Differential role of AHCYL1 gene in tumor plasticity

Malignant reprogramming of cells is responsible for tumor development. During this process stem-like tumor cells that acquired self-renew capacity produce heterogeneity, tumor dissemination, and relapse after cancer therapy. We have previously identified AHCYL1 as a potential regulation target of core transcription factors OCT-4, SOX-2, and NANOG responsible for cell reprogramming. We studied AHCYL1 by analyzing its cellular location and expression levels during cell plasticity events of tumor cells. We used the glioblastoma (GBM) cell line U87 and lung carcinoma (LC) cell line H1299 as in vitro models since brain and lung have the highest Ahcyl1 expression. We cultured these cell lines in a 3D format in DMEM/F12 medium supplied with FGF, EGF, and B27 and compared with 2D format cultured cells with DMEM serum complemented medium. Ahcy1 localization was determined by immunofluorescence assay and cell fractioning followed by western blotting. To generate U87 and H1299 Ahcyl1 knockdown stable lines, three different shRNAs were tested and the expression levels of Ahcyl1 and the core factors were determined by Western blot and RT-qPCR. Stemness potency was evaluated by ELDA assay (extreme limiting dilution analysis). We found that AHCYL1 localizes both in nuclei and cytosol, in addition to a putative processed isoform in nuclei. In 3D cultures, Ahcyl1 expression is differently regulated compared to 2D cultures. Also, in GBM, AHCYL1 expression was significantly increased, in contrast in LC was decreased (p 0.0001 and p 0.05 respectively). In Ahcyl1-depleted LC cells, the core factors expression levels and the stem potency were increased (p 0.05). Altogether, we conclude Ahcyl1 has a key role as a regulator of stem potency and would be dependent on tumor type.Fil: Budnik, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Muñoz Bernart, Melina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Manzi, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Monge, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Espinoza, Joaquin M.. University of Colorado; Estados UnidosFil: Mostoslavsky, Gustavo. University Of Boston. School Of Medicine. Center For Regenerative Medicine.; Estados UnidosFil: Perez Castro, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimental; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas y VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de NanomedicinasAsociación Argentina de Ciencia y Tecnología de Animales de LaboratorioThe Histochemical Societ

S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) inhibits lung cancer tumorigenesis by regulating cell plasticity

Background: Lung cancer is one of the most frequently diagnosed cancers characterized by high mortality, metastatic potential, and recurrence. Deregulated gene expression of lung cancer, likewise in many other solid tumors, accounts for their cell heterogeneity and plasticity. S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as Inositol triphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT), plays roles in many cellular functions, including autophagy and apoptosis but AHCYL1 role in lung cancer is largely unknown. Results: Here, we analyzed the expression of AHCYL1 in Non-Small Cell Lung Cancer (NSCLC) cells from RNA-seq public data and surgical specimens, which revealed that AHCYL1 expression is downregulated in tumors and inverse correlated to proliferation marker Ki67 and the stemness signature expression. AHCYL1-silenced NSCLC cells showed enhanced stem-like properties in vitro, which correlated with higher expression levels of stem markers POU5F1 and CD133. Also, the lack of AHCYL1 enhanced tumorigenicity and angiogenesis in mouse xenograft models highlighting stemness features. Conclusions: These findings indicate that AHCYL1 is a negative regulator in NSCLC tumorigenesis by modulating cell differentiation state and highlighting AHCYL1 as a potential prognostic biomarker for lung cancer.Fil: Muñoz Bernart, Melina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Budnik, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Castro, Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Manzi, Malena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Monge, Maria Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Pioli, Julieta Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Defranchi, Sebastián. Hospital Universitario de la Fundación Favaloro; ArgentinaFil: Parrilla, Gustavo. Hospital Universitario de la Fundación Favaloro; ArgentinaFil: Santilli, Juan Pablo. Hospital Universitario de la Fundación Favaloro; ArgentinaFil: Davies, Kevin Mauro. Hospital Universitario de la Fundación Favaloro; ArgentinaFil: Espinosa, Joaquin M.. University of Colorado; Estados UnidosFil: Kobayashi, Ken. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Fisiología, Biología Molecular y Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Vigliano, Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Perez Castro, Carolina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentin

Medicinal and ethnoveterinary remedies of hunters in Trinidad

BACKGROUND: Ethnomedicines are used by hunters for themselves and their hunting dogs in Trinidad. Plants are used for snakebites, scorpion stings, for injuries and mange of dogs and to facilitate hunting success. RESULTS: Plants used include Piper hispidum, Pithecelobium unguis-cati, Bauhinia excisa, Bauhinia cumanensis, Cecropia peltata, Aframomum melegueta, Aristolochia rugosa, Aristolochia trilobata, Jatropha curcas, Jatropha gossypifolia, Nicotiana tabacum, Vernonia scorpioides, Petiveria alliacea, Renealmia alpinia, Justicia secunda, Phyllanthus urinaria,Phyllanthus niruri,Momordica charantia, Xiphidium caeruleum, Ottonia ovata, Lepianthes peltata, Capsicum frutescens, Costus scaber, Dendropanax arboreus, Siparuma guianensis, Syngonium podophyllum, Monstera dubia, Solanum species, Eclipta prostrata, Spiranthes acaulis, Croton gossypifolius, Barleria lupulina, Cola nitida, Acrocomia ierensis (tentative ID). CONCLUSION: Plant use is based on odour, and plant morphological characteristics and is embedded in a complex cultural context based on indigenous Amerindian beliefs. It is suggested that the medicinal plants exerted a physiological action on the hunter or his dog. Some of the plants mentioned contain chemicals that may explain the ethnomedicinal and ethnoveterinary use. For instance some of the plants influence the immune system or are effective against internal and external parasites. Plant baths may contribute to the health and well being of the hunting dogs

Global burden of respiratory infections associated with seasonal influenza in children under 5 years in 2018: a systematic review and modelling study

