P53 family members regulate the Otx1 gene expression in differentiation of breast cancer stem cells and in mammary gland development.

Tp53, Tp63 and Tp73 family members encode for transcription factors which play a key role in control of the genome integrity inducing cell-cycle arrest, senescence, apoptosis or cell differentiation. They take a part in cell stress response and in tumor suppression (De Young MP and Ellisen LW, 2007). Wild type p53 protein is a growth modulator and its inactivation is a critical event in malignant transformation (Gasco M, 2002). It has been recently demonstrated that p53 has developmental and differentiation functions (Hu W, 2008). Indeed an over-expression of p53 in tumor cells induces asymmetrical division avoiding a self-renewal of cancer stem cells (CSCs) and promoting their differentiation (Cicalese A, 2009). In this study 43 human ductal and lobular invasive breast carcinomas have been analyzed for the expression of p53, p63, p73 and a pool of non-clustered homeobox genes. The homeogenes play a crucial role in embryogenesis, regulating cell differentiation and proliferation (Pagani IS, 2010). They are expressed in adult mammary gland and when deregulated, are involved in breast cancer (Lewis MT, 2000). We demonstrated that the Otx1 homeogene is transcribed in breast cancer, in CSCs differentiation and in adult mammary gland development. We established that the p53 and p73 proteins directly induce the Otx1 expression by acting on its promoter. Otx1 has been described as a critical molecule for axon refinement in corticogenesis (Zhang YA, 2002), and its activity in breast cancer suggests a synergistic function with p53 and p73 in CSCs differentiation. In adult mammary gland development the Otx1 expression is not regulated by p53, but is correlated with the expression of Tp73 in lactation and in regression. This suggests that in physiological conditions Otx1 is regulated by p73, while in the tumors p53 regulates its expression

P53 family members regulate the Otx1 gene expression in differentiation of breast cancer stem cells and in mammary gland development.

Tp53, Tp63 and Tp73 family members encode for transcription factors which play a key role in control of the genome integrity inducing cell-cycle arrest, senescence, apoptosis or cell differentiation. They take a part in cell stress response and in tumor suppression (De Young MP and Ellisen LW, 2007). Wild type p53 protein is a growth modulator and its inactivation is a critical event in malignant transformation (Gasco M, 2002). It has been recently demonstrated that p53 has developmental and differentiation functions (Hu W, 2008). Indeed an over-expression of p53 in tumor cells induces asymmetrical division avoiding a self-renewal of cancer stem cells (CSCs) and promoting their differentiation (Cicalese A, 2009). In this study 43 human ductal and lobular invasive breast carcinomas have been analyzed for the expression of p53, p63, p73 and a pool of non-clustered homeobox genes. The homeogenes play a crucial role in embryogenesis, regulating cell differentiation and proliferation (Pagani IS, 2010). They are expressed in adult mammary gland and when deregulated, are involved in breast cancer (Lewis MT, 2000). We demonstrated that the Otx1 homeogene is transcribed in breast cancer, in CSCs differentiation and in adult mammary gland development. We established that the p53 and p73 proteins directly induce the Otx1 expression by acting on its promoter. Otx1 has been described as a critical molecule for axon refinement in corticogenesis (Zhang YA, 2002), and its activity in breast cancer suggests a synergistic function with p53 and p73 in CSCs differentiation. In adult mammary gland development the Otx1 expression is not regulated by p53, but is correlated with the expression of Tp73 in lactation and in regression. This suggests that in physiological conditions Otx1 is regulated by p73, while in the tumors p53 regulates its expression

A catalogue of nuclear stellar velocity dispersions of nearby galaxies from \u2009H\u3b1 STIS spectra to constrain supermassive black hole masses

