In vivo responses of the primate corpus luteum to luteinizing hormone and chorionic gonadotropin

Although it is well established that the secretory activity of the corpus luteum absolutely depends on the presence of pituitary-derived luteinizing hormone (LH), it is unknown why the life span of the corpus luteum is extended during early pregnancy by the placental production of chorionic gonadotropin (CG) but regresses in the presence of LH despite the fact that CG and LH have similar actions on the corpus luteum. To compare the responses of the corpus luteum to LH and human CG (hCG), cynomolgus monkeys whose endogenous gonadotropin secretion was blocked during the luteal phase of the menstrual cycle with a gonadotropin-releasing hormone antagonist were i.v. infused with either LH or CG. Infusion of LH at a constant rate overcame the gonadotropin-releasing hormone antagonist-mediated premature luteal regression but failed to prolong the functional life span of the corpus luteum. Continuous infusions of hCG did not effect a pregnancy-like pattern of gonadotropin secretion, but the functional life span of the corpus luteun was extended in two of three animals. Infusion of either LH or hCG in an exponentially increasing manner prolonged the functional life span of the corpus luteum beyond its normal duration. These results indicate that luteal regression at the termination of nonfertile menstrual cycles is caused by a large reduction in the responsiveness of the aging corpus luteum to LH, which can be overcome by elevated concentrations of either LH or CG.

The transcript release factor PTRF augments ribosomal gene transcription by facilitating reinitiation of RNA polymerase I

Termination of murine rDNA transcription by RNA polymerase I (Pol I) requires pausing of Pol I by terminator-bound TTF-I (transcription termination factor for Pol I), followed by dissociation of the ternary complex by PTRF (Pol I and transcript release factor). To examine the functional correlation between transcription termination and initiation, we have compared transcription on terminator-containing and terminator-less rDNA templates. We demonstrate that terminated RNA molecules are more efficiently synthesized than run-off transcripts, indicating that termination facilitates reinitiation. Transcriptional enhancement is observed in multiple- but not single-round transcription assays measuring either promoter-dependent or promoter-independent Pol I transcription. Increased synthesis of terminated transcripts is observed in crude extracts but not in a PTRF-free reconstituted transcription system, indicating that PTRF-mediated release of pre-rRNA is responsible for transcriptional enhancement. Consistent with PTRF serving an important role in modulating the efficiency of rRNA synthesis, PTRF exhibits pronounced charge heterogeneity, is phosphorylated at multiple sites and fractionates into transcriptionally active and inactive forms. The results suggest that regulation of PTRF activity may be an as yet unrecognized means to control the efficiency of ribosomal RNA synthesis.

Mammalian orthologues of a yeast regulator of nonsense transcript stability.

All eukaryotes that have been studied to date possess the ability to detect and degrade transcripts that contain a premature signal for the termination of translation. This process of nonsense-mediated RNA decay has been most comprehensively studied in the yeast Saccharomyces cerevisiae where at least three trans-acting factors (Upf1p through Upf3P) are required. We have cloned cDNAs encoding human and murine homologues of Upf1p, termed rent1 (regulator of nonsense transcripts). Rent1 is the first identified mammalian protein that contains all of the putative functional elements in Upf1p including zinc finger-like and NTPase domains, as well as all motifs common to members of helicase superfamily I. Moreover, expression of a chimeric protein, N and C termini of Upf1p, complements the Upf1p-deficient phenotype in yeast. Thus, despite apparent differences between yeast and mammalian nonsense-mediated RNA decay, these data suggest that the two pathways use functionally related machinery.

Genetic ablation of parietal cells in transgenic mice: a new model for analyzing cell lineage relationships in the gastric mucosa.

The gastric mucosa of mammalian stomach contains several differentiated cell types specialized for the secretion of acid, digestive enzymes, mucus, and hormones. Understanding whether each of these cell lineages is derived from a common stem cell has been a challenging problem. We have used a genetic approach to analyze the ontogeny of progenitor cells within mouse stomach. Herpes simplex virus 1 thymidine kinase was targeted to parietal cells within the gastric mucosa of transgenic mice, and parietal cells were ablated by treatment of animals with the antiherpetic drug ganciclovir. Ganciclovir treatment produced complete ablation of parietal cells, dissolution of gastric glands, and loss of chief and mucus-producing cells. Termination of drug treatment led to the reemergence of all major gastric epithelial cell types and restoration of glandular architecture. Our results imply the existence of a pluripotent stem cell for the gastric mucosa. Parietal cell ablation should provide a model for analyzing cell lineage relationships within the stomach as well as mechanisms underlying gastric injury and repair.

Retrotransposon insertion induces an isozyme of sn-glycerol-3-phosphate dehydrogenase in Drosophila melanogaster.

