Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

BACKGROUND: The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. METHODS: A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. RESULTS: We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. CONCLUSIONS: We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents a well standardized experimental model for research on cancer cachexia. We wish to point out that scientists using the C26 model to study cancer and those using the same model to study cachexia may be unaware of each other's works because they use different keywords; we present strategies to eliminate this gap and discuss the benefits of such an exchange of knowledge

Implementation and performances of the IPbus protocol for the JUNO Large-PMT readout electronics

The Jiangmen Underground Neutrino Observatory (JUNO) is a large neutrino detector currently under construction in China. Thanks to the tight requirements on its optical and radio-purity properties, it will be able to perform leading measurements detecting terrestrial and astrophysical neutrinos in a wide energy range from tens of keV to hundreds of MeV. A key requirement for the success of the experiment is an unprecedented 3% energy resolution, guaranteed by its large active mass (20 kton) and the use of more than 20,000 20-inch photo-multiplier tubes (PMTs) acquired by high-speed, high-resolution sampling electronics located very close to the PMTs. As the Front-End and Read-Out electronics is expected to continuously run underwater for 30 years, a reliable readout acquisition system capable of handling the timestamped data stream coming from the Large-PMTs and permitting to simultaneously monitor and operate remotely the inaccessible electronics had to be developed. In this contribution, the firmware and hardware implementation of the IPbus based readout protocol will be presented, together with the performances measured on final modules during the mass production of the electronics

Mass testing of the JUNO experiment 20-inch PMTs readout electronics

The Jiangmen Underground Neutrino Observatory (JUNO) is a multi-purpose, large size, liquid scintillator experiment under construction in China. JUNO will perform leading measurements detecting neutrinos from different sources (reactor, terrestrial and astrophysical neutrinos) covering a wide energy range (from 200 keV to several GeV). This paper focuses on the design and development of a test protocol for the 20-inch PMT underwater readout electronics, performed in parallel to the mass production line. In a time period of about ten months, a total number of 6950 electronic boards were tested with an acceptance yield of 99.1%

Validation and integration tests of the JUNO 20-inch PMTs readout electronics

The Jiangmen Underground Neutrino Observatory (JUNO) is a large neutrino detector currently under construction in China. JUNO will be able to study the neutrino mass ordering and to perform leading measurements detecting terrestrial and astrophysical neutrinos in a wide energy range, spanning from 200 keV to several GeV. Given the ambitious physics goals of JUNO, the electronic system has to meet specific tight requirements, and a thorough characterization is required. The present paper describes the tests performed on the readout modules to measure their performances.Comment: 20 pages, 13 figure

Predictability of orthodontic movement with orthodontic aligners: a retrospective study

The aim of this study was to evaluate the predictability of F22 aligners (Sweden & Martina, Due Carrare, Italy) in guiding teeth into the positions planned using digital orthodontic setup

RNA extraction from plant tissue - The use of calcium to precipitate contaminating pectic sugars

Several protocols and commercial kits are used for the extraction of nucleic acids from different plant tissues. Although there are several procedures available to remove sugars, which hinder the extraction of clean genomic DNA, there are few to assist with extraction of RNA. Those presently used include precipitations with ethylene glycol monobutyl ether or lithium chloride (LiCl), or centrifugation in cesium chloride (CsCl) gradients, but these generally either do not allow high recovery of RNA, are time consuming, rely on hazardous chemicals or need special equipment. Here we present the use of the simple cation, Ca2+, which has been tested and shown to be very efficient for the precipitation of high molecular weight pectic sugars during RNA extraction. Results are presented for different plant tissues, especially tissues of peach and apple fruits at varying ripening stages

Molecular, cellular and physiological characterization of the cancer cachexia-inducing C26 colon carcinoma in mouse

