Zinc Prevents Sickness Behavior Induced by Lipopolysaccharides after a Stress Challenge in Rats

Sickness behavior is considered part of the specific beneficial adaptive behavioral and neuroimmune changes that occur in individuals in response to infectious/inflammatory processes. However, in dangerous and stressful situations, sickness behavior should be momentarily abrogated to prioritize survival behaviors, such as fight or flight. Taking this assumption into account, we experimentally induced sickness behavior in rats using lipopolysaccharides (LPS), an endotoxin that mimics infection by gram-negative bacteria, and then exposed these rats to a restraint stress challenge. Zinc has been shown to play a regulatory role in the immune and nervous systems. Therefore, the objective of this study was to examine the effects of zinc treatment on the sickness response of stress-challenged rats. We evaluated 22-kHz ultrasonic vocalizations, open-field behavior, tumor necrosis factor α (TNF-α), corticosterone, and brain-derived neurotrophic factor (BDNF) plasma levels. LPS administration induced sickness behavior in rats compared to controls, i.e., decreases in the distance traveled, average velocity, rearing frequency, self-grooming, and number of vocalizations, as well as an increase in the plasma levels of TNF-α, compared with controls after a stressor challenge. LPS also decreased BDNF expression but did not influence anxiety parameters. Zinc treatment was able to prevent sickness behavior in LPS-exposed rats after the stress challenge, restoring exploratory/motor behaviors, communication, and TNF-α levels similar to those of the control group. Thus, zinc treatment appears to be beneficial for sick animals when they are facing risky/stressful situations.     

Indoor Tracking to Understand Physical Activity and Sedentary Behaviour: Exploratory Study in UK Office Buildings

Little is known of the patterns of physical activity, standing and sitting by office workers. However, insight into these behaviours is of growing interest, notably in regard to public health priorities to reduce non-communicable disease risk factors associated with high levels of sitting time and low levels of physical activity. With the advent and increasing availability of indoor tracking systems it is now becoming possible to build detailed pictures of the usage of indoor spaces. This paper reports initial results of indoor tracking used in conjunction with the ActivPAL activity monitoring device. In this paper we give an overview of the usage of the tracking system and its installation and illustrate some of the resultant data. We also provide preliminary results that investigate the relationship between location, light physical activity and sitting in a small sample of office workers (n=33) from two separate office environments in order to demonstrate the relevance and explanatory power of the technique.     

ADP-ribose gates the fertilization channel in ascidian oocytes

We report an ionchannel in the plasma membrane of unfertilized oocytes of the ascidianCiona intestinalis that is directly gated by the second messenger ADP-ribose. The ion channel is permeable to Ca²⁺ andNa⁺ and ischaracterized by a reversal potential between 0 and +20 mV and aunitary conductance of 140 pS. Preinjection of theCa²⁺ chelator1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) or antagonists of intracellularCa²⁺ release channels into oocytesdid not inhibit the ADP-ribose current, demonstrating that the channelis activated in a Ca²⁺-independentmanner. Both the fertilization current and the current induced by theinjection of nicotinamide nucleotides are blocked by nicotinamide,suggesting that the ADP-ribose channel is activated at fertilization ina nicotinamide-sensitive manner. These data suggest that ascidian spermtrigger the hydrolysis of nicotinamide nucleotides in the oocyte toADP-ribose and that this mechanism is responsible for the production ofthe fertilization current.

     

Behavioral Phenotyping of Murine Disease Models with the Integrated Behavioral Station (INBEST)

Due to rapid advances in genetic engineering, small rodents have become the preferred subjects in many disciplines of biomedical research. In studies of chronic CNS disorders, there is an increasing demand for murine models with high validity at the behavioral level. However, multiple pathogenic mechanisms and complex functional deficits often impose challenges to reliably measure and interpret behavior of chronically sick mice. Therefore, the assessment of peripheral pathology and a behavioral profile at several time points using a battery of tests are required. Video-tracking, behavioral spectroscopy, and remote acquisition of physiological measures are emerging technologies that allow for comprehensive, accurate, and unbiased behavioral analysis in a home-base-like setting. This report describes a refined phenotyping protocol, which includes a custom-made monitoring apparatus (Integrated Behavioral Station, INBEST) that focuses on prolonged measurements of basic functional outputs, such as spontaneous activity, food/water intake and motivated behavior in a relatively stress-free environment. Technical and conceptual improvements in INBEST design may further promote reproducibility and standardization of behavioral studies.     

