Genomics and pharmacogenomics of colorectal cancer

Se ha estimado que la heredabilidad asociada al cáncer colorrectal (CCR) es de alrededor de un 35%. A pesar de que cerca de un 5% de esta proporción es explicable a través de mutaciones raras de alta penetrancia, y un 7% adicional es debido a la presencia de combinaciones de algunos de los 16 loci de susceptibilidad descritos, existe aún una fracción de esta susceptibilidad genética que no ha podido ser explicada. Por otro lado, existe también una importante variabilidad en la forma en la que los pacientes de CCR responden al tratamiento con quimioterapia. Además, el hecho de que la mayoría de fármacos usados en quimioterapia presentan rangos terapéuticos restringidos resulta en la frecuente aparición de reacciones adversas a fármacos (ADRs). Por ello, la identificación de la variación genética que modula esta respuesta es indispensable a la hora de ofrecer tratamientos personalizados que sean más efectivos, produzcan menos efectos secundarios y se optimicen los costes sanitarios. En este contexto, el trabajo presentado en esta Tesis Doctoral ha tenido dos objetivos principales: en primer lugar, la búsqueda de nuevas variantes de susceptibilidad al CCR. En segundo, el análisis de la variación genética subyacente a las diferencias en las respuestas tóxicas de pacientes de CCR tratados con quimioterapia

Praeornis sharovi Rautian, 1978 a fossil feather from the early Late Jurassic of Kazakhstan

Since its original description as a feather belonging to a basal bird, the phylogenetic position of Praeornis sharovi was debated. It was considered as belonging to a bird, a cycad leaf, or as a ‘transitional’ integumentary structure between reptile scales and bird feathers. Recently, a basal enantiornithine bird was collected in Early Cretaceous beds of Brazil. This specimen shows very well-preserved rachis-dominated tail feathers with a very thick rachis and thick and rigid barbules. These features are present in Praeornis, suggesting that this fossil may be interpreted as the tail feather of a basal bird. In this way, Praeornis constitutes one of the oldest records of rachis-dominated feathers in the world. Rachis-dominated tail feathers, including that of Praeornis appear to be rigid paired structures not performed for aerodynamical purposes, suggesting that may be important in body balance

La revista de Arena

La revista de Arena surge del interés de crear un espacio para el análisis profundo de los escritos de autores conocidos y la necesidad de los desconocidos de llegar al lector. La idea nace, además, como el inicio de lo que puede ser, más adelante, una posibilidad concreta de trabajo. Se considera como interesante, la posibilidad de autogestionar un soporte propio y con él, una fuente laboral. La publicación plantea a priori la dificultad que tienen algunos autores nuevos para publicar sus trabajos. La revista facilitará esta cuestión que es uno de los factores que iniciaron la gestación de esta Tesis. Es importante mencionar que cada número estará atravesado por una temática que será su eje. Entonces, el fin de La revista de Arena es el análisis de una temática de relevancia para los seres humanos, que permita la reflexión y a través de las páginas le otorgue al lector herramientas para conseguir una visión propia.Facultad de Periodismo y Comunicación Socia

Medicalización de la vida en la consulta: ¿hacia dónde caminamos?

