Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism

c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase,SH3 and SH2 domains of c-Src are attached to the membrane-anchoring SH4 domain through the flexible Unique domain. Here we show intra- and intermolecular interactions involving the Unique and SH3 domains suggesting the presence of a previously unrecognized additional regulation layer in c-Src. We have characterized lipid binding by the Unique and SH3 domains, their intramolecular interaction and its allosteric modulation by a SH3-binding peptide or by Calcium-loaded calmodulin binding to the Unique domain. We also show reduced lipid binding following phosphorylation at conserved sites of the Unique domain. Finally, we show that injection of full-length c-Src with mutations that abolish lipid binding by the Unique domain causes a strong in vivo phenotype distinct from that of wild-type c-Src in a Xenopus oocyte model system, confirming the functional role of the Unique domain in c-Src regulation.

Uniform estimates in the Poincare-Aronszajn theorem on the separation of singularities of analytic functions

We study the possibility of splitting any bounded analytic function $f$ with singularities in a closed set $E\cup F$ as a sum of two bounded analytic functions with singularities in $E$ and $F$ respectively. We obtain some results under geometric restrictions on the sets $E$ and $F$ and we provide some examples showing the sharpness of the positive results.

A pathogenic mechanism in Huntington"s disease involves small CAG-repeated RNAs with neurotoxic activity

Huntington's disease (HD) is an autosomal dominantly inherited disorder caused by the expansion of CAG repeats in the Huntingtin (HTT) gene. The abnormally extended polyglutamine in the HTT protein encoded by the CAG repeats has toxic effects. Here, we provide evidence to support that the mutant HTT CAG repeats interfere with cell viability at the RNA level. In human neuronal cells, expanded HTT exon-1 mRNA with CAG repeat lengths above the threshold for complete penetrance (40 or greater) induced cell death and increased levels of small CAG-repeated RNAs (sCAGs), of ≈21 nucleotides in a Dicer-dependent manner. The severity of the toxic effect of HTT mRNA and sCAG generation correlated with CAG expansion length. Small RNAs obtained from cells expressing mutant HTT and from HD human brains significantly decreased neuronal viability, in an Ago2-dependent mechanism. In both cases, the use of anti-miRs specific for sCAGs efficiently blocked the toxic effect, supporting a key role of sCAGs in HTT-mediated toxicity. Luciferase-reporter assays showed that expanded HTT silences the expression of CTG-containing genes that are down-regulated in HD. These results suggest a possible link between HD and sCAG expression with an aberrant activation of the siRNA/miRNA gene silencing machinery, which may trigger a detrimental response. The identification of the specific cellular processes affected by sCAGs may provide insights into the pathogenic mechanisms underlying HD, offering opportunities to develop new therapeutic approaches

Blind channel deconvolution of real world signals using source separation techniques

In this paper we present a method for blind deconvolution of linear channels based on source separation techniques, for real word signals. This technique applied to blind deconvolution problems is based in exploiting not the spatial independence between signals but the temporal independence between samples of the signal. Our objective is to minimize the mutual information between samples of the output in order to retrieve the original signal. In order to make use of use this idea the input signal must be a non-Gaussian i.i.d. signal. Because most real world signals do not have this i.i.d. nature, we will need to preprocess the original signal before the transmission into the channel. Likewise we should assure that the transmitted signal has non-Gaussian statistics in order to achieve the correct function of the algorithm. The strategy used for this preprocessing will be presented in this paper. If the receiver has the inverse of the preprocess, the original signal can be reconstructed without the convolutive distortion.

Why do they separate it or not? Attitudes and behaviors towards organic waste separation

This article shows the results of an exploratory study related to the separation of organic waste in order to offer suggestions for the improvement of waste disposal communication campaigns. The overall objective is to analyze attitude and behavior of those who do and those who do not separate organic waste, related to a specific promotional campaign carried out in two neighborhoods, in the municipality of Badalona (Spain), within the framework of the study of proenvironmental attitudes and behaviors and based on the Psychosocial Four Spheres Model. 1,010 interviews were conducted and data was analyzed using Chi-Squared Automatic Interaction Detector (CHAID). Waste separation behavior was used as a dependent variable. The reasons given to explain why people do or do not separate organic waste and sociodemographic variables, have been introduced as independent variables. In accordance with the Four Spheres Model, results show significant differences in waste separation. Based on the profiles obtained, we find some predictive variables that facilitate the development of communication campaigns according to the requirements of each community.

