Phosphorylation of the human leukemia inhibitory factor (LIF) receptor by mitogen-activated protein kinase and the regulation of LIF receptor function by heterologous receptor activation.

We used a bacterially expressed fusion protein containing the entire cytoplasmic domain of the human leukemia inhibitory factor (LIF) receptor to study its phosphorylation in response to LIF stimulation. The dose- and time-dependent relationships for phosphorylation of this construct in extracts of LIF-stimulated 3T3-L1 cells were superimposable with those for the stimulation of mitogen-activated protein kinase (MAPK). Indeed, phosphorylation of the cytoplasmic domain of the low-affinity LIF receptor alpha-subunit (LIFR) in Mono Q-fractionated, LIF-stimulated 3T3-L1 extracts occurred only in those fractions containing activated MAPK; Ser-1044 served as the major phosphorylation site in the human LIFR for MAPK both in agonist-stimulated 3T3-L1 lysates and by recombinant extracellular signal-regulated kinase 2 in vitro. Expression in rat H-35 hepatoma cells of LIFR or chimeric granulocyte-colony-stimulating factor receptor (G-CSFR)-LIFR mutants lacking Ser-1044 failed to affect cytokine-stimulated expression of a reporter gene under the control of the beta-fibrinogen gene promoter but eliminated the insulin-induced attenuation of cytokine-stimulated gene expression. Thus, our results identify the human LIFR as a substrate for MAPK and suggest a mechanism of heterologous receptor regulation of LIFR signaling occurring at Ser-1044.

CD40 on human endothelial cells: inducibility by cytokines and functional regulation of adhesion molecule expression.

Cultured human umbilical vein endothelial cells (EC) constitutively express a low level of CD40 antigen as detected by monoclonal antibody binding and fluorescence flow cytometric quantitation. The level of expression on EC is increased about 3-fold following 24 h treatment with optimal concentrations of tumor necrosis factor, interleukin 1, interferon beta, or interferon gamma; both interferons show greater than additive induction of CD40 when combined with tumor necrosis factor or interleukin 1. Expression of CD40 increases within 8 h of cytokine treatment and continues to increase through 72 h. A trimeric form of recombinant murine CD40 ligand acts on human EC to increase expression of leukocyte adhesion molecules, including E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1. CD40 may be detected immunocytochemically on human microvascular EC in normal skin. We conclude that endothelial CD40 may play a role as a signaling receptor in the development of T-cell-mediated inflammatory reactions.

Dual transcriptional control by Ear3/COUP: negative regulation through the DR1 direct repeat and positive regulation through a sequence downstream of the transcriptional start site of the mouse mammary tumor virus promoter.

Ear3/COUP is an orphan member of the steroid/thyroid hormone receptor superfamily of transcription factors and binds most tightly to a direct repeat of AGGTCA with 1 nucleotide in between (DR1). Ear3/COUP also binds with a similar affinity to the palindromic thyroid hormone response element (TRE). This binding preference of Ear3/COUP is same as that of the retinoid X receptor (RXR), which is another member of the superfamily. In the present study, we identified a sequence responsible for Ear3/COUP-mediated transactivation in the region downstream of the transcription start site of the mouse mammary tumor virus promoter. This cis-acting sequence was unresponsive to RXR. When the DR1 or TRE sequence was added upstream of the promoter, transactivation by Ear3/COUP was completely abolished, whereas RXR enhanced transcription from the promoter. The mode of action of Ear3/COUP could be utilized to control complex gene expressions in morphogenesis, homeostasis, and development.