ResumenEl poder de la medicina ha hecho atractiva la idea de «medicalizar» aspectos de la vida que se pueden percibir como problemas médicos aun sin serlo. La medicina, como reflejo de la cultura del bienestar, genera en ocasiones falsas necesidades, y aspectos de la vida cotidiana son medicalizados con el pretexto de tratar falsas enfermedades como astenia primaveral y timidez, o procesos biológicos naturales como la menopausia.A pesar del mayor bienestar material, cada día atendemos a más personas que se quejan de malestares que quizá tengan más que ver con «estar mal» que con auténticas «enfermedades». La lista puede ser interminable: tristeza, niños hiperactivos, vigorexias o adolescentes problemáticos, entre otros. En este artículo se revisan algunas intervenciones que desde la consulta contribuyen a fomentar dichas situaciones. La adversidad cotidiana adquiere hoy rango de enfermedad, de ahí el notable aumento de las consultas en los diferentes dispositivos sanitarios.AbstractThe power of medicine has lately enhanced the idea of medicalizing any aspects of life that can be perceived as medical problems. Medicine sometimes creates false needs and there is nowadays an increasing number of situations are medicalized with the pretext of treating fake diseases such as spring fatigue, shyness o natural biological processes like menopause.Despite the better life conditions, we now attend more people that complain about discomfort that may have more to do with «feeling sick» than with authentic disease. There is an endless list: sadness, hyperactive children, anorexia, bulimia, vigorexia or problematic teenagers, amongst others. In this article we revise some interventions that, contribute to promote these situations also from the own doctor's office. Everyday adversity acquires today the status of disease, hence the remarkable increase in these consultations in the diverse sanitary services

The Road so Far in Colorectal Cancer Pharmacogenomics: Are We Closer to Individualised Treatment?

In recent decades, survival rates in colorectal cancer have improved greatly due to pharmacological treatment. However, many patients end up developing adverse drug reactions that can be severe or even life threatening, and that affect their quality of life. These remain a limitation, as they may force dose reduction or treatment discontinuation, diminishing treatment efficacy. From candidate gene approaches to genome-wide analysis, pharmacogenomic knowledge has advanced greatly, yet there is still huge and unexploited potential in the use of novel technologies such as next-generation sequencing strategies. This review summarises the road of colorectal cancer pharmacogenomics so far, presents considerations and directions to be taken for further works and discusses the path towards implementation into clinical practiceThis research was supported by grant FIS PI 16/01057- ISCIII (to Á.C.), ISCIII PFIS grant FI17/00215 (to A.R.S.) and Fundación Olga Torres (to C.F.-R.)S

Inside the gut: Revelations of metatranscriptomic and transcriptomic analyses of Spodoptera frugiperda larvae from an organic maize plantation at 2283 meters above sea level (Tafí del Valle, Tucumán)

Spodoptera frugiperda is a noctuid moth that devastates various crops, including corn, and is found in most of the American continent. Transgenic crops that produce insecticidal proteins from Bacillus thuringiensis are currently the most successful biotechnological pest management application, but S. frugiperda has developed field-evolved resistance. In this regard, insect gut microbiota conform a complex community that establishes symbiotic relationships with its host, contributing to its viability. For this reason, metatranscriptomic and transcriptomic analyses of insect guts in their natural environment are invaluable to better comprehend their biology and to identify genes as targets for pest control. We previously captured S. frugiperda specimens from different environments, altitudes and food sources in the province of Tucumán (Argentina). For all samples, total RNA extracted from fifth instar larval guts was submitted to a one-step reverse transcription and PCR sequence independent amplification procedure, and then pyrosequenced. In this study we analysed one of these samples, namely, larvae that were captured in an organic maize field in Tafí del Valle (26°55´40.75´´S, 65°45´19.90´´W; Tucumán province) at 2283 meters above sea level. Sequence reads were trimmed and assembled. Homology searches were performed against various NCBI databases. Taxonomic and functional contents were analysed with MEGAN. The metatranscriptome, in which we identified sequences from archaea, bacteria, fungi, nematodes and plants, revealed potential biocontrol candidates for this pest, and others related with host metabolism and digestion. Furthermore, the host transcriptome showed that most transcripts were associated with the digestive tract structure and development, among others. Some of these genes could be possible targets for pest control via RNA interference (RNAi). In summary, this study has shown the potential effects of this particular food source (i.e., organic maize) and of the environmental conditions (altitude, among others), on the expression profile of S. frugiperda larval guts, their associated metatranscriptome, and putative interactions between them. Future studies will test the potential biocontrol candidates that we identified.Fil: Rozadilla, Gastón. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabrera, Natalia Alina. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; ArgentinaFil: Virla, Eduardo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Planta Piloto de Procesos Industriales Microbiológicos; ArgentinaFil: Mccarthy, Cristina Beryl. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; ArgentinaX Congreso Argentino de EntomologíaMendozaArgentinaSociedad Argentina de EntomologíaUniversidad Nacional de Cuyo. Facultad de Ciencias AgrariasUniversidad Nacional de Cuyo. Instituto Argentino de Investigaciones de las Zonas ÁridasInstituto Nacional de Tecnología Agropecuari

