Glucocorticoid receptor action in metabolic and neuronal function [version 1; referees: 3 approved]

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them

Sea Otter, Enhydra lutris, mortalities in California, 1968 through 1993

Sea otter, Enhydra lutris, mortality in California and the relative contribution from specific causes was assessed for the 26 years from 1968 through 1993. There were 2,082 dead sea otters recorded from Tomales Bay (Marin County) south to Bluff Cove (Los Angeles County) during that period. The average number of carcasses recorded was 80 per year and seven per month. Sex was identified in 87% (n=1,819) of the cases and was composed of 47% female and 53% male. A relative age was assigned to 97% (n=2,017) of the cases and was composed of 28% pup, 18% subadult and 54% adult. Specific causes of death were determined for 26% (n=55 1) of the cases. The majority of these (n=381) were considered to be due to natural causes and included the following specific causes: shark bitten (n=78), probably shark bitten (n=106), other natural causes (n=140), and mating wounds (n=57). The remaining (n=170) were considered to be due to human-related causes and included the following specific causes: shot (n=72), probably shot (n=8), net drowned (n=76), and other human causes (n=14). The large proportion of carcasses without an identified specific cause of death prompted a more detailed necropsy effort in 1992 and 1993. During that period, 78 of the 232 recovered carcasses were examined by veterinary pathologists and a specific cause of death was determined in 76% (n=59) of the cases. This effort identified a wide range of specific causes of death that otherwise may have been categorized as "unknown without trauma". Considering the variety of diseases diagnosed in this expanded necropsy program, it would be prudent to continue this level of examination to refine our knowledge of sea otter pathology. (48pp.

Treatment Outcomes for At-Risk Young Children With Behavior Problems: Toward a New Definition of Success

This study examined the outcomes of Early Pathways (EP), an in-home parent–child therapy program with 447 at-risk children younger than 5 years of age who were referred for severe behavior and emotional problems, such as aggression, oppositional behavior, and separation anxiety. EP emphasized parent-directed training of child behavior strategies including psychoeducation regarding child development, child-led play, and cognitive-behavioral techniques. Outcomes were assessed using a unique 2-dimensional definition of treatment completion, which consisted of treatment duration and an assessment of reliable change for the primary outcome measure of child behavior problems. Results showed that the majority of children (63.4%) met or exceeded treatment completion. In addition, repeated-measures multivariate analyses of variance at pretest, posttest, and follow-up revealed increased child prosocial behaviors, reduced child behavior problems, improved caregiver nurturing, an increase in parents’ developmentally appropriate expectations of children, improved parent–child relationships, and a decrease in clinical diagnoses following treatment. This study offers guidance for developing effective early-intervention services for families in poverty to enhance outcomes for their young children. Along with its existing large-scale, community-based effectiveness studies, future research should establish additional statistical support including a randomized, waitlist control design of EP

Simultaneous calculation of the helical pitch and the twist elastic constant in chiral liquid crystals from intermolecular torques

We present a molecular simulation method that yields simultaneously the equilibrium pitch wave number q and the twist elastic constant K2 of a chiral nematic liquid crystal by sampling the torque density. A simulation of an untwisted system in periodic boundary conditions gives the product K2q; a further simulation with a uniform twist applied provides enough information to separately determine the two factors. We test our new method for a model potential, comparing the results with K2q from a thermodynamic integration route, and with K2 from an order fluctuation analysis. We also present a thermodynamic perturbation theory analysis valid in the limit of weak chirality

FutureGRID: A Program for long-term research into GRID systems architecture

Proceedings of the 2003 UK e-Science All Hands Meeting, 31st August - 3rd September, Nottingham UKThis is a project to carry out research into long-term GRID architecture, in the University of Cambridge Computer Laboratory and the Cambridge eScience Center, with support from the Microsoft Research Laboratory, Cambridge. It is part of a larger vision for future systems architectures for public computing platforms, including both scientitic GRID and commodity level computing such as games, peer2peer computing and storage services and so forth, based on work in the laboratories in recent years into massively scaleable distributed systems for storage, computation, content distribution and collaboration[26]

