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The JAK-STAT pathway has a substantial role in lymphoid precursor cell proliferation, survival and differentiation. Nonetheless, the contribution of JAK2 to T-cell lymphoblastic lymphoma (T-LBL) development remains poorly understood. We have identified one activating TEL-JAK2 translocation and four missense mutations accumulated in 2 out of 16 T-LBL samples. Two of them are novel JAK2 mutations and the other two are reported for the first time in T-LBL. Notably, R683G and I682T might have arisen owing to RNA editing. Mutated samples showed different mutated transcripts suggesting sub-clonal heterogeneity. Functional approaches revealed that two JAK2 mutations (H574R and R683G) constitutively activate JAK-STAT signaling in ¿2A cells and can drive the proliferation of BaF3-EpoR cytokine-dependent cell line. In addition, aberrant hypermethylation of SOCS3 might contribute to enhance the activation of JAK-STAT signaling. Of utmost interest is that primary T-LBL samples harboring JAK2 mutations exhibited increased expression of LMO2, suggesting a mechanistic link between JAK2 mutations and the expression of LMO2, which was confirmed for the four missense mutations in transfected ¿2A cells. We therefore propose that active JAK2 contribute to T-LBL development by two different mechanisms, and that the use of pan-JAK inhibitors in combination with epigenetic drugs should be considered in future treatments. ; Spanish Ministry of Economy and Competitiveness (SAF2012-36566), Madrid Regional Government (Oncocycle S2011/BMD-2470), Instituto de Salud Carlos III (ACCI-CIBERER-16); financial support to MAP: RTICC SAF2008-03871 (MINECO). Spanish Association Against Cancer (AECC). ; Peer Reviewed

et al. ; [Background]: Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different cancer models. However, the biological role of these receptors in tumor physio-pathology is still unknown. [Methods]: We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen, and Freiburg between 1997 and 2010 and CB2 mRNA expression in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the human V-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog 2 (HER2) rat ortholog (neu) and lacks CB2 and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by colocalization, coimmunoprecipitation, and proximity ligation assays. Statistical tests were two-sided. [Results]: We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis (decreased overall survival, hazard ratio [HR] = 0.29, 95% confidence interval [CI] = 0.09 to 0.71, P = .009) and higher probability to suffer local recurrence (HR = 0.09, 95% CI = 0.049 to 0.54, P = .003) and to develop distant metastases (HR = 0.33, 95% CI = 0.13 to 0.75, P = .009). We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade and that an increased CB2 expression activates the HER2 pro-oncogenic signaling at the level of the tyrosine kinase c-SRC. Finally, we show HER2 and CB2 form heteromers in cancer cells. [Conclusions]: Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and they suggest that CB2 may be a biomarker with prognostic value in these tumors. ; This work was supported by grants from Spanish Ministry of Economy and Competitiveness (PI11/00295 and PI14/01101, supported with European Regional Development (FEDER) funds, to CS, SAF2012-36566 to JFP, SAF2010-22198 to SOG, and Ramón y Cajal fellowship to PJM); GW Pharmaceuticals (to CS); Madrid Regional Government (S2010/BMD-2308 to MG, S2010/BMD-2353 to SOG and S2011/BMD-2470 to JFP); Fundación Mutua Madrileña; Sandra Ibarra Foundation; and Instituto de Salud Carlos III (CIBERER-3–749/172.03 and ACCI-CIBERER-16 to JFP). EPG and EMV are recipients of Postdoctoral Research Contracts from Fundación Científica Asociación Española Contra el Cáncer. MA is a recipient of a Formación de Profesorado Universitario (FPU) fellowship (from the Spanish Ministry of Economy and Competitiveness), and EPG was a recipient of a Federation of the Societies of Biochemistry and Molecular Biology (FEBS) Short-term Fellowship. ; Peer Reviewed

