Prostatectomia com anastomose de uretra para o tratamento de adenocarcinoma prostático

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Coordination of myeloid differentiation with reduced cell cycle progression by PU.1 Induction of microRNAs targeting cell cycle regulators and lipid anabolism

During macrophage development, myeloid progenitor cells undergo terminal differentiation coordinated with reduced cell cycle progression. Differentiation of macrophages from myeloid progenitors is accompanied by increased expression of the E26 transformation-specific transcription factor PU.1. Reduced PU.1 expression leads to increased proliferation and impaired differentiation of myeloid progenitor cells. It is not understood how PU.1 coordinates macrophage differentiation with reduced cell cycle progression. In this study, we utilized cultured PU.1- inducible myeloid cells to perform genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) analysis coupled with gene expression analysis to determine targets of PU.1 that may be involved in regulating cell cycle progression. We found that genes encoding cell cycle regulators and enzymes involved in lipid anabolism were directly and inducibly bound by PU.1 although their steady-state mRNA transcript levels were reduced. Inhibition of lipid anabolism was sufficient to reduce cell cycle progression in these cells. Induction of PU.1 reduced expression of E2f1, an important activator of genes involved in cell cycle and lipid anabolism, indirectly through microRNA 223. Next-generation sequencing identified microRNAs validated as targeting cell cycle and lipid anabolism for downregulation. These results suggest that PU.1 coordinates cell cycle progression with differentiation through induction of microRNAs targeting cell cycle regulators and lipid anabolism

Phosphorylation of zinc channel ZIP7 drives MAPK, PI3K and mTOR growth and proliferation signalling

Zinc is an essential trace element participating in diverse biological processes. Cellular zinc levels are strictly controlled by two families of transport proteins: ZIP channels (SLC39A) and ZnT transporters (SLC30A). ZIP channels increase cytosolic zinc levels by importing zinc into cells or releasing zinc from intracellular stores such as the ER. Among all the 14 human members of the ZIP family, ZIP7 is a gatekeeper of zinc release from intracellular stores, requiring post-translational activation by phosphorylation on residues S275 and S276, resulting in activation of multiple downstream pathways. Employing site-directed mutagenesis, we investigated the importance of these individual serine residues as well as other predicted phosphorylation sites on ZIP7, showing that all four sites are required for maximal ZIP7 activation. Using phosphor-protein arrays, we also discovered the major signalling pathways that were activated as a direct result of ZIP7-mediated zinc release from intracellular stores. These data reveal the role of ZIP7-mediated zinc release from intracellular stores in driving major pathways, such as MAPK, mTOR and PI3K-AKT, involved in providing cell survival and proliferation and often over activated in cancer

Multiple Stellar Populations in Metal-Poor Globular Clusters with JWST: a NIRCam view of M 92

Recent work on metal-intermediate globular clusters (GCs) with [Fe/H]=$-1.5$ and $-0.75$ has illustrated the theoretical behavior of multiple populations in photometric diagrams obtained with the James Webb Space Telescope (JWST). These results are confirmed by observations of multiple populations among M-dwarfs of 47 Tucanae. Here, we explore the multiple populations in metal-poor GCs with [Fe/H]=$-$2.3. We take advantage of synthetic spectra and isochrones that account for the chemical composition of multiple populations to identify photometric diagrams that separate the distinct stellar populations of GCs. We derived high-precision photometry and proper motion for main-sequence stars in the metal-poor GC M 92 from JWST and Hubble Space Telescope (HST) images. We identified a first generation (1G) and two main groups of second-generation stars (2G$_{\rm A}$ and 2G$_{\rm B}$) and investigated their kinematics and chemical composition. We find isotropic motions with no differences among the distinct populations. The comparison between the observed colors of M 92 stars and the colors derived by synthetic spectra reveals that helium abundance of 2G$_{\rm A}$ and 2G$_{\rm B}$ stars are higher than that of the 1G by $\Delta Y \sim 0.01$ and $0.04$, respectively. The $m_{\rm F090W}$ vs. $m_{\rm F090W}-m_{\rm F277W}$ color-magnitude diagram shows that below the knee, MS stars exhibit a wide color broadening due to multiple populations. We constrain the amount of oxygen variation needed to reproduce the observed MS width, which is consistent with results on red-giant branch stars. We conclude that multiple populations with masses of $\sim$0.1-0.8$M_{\odot}$ share similar chemical compositions.Comment: 15 pages, 9 figures. Submitted to ApJ on April 6th, 202

Hubble Space Telescope survey of Magellanic Cloud star clusters. Photometry and astrometry of 113 clusters and early results