The insertion of the blood retrotransposon into the untranslated region of exon 7 of the sn-glycerol-3-phosphate dehydrogenase-encoding gene (Gpdh) in Drosophila melanogaster induces a GPDH isozyme-GPDH-4-and alters the pattern of expression of the three normal isozymes-GPDH-1 to GPDH-3. The process of transcript terminus formation inside the retrotransposon insertion reduces the level of the Gpdh transcript that contains exon 8 and increases the level of the transcript that contains exons 1-7. The induced GPDH-4 isozyme is a translation product of the three transcripts that contain fragments of the blood retrotransposon. The mechanism of mutagenesis by the blood insertion is postulated to involve the pause or termination of transcription within the blood sequence, which in turn is caused by the interference of a DNA-binding protein with the RNA polymerase. Thus, we show the formation of a new functional GPDH protein by the insertion of a transposable element and discuss the evolutionary significance of this phenomenon.

Recovery of respiration following the SOS response of Escherichia coli requires RecA-mediated induction of 2-keto-4-hydroxyglutarate aldolase.

Agents that damage DNA in Escherichia coli or interfere with its replication induce DNA repair and mutagenesis via the SOS response. This well-known activity is regulated by the RecA protein and the LexA repressor. Following repair or bypass of the DNA lesion, the cell returns to its resting state by a largely unknown process. We found that 2-keto-4-hydroxyglutarate aldolase (4-hydroxy-2-oxoglutarate aldolase; EC 4.1.3.16) is necessary for the recovery of respiration and that it is regulated by the SOS response. This protein was induced by DNA-damaging agents. Induction required RecA activation. When the LexA regulon was repressed, activation of RecA was not sufficient for induction, indicating the requirement for an additional protein under LexA control. Finally, a mutant in the corresponding hga gene was UV sensitive. 2-Keto-4-hydroxyglutarate aldolase also plays a role in respiratory metabolic pathways, which suggests a mechanism for respiration resumption during the termination of the SOS response.

Molecular cloning and characterization of a calmodulin-dependent phosphodiesterase enriched in olfactory sensory neurons.

The sensing of an odorant by an animal must be a rapid but transient process, requiring an instant response and also a speedy termination of the signal. Previous biochemical and electrophysiological studies suggest that one or more phosphodiesterases (PDEs) may play an essential role in the rapid termination of the odorant-induced cAMP signal. Here we report the molecular cloning, expression, and characterization of a cDNA from rat olfactory epithelium that encodes a member of the calmodulin-dependent PDE family designated as PDE1C. This enzyme shows high affinity for cAMP and cGMP, having a Km for cAMP much lower than that of any other neuronal Ca2+/calmodulin-dependent PDE. The mRNA encoding this enzyme is highly enriched in olfactory epithelium and is not detected in six other tissues tested. However, RNase protection analyses indicate that other alternative splice variants related to this enzyme are expressed in several other tissues. Within the olfactory epithelium, this enzyme appears to be expressed exclusively in the sensory neurons. The high affinity for cAMP of this Ca2+/calmodulin-dependent PDE and the fact that its mRNA is highly concentrated in olfactory sensory neurons suggest an important role for it in a Ca(2+)-regulated olfactory signal termination.

Uso de Data Mining e do ECR para incremento da competitividade de pequenas e médias empresas: um estudo multicaso sobre varejo e indústria alimentícia

O setor supermercadista sofreu grandes alterações nos últimos anos, principalmente com o avanço das tecnologias, a competição, a concentração e algumas insuficiências em seus processos. Estes e outros fatores favoreceram ao surgimento do movimento de ECR (Resposta de Consumidor Eficiente) que procura criar um relacionamento mais forte entre indústria e varejo através de novas visões para suas estratégias operacionais. A evolução das tecnologias de informação permitiram ao setor varejista gerar uma maior volume de dados a partir, principalmente, de seus check-outs. Entretanto, estes dados nem sempre são armazenados de forma correta ou utilizados de forma a se aproveitar a plenitude das informações neles contidas. O processo de transformar os dados em informação e conhecimento vem evoluindo constantemente. Uma das atuais metodologias de trabalhar dados é o Data Mining ou Mineração de Dados, que pode ser descrito como sendo uma variedade de ferramentas e estratégias que processam dados aumentando a utilidade destes em bancos de dados. Este trabalho analisa através de um estudo multicaso exploratório na região de Ribeirão Preto, no interior de São Paulo, a avaliação da capacidade do uso da tecnologia Data Mining para o fortalecimento do movimento ECR, principalmente em pequenos e médios varejistas e indústrias alimentícias, no sentido de oferecer a estes um diferencial de negociação para formação de alianças estratégias.

