Osteoclast Activated FoxP3+ CD8+ T-Cells Suppress Bone Resorption in vitro

BACKGROUND: Osteoclasts are the body's sole bone resorbing cells. Cytokines produced by pro-inflammatory effector T-cells (T(EFF)) increase bone resorption by osteoclasts. Prolonged exposure to the T(EFF) produced cytokines leads to bone erosion diseases such as osteoporosis and rheumatoid arthritis. The crosstalk between T-cells and osteoclasts has been termed osteoimmunology. We have previously shown that under non-inflammatory conditions, murine osteoclasts can recruit naïve CD8 T-cells and activate these T-cells to induce CD25 and FoxP3 (Tc(REG)). The activation of CD8 T-cells by osteoclasts also induced the cytokines IL-2, IL-6, IL-10 and IFN-γ. Individually, these cytokines can activate or suppress osteoclast resorption. PRINCIPAL FINDINGS: To determine the net effect of Tc(REG) on osteoclast activity we used a number of in vitro assays. We found that Tc(REG) can potently and directly suppress bone resorption by osteoclasts. Tc(REG) could suppress osteoclast differentiation and resorption by mature osteoclasts, but did not affect their survival. Additionally, we showed that Tc(REG) suppress cytoskeletal reorganization in mature osteoclasts. Whereas induction of Tc(REG) by osteoclasts is antigen-dependent, suppression of osteoclasts by Tc(REG) does not require antigen or re-stimulation. We demonstrated that antibody blockade of IL-6, IL-10 or IFN-γ relieved suppression. The suppression did not require direct contact between the Tc(REG) and osteoclasts. SIGNIFICANCE: We have determined that osteoclast-induced Tc(REG) can suppress osteoclast activity, forming a negative feedback system. As the CD8 T-cells are activated in the absence of inflammatory signals, these observations suggest that this regulatory loop may play a role in regulating skeletal homeostasis. Our results provide the first documentation of suppression of osteoclast activity by CD8 regulatory T-cells and thus, extend the purview of osteoimmunology

MicroRNA methodology: Advances in miRNA technologies.

There is an emerging trend in microRNA research and thus substantial progress in microRNA technologies. In this chapter we provide insights into the main microRNA specific methodologies and critical steps of microRNA expression profiling, target gene identification, and functional confirmation of microRNA effects up to in vivo application of antagomirs

Factors which influence the consumption of street foods and fast foods in South Africa-a national survey

<p>Abstract</p> <p>Background</p> <p>Very little is known about street food and fast food consumption patterns in South Africa despite this being a large sector of the national economy in terms of employment provided and sales of food. The objective of this study was to determine the use of street foods and fast foods purchased by South Africans living in different provinces and geographic areas.</p> <p>Methods</p> <p>A cross-sectional survey was conducted. Structured interview-administered questionnaires in 11 official languages were conducted at the participants' homes. A nationally representative sample (n = 3287) was drawn from all ethnic groups, and provinces including participants 16 years and older. Logistic regression was done to evaluate factors impacting on fast food consumption.</p> <p>Results</p> <p>Frequent (2 ≥ times/week) street food consumption ranged from 1.8% in Northern Cape to 20.6% in Limpopo; frequent (2 ≥ times/week) fast food consumption ranged between 1.5% in North West Province to 14.7% in Gauteng. The highest intake of street food was in the medium socio-economic category (14.7%) while the highest intake of fast foods was in the high socio-economic category (13.2%). Overall, fruit was the most commonly purchased street food by all ethnic groups over the previous week although this practice was highest in black participants (35.8%). Purchases of soft drinks ranged from 4.8% in whites to 16.4% in blacks and savoury snacks from 2.3% to 14.5% in whites and blacks, respectively. Consumption of fast foods and street foods were influenced by a number of socio-demographic factors including ownership of major home appliances. Frequent fast food consumers had a significantly higher dietary diversity score (4.69; p < 0.0001) while frequent street food consumers had a significantly lower score (3.81; p < 0.0001).</p> <p>Conclusions</p> <p>A large percentage of the population purchase street foods and fast foods. This is of some concern when one notes the high prevalence of soft drink consumption in terms of its association with obesity and non-communicable diseases. These findings need to be taken into consideration when evaluating dietary patterns and nutritional adequacy of population diets.</p

Neuropeptide S Enhances Memory During the Consolidation Phase and Interacts with Noradrenergic Systems in the Brain

Neuropeptide S (NPS) has been shown to promote arousal and anxiolytic-like effects, as well as facilitation of fear extinction. In rodents, NPS receptors (NPSR) are prominently expressed in brain structures involved in learning and memory. Here, we investigate whether exogenous or endogenous NPS signaling can modulate acquisition, consolidation, or recall of emotional, spatial, and contextual memory traces, using two common behavioral paradigms, inhibitory avoidance (IA) and novel object recognition. In the IA paradigm, immediate and delayed post-training central NPS administration dose dependently enhanced memory retention in mice, indicating that NPS may act during the consolidation phase to enhance long-term memory. In contrast, pre-training or pre-test NPS injections were ineffective, suggesting that NPS had no effect on IA memory acquisition or recall. Peripheral administration of a synthetic NPSR antagonist attenuated NPS-induced IA memory enhancement, showing pharmacological specificity. NPS also enhanced hippocampal-dependent non-aversive memory in the novel object recognition task. In contrast, NPSR knockout mice displayed deficits in IA memory, novel object recognition, and novel place or context recognition, suggesting that activity of the endogenous NPS system is required for memory formation. Blockade of adrenergic signaling by propranolol attenuated NPS-induced memory enhancement in the IA task, indicating involvement of central noradrenergic systems. These results provide evidence for a facilitatory role of NPS in long-term memory, independent of memory content, possibly by acting as a salience signal or as an arousal-promoting factor