Erratum to: Estrogen receptor beta binds Sp1 and recruits a corepressor complex to the estrogen receptor alpha gene promoter.

Erratum to: Breast Cancer Res Treat (2012), 134:569­581, DOI 10.1007/s10549-012-2090-9. Uunfortunately, authors could not find the original film from which the figure was drawn. Therefore, as suggested by the Editor, they have repeated the relative experiment, and ask to publish this new figure as a correction. The authors apologize for any inconvenience that it may cause.

Identification of G protein-coupled estrogen receptor in human and pig spermatozoa.

Estrogens are known to influence functional properties of mammalian spermatozoa inducing rapid responses through the classical estrogen receptors (ERα and ERß). Recently, the G protein-coupled estrogen receptor (GPER) has been identified as mediator of fast non-genomic estrogen effects in different cells. This work investigated the expression of GPER in human and pig spermatozoa using immunofluorescence, Western blot analysis and RT-PCR. GPER was found to be confined to the mid-piece of human sperm cells, whereas it was detected in the acrosomal region, the equatorial segment and the mid-piece of pig spermatozoa. Furthermore, in the male gametes of both species, the immunoblots of sperm extracts revealed a band at ~42 kDa, consistent with the GPER molecular weight, and RT-PCR detected the GPER transcripts. This is the first report demonstrating the expression of GPER in human and pig mature sperm cells and evidencing its species-specific cellular localization.

Bergapten induces ER depletion in breast cancer cells through SMAD4-mediated ubiquitination.

ERα function is crucial for the development of normal mammary gland as well as in the process of progression of breast cancer cells. Signals that target receptor levels contribute to regulate estrogens effects in the cells. An intricate cross-regulation has been documented between ERα and TGF-ß down-stream molecules: SMAD2, SMAD3, and SMAD4, that can bind ERα and regulate their signaling. Thus, identification of natural anticancer drugs able to influence the latter molecule might provide alternative choices for breast cancer treatment. Taking into account our previous published data we wanted to study the effect of 5-Methoxypsoralen (bergapten) on ERα and on TGF-ß pathway. We reported that bergapten, a coumarin containing compound, effectively depletes ERα in MCF-7 breast cancer sensitive cells and in tamoxifen-resistant clone. The decrease of ERα protein after bergapten treatment results from the ubiquitine-proteasome pathway as demonstrated by the use of MG-132. IP experiments with ER antibody, demonstrated that the protein has physical interaction with SMAD4 and poly-ubiquitine and the amount of ubiquitinated receptor, linked to SMAD4, is greater under bergapten. The crucial role played by SMAD4, in this process, emerges from the observation that in breast cancer cells, silencing of SMAD4, resulted in increased expression of endogenous ERα in both control and bergapten-treated cells, compared to wild- type cells. The same results were confirmed in siRNA TGF-ß RII cells. The results suggest a novel negative regulation of ERα by TGF-ß/SMAD4 in breast cancer cells and indicate that the SMAD4 protein is involved in the degradation of ERα induced by bergapten. We propose that bergapten may efficiently act as a natural antitumoral agent, able to deplete ERα from breast cancer tamoxifen-sensitive and resistant cells, thereby retraining the effect of membrane signals targeting ERα and in such way its mitogenic potentiality.

Estrogen receptor beta binds Sp1 and recruits a corepressor complex to the estrogen receptor alpha gene promoter.

Human estrogen receptors alpha and beta are crucially involved in the regulation of mammary growth and development. Normal breast tissues display a relative higher expression of ER beta than ER alpha, which drastically changes during breast tumorogenesis. Thus, it is reasonable to suggest that a dysregulation of the two estrogen receptor subtypes may induce breast cancer development. However, the molecular mechanisms underlying the potential opposing roles played by the two estrogen receptors on tumor cell growth remain to be elucidated. In the present study, we have demonstrated that ER beta overexpression in breast cancer cells decreases cell proliferation and down-regulates ER alpha mRNA and protein content, along with a concomitant repression of estrogen-regulated genes. Transient transfection experiments, using a vector containing the human ER alpha promoter region, showed that elevated levels of ER beta down-regulated basal ER alpha promoter activity. Furthermore, site-directed mutagenesis and deletion analysis revealed that the proximal GC-rich motifs at -223 and -214 are critical for the ER beta-induced ER alpha down-regulation in breast cancer cells. This occurred through ER beta-Sp1 protein-protein interactions within the ER alpha promoter region and the recruitment of a corepressor complex containing the nuclear receptor corepressor NCoR, accompanied by hypoacetylation of histone H4 and displacement of RNA-polymerase II. Silencing of NCoR gene expression by RNA interference reversed the down-regulatory effects of ER beta on ER alpha gene expression and cell proliferation. Our results provide evidence for a novel mechanism by which overexpression of ER beta through NCoR is able to down regulate ER alpha gene expression, thus blocking ER alpha's driving role on breast cancer cell growth.