An Introduction to Conservation Easements in the United States: A Simple Concept and a Complicated Mosaic of Law

The idea of a conservation easement – restrictions on the development and use of land designed to protect the land’s conservation or historic values – can be relatively easily understood. More significant and more challenging is the complex body of state and federal laws that shapes the creation, funding, tax treatment, enforcement, modification, and termination of conservation easements. The explosion in the number of conservation easements over the past four decades has made them one of the most popular land protection mechanisms in the United States. The National Conservation Easement Database estimates that the total number of acres encumbered by conservation easements exceeds 40 million.Because conservation easements are both novel and ubiquitous, understanding how they actual work is essential for practicing lawyers, policymakers, land trust professionals, and students of conservation. This article provides a “quick tour” through some of the most important aspects of the developing mosaic of conservation easement law. It gives the reader a sense of the complex inter-jurisdictional dynamics that shape conservation transactions and disputes about conservation easements. Professors of property law, environmental law, tax law, and environmental studies who wish to cover conservation easements in the context of a more general course can use the article to provide their students with a broad but comprehensive overview of the relevant legal and policy issues.

Comment Letter: The NYSE and the End of the Structural Separation between Regulatory and Commercial Interests of the Exchange

The NYSE transformed into a for profit entity in 2006. As part of the approval process, the NYSE agreed to structurally separate the regulatory function from the business function. In doing so, the NYSE created NYSE Regulation, a non-profit with an independent board, to handle most regulatory matters. During the comment period, a spirited debate arose over the ability of a for profit company to carry out a regulatory mission. Some suggested that the regulatory function was incompatible with a "for profit" motive and that NYSE Regulation should be spun off. Others accepted the proposed structure but called for additional changes designed to reduce the possible influence of the public holding company over the regulatory function. In the end, the SEC approved the structure but with a number of prophylactic safeguards including the requirement that NYSE Regulation have a board consisting of all independent directors (save the CEO) and that directors from the for profit holding company could not make up a majority of the board. More recently, however, the NYSE has proposed to end the structural separation of the two functions and instead put in place a functional separation. The proposal would result in the termination of the delegation agreement between the Exchange and NYSE Regulation and the creation of both a Regulatory Oversight Committee of the Board of Directors of the Exchange and the creation of a Chief Regulatory Officer. This letter examines the history of the separation of the two functions and critiques the NYSE's proposal.

Sc[h]edule of work for finishing inside of dining halls & chapel, [ca. 1814]

Detailed list of twelve interior projects that need to be completed in University Hall. The list includes hinging doors, completing architraves, and installing windows. Appears to be simplified version of Memoranda of contract with carpenters, Moore, and others, in Box 1, Folder 42.

Book of records for the trial of actions begun May 3, 1762 [-1774]

Record book of justice of the peace Eldad Taylor, covering cases of debt, libel, rape, profanity, assault, breach of contract and theft. Each entry gives a full statement of the case and its settlement, including decisions of referees, costs, damages, appeals, etc.

Member State BITS after the Treaty of Lisbon: solid foundation or first victims of EU investment policy? Research Paper in Law, 02/2012

[Introduction.] This paper discusses the uncertain future of Member State BITs with third countries in the light of the developing EU investment policy. The question will be examined on the basis of the proposed Regulation establishing transitional arrangements for bilateral investment agreements between Member States and third countries presented by the Commission on 7 July 20101 and the European Parliament’s Position adopted at first reading on 10 May 2011.2 The proposed Regulation and the Commission Communication of the same day are meant to be the “first steps in the development of an EU international investment policy”.3 The first chapters present the legal framework relevant for this question and its evolution to better understand the particular challenges of this transition process. The second chapter examines the relationship of EU law and investment law, with a brief introduction of the notion of investment law and the scope of the EU’s new investment competence. The third chapter outlines the legal framework for the continuation and termination of treaties under international and EU law. The fourth chapter concerns BITs, first covering the particular nature of BITs and then the CJEU’s judgments in the BIT Cases of 2009. The fifth chapter consists of a step by step analysis of the different provisions of the proposed Regulation.

Inference of binding affinity from neuronal receptors in humans

Tese de mestrado, Bioinformática e Biologia Computacional (Bioinformática), Universidade de Lisboa, Faculdade de Ciências, 2016

No Move without Free Movement: The EU-Swiss controversy over quotas for free movement of persons. CEPS Policy Brief No. 331, 23 April 2015

The focus of this Policy Brief is the Swiss referendum of 2014 against ‘mass immigration’ in Switzerland. It identifies the challenges that a quota on EU citizens’ free movement rights to Switzerland would pose to EU-Swiss relations, considering: i) the value of freedom of movement in the EU and its indivisibility from the internal market and other economic freedoms; ii) the specificity of the EU legal system following the Lisbon Treaty that established democratic and judicial accountability mechanisms; iii) the lack of supranational judicial oversight of the EU-Switzerland agreements framework; and iv) the existence of the so-called guillotine mechanism, according to which the termination of the Free Movement Agreement would entail the automatic termination of the other agreements with the EU. The authors set out a number of options and consider their implications for EU-Swiss relations.