Epsins are endocytic proteins with a structured epsin N-terminal homology (ENTH) domain that binds phosphoinositides and a poorly structured C-terminal region that interacts with ubiquitin and endocytic machinery, including clathrin and endocytic scaffolding proteins. Yeast has two redundant genes encoding epsins, ENT1 and ENT2; deleting both genes is lethal. We demonstrate that the ENTH domain is both necessary and sufficient for viability of ent1⌬ent2⌬ cells. Mutational analysis of the ENTH domain revealed a surface patch that is essential for viability and that binds guanine nucleotide triphosphatase-activating proteins for Cdc42, a critical regulator of cell polarity in all eukaryotes. Furthermore, the epsins contribute to regulation of specific Cdc42 signaling pathways in yeast cells. These data support a model in which the epsins function as spatial and temporal coordinators of endocytosis and cell polarity.actin ͉ endocytosis ͉ polarity E ndocytosis is an essential mechanism for internalizing extracellular material and controlling the composition of the plasma membrane; this is critical for cellular homeostasis, including downregulation of signaling receptors and recycling of transmembrane proteins such as v-SNAREs that reside transiently at the plasma membrane (1). Many cytosolic proteins that contribute to the mechanisms and regulation of endocytosis have been identified, but assigning precise functions to each protein has been more challenging (2, 3). Some of these proteins may also participate in multiple steps or pathways (4, 5), either related to or independent from endocytosis, further complicating the elucidation of their function(s). Additionally, roles for the actin cytoskeleton in regulating or effecting specific stages of endocytosis are another active area of investigation (2). One goal is to identify multifunctional proteins that coordinate these various cellular processes.The epsin proteins are proposed to function as endocytic clathrin adaptors for ubiquitinated cargo (6, 7). They are found in all eukaryotes and have an N-terminal phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P 2 ]-binding epsin N-terminal homology (ENTH) domain, two ubiquitin interaction motifs, and several peptide ligands that bind components of the endocytic machinery (7). In addition to putative adaptor roles, it has been shown previously that mammalian epsin binds RalBP1͞RLIP76, a GTPase-activating protein (GAP) for Cdc42 and Rac1 (8). RalBP1 has been implicated in endocytosis, because it binds the plasma membrane clathrin adaptor AP-2 (8). The Cdc42 and Rac GTPases are key regulators of the actin cytoskeleton (9), thus suggesting that this complex links signaling, endocytosis, and actin cytoskeleton regulation.The budding yeast Saccharomyces cerevisiae has two epsins, Ent1 and Ent2; deleting either alone leads to no detectable phenotype, but a double deletion is lethal (10). Here we show that the ENTH domain of yeast epsin is necessary and sufficient for viability of ent1⌬ent2⌬ cells (⌬⌬). The essential function ...

Our initial results suggest blood pressure, not serum albumin level, as a main biomarker for brain edema in children with PRES. Thus, our study does not suggest a protective role of serum albumin against PRES-related neurotoxicity in children.

While it has long been appreciated that there is considerable variability in host containment of HIV/SIV replication, the determinants of that variability are not fully understood. Previous studies demonstrated that the degree of permissivity of a macaque's peripheral blood mononuclear cells (PBMC) for infection with simian immunodeficiency virus (SIV) in vitro predicted that animal's peak plasma virus RNA levels following SIV infection in vivo. The present study was conducted to define the mechanisms underlying the variable intrinsic susceptibility of rhesus monkey PBMC to SIVsmE660 infection. In a cohort of 15 unrelated Indian-origin rhesus monkeys, infectability of PBMC of individual animals with SIVsmE660, as defined by tissue culture infectious dose (TCID50), varied by more than 3 logs and was a stable phenotype over time. Susceptibility of a monkey's PBMC to wild type SIVsmE660 infection correlated with the susceptibility of that monkey's PBMC to infection with VSV-G pseudotyped SIVsm543-GFP. Moreover, the permissivity of an individual monkey's PBMC for infection with this construct correlated with the permissivity of a B-lymphoblastoid cell line (B-LCL) generated from PBMC of the same animal. We found that the degree of intrinsic resistance of monkey B-LCL correlated with the copy number of early reverse transcription (ERT) SIV DNA. The resistance of monkey B-LCL to SIVsmE660 replication could be abrogated by preincubation of cells with the SIV virus-like particles (VLPs) and SIV resistance phenotype could be transferred to a SIV susceptible B-LCL through cell fusion. Finally, we observed a positive correlation between susceptibility of monkey B-LCL to SIV infection with a VSV-G pseudotyped SIV-GFP construct in vitro and both the peak plasma virus RNA levels in vivo and time to death following wild type SIV infection. These findings suggest that a dominant early RT restricting factor that can be saturated by SIV capsid may contribute to the variable resistance to SIV infection in rhesus monkey B-LCL and that this differential intrinsic susceptibility contributes to the clinical outcome of an SIV infection.

The purpose of this study was to investigate consumer lifestyles and preferences for sofa leather through Literature Review, Focus Group Interview and Experts Interview. The lifestyle questionnaire was created to research into the subjects’ preferences in accordance with 4 kinds of leather types, 5 kinds of grains, and 5 kinds of colors. After the authors’ statistical analysis of 206 copies of the effective questionnaires, the research results among every group showed that the favorites were Aniline Leather of leather types, smaller particles of grains, and high contrast colors, such as white and black. Further, the consumer groups against sofa leather could be divided into 5 difference ones. The taste of the elder subjects in "Appreciate Life" was similar to the overall preferences ; however, the taste of the junior subjects in "Single Learing" and "Youthful & Carefree" was unique and different from the overall preferences.