In the past years, we have undertaken an extensive investigation of LMC and SMC star clusters based on HST data. We present photometry and astrometry of stars in 101 fields observed with the WFC/ACS, UVIS/WFC3 and NIR/WFC3 cameras. These fields comprise 113 star clusters. We provide differential-reddening maps and illustrate various scientific outcomes that arise from the early inspection of the photometric catalogs. In particular, we provide new insights on the extended main-sequence turn-off (eMSTO) phenomenon: i) We detected eMSTOs in two clusters, KMHK361 and NGC265, which had no previous evidence of multiple populations. This finding corroborates the conclusion that the eMSTO is a widespread phenomenon among clusters younger than ~2 Gyr. ii) The homogeneous color-magnitude diagrams (CMDs) of 19 LMC clusters reveal that the distribution of stars along the eMSTO depends on cluster age. iii) We discovered a new feature along the eMSTO of NGC1783, which consists of a distinct group of stars going on the red side of the eMSTO in CMDs composed of ultraviolet filters. Furthermore, we derived the proper motions of stars in the fields of view of clusters with multi-epoch images. Proper motions allowed us to separate the bulk of bright field stars from cluster members and investigate the internal kinematics of stellar populations in various LMC and SMC fields. As an example, we analyze the field around NGC346 to disentangle the motions of its stellar populations, including NGC364 and BS90, young and pre-MS stars in the star-forming region associated with NGC346, and young and old field stellar populations of the SMC. Based on these results and the fields around five additional clusters, we find that young SMC stars exhibit elongated proper-motion distributions that point toward the LMC, thus bringing new evidence for a kinematic connection between the LMC and SMC.Comment: 37 pages, 27 figures, accepted for publication in Astronomy & Astrophysic

Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study

Purpose: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). Methods: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). Results: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. Conclusions: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT

Chemopreventive potential of β-Sitosterol in experimental colon cancer model - an In vitro and In vivo study

<p>Abstract</p> <p>Background</p> <p><it>Asclepias curassavica </it>Linn. is a traditional medicinal plant used by tribal people in the western ghats, India, to treat piles, gonorrhoea, roundworm infestation and abdominal tumours. We have determined the protective effect of β-sitosterol isolated from <it>A. curassavica </it>in colon cancer, using <it>in vitro </it>and <it>in vivo </it>models.</p> <p>Methods</p> <p>The active molecule was isolated, based upon bioassay guided fractionation, and identified as β-sitosterol on spectral evidence. The ability to induce apoptosis was determined by its <it>in vitro </it>antiradical activity, cytotoxic studies using human colon adenocarcinoma and normal monkey kidney cell lines, and the expression of β-catenin and proliferating cell nuclear antigen (PCNA) in human colon cancer cell lines (COLO 320 DM). The chemopreventive potential of β-sitosterol in colon carcinogenesis was assessed by injecting 1,2-dimethylhydrazine (DMH, 20 mg/kg b.w.) into male Wistar rats and supplementing this with β-sitosterol throughout the experimental period of 16 weeks at 5, 10, and 20 mg/kg b.w.</p> <p>Results</p> <p>β-sitosterol induced significant dose-dependent growth inhibition of COLO 320 DM cells (IC₅₀266.2 μM), induced apoptosis by scavenging reactive oxygen species, and suppressed the expression of β-catenin and PCNA antigens in human colon cancer cells. β-sitosterol supplementation reduced the number of aberrant crypt and crypt multiplicity in DMH-initiated rats in a dose-dependent manner with no toxic effects.</p> <p>Conclusion</p> <p>We found doses of 10-20 mg/kg b.w. β-sitosterol to be effective for future <it>in vivo </it>studies. β-sitosterol had chemopreventive potential by virtue of its radical quenching ability <it>in vitro</it>, with minimal toxicity to normal cells. It also attenuated β-catenin and PCNA expression, making it a potential anticancer drug for colon carcinogenesis.</p

Expression of auxin-binding protein1 during plum fruit ontogeny supports the potential role of auxin in initiating and enhancing climacteric ripening

Auxin-binding protein1 (ABP1) is an active element involved in auxin signaling and plays critical roles in auxin-mediated plant development. Here, we report the isolation and characterization of a putative sequence from Prunus salicina L., designated PslABP1. The expected protein exhibits a similar molecular structure to that of well-characterized maize-ABP1; however, PslABP1 displays more sequence polarity in the active-binding site due to substitution of some crucial amino-acid residues predicted to be involved in auxin-binding. Further, PslABP1 expression was assessed throughout fruit ontogeny to determine its role in fruit development. Comparing the expression data with the physiological aspects that characterize fruit-development stages indicates that PslABP1 up-regulation is usually associated with the signature events that are triggered in an auxin-dependent manner such as floral induction, fruit initiation, embryogenesis, and cell division and elongation. However, the diversity in PslABP1 expression profile during the ripening process of early and late plum cultivars seems to be due to the variability of endogenous auxin levels among the two cultivars, which consequently can change the levels of autocatalytic ethylene available for the fruit to co-ordinate ripening. The effect of auxin on stimulating ethylene production and in regulating PslABP1 was investigated. Our data suggest that auxin is involved in the transition of the mature green fruit into the ripening phase and in enhancing the ripening process in both auxin- and ethylene-dependent manners thereafter