We present new measurements for the nuclear stellar velocity dispersion \u3c3* within sub-arcsecond apertures for 28 nearby galaxies. Our data consist of Space Telescope Imaging Spectrograph (STIS) long-slit spectra obtained with the G750M grating centred on the H\u3b1 spectral range. We fit the spectra using a library of single stellar population models and Gaussian emission lines, while constraining in most cases the stellar-population content from an initial fit to G430L STIS spectra. We illustrate how these \u3c3* measurements can be useful for constraining the mass M\u2022 of supermassive black holes (SBHs) by concentrating on the cases of the lenticular galaxies NGC 4435 and NGC 4459. These are characterized by similar ground-based half-light radii stellar velocity dispersion \u3c3e values but remarkably different M\u2022 as obtained from modelling their central ionized-gas kinematics, where NGC 4435 appears to host a significantly undermassive SBH compared to what is expected from the M\u2022 - \u3c3e relation. For both galaxies, we build Jeans axisymmetric dynamical models to match the ground-based stellar kinematics obtained with Spectrographic Areal Unit for Research on Optical Nebulae integral-field spectrograph, including an SBH with M\u2022 value as predicted by the M\u2022 - \u3c3e relation and using high-resolution HST images taken with the Advanced Camera for Surveys to construct the stellar-mass model. By mimicking the HST observing conditions we use such reference models to make a prediction for the nuclear \u3c3* value. Whereas this was found to agree with our nuclear \u3c3* measurement for NGC 4459, for NGC 4435 the observed \u3c3* is remarkably smaller than the predicted one, which further suggests that this galaxy could host an undermassive SBH

Interpretation of CPTu in “unusual” soils

The paper deals with the interpretation of CPTu in unusual soils, such as shallow clayey layers above the water table and loose, intermediate - permeability soils (loose silt mixtures). The paper shows an approach that could be used for the first type of soil to infer the effective vertical stress from CPTu measurements and in particular from the Ic index. The approach has been checked on a very limited amount of experimental evidence. Moreover, an empirical correction of the Ic index is provided in order to obtain a more realistic soil profiling of loose silt mixtures. The foundation soils of the Serchio River levee system and some dredged sediments, which had been stored in the Port of Livorno, have been considered for the second type of soil

Occurrence of two Norovirus outbreaks in the same cafeteria in one week

In October 2017, two outbreaks of gastroenteritis (GE) occurred among patrons of a cafeteria in Italy in one week. Virological and bacteria investigations on stool samples, environment and food were conducted to identify the infectious agents and the possible source of infection. Forty-five cases occurred in the two outbreaks, including 13 laboratory-confirmed cases of norovirus GI. Nine staff members were interviewed, six were confirmed positive for NoV GI and 3 experienced GE symptoms. Bacteria faecal indicators and other bacteria pathogens were not detected in either environmental swab samples or food. A low level of NoV GII was detected in two environmental swab samples. The same GI.6 strain was identified in cases related to both outbreaks, suggesting a common source of infection. Since the two outbreaks occurred in one week, the NoV contamination could have persisted in the cafeteria. Furthermore, virological investigation revealed confirmed cases among food handlers who had worked at the cafeteria between and during the two outbreaks. Several studies highlighted the importance of excluding symptomatic food handlers to prevent contamination of foods and environment

Long-lasting responses with chemotherapy followed by T-cell therapy in recurrent or metastatic EBV-related nasopharyngeal carcinoma

