Engineering a two-helix bundle protein for folding studies

The SAP domain from the Saccharomyces cerevisiae THO1 protein contains a hydrophobic core and just two α-helices. It could provide a system for studying protein folding that bridges the gap between studies on isolated helices and those on larger protein domains. We have engineered the SAP domain for protein folding studies by inserting a tryptophan residue into the hydrophobic core (L31W) and solved its structure. The helical regions had a backbone root mean-squared deviation of 0.9 Å from those of wild type. The mutation L31W destabilised wild type by 0.8 ± 0.1 kcal mol−1. The mutant folded in a reversible, apparent two-state manner with a microscopic folding rate constant of around 3700 s−1 and is suitable for extended studies of folding

Standardisation of rates using logistic regression: a comparison with the direct method

<p>Abstract</p> <p>Background</p> <p>Standardisation of rates in health services research is generally undertaken using the direct and indirect arithmetic methods. These methods can produce unreliable estimates when the calculations are based on small numbers. Regression based methods are available but are rarely applied in practice. This study demonstrates the advantages of using logistic regression to obtain smoothed standardised estimates of the prevalence of rare disease in the presence of covariates.</p> <p>Methods</p> <p>Step by step worked examples of the logistic and direct methods are presented utilising data from BETS, an observational study designed to estimate the prevalence of subclinical thyroid disease in the elderly. Rates calculated by the direct method were standardised by sex and age categories, whereas rates by the logistic method were standardised by sex and age as a continuous variable.</p> <p>Results</p> <p>The two methods produce estimates of similar magnitude when standardising by age and sex. The standard errors produced by the logistic method were lower than the conventional direct method.</p> <p>Conclusion</p> <p>Regression based standardisation is a practical alternative to the direct method. It produces more reliable estimates than the direct or indirect method when the calculations are based on small numbers. It has greater flexibility in factor selection and allows standardisation by both continuous and categorical variables. It therefore allows standardisation to be performed in situations where the direct method would give unreliable results.</p

Cold gas accretion in galaxies

Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

Umbilical endosalpingiosis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Endosalpingiosis describes the ectopic growth of Fallopian tube epithelium. Pathology confirms the presence of a tube-like epithelium containing three types of cells: ciliated, columnar cells; non-ciliated, columnar secretory mucous cells; and intercalary cells.</p> <p>We report the case of a woman with umbilical endosalpingiosis and examine the nature and characteristics of cutaneous endosalpingiosis by reviewing and combining the other four cases existing in the international literature.</p> <p>Case presentation</p> <p>A 50-year-old Caucasian, Greek woman presented with a pale brown nodule in her umbilicus. The nodule was asymptomatic, with no cyclical discomfort or variation in size. Her personal medical, surgical and gynecologic history was uneventful. An excision within healthy margins was performed under local anesthesia. A cystic formation measuring 2.7×1.7×1 cm was removed. Histological examination confirmed umbilical endosalpingiosis.</p> <p>Conclusions</p> <p>Umbilical endosalpingiosis is a very rare manifestation of the non-neoplasmatic disorders of the Müllerian system. It appears with cyclic symptoms of pain and swelling of the umbilicus, but not always. The disease is diagnosed using pathologic findings and surgical excision is the definitive treatment.</p

Anticancer Gene Transfer for Cancer Gene Therapy

Gene therapy vectors are among the treatments currently used to treat malignant tumors. Gene therapy vectors use a specific therapeutic transgene that causes death in cancer cells. In early attempts at gene therapy, therapeutic transgenes were driven by non-specific vectors which induced toxicity to normal cells in addition to the cancer cells. Recently, novel cancer specific viral vectors have been developed that target cancer cells leaving normal cells unharmed. Here we review such cancer specific gene therapy systems currently used in the treatment of cancer and discuss the major challenges and future directions in this field