Structural and Functional Analysis of a Novel Coiled-Coil Protein Involved in Ypt6 GTPase-regulated Protein Transport in Yeast

The yeast transport GTPase Ypt6p is dispensable for cell growth and secretion, but its lack results in temperature sensitivity and missorting of vacuolar carboxypeptidase Y. We previously identified four yeast genes (SYS1, 2, 3, and 5) that on high expression suppressed these phenotypic alterations. SYS3 encodes a 105-kDa protein with a predicted high α-helical content. It is related to a variety of mammalian Golgi-associated proteins and to the yeast Uso1p, an essential protein involved in docking of endoplasmic reticulum–derived vesicles to the cis-Golgi. Like Uso1p, Sys3p is predominatly cytosolic. According to gel chromatographic, two-hybrid, and chemical cross-linking analyses, Sys3p forms dimers and larger protein complexes. Its loss of function results in partial missorting of carboxypeptidase Y. Double disruptions of SYS3 and YPT6 lead to a significant growth inhibition of the mutant cells, to a massive accumulation of 40- to 50-nm vesicles, to an aggravation of vacuolar protein missorting, and to a defect in α-pheromone processing apparently attributable to a perturbation of protease Kex2p cycling between the Golgi and a post-Golgi compartment. The results of this study suggest that Sys3p, like Ypt6p, acts in vesicular transport (presumably at a vesicle-docking stage) between an endosomal compartment and the most distal Golgi compartment.

Modulation of the baboon (Papio anubis) uterine endometrium by chorionic gonadotrophin during the period of uterine receptivity

This study was undertaken to determine the modulation of uterine function by chorionic gonadotrophin (CG) in a nonhuman primate. Infusion of recombinant human CG (hCG) between days 6 and 10 post ovulation initiated the endoreplication of the uterine surface epithelium to form distinct epithelial plaques. These plaque cells stained intensely for cytokeratin and the proliferating cell nuclear antigen. The stromal fibroblasts below the epithelial plaques stained positively for α-smooth muscle actin (αSMA). Expression of αSMA is associated with the initiation of decidualization in the baboon endometrium. Synthesis of the glandular secretory protein glycodelin, as assessed by Western blot analysis, was markedly up-regulated by hCG, and this increase was confirmed by immunocytochemistry, Northern blot analysis, and reverse transcriptase-PCR. To determine whether hCG directly modulated these uterine responses, we treated ovariectomized baboons sequentially with estradiol and progesterone to mimic the hormonal profile of the normal menstrual cycle. Infusion of hCG into the oviduct of steroid-hormone-treated ovariectomized baboons induced the expression of αSMA in the stromal cells and glycodelin in the glandular epithelium. The epithelial plaque reaction, however, was not readily evident. These studies demonstrate a physiological effect of CG on the uterine endometrium in vivo and suggest that the primate blastocyst signal, like the blastocyst signals of other species, modulates the uterine environment prior to implantation.

Long-term potentiation increases tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit 2B in rat dentate gyrus in vivo.

Long-term potentiation (LTP) is a form of synaptic memory that may subserve developmental and behavioral plasticity. An intensively investigated form of LTP is dependent upon N-methyl-D-aspartate (NMDA) receptors and can be elicited in the dentate gyrus and hippocampal CA1. Induction of this type of LTP is triggered by influx of Ca2+ through activated NMDA receptors, but the downstream mechanisms of induction, and even more so of LTP maintenance, remain controversial. It has been reported that the function of NMDA receptor channel can be regulated by protein tyrosine kinases and protein phosphatases and that inhibition of protein tyrosine kinases impairs induction of LTP. Herein we report that LTP in the dentate gyrus is specifically correlated with tyrosine phosphorylation of the NMDA receptor subunit 2B in an NMDA receptor-dependent manner. The effect is observed with a delay of several minutes after LTP induction and persists in vivo for several hours. The potential relevance of this post-translational modification to mechanisms of LTP and circuit plasticity is discussed.

The Effects of Father Absence Due to Divorce: A Systems Interpretation.

In American society, the incidence of divorce continues to rise. In 1974, the estimate was that 40% of all new marriages would end in divorce. When children are involved, the mother usually regains custody. Although the number of children of divorce living with their fathers is increasing, it is still a small percent. In addition, the rate of remarriages is lower when children are involved (Hetherington.et al.,1977). Consequently, a large number of children are being raised in father-absent homes, and indications are that the numbers are increasing. A recent Denver Post article predicted that 50% of all children now being born will spend some of their childhood in a single-parent home. In terms of frequency, the father-absent family is becoming quite common, even "normal," yet it often continues to be considered a "broken" home and, when compared to the two-parent family, an inadequate structure in which to raise healthy children. Since father-absent families are so common these days, this opinion is in need of review.This paper will present a review of the father absence research in three areas: sex role development, cognitive development and personality development. The role of moderator variables will be discussed. And, finally,an open systems model will be proposed as a vehicle to better understand the effects of father absence and as a guide for future research.

