The role of Sse1 in the de novo formation and variant determination of the [PSI+] prion.

Yeast prions are a group of non-Mendelian genetic elements transmitted as altered and self-propagating conformations. Extensive studies in the last decade have provided valuable information on the mechanisms responsible for yeast prion propagation. How yeast prions are formed de novo and what cellular factors are required for determining prion "strains" or variants--a single polypeptide capable of existing in multiple conformations to result in distinct heritable phenotypes--continue to defy our understanding. We report here that Sse1, the yeast ortholog of the mammalian heat-shock protein 110 (Hsp110) and a nucleotide exchange factor for Hsp70 proteins, plays an important role in regulating [PSI+] de novo formation and variant determination. Overproduction of the Sse1 chaperone dramatically enhanced [PSI+] formation whereas deletion of SSE1 severely inhibited it. Only an unstable weak [PSI+] variant was formed in SSE1 disrupted cells whereas [PSI+] variants ranging from very strong to very weak were formed in isogenic wild-type cells under identical conditions. Thus, Sse1 is essential for the generation of multiple [PSI+] variants. Mutational analysis further demonstrated that the physical association of Sse1 with Hsp70 but not the ATP hydrolysis activity of Sse1 is required for the formation of multiple [PSI+] variants. Our findings establish a novel role for Sse1 in [PSI+] de novo formation and variant determination, implying that the mammalian Hsp110 may likewise be involved in the etiology of protein-folding diseases.

Los Judios en el Pais Vasco : su influencia social, religiosa y politica ; memoria leida el dia 9 de sept. de 1904 ...

por Mariano Arigita y Lasa

Comparison of Bispectral Index (BIS) and Patient State Index (PSI) as objective measures of sedation and analgesia in critically ill/injured patients

Critically ill and injured patients require pain relief and sedation to reduce the body's stress response and to facilitate painful diagnostic and therapeutic procedures. Presently, the level of sedation and analgesia is guided by the use of clinical scores which can be unreliable. There is therefore, a need for an objective measure of sedation and analgesia. The Bispectral Index (BIS) and Patient State Index (PSI) were recently introduced into clinical practice as objective measures of the depth of analgesia and sedation. ^ Aim. To compare the different measures of sedation and analgesia (BIS and PSI) to the standard and commonly used modified Ramsay Score (MRS) and determine if the monitors can be used interchangeably. ^ Methods. MRS, BIS and PSI values were obtained in 50 postoperative cardiac surgery patients requiring analgesia and sedation from June to December 2004. The MRS, BIS and PSI values were assessed hourly for up to 6-h by a single observer. ^ The relationship between BIS and PSI values were explored using scatter plots and correlation between MRS, BIS and PSI was determined using Spearman's correlation coefficient. Intra-class correlation (ICC) was used to determine the inter-rater reliability of MRS, BIS and PSI. Kappa statistics was used to further evaluate the agreement between BIS and PSI at light, moderate and deep levels of sedation. ^ Results. There was a positive correlation between BIS and PSI values (Rho = 0.731, p<0.001). Intra-class correlation between BIS and PSI was 0.58, MRS and BIS 0.43 and MRS and PSI 0.27. Using Kappa statistics, agreement between MRS and BIS was 0.35 (95% CI: 0.27–0.43) and for MRS and PSI was 0.21 (95% CI: 0.15–0.28). The kappa statistic for BIS and PSI was 0.45 (95% CI: 0.37–0.52). Receiver operating characteristics (ROC) curves constructed to detect undersedation indicated an area under the curve (AUC) of 0.91 (95% CI = 0.87 to 0.94) for the BIS and 0.84 (95% CI = 0.79 to 0.88) for the PSI. For detection of oversedation, AUC for the BIS was 0.89 (95% CI = 0.84 to 0.92) and 0.80 (95% CI = 0.75 to 0.85) for the PSI. ^ Conclusions. There is a statistically significant positive correlation between the BIS and PSI but poor correlation and poor test agreement between the MRS and BIS as well as MRS and PSI. Both the BIS and PSI demonstrated a high level of prediction for undersedation and oversedation; however, the BIS and PSI can not be considered interchangeable monitors of sedation. ^

Da informação nossa de cada dia à Ciência da Informação : Conceitos, história, teorias e questões recentes

The work has as objective to produce a look about what we can think as a long history of information, what we think out from the most remote times until its conversion to theástatusáof object of the Information Science (IS) in the second half of 20th century. Of theorical nature and keeping up itself by the literature in IS and in similar areas, a discussion is made about the concept of information to then to list names, happenings and theories that contributed in the passage of the domain of the daily life to the domain of the Science. From a distant past to the most recent happenings connected to the problem of the privacity of the citizens in the digital networks, it is verified in the history of information a closed relation with the power, reason that suggests the deepening of the studies in IS about the political and ethical issues in the contemporary society.

Da informação nossa de cada dia à Ciência da Informação : Conceitos, história, teorias e questões recentes

The work has as objective to produce a look about what we can think as a long history of information, what we think out from the most remote times until its conversion to theástatusáof object of the Information Science (IS) in the second half of 20th century. Of theorical nature and keeping up itself by the literature in IS and in similar areas, a discussion is made about the concept of information to then to list names, happenings and theories that contributed in the passage of the domain of the daily life to the domain of the Science. From a distant past to the most recent happenings connected to the problem of the privacity of the citizens in the digital networks, it is verified in the history of information a closed relation with the power, reason that suggests the deepening of the studies in IS about the political and ethical issues in the contemporary society.

Da informação nossa de cada dia à Ciência da Informação : Conceitos, história, teorias e questões recentes

The work has as objective to produce a look about what we can think as a long history of information, what we think out from the most remote times until its conversion to theástatusáof object of the Information Science (IS) in the second half of 20th century. Of theorical nature and keeping up itself by the literature in IS and in similar areas, a discussion is made about the concept of information to then to list names, happenings and theories that contributed in the passage of the domain of the daily life to the domain of the Science. From a distant past to the most recent happenings connected to the problem of the privacity of the citizens in the digital networks, it is verified in the history of information a closed relation with the power, reason that suggests the deepening of the studies in IS about the political and ethical issues in the contemporary society.