Limited Joint Mobility Progression In Type 1 Diabetes: A 15-year Follow-up Study

Objective. To assess the evolution of joint mobility over a period of 15 years in type 1 diabetic patients and healthy controls and to determine whether microalbuminuria is associated with a different evolution of joint mobility. Methods. Joint mobility of hand and wrist was determined in 63 patients with type 1 diabetes and 63 healthy subjects. Fifteen years later, 37 (58.7%) diabetic patients and 16 (25.4%) healthy subjects were studied again. Joint mobility was assessed with the Prayer sign and by measuring the angle of maximal flexion of the fifth and third metacarpophalangeal (MCP) joints and wrist. Patients with diabetes were visited 2-4 times every year with regular assessment of glycated hemoglobin (HbA1(c)), urinary albumin excretion (UAE), and ophthalmoscopy. Results. Fifteen years after the initial exam, diabetic patients showed reduced flexion of the fifth MCP joint (82.6 +/- 5.8 versus 76.0 +/- 6.4 degrees, p < 0 001) and wrist (75.9 +/- 8.1 versus 73.2 +/- 7.4 degrees, p = 0 015) compared to baseline examination. Joint mobility did not change significantly in healthy subjects. Patients with microalbuminuria showed greater reduction in hand joint mobility than diabetic patients with normal UAE or than healthy subjects (p < 0 001). Conclusions. In type 1 diabetic patients, the severity of LJM progresses with time, and the progression is enhanced in patients with microalbuminuria

Água não potável para consumo na Horticultura de La Plata (Buenos Aires). Causas, consequências e alternativas

The peri-urban region of La Plata stands out in the production by small family farmers of fresh vegetables. Within the framework of the problems of habitat and health, a series of symptomatologies are observed that affect both the producers / workers and their families -mainly the children who live there- as well as the consumers of the horticultural products. These symptomologies have as their main source the utilizationof non-potable water. The work aims to determine the type and magnitude of water pollution, identify the causes thereof and evaluate technological alternatives that solve the present problem. The results indicate that a complex problem, such as the one proposed, requires technological solutions to be accompanied by political actions that modify the structural conditions of the producers' lives in the La Plata horticultural belt.En la región periurbana de La Plata se destaca la producción de hortalizas frescas llevada a cabo por pequeños agricultores familiares. En el marco de las problemáticas de hábitat y salud, se observa una serie de sintomatologías que afectan tanto a los productores/trabajadores y sus familias -principalmente los chicos que allí habitan- como así también a los consumidores de los productos hortícolas. Estas sintomatologías tienen como origen principal la utilización de agua no potable. El trabajo se propone determinar el tipo y magnitud de la contaminación del agua, identificar los causales del mismo y evaluar alternativas que resuelvan el presente inconveniente. Los resultados indican que una problemática compleja como la planteada, requiere que las soluciones tecnológicas sean acompañadas de acciones políticas que modifiquen condiciones estructurales de la vida de los productores en el cinturón hortícola platense.Na região periurbana de La Plata, destaca-se a produção de hortaliças frescas realizadas por pequenos agricultores familiares. Como parte das questões de hábitat e saúde, observa-se uma série de sintomas que afetam tanto os produtores/trabalhadores e suas famílias -principalmente as crianças que vivem lá- como os consumidores dos produtos hortícolas. Essas sintomatologias têm como principal origem o uso de água não potável. O trabalho visa determinar o tipo e magnitude da contaminação da água, identificar suas causas e avaliar alternativas que resolvam o problema atual. Os resultados indicam que um problema complexo como o apresentado, exige que as soluções tecnológicas sejam acompanhadas de ações políticas que modifiquem condições estruturais da vida dos produtores no cinturão hortícola de La Plata

