early successional group > late successional group. Evergreen plants had a higher tendency to form Paris-type AM than annuals, perennials and deciduous plants. The results indicate that environmental changes, such as shade during plant succession, control the distribution of plant growth forms in mixed pine forest and may also play a part in the distribution of Arum- and Paris-type morphology. The identity of the plant seems to strongly influence AM morphology, though control by the fungal genome cannot be ruled out.