Efecto protector del factor de crecimiento de hepatocitos (HGF) a nivel intestinal en un modelo murino de colestasis química inducida por α-Naftilisotiocianato (ANIT)

La colestasis es una condición del hígado en la que el flujo de la bilis se ve interrumpido por diversos factores. Actualmente existen una serie de modelos para el estudio de esta enfermedad, como el inducido por ANIT. El daño causado por ANIT se incrementa por una producción elevada de especies reactivas de oxigeno. El factor de crecimiento de hepatocitos (HGF) ha demostrado tener propiedades reguladoras sobre la producción de ROS, y gracias a esto, se ha sugerido como una molécula protectora en enfermedades donde el estrés oxidante es determinante para el daño. El estrés oxidante es regulado por HGF ya que puede desencadenar la transcripción de genes blancos regulados por Nrf2. Lo que observamos en el presente estudio fue que HGF pudo contrarrestar el daño en el intestino inducido por ANIT, principalmente la colestasis característica del modelo. En nuestros resultados, HGF mostró proteger la obstrucción intestinal. Así mismo, se demostró que el tratamiento con HGF protegió las zonas mas susceptibles del intestino. A nivel de íleon y colon se observó el incremento del tamaño de criptas y vellosidades, como un evento de proliferación y diferenciación desencadenados por HGF. Estos eventos favorecieron la actividad y protección del íleon y colon, principalmente por el incremento de la secreción de mucinas, disminuyendo la muerte celular. De igual manera, HGF reguló la respuesta inflamatoria entre el colon y el intestino, ya que por un lado disminuyó la inflamación de íleon, y por otro lado incrementó la respuesta reparadora en el colon, principalmente a nivel de translocación de bacterias. Finalmente, HGF mostró tener regulación de ROS en los ratones tratados previamente con ANIT, fenómeno caracterizado por el incremento de proteínas antioxidantes y disminución de presencia de anión superóxido en el tejido observado por la tinción por dihidroetidio. En conclusión, los resultados demostraron que HGF ejerce protección a nivel intestinal en la enfermedad colestásica inducido por ANIT.Cholestasis is a condition of the liver in which the flow of bile is interrupted by various factors. Currently there are several models for the study of this disease, such as the one induced by ANIT. The damage caused by ANIT is increased by an explosion of reactive oxygen species. Hepatocyte growth factor has been shown to have regulatory properties of ROS and thanks to this it has been presented as a protective molecule in diseases where oxidative stress is decisive for damage. Oxidative stress is regulated by HGF as it can trigger the transcription of Nrf2 target genes. What we observed in the present study was that HGF was able to sustain the damage to the gut caused by ANITinduced cholestasis. In our results, HGF was shown to protect the jejunum from intestinal obstruction. Later it was shown that treatment with HGF protected the most susceptible areas of the intestine. At the level of the ileum and colon, the increase in the size of crypts and villi was observed as an event of proliferation and differentiation triggered by HGF. These events favored the activity and protection of the ileum and colon seen by increasing mucin secretion and decreasing cell death in A+H treatments. Similarly, HGF regulated in an interesting way the inflammatory response between the colon and the intestine, on the one hand, decreasing the inflammation of the ileum and on the other, increasing the reparative response in the colon where the translocation of bacteria could increase the damage. Finally, HGF was shown to upregulate ROS in ANIT-pretreated mice seen by increased antioxidant proteins and decreased dihydroethidium staining. In conclusion, the results demonstrated that HGF exerted protection at the intestinal level in cholestatic disease induced by ANIT

Formative E-Assessment of Schema Acquisition in the Human Lexicon as a Tool in Adaptive Online Instruction

This chapter presents a comprehensive method of implementing e-assessment in adaptive e-instruction systems. Specifically, a neural net classifier capable of discerning whether a student has integrated new schema-related concepts from course content into her/his lexicon is used by an expert system with a database containing natural mental representations from course content obtained from students and teachers for adapting e-instruction. Mental representation modeling is used to improve student modeling. Implications for adaptive hypermedia systems and hypertext-based instructions are discussed. Furthermore, it is argued that the current research constitutes a new cognitive science empirical direction to evaluate knowledge acquisition based on meaning information

Global patterns in monthly activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus: a systematic analysis

Background: Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control. Methods: In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628. Findings: We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI −0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus −0·2 months [−0·6 to 0·1]; respiratory syncytial virus 0·1 months [−0·2 to 0·4]). Interpretation: This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination. Funding: European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU)

Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer

Abstract: Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for ‘selfish’ traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby ‘selfish’ positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells

Cholangiocyte death in ductopenic cholestatic cholangiopathies: Mechanistic basis and emerging therapeutic strategies