Trace element determination in humans

With the present study, we intend to verify the utility of hair as diagnostic tool for trace element analysis, to substitute, perhaps, conventional materials, such as blood serum. Blood and hair were collected from male individuals (n=107) aged 20–59 y. Determinations of Cu and Zn concentrations were performed with atomic absorption spectrometry. An influence of age on Zn in hair has been found, with significantly different values before and after age 30 y. There is no correlation between Cu concentrations in hair and in serum, and a positive one (r=0.3554,p<0.05) between Zn levels in hair and in serum. No association between Zn and Cu levels in hair has been demonstrated; on the contrary, these elements have a moderate positive correlation in serum (r=0.3586,p<0.01). The data indicate that hair may represent an additional analytical material for Cu and Zn to complement blood serum.     

814. VARRONIA RUPICOLA

Varronia rupicola (Urb.) Britton (Boraginaceae) a Critically Endangered shrub, restricted to three Caribbean islands – Puerto Rico, Vieques and Anegada—is described and illustrated. Its conservation status and distribution are reviewed.     

Release of3H-dopamine and Analogous monoamines from rat striatal tissue

1. The release of previously accumulated 3H-dopamine (DA) from minces of striatal tissue prepared from the brains of pargyline-pretreated rats was evaluated by superfusion with a physiological buffer solution in a six-chamber apparatus with silver toroid electrodes to provide electrical field stimuli. The identity of released tritium as 3H-DA was demonstrated chromatographically and 3H-DA taken up was found in a synaptosomal subcellular fraction. 2. Release of 3H-DA previously accumulated at 0.3 microM was found to be linearly dependent on stimulus intensity between 1 and 10 V (for 60 sec); 5 V was selected as a standard stimulus. 3. Release of 3H-DA did not occur from minces of rat liver, nor was there release of previously accumulated labeled urea or leucine from striatal tissue by electrical stimulation, 50 mM KCL, or 0.1 mM (+)-amphetamine. When 3H-DA was taken up in the presence of cocaine (1 mM) or benztropine (100 microM), electrically induced release of 3H-DA was markedly reduced, while spontaneous efflux was much less altered. 4. Release of 3H-DA was also induced by depolarizing concentrations of K+, as well as by Rb+ or NH4+, and by veratridine. Electrical release and that induced by 50 mM K+ or 100 microM veratridine was blocked by the omission of Ca2+ (with EDTA added) and that induced by veratridine was blocked by tetrodotoxin (30 microM).     

PRMT5 silencing selectively affects MTAP-deleted mesothelioma: In vitro evidence of a novel promising approach

Malignant mesothelioma (MM) is an aggressive asbestos-related cancer of the serous membranes. Despite intensive treatment regimens, MM is still a fatal disease, mainly due to the intrinsic resistance to current therapies and the lack of predictive markers and new valuable molecular targets. Protein arginine methyltransferase 5 (PRMT5) inhibition has recently emerged as a potential therapy against methylthioadenosine phosphorylase (MTAP)-deficient cancers, in which the accumulation of the substrate 5'-methylthioadenosine (MTA) inhibits PRMT5 activity, thus sensitizing the cells to further PRMT5 inhibition. Considering that the MTAP gene is frequently codeleted with the adjacent cyclin-dependent kinase inhibitor 2A (CDKN2A) locus in MM, we assessed whether PRMT5 could represent a therapeutic target also for this cancer type. We evaluated PRMT5 expression, the MTAP status and MTA content in normal mesothelial and MM cell lines. We found that both administration of exogenous MTA and stable PRMT5 knock-down, by short hairpin RNAs (shRNAs), selectively reduced the growth of MTAP-deleted MM cells. We also observed that PRMT5 knock-down in MTAP-deficient MM cells reduced the expression of E2F1 target genes involved in cell cycle progression and of factors implicated in epithelial-to-mesenchymal transition. Therefore, PRMT5 targeting could represent a promising new therapeutic strategy against MTAP-deleted MMs.