Tipificación de las especies de Lutzomyia que actúan como potenciales vectores de Leishmania spp. en la provincia de Salta.

La leishmaniasis tegumentaria americana (LTA) es una enfermedad protozoaria causada por parásitos del género Leishmania que se transmiten a través de la picadura de flebótomos hembras. La LTA es endémica en diez provincias de Argentina, siendo el departamento de Orán la región más comprometida en la provincia de Salta (Salomón et al., 2008, Krolewiecki et al., 2017). La zona se caracteriza por la prevalencia de Leishmania (Viannia) braziliensis cuyo vector putativo es Nyssomyia neivai, la especie de flebótomos más abundante, y los reservorios se desconocen hasta el momento (Salomón et al., 2004, Marco et al., 2005).El área de estudio de esta tesis fue el departamento de Orán. A lo largo de los años 2015, 2016 y 2017 se capturaron flebótomos en siete sitios periurbanos y rurales para búsqueda de infección natural, la tipificación molecular de flebótomos y parásitos y el estudio de la abundancia estacional de las especies capturadas.Inicialmente, se analizó la variación estacional de las hembras capturadas en dos sitios periurbanos colindantes a parches de vegetación secundaria, emplazados en zonas con reporte de casos humanos de LTA. La abundancia media estacional de las hembras capturadas se analizó en forma conjunta con la variación mensual de casos de LTA diagnosticados en el Instituto de Investigaciones de Enfermedades Tropicales (IIET) durante el periodo de muestreos entomológicos de esta tesis. Así se determinó la existencia de un intervalo de tiempo de aproximadamente 90 días entre los meses de gravidez de hembras y los meses en que se registra un mayor número de casos humanos.A lo largo de esta tesis se buscó, principalmente, abordar molecularmente a los vectores potenciales de LTA que fueron capturados en sitios con riesgo de transmisión. Para esto, se normalizó y aplicó la combinación de PCR-RFLP del gen 18S ARN ribosomal (18S ARNr) para la tipificación molecular de hembras. Como resultado, las especies circulantes en los sitios de muestreo: Nyssomyia neivai, Migonemyia migonei, complejo cortelezzii y Psathyromyia shannoni pudieron ser identificadas molecularmente; siendo la combinación PCR-RFLP 18S ARNr capaz de incluso identificar ejemplares que la metodología tradicional no había podido determinar por la ruptura de estructuras de valor taxonómico o por un montaje inadecuado. Los patrones de restricción obtenidos fueron especie-específicos y fueron validados por la identificación morfológica tradicional.Por otra parte, 1.671 hembras fueron capturadas y analizadas molecularmente para la detección de ADN de Leishmania spp. Previamente, se puso a punto la PCR ADN kinetoplastídico (ADNk) para la búsqueda de material genético parasitario, con una sensibilidad de 25 promastigotes por flebótomo. Luego, esta fue combinada con PCR de Actina para que la resultante PCR dúplex ADNk-actina permita el análisis de pooles de 10 hembras. Además, para tipificar y genotipificar la especie parasitaria en flebótomos, se estandarizó la PCR del gen de proteína heat shock 70 (hsp70) y PCR de citocromo b (cyt b) con cepas de Leishmania de referencia, asilados de pacientes con LTA y aislados de perros con leishmaniosis canina previamente tipificados.Finalmente, para búsqueda tradicional de infección natural, 254 hembras fueron capturadas y diseccionadas para la observación microscópica de su contenido intestinal. Tanto las hembras analizadas por disección como aquellas analizadas molecularmente resultaron negativas para infección por Leishmania spp. lo que destaca la baja tasa de infección de los vectores de LTA y el carácter microfocal de la transmisión cuya dinámica depende principalmente de los reservorios, que se desconocen en la zona hasta el momento.The American tegumentary leishmaniasis (ATL) is a protozoan disease caused by parasites of the genus Leishmania that are transmitted through the bite of female sandflies. The ATL is endemic in ten provinces of Argentina, being the department of Orán the most affected region in the province of Salta (Salomón et al., 2008, Krolewiecki et al., 2017). The area is characterized by the prevalence of Leishmania (Viannia) braziliensis whose putative vector is Nyssomyia neivai, the most abundant sandfly species; the reservoirs are unknown until now (Salomón et al., 2004, Marco et al., 2005). In this work, the captures of sandflies were undertaken in seven periruban and rural sites from the department of Oran in the years 2015, 2016 and 2017. Sandflies were analyzed with the purpose of searching natural infection, the molecular typing of sandflies and parasites, and to study the abundance of the species caught. The seasonal variation of sand fly females that were captured in two periurban sites adjacent to patches of secondary vegetation was analyzed together with the monthly variation of ATL cases diagnosed at Instituto de Investigaciones de Enfermedades Tropicales (IIET) since 1986. The highest number of ATL cases occurred in August, and this coincides with the peak of abundance of Ny. neivai from site 1. Instead, one of the abundance peaks of Ny. neivai from the site2 took place in June; the gap between abundance of sandflies and peak of patients, could be attributed to the incubation period of the disease and the time of evolution of the lesions that have the patients. In addition, the combination of PCR-RFLP of the 18S RNA ribosomal RNA (18S rRNA) was standardized to typify the sandflies molecularly. As a result, all the circulating species in the sampling sites: Nyssomyia neivai, Migonemyia migonei, complex cortelezzii and Psathyromyia shannoni could be identified successfully. The restriction patterns obtained were species-specific and were validated by traditional morphology. Also, the techniques were able to identify specimens that the traditional methodology could not determine due to the rupture of structures of taxonomic value. On the other hand, 1671 females were captured and analyzed molecularly for the detection of Leishmania spp DNA. Previously, a PCR based on kinetoplast DNA (DNAk) was standardized, and its sensitivity was 25 promastigotes per sand fly. Then, the PCR DNAk was combined with PCR actin, the resulting duplex PCR DNAk-actin allows the analysis of pools of 10 females. Moreover, to tipify and genotype the parasitic species in sandflies, the heat shock 70 protein gene (hsp70) and cytochrome b (cyt b) PCR were standardized with reference Leishmania strains, isolated from ATL patients and isolates from dogs with canine leishmaniosis previously typified. Finally, 254 females were captured and dissected for detecting natural infection through the microscopic observation of their guts. Both the females analyzed by dissection and those analyzed molecularly were negative for infection by Leishmania spp. which highlights the low infection rate of vectors and the microfocal character of ATL transmission whose dynamics depends mainly on the reservoirs, which are unknown in the area until now.Fil: Almazán, María Cristina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentin

Chiari Syndrome: Advances in Epidemiology and Pathogenesis: A Systematic Review

Arnold Chiari Syndrome; Hydrocephalus; ScoliosisSíndrome de Arnold Chiari; Hidrocefalia; EscoliosisSíndrome d'Arnold Chiari; Hidrocefàlia; EscoliosiArnold Chiari syndrome is a rare congenital disease of unknown prevalence and whose origin is still under study. It is encompassed within the posterior cranial malformations, showing a wide spectrum of symptomatology that can range from severe headache, dizziness, and paresthesia to complete asymptomatology. It is for this reason that early diagnosis of the disease is difficult, and it is usually diagnosed in adolescence. Treatment is based on remodeling and decompression of the malformed posterior cranial fossa, although the risk of residual symptoms after surgery is high. The aim of this review is to update all the existing information on this pathology by means of an exhaustive analysis covering all the scientific literature produced in the last 5 years. In addition, it has been carried out following the PRISMA model and registered in PROSPERO with code CRD42023394490. One of the main conclusions based on the results obtained in this review is that the origin of the syndrome could have a genetic basis and that the treatment of choice is the decompression of the posterior cerebral fossa

Estudio y análisis de dificultades detectadas en el tema “ecuaciones con parámetros- sistemas de ecuaciones lineales con parámetros”

Los autores de este trabajo docentes del área matemática, integrantes de proyectos de Investigación del CIUNSa: Consejo de Investigación de la Universidad Nacional de Salta, tales como: “Estudio y análisis de los factores que influyen en la deserción de los alumnos…estrategias de retención” nos abocamos al estudio de algunas de las distintas variables intervinientes en esta temática, estudiando por ello, algunas de las dificultades frecuentes que cometen los alumnos. Este equipo docente que se desempeña en el dictado de álgebra Lineal y geometría analítica, asignatura de primer año de las carreras del profesorado en matemática y de licenciatura en sistema, viene observando, tanto en clases teóricas como prácticas y a través de los años, que los estudiantes tienen dificultades frecuentes, en algunos temas del programa, por ello realizaron actividades para detectarlas y estudiarlas. En esta ocasión expondremos lo referido a la enseñanza del tema “Ecuaciones con parámetros - Sistemas de ecuaciones lineales con parámetros” observando que algunas dificultades frecuentes: • interpretación de consignas. • planteo y resolución de problemas • empleo acertado del lenguaje simbólico, y/o gráfico de una situación problemática proponiendo también estrategias tendientes a favorecer la enseñanza-aprendizaje

