An In Vivo Screen Identifies PYGO2 as a Driver for Metastatic Prostate Cancer

Advanced prostate cancer displays conspicuous chromosomal instability and rampant copy number aberrations, yet the identity of functional drivers resident in many amplicons remain elusive. Here, we implemented a functional genomics approach to identify new oncogenes involved in prostate cancer progression. Through integrated analyses of focal amplicons in large prostate cancer genomic and transcriptomic datasets as well as genes upregulated in metastasis, 276 putative oncogenes were enlisted into an in vivo gain-of-function tumorigenesis screen. Among the top positive hits, we conducted an in-depth functional analysis on Pygopus family PHD finger 2 (PYGO2), located in the amplicon at 1q21.3. PYGO2 overexpression enhances primary tumor growth and local invasion to draining lymph nodes. Conversely, PYGO2 depletion inhibits prostate cancer cell invasion in vitro and progression of primary tumor and metastasis in vivo In clinical samples, PYGO2 upregulation associated with higher Gleason score and metastasis to lymph nodes and bone. Silencing PYGO2 expression in patient-derived xenograft models impairs tumor progression. Finally, PYGO2 is necessary to enhance the transcriptional activation in response to ligand-induced Wnt/β-catenin signaling. Together, our results indicate that PYGO2 functions as a driver oncogene in the 1q21.3 amplicon and may serve as a potential prognostic biomarker and therapeutic target for metastatic prostate cancer.Significance: Amplification/overexpression of PYGO2 may serve as a biomarker for prostate cancer progression and metastasis. Cancer Res; 78(14); 3823-33. ©2018 AACR

An analysis of the most distant catalogued open clusters -- Re-assessing fundamental parameters with Gaia EDR3 and ASteCA\texttt{ASteCA}

Several studies have been presented in the last few years applying some kind of automatic processing of data to estimate the fundamental parameters of open clusters. These parameters are later on employed in larger scale analyses, for example the structure of the Galaxy's spiral arms. The distance is one of the more straightforward parameters to estimate, yet enormous differences can still be found among published data. This is particularly true for open clusters located more than a few kpc away. We cross-matched several published catalogues and selected the twenty-five most distant open clusters ($>$9000 pc). We then performed a detailed analysis of their fundamental parameters, with emphasis on their distances, to determine the agreement between catalogues and our estimates.} Photometric and astrometric data from the Gaia EDR3 survey was employed. The data was processed with our own membership analysis code (pyUPMASK), and our package for automatic fundamental cluster's parameters estimation ($\texttt{ASteCA}$). We find differences in the estimated distances of up to several kpc between our results and those catalogued, even for the catalogues that show the best matches with $\texttt{ASteCA}$ values. Large differences are also found for the age estimates. As a by-product of the analysis we find that vd Bergh-Hagen 176 could be the open cluster with the largest heliocentric distance catalogued to date. Caution is thus strongly recommended when using catalogued parameters of open clusters to infer large-scale properties of the Galaxy, particularly for those located more than a few kpc away.Comment: Accepted for publication in A&

Sphingosine-1-Phosphate in the Tumor Microenvironment: A Signaling Hub Regulating Cancer Hallmarks

As a key hub of malignant properties, the cancer microenvironment plays a crucial role intimately connected to tumor properties. Accumulating evidence supports that the lysophospholipid sphingosine-1-phosphate acts as a key signal in the cancer extracellular milieu. In this review, we have a particular focus on glioblastoma, representative of a highly aggressive and deleterious neoplasm in humans. First, we highlight recent advances and emerging concepts for how tumor cells and different recruited normal cells contribute to the sphingosine-1-phosphate enrichment in the cancer microenvironment. Then, we describe and discuss how sphingosine-1-phosphate signaling contributes to favor cancer hallmarks including enhancement of proliferation, stemness, invasion, death resistance, angiogenesis, immune evasion and, possibly, aberrant metabolism. We also discuss the potential of how sphingosine-1-phosphate control mechanisms are coordinated across distinct cancer microenvironments. Further progress in understanding the role of S1P signaling in cancer will depend crucially on increasing knowledge of its participation in the tumor microenvironment

Nematodes from <i>Achatina fulica</i> Bowdich, 1822 (Mollusca: Gastropoda) in Argentina

The aim of this study is to describe the nematode cysts and larvae found in Achatina fulica, the giant African snail, in the northeast of Argentina. A total of 373 snails were collected from the cities of Puerto Iguazú and Corrientes. Cysts (N= 2958) containing nematodes identified as L3 Strongyluris sp. were found in the mantle cavity of 87 snails from Puerto Iguazú City (Prevalence 23 %; Mean Intensity= 34; Mean Abundance= 8). The shell size correlated with prevalence, mean intensity and mean abundance (p < 0.05) indicating that there is an exposure-infection constant rather than an accidental one. In other hand, the absence of infection in the smallest shell size suggests a threshold of size to be infected. Taking into account that there exist records of A. fulica infected by nematodes of medical and veterinary importance such as Angiostrongylus and Aelurostrongylus in some Brazilian states near Puerto Iguazú, we emphasize the need for snail surveillance.Centro de Estudios Parasitológicos y de Vectore

