The urokinase receptor, cell migration, proliferation and cancer

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Purification and characterization of UEF3, a novel factor involved in the regulation of the urokinase and other AP-1 controlled promoters.

Basal as well as induced transcription from the human urokinase-type plasminogen activator gene requires an enhancer containing two elements, a combined PEA3/AP-1 and a consensus AP-1 site. The integrity of each of these binding sites as well as their cooperation is required for activating transcription. The two elements are separated by a 74-base pair cooperation mediating (COM) region required for the cooperation between the transactivating sites. The COM region contains binding sites for four different unidentified urokinase-type plasminogen activator enhancer factors (UEF 1 to 4), all four required for correct COM activity. We have purified UEF3 from HeLa nuclear extracts by several chromatographic steps including DNA affinity purification. Purification and UV cross-linking data showed that UEF3 is a complex of three polypeptides (p40, p50, and p64). Amino acid sequence from one peptide of p64 was obtained, which showed no homology to other known proteins. Both crude and purified UEF3 specifically bound to the sequence TGACAG as shown by electrophoretic mobility shifts and methylation interference studies. DNA-binding specificity of purified UEF3 was identical to that of NIP, a non-characterized factor binding and regulating multiple AP-1-regulated promoters like stromelysin and interleukin-3. Thus UEF3 appears to be a general DNA-binding factor involved in modulating the transcriptional response of AP-1 containing promoters

Relationship between device acceptance and patient-reported outcomes in left ventricular assist device (LVAD) recipients

The number of Left Ventricular Assist Devices (LVADs) implanted each year is rising. Nevertheless, there are minimal data on device acceptance after LVAD implant, and on its relationship with patient-reported outcomes. We designed a cross-sectional study to address this knowledge gap and test the hypothesis that low device acceptance is associated with poorer quality of life, depression and anxiety. Self-report questionnaires were administered to assess quality of life (12-item Kansas City Cardiomyopathy Questionnaire quality of life subscale), level of anxiety (7-item Generalized Anxiety Disorder; GAD-7), level of depression (9-item Patient Health Questionnaire; PHQ-9) and device acceptance (Florida Patient Acceptance Survey; FPAS) to 101 consecutive patients presenting to LVAD clinic. Regression analysis showed a strong correlation between device acceptance and both psychological distress (p\u2009<\u20090.001) and quality of life (p\u2009<\u20090.001). Analysis of the sub-scales of the FPAS showed that patients had significant body image concerns, but return to function and device-related distress were the main drivers of the observed correlation between device acceptance and patient well-being. Younger age was associated with lower device acceptance (r\u2009=\u20090.36, p\u2009<\u20090.001) and lower quality of life (r\u2009=\u20090.54, p\u2009<\u20090.001). These findings suggest that interventions targeting device acceptance should be explored to improve outcomes in LVAD recipients

Reading decoding and comprehension in children with autism spectrum disorders: Evidence from a language with regular orthography

Decoding and comprehension skills in children with autism spectrum disorders (ASD) were analysed in children native speakers of a language (Italian) with a highly regular orthography. Children with ASD were compared to children with matched intellectual functioning: a subgroup of children with ASD and borderline intellectual functioning (BIF) was compared to a subgroup of children with BIF but no signs of ASD; a subgroup of children with ASD and cognitive functioning within normal limits was compared to a group of typically developing children. Children with ASD (whether with or without BIF) showed essentially spared decoding skills in text as well as word and pseudo-word reading; this was at variance with children with BIF who, as a group, showed overall deficient decoding skills, despite considerable individual differences. By contrast, children with ASD (once again, irrespective of the presence of BIF) showed a selective impairment in reading comprehension, just like children with BIF but unlike the typically developing ones. Therefore, results are generally consistent with a profile of hyperlexia for children with ASD learning a regular orthography, as previously reported for other languages. Notably, this pattern was present irrespective of the degree of cognitive impairment, and clearly distinguished these children from those with borderline intellectual functioning but not signs of autism

Thyroidal phenylpyruvate tautomerase. Isolation and characterization.

Hog thyroid tautomerase (EC 5.3.2.1, phenylpyruvate keto-enol isomerase), an enzyme which is believed to play a role in the biosynthesis of thyroxine, has been purified over 1000-fold. The purification procedure involves a heat step at 70°, gel filtration on Sephadex G-100, ion exchange chromatography on carboxymethyl Sephadex C-50, and, finally, gel filtration on Sephadex G-50. The enzyme is homogeneous by the following criteria. It gives a single peak in sedimentation velocity analysis and shows a single band on disc polyacrylamide gel and starch gel electrophoresis, and the sedimentation equilibrium plot is linear, even at the lowest protein concentrations. The pH optimum of the purified tautomerase is 6.2. Its molecular weight is 44,000. The amino acid composition of the enzyme, as well as some of its physico-chemical properties, are presented. The enzyme is able to substitute for borate ions in the coupling reaction of thyroxine synthesis