Clinical Presentation of American Tegumentary Leishmaniasis in a Leishmania (Viannia) braziliensis Endemic Hotspot: A 35-Year History

American tegumentary leishmaniasis (ATL) is a neglected tropical disease affecting the skin and mucosa. American tegumentary leishmaniasis due to Leishmania (Viannia) braziliensis is endemic in Argentina, where the Department of Oran is a hyperendemic focus. All cases of ATL with laboratory confirmation evaluated at a referral center in Oran city between 1985 and 2019 were analyzed retrospectively. Information from cases included clinical form, lesion size and number, time of evolution, and anatomical location; sex, age, and geographic origin were also studied. The temporal distribution of cases was analyzed. A total of 3,573 cases were included in the analysis. The ratio of males to females was 3:1 and the median age was 33 years old. Eighty-seven percent of cases were from Oran city and its surroundings, highlighting the hyperendemic nature of the area. Regarding clinical forms, 92.5% of cases were cutaneous and 7.5% were mucosal, with a median evolution time until clinical evaluation of 30 days and 7 months, respectively. Single cutaneous lesions were more frequent, localized mainly on the exposed areas in the upper and lower limbs. Secondary events were observed and described in 140 (4%) cases, with a median interval of 3.8 years for the appearance of recurrent mucosal disease in previously cutaneous forms. This is the largest case series of ATL due to L. (V.) braziliensis. The most classic presentation is of adult males with single cutaneous ulcers in exposed body areas, with, 10% of cases with mucosal complications. This comprehensive clinical characterization serves as a basis for future studies of the care and control of this neglected tropical disease.Fil: Almazán, María Cristina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cajal, Silvana Pamela. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Díaz Fernández, Melisa Evangelina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Juárez, Marisa. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; ArgentinaFil: Quipildor, Marcelo Omar. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Portal, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Tejerina, Valeria. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Vargas, Carlos. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Copa, Griselda Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Gil, José Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Cimino, Rubén Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentin

Sand fly typing: a simple and morphologically-supported method based on polymorphism of 18S rRNA gene in a Leishmaniasis endemic area of Argentina

Leishmaniases are vector-borne diseases that in the Americas are distributed from southern United States to northern Argentina. The vectors for this disease are small dipterans known as sand flies that are usually identified morphologically by observing structures with taxonomic value; but it is time-consuming, laborious, and requires entomological expertise. Then, this work was aimed at identifying sand flies with molecular techniques, using the morphological identification as a reference technique, in an endemic area of American Tegumentary Leishmaniasis (ATL) located in northern Argentina. For this, sand flies were caught at two patches of vegetation adjacent to rural areas in Orán department, Salta Province. Females were dissected with sterile needles; the head and last abdominal segments were analyzed for morphological identification. The remaining thorax and abdominal segments were used to extract DNA, which was amplified by PCR of the small subunit (SSU), 18S rRNA gene. PCR products were digested with CviQI and DdeI enzymes to identify sand fly species by Restriction Fragment Length Polymorphism (RFLP) analysis. Thus, the restriction pattern of each caught species was defined according to morphological identification. A total of 1501 females, belonging to four sand fly species, were captured. Nyssomyia neivai (1347/1501) was the most abundant species, followed by Migonemyia migonei (90/ 1501). From the total, 801 females were morphologically and molecularly identified, while 700 females were characterized only molecularly. For those females analyzed by both methods, there was total coincidence in the achieved result. Besides, the 5% (38/801) of females that could not be determined morphologically due to inadequate mounting were molecularly identified. All the females characterized just by PCR-RFLP, were successfully identified. Our results indicate that the explored method is capable of identifying the sand fly species that circulate in an ATL endemic area. Since this method is based on the analysis of markedly different patterns, the identification process might be more easily reproduced, as the bias introduced by the technician's lack of experience is removed.Fil: Almazán, María Cristina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Copa, Griselda Noemi. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lauthier, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Kochi University. Kochi Medical School; JapónFil: Gil, José Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; ArgentinaFil: López Quiroga, Inés Raquel. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; ArgentinaFil: Hoyos, Carlos Lorenzo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Díaz Fernández, Melisa Evangelina. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; ArgentinaFil: Nasser, Julio Rubén. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; ArgentinaFil: Korenaga, Masataka. Kochi University. Kochi Medical School; JapónFil: Marco, Jorge Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Barroso, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentin

Tegumentary leishmaniasis and sand flies in a border area between Argentina and Bolivia

Background: Some sand flies are of medical importance because they are vectors of Leishmania parasites that are responsible for leishmaniasis. The aim of this study was to make a retrospective epidemiological analysis of tegumentary leishmaniasis (TL), to identify Leishmania spp. from patient isolates and to describe the diversity of sand flies from a border area between Bolivia and Argentina. Methods: TL cases included in the study were diagnosed in an endemic area of the north of Argentina from 1985 to 2017. The parasites isolated were characterized by the cytochrome B method. Sand flies were captured with Centers for Disease Control traps in Aguas Blancas and Media Luna-Algarrobito localities. Results: A total of 118 cases of TL were analysed. Eight isolates were characterized as Leishmania (Viannia) braziliensis. A total of 1291 sand flies were captured, including Nyssomyia neivai, Cortelezzii complex, Evandromyia sallesi, Migonemyia migonei and Micropygomyia quinquefer. Within the area, sand flies were found in the backyards of houses. Conclusions: In this region there exists the possibility of peridomestic transmission of TL in the neighbourhoods peripheral to the urban area and in rural environments as well as the risk of transmission to travellers that pass through the customs offices.Fil: Copa, Griselda Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales; ArgentinaFil: Almazán, María Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; Argentina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales; ArgentinaFil: Aramayo, Lorena Vanesa. Universidad Nacional de Salta; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: Cajal, Silvana Pamela. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Juarez, Marisa. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Lauthier, Juan José. Kochi University. Kochi Medical School; JapónFil: Korenaga, Masataka. Kochi University. Kochi Medical School; JapónFil: Barroso, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Nasser, Julio Rubén. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Marco, Jorge Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Gil, José Fernando. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones en Energía no Convencional. Universidad Nacional de Salta. Facultad de Ciencias Exactas. Departamento de Física. Instituto de Investigaciones en Energía no Convencional; Argentin

Tegumentary leishmaniasis and sandflies in Colonia Santa Rosa locality in northern Argentina

La leishmaniasis tegumentaria (LT) es causada por parásitos del género Leishmania y transmitida por especies de flebótomos, insectos pertenecientes al orden Diptera, familia Psychodidae. El objetivo de este trabajo fue analizar la presencia de casos de LT y su variación temporal entre 1985 y 2019, las formas clínicas, la ubicación de las lesiones en los pacientes y la presencia de flebótomos en la localidad de Colonia Santa Rosa, del norte de Argentina. Los pacientes se diagnosticaron mediante frotis e intradermorreacción de Montenegro. Se colocaron trampas CDC en 14 sitios en el horario de 19 a 7. Se diagnosticaron 120 casos de LT y la prevalencia global fue del 0,75% (≈16.000 habitantes). Los pacientes presentaron formas cutá- neas simples y múltiples (88,79%) y mucocutáneas (10,83%). Las lesiones cutáneas fueron más frecuentes en extremidades inferiores. Del total de flebótomos, Nyssomyia neivai fue la especie predominante (95%), y, en menor proporción, estuvieron presentes Migonemyia migonei (1,9%), complejo cortelezzii (1,3%) y Evandromyia sallesi (0,09%). La persistente ocurrencia de casos y la presencia de flebótomos en la citada localidad nos sugiere la transmisión endémica en la zona. Esto senala ˜ la necesidad de planificar medidas preventivas y de control de la LT en el norte de Argentina.Tegumentary leishmaniasis (TL) is caused by parasites of the genus Leishmania and transmitted by the sandfly species, insects belonging to the order Diptera, family Psychodidae. Historically, the most endemic area of TL in Argentina has been the northern region. The aim of this work was to analyze the presence and temporal variation of TL cases reported between 1985 and 2019 in Colonia Santa Rosa locality, northern Argentina. Furthermore, its clinical forms were characterized and sandflies were captured. Patients were diagnosed by smear and the Montenegro skin test. For sampling, CDC light traps were placed at 14 sites from 7pm to 7am. The correlation between vegetation cover and sandfly abundance was also studied. One hundred and twenty TL cases were diagnosed and the overall prevalence was 0.75% (≈16 000 inhabitants). Patients presented simple and multiple cutaneous leishmaniasis (88.79%) and the mucocutaneous form (10.83%). Skin lesions were more frequent on the lower extremities (46.73%). Of the total number of sandflies, Nyssomyia neivai (95%) was the predominant species followed by Migonemyia migonei (1.9%), cortelezzii complex (1.3%) and Evandromyia sallesi (0.09%). The persistent occurrence of cases and the presence of sandflies in the locality suggest the existence of endemic transmission in the area. This highlights the need to design prevention and control measures for TL in northern Argentina.Fil: Aramayo, Lorena Vanesa. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; ArgentinaFil: Copa, Griselda Noemi. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: Hoyos, Carlos Lorenzo. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Almazán, María Cristina. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: Juarez, Marisa del Valle. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Cajal, Silvana Pamela. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta; ArgentinaFil: Nasser, Julio Rubén. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; ArgentinaFil: Gil, José Fernando. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Universidad Nacional de Salta. Facultad de Ciencias Naturales. Escuela de Biología. Cátedra de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones en Energía no Convencional. Universidad Nacional de Salta. Facultad de Ciencias Exactas. Departamento de Física. Instituto de Investigaciones en Energía no Convencional; Argentin