Since 2006, our research team has been establishing in the islands of Livingston and Deception, (South Shetland archipelago, Antarctica) several monitoring stations of the active layer thickness within the international network Circumpolar Active Layer Monitoring (CALM), and the ground thermal regime for the Ground Terrestrial Network-Permafrost (GTN-P). Both networks were developed within the International Permafrost Association (IPA). In the GTN-P stations, in addition to the temperature of the air, soil, and terrain at different depths, the snow thickness is also monitored by snow poles. Since 2006, a delay in the disappearance of the snow layer has been observed, which could explain the variations we observed in the active layer thickness and permafrost temperatures. Therefore, in late 2015 our research group started the PERMASNOW project (2015-2019) to pay attention to the effect of snow cover on ground thermal This project had two different ways to study the snow cover. On the first hand, in early 2017 we deployed new instrumentation, including new time lapse cameras, snow poles with high number of sensors and a complete and complex set of instruments and sensors to configure a snow pack analyzer station providing 32 environmental and snow parameters. We used the data acquired along 2017 and 2018 years with the new instruments, together with the available from all our already existing sensors, to study in detail the snow cover. On the other hand, remote sensing data were used to try to map the snow cover, not only at our monitoring stations but the entire islands in order to map and study the snow cover distribution, as well as to start the way for future permafrost mapping in the entire islands. MODIS-derived surface temperatures and albedo products were used to detect the snow cover and to test the surface temperature. Since cloud presence limited the acquisition of valid observations of MODIS sensor, we also analyzed Terrasar X data to over-come this limitation. Remote sensing data validation required the acquirement of in situ ground-true data, consisting on data from our permanent instruments, as well as ad hoc measurements in the field (snow cover mapping, snow pits, albedo characterization, etc.). Although the project is finished, the data analysis is still ongoing. We present here the different research tasks we are developing as well as the most important results we already obtained about the snow cover. These results confirm how the snow cover duration has been changing in the last years, affecting the ground thermal behavior. ; With funding from the Spanish government through the "María de Maeztu Unit of Excellence" accreditation (MDM-2017-0737)

This article does a historical review of local governments in Argentina and how they work in reallife today; it recovers the local political actors' debate and the roles of the mid XIX Century, bringing local governments' related questions to federalism, categories and roles. ; Este trabajo aborda la configuración histórica del régimen municipal en Argentina y su funcionamiento actual. Para ello se retoma el debate de los principales actores políticos de mediados del siglo XIX sobre el papel que consideraban debía tener. Para su vigencia se aborda al municipio con relación al federalismo, así como las categorías y competencias que éste desempeña.

The process of transformation of the Province of Chacabuco throughout its history according to historical, cartographic and testimonial background, constitutes the central objective in this writing. The facts that describe the process of territorial occupation and the different forms it has taken over time identifying five settlement impulses that are related to the structures that were formed in the territory, with the objective of understanding in detail the occupation of the territory and explaining the causes that impulse it. Since the 17th century, the territory of Chacabuco had scattered human settlements and a countryside organized under the hacienda system for agricultural and livestock use, with a small population around the houses, which after the appearance of the Santiago- Valparaíso railroad generated an agglomeration of dwellings around the stations. From the seventeenth century until the first half of the twentieth century, the territory lacked housing and was mainly devoted to livestock, agriculture or remained unused. However, in the second half of the 20th century, the settlement had an explosive development, linked to urban expansion processes of the city of Santiago, the main metropolis of the country.

Financial support to JFP: grants from Spanish Ministry of Economy and Competitiveness (SAF2012-36566), Madrid Regional Government (Oncocycle S2011/BMD-2470), Instituto de Salud Carlos III (ACCI-CIBERER-16); financial support to MAP: RTICC SAF2008-03871 (MINECO). Spanish Association Against Cancer (AECC).

The scientific community has made great efforts in advancing magnetic hyperthermia for the last two decades after going through a sizeable research lapse from its establishment. All the progress made in various topics ranging from nanoparticle synthesis to biocompatibilization and in vivo testing have been seeking to push the forefront towards some new clinical trials. As many, they did not go at the expected pace. Today, fruitful international cooperation and the wisdom gain after a careful analysis of the lessons learned from seminal clinical trials allow us to have a future with better guarantees for a more definitive takeoff of this genuine nanotherapy against cancer. Deliberately giving prominence to a number of critical aspects, this opinion review offers a blend of state-of-the-art hints and glimpses into the future of the therapy, considering the expected evolution of science and technology behind magnetic hyperthermia. ; This work was supported by the NoCanTher project, which has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 685795. The authors acknowledge support from the COST Association through the COST actions "RADIOMAG" (TD1402) and "MyWAVE" (CA17115). D.O., A.S.-O. and I.R.-R. acknowledge financial support from the Community of Madrid under Contracts No. PEJD-2017-PRE/IND-3663 and PEJ-2018-AI/IND-11069, from the Spanish Ministry of Science through the Ramon y Cajal grant RYC2018-025253-I and Research Networks RED2018-102626-T, as well as the Ministry of Economy and Competitiveness through the grants MAT2017-85617-R, MAT2017-88148R and the "Severo Ochoa" Program for Centers of Excellence in R&D (SEV-2016-0686). M.B. and N.T.K.T. would like to thank EPSRC for funding (grant EP/K038656/1 and EP/M015157/1) and AOARD (FA2386-171-4042) award. This work was additionally supported by the EMPIR program co-financed by the Participating States and from the European Union's Horizon 2020 research and innovation program, grant no. 16NRM04 "MagNaStand". The work was further supported by the DFG grant CRC "Matrix in Vision" (SFB 1340/1 2018, no 372486779, project A02).