Why do they separate it or not? Attitudes and behaviors towards organic waste separation

This article shows the results of an exploratory study related to the separation of organic waste in order to offer suggestions for the improvement of waste disposal communication campaigns. The overall objective is to analyze attitude and behavior of those who do and those who do not separate organic waste, related to a specific promotional campaign carried out in two neighborhoods, in the municipality of Badalona (Spain), within the framework of the study of proenvironmental attitudes and behaviors and based on the Psychosocial Four Spheres Model. 1,010 interviews were conducted and data was analyzed using Chi-Squared Automatic Interaction Detector (CHAID). Waste separation behavior was used as a dependent variable. The reasons given to explain why people do or do not separate organic waste and sociodemographic variables, have been introduced as independent variables. In accordance with the Four Spheres Model, results show significant differences in waste separation. Based on the profiles obtained, we find some predictive variables that facilitate the development of communication campaigns according to the requirements of each community.

Why do they separate it or not? Attitudes and behaviors towards organic waste separation

This article shows the results of an exploratory study related to the separation of organic waste in order to offer suggestions for the improvement of waste disposal communication campaigns. The overall objective is to analyze attitude and behavior of those who do and those who do not separate organic waste, related to a specific promotional campaign carried out in two neighborhoods, in the municipality of Badalona (Spain), within the framework of the study of proenvironmental attitudes and behaviors and based on the Psychosocial Four Spheres Model. 1,010 interviews were conducted and data was analyzed using Chi-Squared Automatic Interaction Detector (CHAID). Waste separation behavior was used as a dependent variable. The reasons given to explain why people do or do not separate organic waste and sociodemographic variables, have been introduced as independent variables. In accordance with the Four Spheres Model, results show significant differences in waste separation. Based on the profiles obtained, we find some predictive variables that facilitate the development of communication campaigns according to the requirements of each community.

Why do they separate it or not? Attitudes and behaviors towards organic waste separation

This article shows the results of an exploratory study related to the separation of organic waste in order to offer suggestions for the improvement of waste disposal communication campaigns. The overall objective is to analyze attitude and behavior of those who do and those who do not separate organic waste, related to a specific promotional campaign carried out in two neighborhoods, in the municipality of Badalona (Spain), within the framework of the study of proenvironmental attitudes and behaviors and based on the Psychosocial Four Spheres Model. 1,010 interviews were conducted and data was analyzed using Chi-Squared Automatic Interaction Detector (CHAID). Waste separation behavior was used as a dependent variable. The reasons given to explain why people do or do not separate organic waste and sociodemographic variables, have been introduced as independent variables. In accordance with the Four Spheres Model, results show significant differences in waste separation. Based on the profiles obtained, we find some predictive variables that facilitate the development of communication campaigns according to the requirements of each community.

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem

A mechanism of carbapenem resistance due to a new insertion element (ISPa133) in Pseudomonas aeruginosa

This study explored the evolutionary mechanism by which the clinical isolate PA110514 yields the imipenemresistant derivative PA116136. Both isolates were examined by PFGE and SDS-PAGE, which led to the identification of a new insertion sequence, ISPa133. This element was shown to have distinct chromosomal locations in each of the original isolates that appeared to explain the differences in imipenem susceptibilty. In strain PA110514, ISPa133 is located 56 nucleotides upstream of the translational start codon, which has no effect on expression of the porin OprD. However, in strain PA116136 ISPa133 it is located in front of nucleotide 696 and, by interrupting the coding region, causes a loss of OprD expression, thus conferring imipenem resistance. In vitro experiments mimicking the natural conditions of selective pressure yielded imipenem-resistant strains in which ISPa133 similarly interrupted oprD. A mechanism is proposed whereby ISPa133 acts as a mobile switch, with its position in oprD depending on the degree of selective pressure exerted by imipenem