Inhibition of the epidermal growth factor receptor by erlotinib prevents immortalization of human cervical cells by Human Papillomavirus type 16

AbstractThe Human Papillomavirus type-16 (HPV-16) E6 and E7 oncogenes are selectively retained and expressed in cervical carcinomas, and expression of E6 and E7 is sufficient to immortalize human cervical epithelial cells. Expression of the epidermal growth factor receptor (EGFR) is often increased in cervical dysplasia and carcinoma, and HPV oncoproteins stimulate cell growth via the EGFR pathway. We found that erlotinib, a specific inhibitor of EGFR tyrosine kinase activity, prevented immortalization of cultured human cervical epithelial cells by the complete HPV-16 genome or the E6/E7 oncogenes. Erlotinib stimulated apoptosis in cells that expressed HPV-16 E6/E7 proteins and induced senescence in a subpopulation of cells that did not undergo apoptosis. Since immortalization by HPV E6/E7 is an important early event in cervical carcinogenesis, the EGFR is a potential target for chemoprevention or therapy in women who have a high risk for cervical cancer

Spelling pronunciation and visual preview both facilitate learning to spell irregular word

Spelling pronunciations are hypothesized to be helpful in building up relatively stable phonologically underpinned orthographic representations, particularly for learning words with irregular phoneme-grapheme correspondences. In a four-week computer-based training, the efficacy of spelling pronunciations and previewing the spelling patterns on learning to spell loan words in Dutch, originating from French and English, was examined in skilled and less skilled spellers with varying ages. Reading skills were taken into account. Overall, compared to normal pronunciation, spelling pronunciation facilitated the learning of the correct spelling of irregular words, but it appeared to be no more effective than previewing. Differences between training conditions appeared to fade with older spellers. Less skilled young spellers seemed to profit more from visual examination of the word as compared to practice with spelling pronunciations. The findings appear to indicate that spelling pronunciation and allowing a preview can both be effective ways to learn correct spellings of orthographically unpredictable words, irrespective of age or spelling ability. Copyright © 2006 by The International Dyslexia Association®

Taspase1 orchestrates fetal liver hematopoietic stem cell and vertebrae fates by cleaving TFIIA

Taspase1, a highly conserved threonine protease encoded by TASP1, cleaves nuclear histone-modifying factors and basal transcription regulators to orchestrate diverse transcription programs. Hereditary loss-of-function mutation of TASP1 has recently been reported in humans as resulting in an anomaly complex syndrome, which manifests with hematological, facial, and skeletal abnormalities. Here, we demonstrate that Taspase1-mediated cleavage of TFIIAα-β, rather than of MLL1 or MLL2, in mouse embryos was required for proper fetal liver hematopoiesis and correct segmental identities of the axial skeleton. Homozygous genetic deletion of Taspase1 disrupted embryonic hematopoietic stem cell self-renewal and quiescence states and axial skeleton fates. Strikingly, mice carrying knockin noncleavable mutations of TFIIAα-β, a well-characterized basal transcription factor, displayed more pronounced fetal liver and axial skeleton defects than those with noncleavable MLL1 and MLL2, 2 trithorax group histone H3 trimethyl transferases. Our study offers molecular insights into a syndrome in humans that results from loss of TASP1 and describes an unexpected role of TFIIAα-β cleavage in embryonic cell fate decisions

Long-term Cognitive Decline in Older Subjects Was Not Attributable to Noncardiac Surgery or Major Illness

West elevation, general view; The ceiling area, which surrounds the chandelier, was given a new painting in 1964 by Marc Chagall. "Garnier had the idea of constructing the different parts of the building (the foyer, the auditorium and the fly) in distinct masses and decided to arrange them in tiers in such a way that the perspective varied in depth, gradually increasing the concentration on the façade...Garnier set out the low volume of the foyer in a very emphatic manner, as he did the auditorium and the immense gabled fly tower, which was of an impressive height: more than 60 m high, or three times the height of Parisian buildings at that time. The heart of the building is the great stairway. This colossal, brightly lit and multicoloured space, with its imperial flights of stairs with bronze statues and marble columns, culminates in the ivory caryatids at the entry to the theatre boxes. The progression of effects is spectacular and makes the Opéra the most exuberant building of its time and the most characteristic of the Second Empire, although it was not completed until 1875, under the Third Republic." Source: Grove Art Online; http://www.groveart.com/ (accessed 1/16/2008

Assessment of an in vitro model of rotator cuff degeneration using quantitative magnetic resonance and ultrasound imaging with biochemical and histological correlation

PURPOSE:Quantitative imaging methods could improve diagnosis of rotator cuff degeneration, but the capability of quantitative MR and US imaging parameters to detect alterations in collagen is unknown. The goal of this study was to assess quantitative MR and US imaging measures for detecting abnormalities in collagen using an in vitro model of tendinosis with biochemical and histological correlation. METHOD:36 pieces of supraspinatus tendons from 6 cadaveric donors were equally distributed into 3 groups (2 subjected to different concentrations of collagenase and a control group). Ultrashort echo time MR and US imaging measures were performed to assess changes at baseline and after 24 h of enzymatic digestion. Biochemical and histological measures, including brightfield, fluorescence, and polarized microscopy, were used to verify the validity of the model and were compared with quantitative imaging parameters. Correlations between the imaging parameters and biochemically measured digestion were analyzed. RESULTS:Among the imaging parameters, macromolecular fraction (MMF), adiabatic T1ρ, T2*, and backscatter coefficient (BSC) were useful in differentiating between the extent of degeneration among the 3 groups. MMF strongly correlated with collagen loss (r=-0.81; 95% confidence interval [CI]: -0.90,-0.66), while the adiabatic T1ρ (r = 0.66; CI: 0.42,0.81), T2* (r = 0.58; CI: 0.31,0.76), and BSC (r = 0.51; CI: 0.22,0.72) moderately correlated with collagen loss. CONCLUSIONS:MMF, adiabatic T1ρ, and T2* measured and US BSC can detect alterations in collagen. Of the quantitative MR and US imaging measures evaluated, MMF showed the highest correlation with collagen loss and can be used to assess rotator cuff degeneration