Among hepatic diseases, cholestatic ductopenic cholangiopathies are poorly studied, and they are rarely given the importance they deserve, especially considering their high incidence in clinical practice. Although cholestatic ductopenic cholangiopathies have different etiologies and pathogenesis, all have the same target (the cholangiocyte) and similar mechanistic basis of cell death. Cholestatic cholangiopathies are characterized, predominantly, by obstructive or functional damage in the biliary epithelium, resulting in an imbalance between proliferation and cholangiocellular death; this leads to the progressive disappearance of bile ducts, as has been shown to occur in primary sclerosing cholangitis, primary biliary cholangitis, low-phospholipid-associated cholelithiasis syndrome, cystic fibrosis-related liver disease, and drug-induced ductopenia, among other biliary disorders. This review summarizes the features of the more common ductopenic syndromes and the cellular mechanisms involved in cholengiocellular death, with focus on the main forms of cholangiocyte death described so far, namely apoptosis, autophagy, necrosis, and necroptosis. It also emphasizes the importance to study in depth the molecular mechanisms of cholengiocyte death to make possible to counteract them with therapeutic purposes. These therapeutic strategies are limited in number and efficacy at present, and this is why it is important to find complementary, safe strategies to stimulate cholangiocellular proliferation in order favor bile duct replenishment as well. Successful in finding appropriate treatments would prevent the patient from having liver transplantation as the only therapeutic alternative.Fil: Salas Silva, Soraya. Universidad Autónoma Metropolitana; MéxicoFil: Simoni Nieves, Arturo. Universidad Autónoma Metropolitana; MéxicoFil: Lopez Ramirez, Jocelyn. Universidad Autónoma Metropolitana; MéxicoFil: Bucio, Leticia. Universidad Autónoma Metropolitana; México. Instituto Nacional de Cardiología Ignacio Chavez; México. Universidad Nacional Autónoma de México; MéxicoFil: Gómez Quiroz, Luis E.. Universidad Autónoma Metropolitana; México. Instituto Nacional de Cardiología Ignacio Chavez; México. Universidad Nacional Autónoma de México; MéxicoFil: Gutiérrez Ruiz, María Concepción. Universidad Autónoma Metropolitana; México. Instituto Nacional de Cardiología Ignacio Chavez; México. Universidad Nacional Autónoma de México; MéxicoFil: Roma, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Fisiología Experimental. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Fisiología Experimental; Argentin

miRNA signature associated with R–CHOP refractoriness in patients diagnosed with diffuse large B cell lymphoma

Refractoriness remains as one of the challenges in patients with lymphoma under chemotherapy, and among biological regulators in cells driving this type of response are microRNAs (miRNAs). Different genes are constantly turned on or off according to the miRNAs expression profiles affecting the drug response in patients and their stability in serum and plasma makes them potential prognostic biomarkers in several diseases. Here we described a profile of miRNAs in plasma of diffuse large B cell lymphoma (DLBCL) patients. miRNA expression arrays were carried using pre-treatment plasma samples of sixteen patients, followed by a comparison between the responder and the non-responders. After six cycles of R–CHOP treatment, twelve out of sixteen patients were clinically diagnosed with complete response while in four patients no clinical response was observed. Between these groups, a signature of fifteen differential expressed miRNAs was found. The circulating miRNAs in plasma of patients with no response were related to the drug resistance in other types of cancer, by targeting genes involved in cell proliferation and apoptosis, among other cell processes

Where Brain, Body and World Collide

The production cross section of electrons from semileptonic decays of beauty hadrons was measured at mid-rapidity (|y| &lt; 0.8) in the transverse momentum range 1 &lt; pt &lt; 8 Gev/c with the ALICE experiment at the CERN LHC in pp collisions at a center of mass energy sqrt{s} = 7 TeV using an integrated luminosity of 2.2 nb^{-1}. Electrons from beauty hadron decays were selected based on the displacement of the decay vertex from the collision vertex. A perturbative QCD calculation agrees with the measurement within uncertainties. The data were extrapolated to the full phase space to determine the total cross section for the production of beauty quark-antiquark pairs

Yorba Times: Global Issues

During the Spring 2017 semester, Dr. Noah Asher Golden\u27s Teaching of Writing K-12 students partnered with the Journalism class at Yorba Academy for the Arts. Through collaboration over a four-month period, Chapman\u27s future teachers and Yorba\u27s junior high journalists engaged a deep writing process to write a series of features, editorials, and news articles related to a number of global issues. Thank you to Ms. Andrea Lopez, Ms. Tracy Knibb, and the Lloyd E. and Elisabeth H. Klein Family Foundation for supporting this project.https://digitalcommons.chapman.edu/yorba-chapman/1002/thumbnail.jp