[Work-related musculo-skeletal disorders in apiculture: a biomechanical approach to the risk assessment]. / Apicoltura e patologie muscolo-scheletriche: un approccio metodologico alla valutazione del rischio.

The risk assessment in apiculture points out methodological problems due to discontinuities and variability of exposure. This study analyzes a comprehensive set of potential determinants influencing the biomechanical risks in apiarists using recognized technical standards to ensure the technical-scientific accuracy; it offers a simplified methodological toolkit to be used in the risk assessment process and provides a user-friendly computer application. The toolkit asks the beekeeper to specify, for each month, the total number of hours worked, specifying the distribution among different tasks. As a result, the application calculates the average index risk and the peak index risk. The evidence of the study indicates that there are activities in this occupational area with biomechanical risks that remain for some tasks, while reducing the exposure time.

Rosiglitazone reduces the evolution of experimental periodontitis in the rat.

The peroxisome proliferator-activated receptor-gamma (PPAR-gamma) receptor appears to play a pivotal role in the regulation of cellular proliferation and inflammation. Recent evidence also suggests that rosiglitazone, a PPAR-gamma agonist, reduces acute and chronic inflammation. We hypothesized that rosiglitazone would attenuate periodontal inflammation. In the present study, we investigated the effects of rosiglitazone in a rat model of ligature-induced periodontitis. At day 8, ligation significantly induced an increase in neutrophil infiltration, as well as of gingivomucosal tissue expression of iNOS, nitrotyrosine formation, and poly (ADP-ribose) polymerase activation. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction. Intraperitoneal injection of rosiglitazone (10 mg/kg 10% DMSO daily for 8 days) significantly decreased all of the parameters of inflammation, as described above. Analysis of these data demonstrated that rosiglitazone exerted an anti-inflammatory role during experimental periodontitis, and was able to ameliorate the tissue damage associated with ligature-induced periodontitis.

DNA damage and repair in L1210 cells exposed to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

The DNA of L1210 cells exposed to low concentrations of 1-(2-chloroethyl)=3-cyclohexyl-1-nitrosourea has been analyzed for the presence of single-strand breaks. DNA from 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-treated cells both sediments more slowly than control DNA on alkaline sucrose gradients andshows a greater extent of strand separation of the DNA helix in alkali. These effects are a typical result of exposure of cellular DNA to alkylating agents or ionizing radiation. The extent of DNA damage caused by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea has been related to the same amount of damage resulting from exposure of cells to low doses of gamma-irradiation. The rate and extent of repair of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-induced damage is slow and incomplete, compared with the repair of gamma-irradiation damage to DNA. It is concluded that 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea behaves as a weak alkylating agent, a property that may explain its antitumor properties.

Hepatitis B virus serology. Loss of antibody to surface antigen.

A retrospective review of hepatitis B serologies from 6,686 patients was conducted to determine the incidence of loss of antibody to hepatitis B surface antigen (anti-HBs) with retention of antibody to the core antigen of hepatitis B virus (anti-HBc) activity. In a subgroup of 48 multiply tested patients who were presumed to have resolved their acute or subacute hepatitis B virus infection, 9 (19%) were found to have lost anti-HBs while retaining anti-HBc activity.

Cohort study of human immunodeficiency virus (HIV) antibody testing among patients receiving long-term dialysis at a university hospital.

In a longitudinal study to determine the seroprevalence of antibody to the human immunodeficiency virus (HIV) and the natural history of a positive enzyme immunoassay (EIA) result we followed a cohort of 98 patients receiving long-term dialysis. Eight patients (8.2%) in the cohort had a positive EIA and a negative Western blot test result. The EIA-positive results of all patients seroconverted to negative during follow-up. No illness suggestive of HIV infection developed in any of the patients. Significantly associated with a false positive EIA were prior renal transplantation, transfusions during the months just before the positive EIA result, and a greater number of lifetime transfusions before the positive test result. We confirm that routine HIV screening of patients receiving long-term dialysis is associated with a high rate of false positive EIA results and conclude that such testing is unnecessary in the absence of established risk factors for HIV infection.

Lymphocyte subsets in normal airway mucosa of the human nose.

