Antibody Responses against Xenotropic Murine Leukemia Virus-Related Virus Envelope in a Murine Model

Xenotropic murine leukemia virus-related virus (XMRV) was recently discovered to be the first human gammaretrovirus that is associated with chronic fatigue syndrome and prostate cancer (PC). Although a mechanism for XMRV carcinogenesis is yet to be established, this virus belongs to the family of gammaretroviruses well known for their ability to induce cancer in the infected hosts. Since its original identification XMRV has been detected in several independent investigations; however, at this time significant controversy remains regarding reports of XMRV detection/prevalence in other cohorts and cell type/tissue distribution. The potential risk of human infection, coupled with the lack of knowledge about the basic biology of XMRV, warrants further research, including investigation of adaptive immune responses. To study immunogenicity in vivo, we vaccinated mice with a combination of recombinant vectors expressing codon-optimized sequences of XMRV gag and env genes and virus-like particles (VLP) that had the size and morphology of live infectious XMRV.Immunization elicited Env-specific binding and neutralizing antibodies (NAb) against XMRV in mice. The peak titers for ELISA-binding antibodies and NAb were 1:1024 and 1:464, respectively; however, high ELISA-binding and NAb titers were not sustained and persisted for less than three weeks after immunizations.Vaccine-induced XMRV Env antibody titers were transiently high, but their duration was short. The relatively rapid diminution in antibody levels may in part explain the differing prevalences reported for XMRV in various prostate cancer and chronic fatigue syndrome cohorts. The low level of immunogenicity observed in the present study may be characteristic of a natural XMRV infection in humans

Evidence-Based Management of Hand Eczema

Hand eczema is a common skin disease with a wide variation in morphology and a complex etiology based on endogenous and exogenous factors.The diagnosis of hand eczema is based on patient history, exposure assessment, physical examination, and the results of patch testing. Management of hand eczema starts with education of the patient on the etiology of the disease, and the needed changes in behavior regarding skin care and preventive measures, and avoidance of relevant exposure factors. In many cases, medical treatment is needed for successful management of the disease; use of medication can only be successful with proper education and avoidance of relevant exposure

Cooperative Renewable Energy Expansion in Europe: Cost Savings and Trade Dependencies

Using the best variable renewable energy (VRE) resources available for power generation and exploiting spatio-temporal balancing effects of renewable power generation and electricity demand can help to minimize capacity requirements and thus costs for future power supply. The larger the region, the higher the benefits. From the EU perspective, it is therefore clear that markets should be coupled and policies harmonized as far as possible. One question that arises in this context is whether VRE capacity expansion should be planned and executed cooperatively in Europe to maximize the benefits. From the perspective of individual countries, the potential benefits are accompanied by a potential increase of national import and export dependencies. This chapter deals with the questions: How high are the potential cooperation benefits? How high can import and export dependencies become

From Parkinsonian thalamic activity to restoring thalamic relay using deep brain stimulation: new insights from computational modeling.

We present a computational model of a thalamocortical relay neuron for exploring basal ganglia thalamocortical loop behavior in relation to Parkinson's disease and deep brain stimulation (DBS). Previous microelectrode, single-unit recording studies demonstrated that oscillatory interaction within and between basal ganglia nuclei is very often accompanied by synchronization at Parkinsonian rest tremor frequencies (3-10 Hz). These oscillations have a profound influence on thalamic projections and impair the thalamic relaying of cortical input by generating rebound action potentials. Our model describes convergent inhibitory input received from basal ganglia by the thalamocortical cells based on characteristics of normal activity, and/or low-frequency oscillations (activity associated with Parkinson's disease). In addition to simulated input, we also used microelectrode recordings as inputs for the model. In the resting state, and without additional sensorimotor input, pathological rebound activity is generated for even mild Parkinsonian input. We have found a specific stimulation window of amplitudes and frequencies for periodic input, which corresponds to high-frequency DBS, and which also suppresses rebound activity for mild and even more prominent Parkinsonian input. When low-frequency pathological rebound activity disables the thalamocortical cell's ability to relay excitatory cortical input, a stimulation signal with parameter settings corresponding to our stimulation window can restore the thalamocortical cell's relay functionality

Frequency-selectivity of a thalamocortical relay neuron during Parkinson's disease and deep brain stimulation: a computational study.

In this computational study, we investigated (i) the functional importance of correlated basal ganglia (BG) activity associated with Parkinson's disease (PD) motor symptoms by analysing the effects of globus pallidus internum (GPi) bursting frequency and synchrony on a thalamocortical (TC) relay neuron, which received GABAergic projections from this nucleus; (ii) the effects of subthalamic nucleus (STN) deep brain stimulation (DBS) on the response of the TC relay neuron to synchronized GPi oscillations; and (iii) the functional basis of the inverse relationship that has been reported between DBS frequency and stimulus amplitude, required to alleviate PD motor symptoms [A. L. Benabid et al. (1991)Lancet, 337, 403-406]. The TC relay neuron selectively responded to and relayed synchronized GPi inputs bursting at a frequency located in the range 2-25 Hz. Input selectivity of the TC relay neuron is dictated by low-threshold calcium current dynamics and passive membrane properties of the neuron. STN-DBS prevented the TC relay neuron from relaying synchronized GPi oscillations to cortex. Our model indicates that DBS alters BG output and input selectivity of the TC relay neuron, providing an explanation for the clinically observed inverse relationship between DBS frequency and stimulus amplitude