Abstract Background The majority of cancer patients experience dramatic weight loss, due to cachexia and consisting of skeletal muscle and fat tissue wasting. Cachexia is a negative prognostic factor, interferes with therapy and worsens the patients' quality of life by affecting muscle function. Mice bearing ectopically-implanted C26 colon carcinoma are widely used as an experimental model of cancer cachexia. As part of the search for novel clinical and basic research applications for this experimental model, we characterized novel cellular and molecular features of C26-bearing mice. Methods A fragment of C26 tumor was subcutaneously grafted in isogenic BALB/c mice. The mass growth and proliferation rate of the tumor were analyzed. Histological and cytofluorometric analyses were used to assess cell death, ploidy and differentiation of the tumor cells. The main features of skeletal muscle atrophy, which were highlighted by immunohistochemical and electron microscopy analyses, correlated with biochemical alterations. Muscle force and resistance to fatigue were measured and analyzed as major functional deficits of the cachectic musculature. Results We found that the C26 tumor, ectopically implanted in mice, is an undifferentiated carcinoma, which should be referred to as such and not as adenocarcinoma, a common misconception. The C26 tumor displays aneuploidy and histological features typical of transformed cells, incorporates BrdU and induces severe weight loss in the host, which is largely caused by muscle wasting. The latter appears to be due to proteasome-mediated protein degradation, which disrupts the sarcomeric structure and muscle fiber-extracellular matrix interactions. A pivotal functional deficit of cachectic muscle consists in increased fatigability, while the reported loss of tetanic force is not statistically significant following normalization for decreased muscle fiber size. Conclusions We conclude, on the basis of the definition of cachexia, that ectopically-implanted C26 carcinoma represents a well standardized experimental model for research on cancer cachexia. We wish to point out that scientists using the C26 model to study cancer and those using the same model to study cachexia may be unaware of each other's works because they use different keywords; we present strategies to eliminate this gap and discuss the benefits of such an exchange of knowledge.</p

70º Aniversario de la declaración universal de derechos humanos. La protección internacional de los Derechos Humanos en cuestión

Segundo volúmen de la Colección Perspectivas Iberoamericanas sobre la justicia. La Declaración Universal de los Derechos Humanos de las Naciones Unidas cumple, el 10 de diciembre de 2018, setenta años. La simbólica fecha obliga a los investigadores en derechos humanos a reflexionar críticamente sobre los avances y límites de un complejo sistema de normas y, sobre todo, de valores culturales sustentados en la matriz liberal occidental. Desde entonces, ha habido indiscutibles avances institucionales y normativos, como la creación del Consejo de Derechos Humanos, varios pactos y declaraciones complementarias, órganos específicos, tribunales internacionales, jurisprudencia, constituciones estatales, una infinidad de instituciones basadas en esta “ética mínima universal” que, contradictoriamente, no logró evitar un conjunto de catástrofes humanitarias y de vulneración de derechos. La primera década del siglo XX trae un reflejo limitante al consenso de la posguerra, pues la agresividad de los Estados hegemónicos, en alianza con intereses privados transnacionales, pone en jaque la capacidad del sistema protector frente a guerras humanitarias e internacionales. tratados económicos de nueva generación aquellos que excluyen por completo a la democracia del proceso de negociación.A Declaração Universal dos Direitos Humanos das Nações Unidas completa, em 10 de diciembre de 2018, setenta años. A data simbólica exige dos pesquisadores em direitos humanos uma reflexão crítica a respeito dos avanços y dos limites de um sistema complexo de normas e, principalmente, de valores culturales apoiados na matriz liberal ocidental. De lá para cá, houve indiscutível avanço institucional e normativo, do qual é exemplo a criação do Conselho de Direitos Humanos, diversos pactos e declarações complementarios, órgão específicos, tribunais internacionais, jurisprudência, constituições dos States, uma infinidade de instituições pautadas nesse “mínimo ético universal” que, contraditoriamente, não conseguiu evitar um conjunto de catástrofes humanitárias e de violação de direitos. A primeira década do século XX traz uma reflexão limite para o consenso do pós-guerra, pois a agressividade dos States hegemônicos, em aliança com interesses private transnacionais, põe em check a capacidade do sistema protectivo diante das guerras humanitárias e dos tratados internacionais econômicos de nueva generación aqueles que excluem completamente a democracia do processo negociador