Regulation of Synaptogenesis by the miRNA Pathway and FMR/P Bodies

Post-transcriptional regulation of mRNA is facilitated by different mechanisms, such as microRNA (miRNA) induced gene silencing or fragile X mental retardation protein (FMRP) mediated repression either independent of or acting through cytoplasmic RNA Processing bodies (P bodies). DPTP99A, Lar, and Wg have known functions during synaptogenesis and may be targets of miR-8. Here, we provide evidence that miR-8 regulates DPTP99A in vitro. Non-endogenous miR-8 expressed using an UAS driver regulates Lar. Endogenous miR-8 may regulate DPTP99A in vivo. Here we show that FMRP is capable of colocalizing with the P body components: DCP1, HPat, and Me31B, but not CCR4. We also show that RNAi against HPat and Me31B but not CCR4 and DCP1 are required for FMRP’s repression of a translational reporter in vivo. This functional analysis provides additional insight into another aspect of FMRP’s and P bodies’ ability to cooperatively control repression of mRNA targets.

Alergologias. De uma analogia da soberania aos atributos da violência

This paper is a reconstruction of Levinas’ reading of Hegel and his understanding of violence (of the enemy and the war). Combining Franz Rosenzweig’s reflections which concern the sick philosopher and Hegel’s State, as well as Derrida’s interpretation of the different attributes of violence, our aim is also to give full evidence of Derrida’s critical reading of Levinas. The first part illustrates the various classifications of the figures of violence from the different periods of Hegel’s life and the traces that these figures have left in Levinas’ texts beginning with „Liberté et commandement” in 1953. In the second part we discuss Hegel’s well-known analogy from his Rechtsphilosophie on sovereignty and the organism – that is to say the parallel reading of some paragraphs of Naturphilosophie too – and the relation between totality and violence, in Levinas’ “ontology as allergy” and in Derrida’s autoimmunology.

Farmacogenética em toxicologia forense : estudo do gene CYP2D6 em amostras post mortem com tramadol

Tese de mestrado, Medicina Legal e Ciências Forenses, Universidade de Lisboa, Faculdade de Medicina, 2016

Profound activity of the anti-cancer drug bortezomib against Echinococcus multilocularis metacestodes identifies the proteasome as a novel drug target for cestodes.

A library of 426 FDA-approved drugs was screened for in vitro activity against E. multilocularis metacestodes employing the phosphoglucose isomerase (PGI) assay. Initial screening at 20 µM revealed that 7 drugs induced considerable metacestode damage, and further dose-response studies revealed that bortezomib (BTZ), a proteasome inhibitor developed for the chemotherapy of myeloma, displayed high anti-metacestodal activity with an EC50 of 0.6 µM. BTZ treatment of E. multilocularis metacestodes led to an accumulation of ubiquinated proteins and unequivocally parasite death. In-gel zymography assays using E. multilocularis extracts demonstrated BTZ-mediated inhibition of protease activity in a band of approximately 23 kDa, the same size at which the proteasome subunit beta 5 of E. multilocularis could be detected by Western blot. Balb/c mice experimentally infected with E. multilocularis metacestodes were used to assess BTZ treatment, starting at 6 weeks post-infection by intraperitoneal injection of BTZ. This treatment led to reduced parasite weight, but to a degree that was not statistically significant, and it induced adverse effects such as diarrhea and neurological symptoms. In conclusion, the proteasome was identified as a drug target in E. multilocularis metacestodes that can be efficiently inhibited by BTZ in vitro. However, translation of these findings into in vivo efficacy requires further adjustments of treatment regimens using BTZ, or possibly other proteasome inhibitors.

Geological map of Heimefrontfjella, Dronning Maud Land, Antarctica (Scale 1:250,000)

The geological overview map was compiled from 15 geological maps (1 : 25,000) and is based on Jacobs et al. 1996. The topographic basemaps were adapted from unpublished 1:250,000 provisional topographic maps, Institut f. Angewandte Geodäsie, Frankfurt, 1983. Part of the contour lines are from Radarsat (Liu et al. 2001).

World Beats : Beat Generation Writing and the Worlding of U.S. Literature /

A study of the Beat-era writers in a global context. This title was made Open Access by libraries from around the world through Knowledge Unlatched.

Harry A. Levinson, 9527 Brighton Way, Beverly Hills, California, plaintiff, v. Arthur E. Summerfield, individually and as Postmaster General of the United States, Washington D.C., defendent : points and authorities in support of mottion for preliminary injunction, in the United States District Court for the District of Columbia.

Mode of access: Internet.

Report of the Honourable the Postmaster General of the methods adopted in Canada in the carrying out of government clothing contracts,

Mode of access: Internet.

Fate of the children of Usnach [manuscript] /

Binding: Contemporary Niger morocco; gold-stamped title on front board; leather clasps; stamped on inside of back board "C. & C. McLeish".

Io. Mabillonii Iter Germanicum et Io. Launoii De scholis celebribus a Carolo M. et post Carolum M. in Occidente instauratis liber. Accedunt: Facultas parisiensis de doctrina pronuncians, et veteres formulae proteststionum Romae a Pontificibus in Parisiensi et quibusdam aliis academiis a doctoribus fieri solitarum.

Mode of access: Internet.

Better health for rural America; plans of action for farm communities.

Mode of access: Internet.