Public Lawyers and Marijuana Regulation

Although 23 states and the District of Columbia have now legalized marijuana for medical purposes, marijuana remains a prohibited substance under federal law. Because the production, sale, possession and use of marijuana remain illegal, there is a risk of prosecution under federal laws. Furthermore, those who help marijuana users and providers put themselves at risk — federal law punishes not only those who violate drug laws but also those who assist or conspire with them to do so. In the case of lawyers representing marijuana users and businesspeople, this means not only the real (though remote) risk of criminal prosecution but also the more immediate risk of professional discipline. Elsewhere, we wrote about the difficult place in which lawyers find themselves when representing marijuana clients. We argued that while both the criminal law and the rules of professional conduct rightly require legal obedience from lawyers, other countervailing factors must be considered when evaluating lawyers’ representation of marijuana clients. In particular, we asserted that considerations of equity and access to justice weigh dispositively in favor of protecting lawyers who endeavor to help their clients comply with state marijuana laws, and we suggested means of interpreting relevant criminal law provisions and rules of professional conduct to achieve this result. This article builds on that analysis, taking on the particular issue of the public lawyer’s’ role in marijuana regulation. For government lawyers, the key issues in exercising discretion in the context of marijuana are not clients’ access to the law and equality but rather determining the clients’ wishes and serving them diligently and ethically. Lawyers representing state agencies, legislatures and the executive branch of government draft and interpret the rules and regulations regarding marijuana. Lawyers for federal, state and local governments then interpret those rules to determine the obligations and responsibilities of those they represent and to help their clients meet those obligations and carry out their required tasks. Both state and federal prosecutors are charged with determining what conduct remains illegal under the new rules and, perhaps more importantly, with exercising discretion regarding whom to prosecute and to what extent. Marijuana regulation is not a niche area of government regulation; it will influence the practice of virtually every public lawyer in the years to come. Public lawyers must understand the changes in marijuana law and the implications for government clients. Given the pervasiveness of the modern regulatory state, the situation is no easier — and, in many ways, it is more complicated — for public lawyers than it is for private ones. Public lawyers face myriad practice challenges with respect to marijuana law reform, and while we do not purport to identify and resolve all of the issues that are sure to arise in this short paper, we hope that the article helps alert public lawyers to some of the risks involved in participating in marijuana regulation so that they can think carefully about their obligations when these issues arise.

Multi-agent system for control of robots inspired on the distributed activity and hormonal regulation of humans

Robotics is an emerging field with great activity. Robotics is a field that presents several problems because it depends on a large number of disciplines, technologies, devices and tasks. Its expansion from perfectly controlled industrial environments toward open and dynamic environment presents a many new challenges. New uses are, for example, household robots or professional robots. To facilitate the low cost, rapid development of robotic systems, reusability of code, its medium and long term maintainability and robustness are required novel approaches to provide generic models and software systems who develop paradigms capable of solving these problems. For this purpose, in this paper we propose a model based on multi-agent systems inspired by the human nervous system able to transfer the control characteristics of the biological system and able to take advantage of the best properties of distributed software systems. Specifically, we model the decentralized activity and hormonal variation.

The impact of marketing practices and its regulation policies on childhood obesity. Opinions of stakeholders in Spain

The aim of this study was to identify Spanish stakeholders’ views on the relationship between childhood obesity and the marketing and advertising of food and beverages aimed at children in Spain, as well as on the corresponding of regulations. We performed a qualitative study based on semi-structured interviews with Stakeholders/Key Informants (KI) from 13 organisations: experts (2), consumer advocates (1), public health advocates (2), food manufacturers (2), advertising advocates (1), government representatives (1), child/family/school advocates (2) and media (1). The variables studied were Prevalence of childhood obesity and its relationship to marketing/advertising and Regulation of marketing. In order to identify the most relevant arguments (pearls) in the discourses, a blind independent analysis by four members of the research team was performed. We found that the prevalence of childhood obesity was perceived to be higher than the European average. Self-regulation was identified as the main form of marketing control. Only food manufacturers and advertising agencies considered voluntary action and supervisory procedures to be effective. The other stakeholders advocated state control through legislation and non-state actions such as external assessment and sanctions. Despite the divergence of opinion between stakeholders, there was agreement on the need to improve supervision and to ensure compliance with current self-regulatory codes in Spain.