BackgroundRefractory or metastatic nasopharyngeal carcinoma (NPC) patients have a poor prognosis due to the lack of effective salvage treatments and prolonged survival by means of combination chemotherapy being described only for a minority of younger patients with oligometastatic disease. Targeting the Epstein - Barr virus (EBV) proteins expressed in NPC cells has been shown to be a feasible strategy that could help control systemic disease.Patients and MethodsBetween 2011 and 2014, 16 patients with recurrent/metastatic EBV-NPC received first-line chemotherapy (CT) followed by 2 doses of autologous cytotoxic EBV specific T-lymphocytes (15-25 x 107 total cells/dose, 2 weeks apart), based on our previous studies showing the feasibility and efficacy of this infusion regimen. Cumulative overall survival (OS) and median OS were analysed in the whole population and according to specific clinical and biological parameters.ResultsAll patients received the planned T-cell therapy schedule, 9 after reaching partial (n=5) or complete (n=4) disease remission with CT, and 7 after failing to obtain benefit from chemotherapy. No severe adverse events were recorded. Patients who received cytotoxic T-lymphocytes (CTLs) had a cumulative 10-year OS of 44%, with a median OS of 60 months (95% CI 42-62). Patients responding to CT, with oligometastatic disease (<3 disease sites), and plasma EBV-DNA <1000 copies/mL had a better outcome.ConclusionsAutologous EBV-specific CTLs transplanted following conventional first-line CT demonstrated promising efficacy with several patients obtaining long-lasting disease control. The rationale provided by this study, with the crucial role likely played by the timing of CTL administration when trying to induce synergy with conventional treatment needs to be confirmed in a prospective controlled trial

Gaia Early Data Release 3: Structure and properties of the Magellanic Clouds

We compare the Gaia DR2 and Gaia EDR3 performances in the study of the Magellanic Clouds and show the clear improvements in precision and accuracy in the new release. We also show that the systematics still present in the data make the determination of the 3D geometry of the LMC a difficult endeavour; this is at the very limit of the usefulness of the Gaia EDR3 astrometry, but it may become feasible with the use of additional external data. We derive radial and tangential velocity maps and global profiles for the LMC for the several subsamples we defined. To our knowledge, this is the first time that the two planar components of the ordered and random motions are derived for multiple stellar evolutionary phases in a galactic disc outside the Milky Way, showing the differences between younger and older phases. We also analyse the spatial structure and motions in the central region, the bar, and the disc, providing new insights into features and kinematics. Finally, we show that the Gaia EDR3 data allows clearly resolving the Magellanic Bridge, and we trace the density and velocity flow of the stars from the SMC towards the LMC not only globally, but also separately for young and evolved populations. This allows us to confirm an evolved population in the Bridge that is slightly shift from the younger population. Additionally, we were able to study the outskirts of both Magellanic Clouds, in which we detected some well-known features and indications of new ones

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

The Gaia mission

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page. http://www.cosmos.esa.int/gai

P53 family members regulate the Otx1 gene expression in differentiation of breast cancer stem cells and in mammary gland development.

Tp53, Tp63 and Tp73 family members encode for transcription factors which play a key role in control of the genome integrity inducing cell-cycle arrest, senescence, apoptosis or cell differentiation. They take a part in cell stress response and in tumor suppression (De Young MP and Ellisen LW, 2007). Wild type p53 protein is a growth modulator and its inactivation is a critical event in malignant transformation (Gasco M, 2002). It has been recently demonstrated that p53 has developmental and differentiation functions (Hu W, 2008). Indeed an over-expression of p53 in tumor cells induces asymmetrical division avoiding a self-renewal of cancer stem cells (CSCs) and promoting their differentiation (Cicalese A, 2009). In this study 43 human ductal and lobular invasive breast carcinomas have been analyzed for the expression of p53, p63, p73 and a pool of non-clustered homeobox genes. The homeogenes play a crucial role in embryogenesis, regulating cell differentiation and proliferation (Pagani IS, 2010). They are expressed in adult mammary gland and when deregulated, are involved in breast cancer (Lewis MT, 2000). We demonstrated that the Otx1 homeogene is transcribed in breast cancer, in CSCs differentiation and in adult mammary gland development. We established that the p53 and p73 proteins directly induce the Otx1 expression by acting on its promoter. Otx1 has been described as a critical molecule for axon refinement in corticogenesis (Zhang YA, 2002), and its activity in breast cancer suggests a synergistic function with p53 and p73 in CSCs differentiation. In adult mammary gland development the Otx1 expression is not regulated by p53, but is correlated with the expression of Tp73 in lactation and in regression. This suggests that in physiological conditions Otx1 is regulated by p73, while in the tumors p53 regulates its expression