ERK5 Is a Major Determinant of Chemical Sarcomagenesis : Implications in Human Pathology

Sarcoma is a heterogeneous group of tumors poorly studied with few therapeutic opportunities. Interestingly, the role of MAPKs still remains unclear in sarcomatous pathology. Here, we describe for the first time the critical role of ERK5 in the biology of soft tissue sarcoma by using in vitro and in vivo approaches in a murine experimental model of chemical sarcomagenesis. Indeed, our observations were extrapolated to a short series of human leiomyosarcoma and rhabdomyosarcomas. Furthermore, transcriptome analysis allows us to demonstrate the critical role of KLF2 in the biological effects of ERK5. Therefore, the data presented here open new windows in the diagnosis and therapy of soft tissue sarcomas. Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5-KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology

ERK5 Is a major determinant of chemical sarcomagenesis: implications in human pathology

Sarcomas are a heterogeneous group of tumors in which the role of ERK5 is poorly studied. To clarify the role of this MAPK in sarcomatous pathology, we used a murine 3-methyl-cholanthrene (3MC)-induced sarcoma model. Our data show that 3MC induces pleomorphic sarcomas with muscle differentiation, showing an increased expression of ERK5. Indeed, this upregulation was also observed in human sarcomas of muscular origin, such as leiomyosarcoma or rhabdomyosarcoma. Moreover, in cell lines derived from these 3MC-induced tumors, abrogation of Mapk7 expression by using specific shRNAs decreased in vitro growth and colony-forming capacity and led to a marked loss of tumor growth in vivo. In fact, transcriptomic profiling in ERK5 abrogated cell lines by RNAseq showed a deregulated gene expression pattern for key biological processes such as angiogenesis, migration, motility, etc., correlating with a better prognostic in human pathology. Finally, among the various differentially expressed genes, Klf2 is a key mediator of the biological effects of ERK5 as indicated by its specific interference, demonstrating that the ERK5–KLF2 axis is an important determinant of sarcoma biology that should be further studied in human pathology.This work has been supported with Grant RTI2018-094093-B-I00 funded by MCIN/AEI/10.13039/501100011033, “ERDF A way of making Europe” to RSP. Also supported with funds from Fundación Leticia Castillejo Castillo, Roche España and ACEPAIN to RSP and MJRH. RSP and MJRH’s Research Institute and the work carried out in their laboratory, received partial support from the European Community through the FEDER. JJ and EAL hold a predoctoral research contract cofounded by the European Social Fund and UCLM. OR holds a contract for accessing the Spanish System of Science, Technology, and Innovation (SECTI) funded by the University of Castilla-La Mancha (UCLM) and received partial support from the European Social Fund (FSE) through its Operative Program for Castilla-La Mancha (2007–2013)