Background: Seasonal influenza virus is a common cause of acute lower respiratory infection (ALRI) in young children. In 2008, we estimated that 20 million influenza-virus-associated ALRI and 1 million influenza-virus-associated severe ALRI occurred in children under 5 years globally. Despite this substantial burden, only a few low-income and middle-income countries have adopted routine influenza vaccination policies for children and, where present, these have achieved only low or unknown levels of vaccine uptake. Moreover, the influenza burden might have changed due to the emergence and circulation of influenza A/H1N1pdm09. We aimed to incorporate new data to update estimates of the global number of cases, hospital admissions, and mortality from influenza-virus-associated respiratory infections in children under 5 years in 2018. Methods: We estimated the regional and global burden of influenza-associated respiratory infections in children under 5 years from a systematic review of 100 studies published between Jan 1, 1995, and Dec 31, 2018, and a further 57 high-quality unpublished studies. We adapted the Newcastle-Ottawa Scale to assess the risk of bias. We estimated incidence and hospitalisation rates of influenza-virus-associated respiratory infections by severity, case ascertainment, region, and age. We estimated in-hospital deaths from influenza virus ALRI by combining hospital admissions and in-hospital case-fatality ratios of influenza virus ALRI. We estimated the upper bound of influenza virus-associated ALRI deaths based on the number of in-hospital deaths, US paediatric influenza-associated death data, and population-based childhood all-cause pneumonia mortality data in six sites in low-income and lower-middle-income countries. Findings: In 2018, among children under 5 years globally, there were an estimated 109·5 million influenza virus episodes (uncertainty range [UR] 63·1–190·6), 10·1 million influenza-virus-associated ALRI cases (6·8–15·1); 870 000 influenza-virus-associated ALRI hospital admissions (543 000–1 415 000), 15 300 in-hospital deaths (5800–43 800), and up to 34 800 (13 200–97 200) overall influenza-virus-associated ALRI deaths. Influenza virus accounted for 7% of ALRI cases, 5% of ALRI hospital admissions, and 4% of ALRI deaths in children under 5 years. About 23% of the hospital admissions and 36% of the in-hospital deaths were in infants under 6 months. About 82% of the in-hospital deaths occurred in low-income and lower-middle-income countries. Interpretation: A large proportion of the influenza-associated burden occurs among young infants and in low-income and lower middle-income countries. Our findings provide new and important evidence for maternal and paediatric influenza immunisation, and should inform future immunisation policy particularly in low-income and middle-income countries. Funding: WHO; Bill & Melinda Gates Foundation.Fil: Wang, Xin. University of Edinburgh; Reino UnidoFil: Li, You. University of Edinburgh; Reino UnidoFil: O'Brien, Katherine L.. University Johns Hopkins; Estados UnidosFil: Madhi, Shabir A.. University of the Witwatersrand; SudáfricaFil: Widdowson, Marc Alain. Centers for Disease Control and Prevention; Estados UnidosFil: Byass, Peter. Umea University; SueciaFil: Omer, Saad B.. Yale School Of Public Health; Estados UnidosFil: Abbas, Qalab. Aga Khan University; PakistánFil: Ali, Asad. Aga Khan University; PakistánFil: Amu, Alberta. Dodowa Health Research Centre; GhanaFil: Azziz-Baumgartner, Eduardo. Centers for Disease Control and Prevention; Estados UnidosFil: Bassat, Quique. University Of Barcelona; EspañaFil: Abdullah Brooks, W.. University Johns Hopkins; Estados UnidosFil: Chaves, Sandra S.. Centers for Disease Control and Prevention; Estados UnidosFil: Chung, Alexandria. University of Edinburgh; Reino UnidoFil: Cohen, Cheryl. National Institute For Communicable Diseases; SudáfricaFil: Echavarría, Marcela Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas "Norberto Quirno". CEMIC-CONICET; ArgentinaFil: Fasce, Rodrigo A.. Public Health Institute; ChileFil: Gentile, Angela. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; ArgentinaFil: Gordon, Aubree. University of Michigan; Estados UnidosFil: Groome, Michelle. University of the Witwatersrand; SudáfricaFil: Heikkinen, Terho. University Of Turku; FinlandiaFil: Hirve, Siddhivinayak. Kem Hospital Research Centre; IndiaFil: Jara, Jorge H.. Universidad del Valle de Guatemala; GuatemalaFil: Katz, Mark A.. Clalit Research Institute; IsraelFil: Khuri Bulos, Najwa. University Of Jordan School Of Medicine; JordaniaFil: Krishnan, Anand. All India Institute Of Medical Sciences; IndiaFil: de Leon, Oscar. Universidad del Valle de Guatemala; GuatemalaFil: Lucero, Marilla G.. Research Institute For Tropical Medicine; FilipinasFil: McCracken, John P.. Universidad del Valle de Guatemala; GuatemalaFil: Mira-Iglesias, Ainara. Fundación Para El Fomento de la Investigación Sanitaria; EspañaFil: Moïsi, Jennifer C.. Agence de Médecine Préventive; FranciaFil: Munywoki, Patrick K.. No especifíca;Fil: Ourohiré, Millogo. No especifíca;Fil: Polack, Fernando Pedro. Fundación para la Investigación en Infectología Infantil; ArgentinaFil: Rahi, Manveer. University of Edinburgh; Reino UnidoFil: Rasmussen, Zeba A.. National Institutes Of Health; Estados UnidosFil: Rath, Barbara A.. Vienna Vaccine Safety Initiative; AlemaniaFil: Saha, Samir K.. Child Health Research Foundation; BangladeshFil: Simões, Eric A.F.. University of Colorado; Estados UnidosFil: Sotomayor, Viviana. Ministerio de Salud de Santiago de Chile; ChileFil: Thamthitiwat, Somsak. Thailand Ministry Of Public Health; TailandiaFil: Treurnicht, Florette K.. University of the Witwatersrand; SudáfricaFil: Wamukoya, Marylene. African Population & Health Research Center; KeniaFil: Lay-Myint, Yoshida. Nagasaki University; JapónFil: Zar, Heather J.. University of Cape Town; SudáfricaFil: Campbell, Harry. University of Edinburgh; Reino UnidoFil: Nair, Harish. University of Edinburgh; Reino Unid