Multiple Species of Noninteracting Molecules Adsorbed on a Bethe Lattice

A simple method, previously used to calculate the equilibrium concentration of dimers adsorbed on a Bethe lattice as a function of the dimer activity, is generalized to solve the problem of a Bethe lattice in contact with a reservoir containing a mixture of molecules. The molecules may have arbitrary sizes and shapes consistent with the geometry of the lattice and the molecules do not interact with one another except for the hard-core restriction that two molecules cannot touch the same site. We obtain a set of simultaneous nonlinear equations, one equation for each species of molecule, which determines the equilibrium concentration of each type of molecule as a function of the (arbitrary) activities of the various species. Surprisingly, regardless of the number of species, the equilibrium concentrations are given explicitly in terms of the solution of a single equation in one unknown which can be solved numerically, if need be. Some numerical examples show that increasing the activity of one species need not necessarily decrease the equilibrium concentration of all other species. We also calculate the adsorption isotherm of an “annealed” Bethe lattice consisting of two types of sites which differently influence the activity of an adsorbed molecule. We prove that if the reservoir contains a finite number of molecular species, regions of two different polymer densities cannot simultaneously exist on the lattice. The widely used Guggenheim theory of mixtures, which can also be construed as a theory of adsorption, assumes for simplicity that the molecules in the mixture are composed of elementary units, which occupy sites of a lattice of coordination number q. Guggenheim’s analysis relies on approximate combinatorial formulas which become exact on a Bethe lattice of the same coordination number, as we show in an appendix. Our analysis involves no combinatorics and relies only on recognizing the statistical independence of certain quantities. Despite the nominal equivalence of the two approaches, the easily visualized properties of the Bethe lattice enable one to solve some apparently difficult problems by quite elementary methods

Dimer Statistics on a Bethe Lattice

We discuss the exact solutions of various models of the statistics of dimer coverings of a Bethe lattice.We reproduce the well-known exact result for noninteracting hard-core dimers by both a very simple geometrical argument and a general algebraic formulation for lattice statistical problems. The algebraic formulation enables us to discuss loop corrections for finite dimensional lattices. For the Bethe lattice we also obtain the exact solution when either (a) the dimers interact via a short-range interaction or (b) the underlying lattice is anisotropic. We give the exact solution for a special limit of dimers on a Bethe lattice in a quenched random potential in which we consider the maximal covering of dimers on random clusters at site occupation probability p. Surprisingly the partition function for “maximal coverage” on the Bethe lattice is identical to that for the statistics of branched polymers when the activity for a monomer unit is set equal to −p. Finally we give an exact solution for the number of residual vacancies when hard-core dimers are randomly deposited on a one dimensional lattice

Scaling of Negative Moments of the Growth Probability of Diffusion-Limited Aggregates

The qth moment M(q) of the growth probability of diffusion-limited aggregates is studied for q\u3c0 in terms of the value [M(q,N)]av obtained by averaging M(q) over the ensemble of all aggregates of a given number of particles N. For a range of structures that are susceptible to precise analysis, we verify that all moments, even those for q\u3c0, obey asymptotic power-law scaling in N. Since we cannot analyze completely arbitrary structures, our analysis is not definitive. However, it does suggest the validity of a recent proposal by one of us that there is no Lifshitz-like anomaly (similar to that found for the distribution of currents in the random resistor network) leading to non-power-law scaling of the negative moments of the growth probability

Dendritic cells in dengue virus infection: Targets of virus replication and mediators of immunity

Dendritic cells (DCs) are sentinels of the immune system and detect pathogens at sites of entry, such as the skin. In addition to the ability of DCs to control infections directly via their innate immune functions, DCs help to prime adaptive B and T cell responses via antigen presentation in lymphoid tissues. Infected Aedes aegypti or Ae. albopictus mosquitoes transmit the four dengue virus (DENV) serotypes to humans while probing for small blood vessels in the skin. DENV causes the most prevalent arthropod-borne viral disease in humans, yet no vaccine or specific therapeutic is currently approved. Although primary DENV infection confers life-long protective immunity against re-infection with the same DENV serotype, secondary infection with a different DENV serotype can lead to increased disease severity via cross-reactive T cells or enhancing antibodies. This review summarizes recent findings in humans and animal models about DENV infection of DCs, monocytes and macrophages. We discuss the dual role of DCs as both targets of DENV replication and mediators of innate and adaptive immunity, and summarize immune evasion strategies whereby DENV impairs the function of infected DCs. We suggest that DCs play a key role in priming DENV-specific neutralizing or potentially harmful memory B and T cell responses, and that future DC-directed therapies may help induce protective memory responses and reduce dengue pathogenesis

Culture and rapport promotion in service encounters: protecting the ties that bind

The present study aimed at investigating possible cultural effects on the perceived importance of interactional concerns in service encounters. Individual values were examined to establish an explanatory framework for any effects that might emerge. Hong Kong Chinese and Filipinos participated in the present study by rating the importance of 12 interactional concerns in five hypothetical scenarios involving service provision. “Rapport promotion” was the only consistent factor of interactional concerns to emerge from the five scenarios in each of the two cultural groups. The dimensions of individual values, labeled “Conservation” and “Self-Transcendence” by Schwartz (1992), significantly predicted a respondent’s level of rapport promotion across all scenarios, with self-transcendence partially unpackaging the cultural difference that emerged in one of the service scenarios. We use these results to support a model of communication in service provision that predicts communication concerns as arising from cultural socialization for personal characteristics and situational features of the encounter, leading to the petitioner’s being more dependent on the good will of the service provider