Role of androgens in dhea-induced rack1 expression and cytokine modulation in monocytes

Background

Over the past fifteen years, we have demonstrated that cortisol and dehydroepiandrosterone (DHEA) have opposite effects on the regulation of protein kinase C (PKC) activity in the context of the immune system. The anti-glucocorticoid effect of DHEA is also related to the regulation of splicing of the glucocorticoid receptor (GR), promoting the expression of GRβ isoform, which acts as a negative dominant form on GRα activity. Moreover, it is very well known that DHEA can be metabolized to androgens like testosterone, dihydrotestosterone (DHT), and its metabolites 3α-diol and 3β-diol, which exert their function through the binding of the androgen receptor (AR). Based on this knowledge, and on early observation that castrated animals show results similar to those observed in old animals, the purpose of this study is to investigate the role of androgens and the androgen receptor (AR) in DHEA-induced expression of the PKC signaling molecule RACK1 (Receptor for Activated C Kinase 1) and cytokine production in monocytes.

Results

Here we demonstrated the ability of the anti-androgen molecule, flutamide, to counteract the stimulatory effects of DHEA on RACK1 and GRβ expression, and cytokine production. In both THP-1 cells and human peripheral blood mononuclear cells (PBMC), flutamide blocked the effects of DHEA, suggesting a role of the AR in these effects. As DHEA is not considered a direct AR agonist, we investigated the metabolism of DHEA in THP-1 cells. We evaluated the ability of testosterone, DHT, and androstenedione to induce RACK1 expression and cytokine production. In analogy to DHEA, an increase in RACK1 expression and in LPS-induced IL–8 and TNF–α production was observed after treatment with these selected androgens. Finally, the silencing of AR with siRNA completely prevented DHEA-induced RACK1 mRNA expression, supporting the idea that AR is involved in DHEA effects.

Conclusions

We demonstrated that the conversion of DHEA to active androgens, which act via AR, is a key mechanism in the effect of DHEA on RACK1 expression and monocyte activation. This data supports the existence of a complex hormonal balance in the control of immune modulation, which can be further studied in the context of immunosenescence and endocrinosenescence.

     

Epidemiology of Idiopathic Pulmonary Fibrosis in Northern Italy

Background

Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of idiopathic interstitial pneumonia. Despite its clinical relevance, few studies have examined the epidemiology of IPF and temporal variation in disease incidence and prevalence. Aim of the study was to investigate the prevalence, incidence and trends of IPF in Lombardy, a region with nearly 10 million inhabitants, during 2005–2010.

Methods

For the identification of IPF patients, we used healthcare administrative databases of Lombardy Healthcare System and adopted three algorithms: generic, broad and narrow case definition (GCD, BCD, NCD). IPF cases were identified according to diagnoses reported in inpatient and outpatient claims occurred during 2000–2010. We estimated age- and sex-adjusted annual prevalence and incidence rates from 2005 to 2010, thus allowing for a 5-year washout period.

Results

The mean annual incidence rate was estimated at 2.3 and 5.3 per 100,000 person-years using NCD and GCD, respectively. IPF incidence was higher among males, and increased with age. Trend remained stable over the years. The estimated annual prevalence rate was 35.5, 22.4, and 12.6 per 100,000 person-years using GCD, BCD and NCD, respectively, and increased with age. Moreover, we observed a positive trend over the years. Using BCD and NCD, prevalence was higher among males.

Conclusions

The results of this study, which is one of the largest population-based survey ever conducted according to strict criteria, indicated that prevalence of IPF increased across the years while incidence remained stable, thus suggesting that survival with IPF has improved.     

Electromagnetic information transfer through aqueous system

Several beneficial effects of the electromagnetic information transfer through aqueous system (EMITTAS) procedure have previously been reported in vitro. The clinical potential of this procedure has also started to be evaluated. Information flow in biological systems can be investigated through chemical and molecular approaches or by a biophysical approach focused on endogenous electrodynamic activities. Electromagnetic signals are endogenously generated at different levels of the biological organization and, likely, play an active role in synchronizing internal cell function or local/systemic adaptive response. Consequently, each adaptive response can be described by its specific electromagnetic pattern and, therefore, correlates with a unique and specific electromagnetic signature. A biophysical procedure synchronously integrating the EMITTAS procedure has already been applied for the treatment of articular pain, low-back pain, neck pain and mobility, fluctuating asymmetry, early-stage chronic kidney disease, refractory gynecological infections, minor anxiety and depression disorders. This clinical strategy involves a single treatment, since the EMITTAS procedure allows the patient to continue his/her own personal treatment at home by means of self-administration of the recorded aqueous system. A significant and long-lasting improvement has been reported, showing a potential beneficial use of this biophysical procedure in the management of common illnesses in an efficient, effective and personalized way. Data from recent studies suggest that aqueous systems may play a key role in providing the basis for recording, storing, transferring and retrieving clinically effective quanta of biological information. These features likely enable to trigger local and systemic self-regulation and self-regeneration potential of the organism.     