Nematodes from <i>Achatina fulica</i> Bowdich, 1822 (Mollusca: Gastropoda) in Argentina

The aim of this study is to describe the nematode cysts and larvae found in Achatina fulica, the giant African snail, in the northeast of Argentina. A total of 373 snails were collected from the cities of Puerto Iguazú and Corrientes. Cysts (N= 2958) containing nematodes identified as L3 Strongyluris sp. were found in the mantle cavity of 87 snails from Puerto Iguazú City (Prevalence 23 %; Mean Intensity= 34; Mean Abundance= 8). The shell size correlated with prevalence, mean intensity and mean abundance (p < 0.05) indicating that there is an exposure-infection constant rather than an accidental one. In other hand, the absence of infection in the smallest shell size suggests a threshold of size to be infected. Taking into account that there exist records of A. fulica infected by nematodes of medical and veterinary importance such as Angiostrongylus and Aelurostrongylus in some Brazilian states near Puerto Iguazú, we emphasize the need for snail surveillance.Centro de Estudios Parasitológicos y de Vectore

Nematodes from <i>Achatina fulica</i> Bowdich, 1822 (Mollusca: Gastropoda) in Argentina

The aim of this study is to describe the nematode cysts and larvae found in Achatina fulica, the giant African snail, in the northeast of Argentina. A total of 373 snails were collected from the cities of Puerto Iguazú and Corrientes. Cysts (N= 2958) containing nematodes identified as L3 Strongyluris sp. were found in the mantle cavity of 87 snails from Puerto Iguazú City (Prevalence 23 %; Mean Intensity= 34; Mean Abundance= 8). The shell size correlated with prevalence, mean intensity and mean abundance (p < 0.05) indicating that there is an exposure-infection constant rather than an accidental one. In other hand, the absence of infection in the smallest shell size suggests a threshold of size to be infected. Taking into account that there exist records of A. fulica infected by nematodes of medical and veterinary importance such as Angiostrongylus and Aelurostrongylus in some Brazilian states near Puerto Iguazú, we emphasize the need for snail surveillance.Centro de Estudios Parasitológicos y de Vectore

Evaluación energética de una vivienda del plan Procrear. Primeras propuestas de mejoras

En este trabajo se analizó el comportamiento térmico de una vivienda propuesta por el plan argentino PROCREAR en la ciudad de Rosario con el objetivo de estimar el consumo de energía requerido para brindar confort térmico a sus habitantes. Se modelizó el Prototipo 5 del programa y se implementaron simulaciones sobre su comportamiento térmico en la plataforma de cálculo EnergyPlus. Se analizó la influencia de distintos elementos constructivos de dicha vivienda y se propusieron alternativas destinadas a mejorar la eficiencia energética de la vivienda. Finalmente, se evaluó el aprovechamiento de ventilación natural durante el verano y se cuantificó el ahorro en la demanda energética para climatización producido por las modificaciones implementadas. Se concluyó que la propuesta elegida no resulta apropiada para zonas climáticas con días de elevada temperatura. Las simulaciones permitieron detectar los mayores inconvenientes presentes y delinear modificaciones constructivas apropiadas para adaptar la vivienda al clima de la ciudad

Biomolecular, histological, clinical, and radiological analyses of dental implant bone sites prepared using magnetic mallet technology: A pilot study in animals

Background. A new instrumentation exploiting magneto-dynamic technology (mallet) proposed for implant site preparation was investigated. Methods. In the tibias of three minipigs, two sites were prepared by mallet and two by drill technique. Primary stability (ISQ) was detected after implant positioning (T0) and at 14 days (T14). X-rays and computed tomography were performed. At T14, bone samples were utilized for histological and biomolecular analyses. Results. In mallet sites, histological evaluations evidenced a significant increase in the newly formed bone, osteoblast number, and a smaller quantity of fibrous tissue. These results agree with the significant BMP-4 augmentation and the positive trend in other osteogenic factors (biological and radiological investigations). Major, albeit IL-10-controlled, inflammation was present. For both techniques, at T14 a significant ISQ increase was evidenced, but no significant difference was observed at T0 and T14 between the mallet and drill techniques. In mallet sites, lateral bone condensation was observed on computed tomography. Conclusions. Using biological, histological, clinical, and radiological analyses, this study first shows that the mallet technique is effective for implant site preparation. Based on its ability to cause osseocondensation and improve newly formed bone, mallet technology should be chosen in all clinical cases of poor bone quality