Nonhalogenated organic molecules from Laurencia algae

The marine red algae of the genus Laurencia have produced more 700 secondary metabolites and exhibited high molecular diversity and intriguing bioactivity. Since the halogenated structures have been comprehensively reviewed previously, this review, covering up to the end of 2012, mainly focuses on the source, structure elucidation, and bioactivity of nonhalogenated organic molecules from Laurencia spp. as well as the relationship between nonhalogenated and halogenated products. Overall, 173 new or new naturally occurring compounds with 58 skeletons, mainly including sesquiterpenes, diterpenes, triterpenes, and C15-acetogenins, are described.The marine red algae of the genus Laurencia have produced more 700 secondary metabolites and exhibited high molecular diversity and intriguing bioactivity. Since the halogenated structures have been comprehensively reviewed previously, this review, covering up to the end of 2012, mainly focuses on the source, structure elucidation, and bioactivity of nonhalogenated organic molecules from Laurencia spp. as well as the relationship between nonhalogenated and halogenated products. Overall, 173 new or new naturally occurring compounds with 58 skeletons, mainly including sesquiterpenes, diterpenes, triterpenes, and C-15-acetogenins, are described

Testimonianza

In dialogo con la relazione di Anna Foa sulla comunit\ue0 ebraica di Roma al tempo della deportazione, sono presentate una testimonianza ed una riflessione sul problema della "cultura del patto", nell'ebraismo e invece nel fascismo e nel nazismo

MULTIPLE TRANSITIONS. GROWING UP GYPSIES.

The paper, presenting some original results of a longitudinal research, deals with the problem of multiple transitions of Roma Gypsy youth - in particular, of former Yugoslavians reaching Italy and Bologna in the early 90s - also due to the past history of their people, and to O Baro Porrajmos, the genocide they experienced at the same time when Shoah occurred

Questioni di lingua e di cittadinanza: il "diritto ad avere diritti" ed alcuni aspetti di integrazione politica

Nell'ambito del Rapporto nazionale ISMU sugli indicatori di integrazione, per la parte romagnola e comparativamente, esamina le interrelazioni tra lingua, cittadinanza e integrazione, e costruisce due indici - di "competenze linguistiche formali" e di "competenze linguistiche quotidiane" - sulla cui base analizza empiricamente alcuni aspetti delle interrelazioni di cui sopra

Shoah e coscienza europea: un percorso di storia del pensiero sociologico

Il contributo descrive un percorso originale di Storia del pensiero sociologico condotto, per oltre dieci anni, trattando della Shoah (Olocausto), e della comprensione o mancata comprensione di essa da parte della sociologia precedente, concomitante e successiva, in un contesto di studi di Scienze Politiche a forte indirizzo europeistico e internazionalistico. Pi\uf9 che proporre o riproporre le esperienze ormai consolidate della Sociologia dell'olocausto e del Genocidio, esso affronta dunque alcuni specifici interrogativi, relativi alla consapevolezza della Shoah in diversi contesti all'epoca dei fatti e negli anni successivi, fino ai nostri tempi, in chiave intergenerazionale ed in dialogo con gli studenti

Terremoto in Emilia e anziani: la �vulnerabilit� differenziale� degli anziani fragili e l'esperienza di Cavezzo (Mo)

Scientific literature is first examined, concerning disasters and age. Only recently age as a relevant variable has been considered, thus developing the concept of \uabdifferential vulnerability\ubb and realizing the need to specifically care for the aged in all phases (before, during and after earthquakes) in the same way we have started doing with children. Some data are offered, on how much and how the Emilia earthquake of May 2012, has affected the aged, and on the extent of emergency and post-emergency responses specifically devoted to them. Finally, it is described the experience of Cavezzo, one of most stricken municipalities in Modena province, where through the cooperation of local institutions and Ngos an emergency unit has been set up for 40 very frail aged persons, allowing them to remain in their home town. Rivello (St. Egidio Community) offers a touching diary of these days, and of his encounters with the aged. A few conclusions are drawn, which might be useful in other cases