Emission and Transmission Properties of a Doubly Resonant 3D Nanodisk Yagi–Uda Antenna for Wireless Optical Communications

In this paper, a novel doubly resonant three-dimensional (3D) nanodisk Yagi–Uda antenna, conceived for realizing wireless optical links within electronic circuits, is proposed. The prominent emitting properties of this nanoantenna have been deeply investigated both in the near and far field through a useful comparison with a more traditional 3D nanorod Yagi–Uda antenna. The behavior of the nanodisk antenna, both configured as a single nanoantenna and arranged in planar arrays, have been illustrated, emphasizing its improved performances with relation to crucial aspects as directional features, wavelength bands of operation, frequency tuning, and polarization influence on radiation. In particular, the single nanodisk antenna has been accurately designed to enhance the transmission feature in the near field at the wavelengths λ?=?1.3 and λ?=?1.55 μm. Also, the emission pattern of the array of nanodisk antennas has been properly tailored to ensure high peaks of directivity and narrow beam width in those ranges. Hence, efficient unidirectional angle patterns have been shaped for any operation wavelength and dimensions of the array, reaching extremely effective outcomes for a 3?×?3 array, which exhibits a maximum of directivity of 19 and 17.6 and ?3 dB points at 18° and 21° for λ?=?1.3 and λ?=?1.55 μm, respectively.     

Role of Upwelling on Larval Dispersal and Productivity of Gooseneck Barnacle Populations in the Cantabrian Sea: Management Implications

The effect of coastal upwelling on the recruitment and connectivity of coastal marine populations has rarely been characterized to a level of detail to be included into sound fishery management strategies. The gooseneck barnacle (Pollicipes pollicipes) fishery at the Cantabrian Coast (Northern Spain) is located at the fringes of the NW Spanish Upwelling system. This fishery is being co-managed through a fine-scale, interspersed set of protected rocks where each rock receives a distinct level of protection. Such interspersion is potentially beneficial, but the extent to which such spacing is consistent with mean larval dispersal distances is as yet unknown. We have simulated the spread of gooseneck barnacle larvae in the Central Cantabrian Coast using a high-resolution time-series of current profiles measured at a nearshore location. During a year of high upwelling activity (2009), theoretical recruitment success was 94% with peak recruitment predicted 56 km west of the emission point. However, for a year of low upwelling activity (2011) theoretical recruitment success dropped to 15.4% and peak recruitment was expected 13 km east of the emission point. This is consistent with a positive correlation between catch rates and the Integrated Upwelling Index, using a 4-year lag to allow recruits to reach commercial size. Furthermore, a net long-term westward larval transport was estimated by means of mitochondrial cytochrome c oxidase subunit I (COI) sequences for five populations in the Cantabrian Sea. Our results call into question the role of long distance dispersal, driven by the mesoscale processes in the area, in gooseneck barnacle populations and point to the prevalent role of small-scale, asymmetric connectivity more consistent with the typical scale of the co-management process in this fishery.     

The isolectin IB4 binds RET receptor tyrosine kinase in microglia

Ret receptor tyrosine kinase is the signaling component of the receptor complex for the family ligands of the glial cell line‐derived neurotrophic factor (GDNF). Ret is involved in the development of enteric nervous system, of sympathetic, parasympathetic, motor and sensory neurons, and it is necessary for the post‐natal maintenance of dopaminergic neurons. Ret expression has been as well demonstrated on microglia and several evidence indicate that GDNF regulates not only neuronal survival and maturation but also certain functions of microglia in the brain. Here, we demonstrated that the plant lectin Griffonia (Bandeiraea) simplicifolia lectin I, isolectin B4 (IB4), commonly used as a microglial marker in the brain, binds to the glycosylated extracellular domain of Ret on the surface of living NIH3T3 fibroblasts cells stably transfected with Ret as well as in adult rat brain as revealed by immunoblotting. Furthermore, confocal immunofluorescence analysis demonstrated a clear overlap in staining between pRet and IB4 in primary microglia cultures as well as in adult rat sections obtained from control or post‐ischemic brain after permanent middle artery occlusion (pMCAO). Interestingly, IB4 staining identified activated or ameboid Ret‐expressing microglia under ischemic conditions. Collectively, our data indicate Ret receptor as one of the IB4‐reactive glycoconjugate accounting for the IB4 stain in microglia under physiological and ischemic conditions.     

SHIFT FROM CHLOROPHYTES TO CYANOBACTERIA IN BENTHIC MACROALGAE ALONG A GRADIENT OF NITRATE DEPLETION1

A survey of the spatial distribution of benthic macroalgae in a fluvial lake of the St. Lawrence River (Lake Saint‐Pierre, Quebec, Canada) revealed a shift in composition from chlorophytes to cyanobacteria along the flow path of nutrient‐rich waters originating from tributaries draining farmlands. The link between this shift and changes in water quality characteristics was investigated by sampling at 10 sites along a 15 km transect. Conductivity, current, light extinction, total phosphorus (TP; >25 μg P · L^?1), and ammonium (8–21 μg N · L^?1) remained fairly constant along the transect in contrast to nitrate concentrations, which fell sharply. Filamentous and colonial chlorophytes [Cladophora sp. and Hydrodictyon reticulatum (L.) Bory] dominated in the first 5 km where nitrate concentrations were >240 μg N · L^?1. A mixed assemblage of chlorophytes and cyanobacteria characterized a 1 km transition zone where nitrate decreased to 40–80 μg N · L^?1. In the last section of the transect, nitrate concentrations dropped below 10 μg N · L^?1, and cyanobacteria (benthic filamentous mats of Lyngbya wollei Farl. ex Gomont and epiphytic colonies of Gloeotrichia) dominated the benthic community. The predominance of nitrogen‐fixing, potentially toxic cyanobacteria likely resulted from excessive nutrient loads and may affect nutrient and trophic dynamics in the river.