The distribution and number of lymphocytes, monocytes/macrophages, and cells expressing HLA-DR antigen were studied in frozen biopsy sections of nasal mucosa from 40 healthy adults, using monoclonal antibody avidin-biotin immunoperoxidase techniques. The lymphocyte to monocyte/macrophage ratio was estimated to be 10:1; the T cell to B cell ratio was 3:1; and the T helper/inducer cell to T suppressor/cytotoxic cell ratio averaged 2.5:1. Regional differences were observed with a relatively increased number of T suppressor/cytotoxic cells around submucosal glands, and a relatively large number of B cells in lymphocyte aggregates in the lamina propria. The HLA-DR antigen was expressed in epithelial cells, suggesting involvement of surface epithelium of human airway in local immune responses.

SoC CMOS UWB Pulse Radar Sensor for Contactless Respiratory Rate Monitoring.

An ultra wideband (UWB) system-on-chip radar sensor for respiratory rate monitoring has been realized in 90 nm CMOS technology and characterized experimentally. The radar testchip has been applied to the contactless detection of the respiration activity of adult and baby. The field operational tests demonstrate that the UWB radar sensor detects the respiratory rate of person under test (adult and baby) associated with sub-centimeter chest movements, allowing the continuous-time non-invasive monitoring of hospital patients and other people at risk of obstructive apneas such as babies in cot beds, or other respiratory diseases.

Wearable system-on-a-chip UWB radar for contact-less cardiopulmonary monitoring: present status.

The present status of the project aimed at the realization of an innovative wearable system-on-chip UWB radar for the cardiopulmonary monitoring is presented. The overall system consists of a wearable wireless interface including a fully integrated UWB radar for the detection of the heart beat and breath rates, and a IEEE 802.15.4 ZigBee low-power radio interface. The principle of operation of the UWB radar for the monitoring of the heart wall is summarized. With respect to the prior art, this paper reports the results of the experimental characterization of the intra-body channel loss, which has been carried out successfully in order to validate the theoretical model employed for the radar system analysis. Moreover, the main building blocks of the radar have been manufactured in 90 nm CMOS technology by ST-Microelectronics and the relevant performance are resulted in excellent agreement with those expected by post-layout simulations.

Wearable microwave radiometers for remote fire detection: System-on-Chip (SoC) design and proof of the concept.

The paper reports the present status of the project aimed at the realization of a wearable low-cost low-power System-on-Chip (SoC) 13-GHz passive microwave radiometer in CMOS 90 nm technology. This sensor has been thought to be inserted into the firemen jacket in order to help them in the detection of a hidden fire behind a door or a wall, especially where the IR technology fail. With respect of the prior art, the SoC is further developed and a proof of the concept is provided by means of a discrete-component prototype.

Wearable system-on-a-chip radiometer for remote temperature sensing and its application to the safeguard of emergency operators.

The remote sensing and the detection of events that may represent a danger for human beings have become more and more important thanks to the latest advances of the technology. A microwave radiometer is a sensor capable to detect a fire or an abnormal increase of the internal temperature of the human body (hyperthermia), or an onset of a cancer, or even meteorological phenomena (forest fires, pollution release, ice formation on road pavement). In this paper, the overview of a wearable low-cost low-power system-on-a-chip (SoaC) 13 GHz passive microwave radiometer in CMOS 90 nm technology is presented. In particular, we focused on its application to the fire detection for civil safeguard. In detail, this sensor has been thought to be inserted into the fireman jacket in order to help the fireman in the detection of a hidden fire behind a door or a wall. The simulation results obtained by Ptolemy system simulation have confirmed the feasibility of such a SoaC microwave radiometer in a low-cost standard silicon technology for temperature remote sensing and, in particular, for its application to the safeguard of emergency operators.

Effects of pyridoxine on hepatic tryptophan pyrrolase activity in rat during chronic ethanol administration.

Tryptophan pyrrolase activity has been assayed in crude liver homogenates prepared from rats submitted to chronic ethanol treatment. The results show that chronic ethanol treatment causes a marked reduction in the apoenzyme form of tryptophan pyrrolase. This reduction can be reversed by administration pyridoxine hydrochloride (100 mg/kg i.p. pro die for 8 days). Since chronic ethanol treatment increases cellular levels of NADH and NADPH which are known to inhibit tryptophan pyrrolase activity, it is suggested that the potentiating effect of pyridoxine might be due to the maintenance of normal ratios of cellular NAD+/NADH and BADP+/NADPH. In ethanol treated rats, pyridoxine was as effective as fructose, a regenerator of NAD+ and NADP+ in maintaining control levels of the apo-[tryptophan pyrrolase].