Comments on the morphology of basal paravian shoulder girdle: New data based on unenlagiid Theropods and Paleognath birds

In 1976 John Ostrom published an enlightening paper about the anatomical transformations in the shoulder girdle and forelimb elements along the origin of birds. Most of his ideas were based on comparing Archaeopteryx lithographica with the extant New World vulture Cathartes aura. Ostrom offered innovative ideas about range of movements and function of wing elements in the basal bird Archaeopteryx. Further, he explored anatomical transformations that may have occurred at early stages of the evolution of flight and established several hypothetical steps toward the acquisition of flapping flight in modern birds. Since then, however, our understanding of paravian diversity and anatomy has increased dramatically. Based on novel information derived from recent experiments, and currently available anatomical evidence of basal paravians, the present paper aims to review some important topics on pectoral girdle anatomy related to flight origins. Further, a brief analysis of pectoral girdle osteology and myology of the extant paleognath Rhea americana is also included with the aim to test whether Ostrom?s ideas still remain valid under this new context, based on available phylogenetic and anatomical frameworks.Fil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Motta, Matias Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Agnolin, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina. Universidad Maimónides; ArgentinaFil: Rozadilla, Sebastian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Lo Coco, Gastón Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Brissón Egli, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentin

Água não potável para consumo na Horticultura de La Plata (Buenos Aires). Causas, consequências e alternativas

En la región periurbana de La Plata se destaca la producción de hortalizas frescas llevada a cabo por pequeños agricultores familiares. En el marco de las problemáticas de hábitat y salud, se observa una serie de sintomatologías que afectan tanto a los productores/trabajadores y sus familias –principalmente los chicos que allí habitan– como así también a los consumidores de los productos hortícolas. Estas sintomatologías tienen como origen principal la utilización de agua no potable. El trabajo se propone determinar el tipo y magnitud de la contaminación del agua, identificar los causales del mismo y evaluar alternativas que resuelvan el presente inconveniente. Los resultados indican que una problemática compleja como la planteada, requiere que las soluciones tecnológicas sean acompañadas de acciones políticas que modifiquen condiciones estructurales de la vida de los productores en el cinturón hortícola platense.The peri-urban region of La Plata stands out in the production by small family farmers of fresh vegetables. Within the framework of the problems of habitat and health, a series of symptomatologies are observed that affect both the producers / workers and their families –mainly the children who live there– as well as the consumers of the horticultural products. These symptomologies have as their main source the utilizationof non-potable water. The work aims to determine the type and magnitude of water pollution, identify the causes thereof and evaluate technological alternatives that solve the present problem. The results indicate that a complex problem, such as the one proposed, requires technological solutions to be accompanied by political actions that modify the structural conditions of the producers' lives in the La Plata horticultural belt.Na região periurbana de La Plata, destaca-se a produção de hortaliças frescas realizadas por pequenos agricultores familiares. Como parte das questões de hábitat e saúde, observa-se uma série de sintomas que afetam tanto os produtores/trabalhadores e suas famílias –principalmente as crianças que vivem lá– como os consumidores dos produtos hortícolas. Essas sintomatologias têm como principal origem o uso de água não potável. O trabalho visa determinar o tipo e magnitude da contaminação da água, identificar suas causas e avaliar alternativas que resolvam o problema atual. Os resultados indicam que um problema complexo como o apresentado, exige que as soluções tecnológicas sejam acompanhadas de ações políticas que modifiquem condições estruturais da vida dos produtores no cinturão hortícola de La Plata.Facultad de Ciencias ExactasFacultad de Ciencias Agrarias y Forestale