ABSTRACT
Reliable establishment of tumor organoids is paramount to advance applications of organoid technology for personalized medicine. Here, we share our multi-center experience on initiation and tumorigenic confirmation of hepatobiliary cancer organoids. We discuss current concerns, propose potential solutions, and provide future perspectives for improvements in hepatobiliary cancer organoid establishment.
Subject(s)
Gastrointestinal Neoplasms , Organoids , Humans , Precision MedicineABSTRACT
Organoid cultures have emerged as an alternative in vitro system to recapitulate tissues in a dish. While mouse models and cell lines have furthered our understanding of liver biology and associated diseases, they suffer in replicating key aspects of human liver tissue, in particular its complex architecture and metabolic functions. Liver organoids have now been established for multiple species from induced pluripotent stem cells, embryonic stem cells, hepatoblasts and adult tissue-derived cells. These represent a promising addition to our toolbox to gain a deeper understanding of this complex organ. In this perspective we will review the advances in the liver organoid field, its limitations and potential for biomedical applications.
Subject(s)
Biomedical Research/methods , Liver/cytology , Models, Biological , Organoids/physiology , Regenerative Medicine/methods , Animals , Cell Culture Techniques , Cell Line , Humans , Organoids/cytologyABSTRACT
The femtosecond-laser pulse inscription and characterization of fiber Bragg gratings for operation at visible wavelengths was performed using several types of optical fibers, including single-mode and graded-index fibers designed for near-infrared wavelengths. The obtained bandwidths are very narrow (â¼0.12-0.36 nm) for the used exposure conditions, even in graded-index fibers. Thermal and strain characterization was performed, with results about half of those found for C-band gratings. The wavelength dependence of the sensitivity is compared with a Sellmeier model.
ABSTRACT
We performed a complete study of angle noncritical phase-matched second-harmonic generation in BaGa4Se7 in the mid-infrared region. We measured the dielectric frame orientation and showed that it does not rotate as a function of wavelength. We determined the phase-matching wavelengths and the associated spectral and angular acceptances along the x and y axes of the dielectric frame. We also estimated the magnitude of the nonlinear coefficients involved.
ABSTRACT
Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s--the active form of the UPR mediator XBP1--and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection.
Subject(s)
Endoplasmic Reticulum Stress , Hepatocytes/parasitology , Host-Parasite Interactions , Malaria/parasitology , Plasmodium berghei/growth & development , Unfolded Protein Response , Animals , DNA-Binding Proteins/genetics , Gene Expression Profiling , Hepatocytes/physiology , Hepatocytes/ultrastructure , Life Cycle Stages , Malaria/physiopathology , Male , Mice, Inbred C57BL , Parasite Load , Plasmodium berghei/pathogenicity , Proteomics , Regulatory Factor X Transcription Factors , Signal Transduction/genetics , Transcription Factors/genetics , X-Box Binding Protein 1ABSTRACT
The development of new conductive polymers nowadays is one of the most important technological areas in materials design. Computational investigation of desired properties in conductive polymers could save financial resources and time, but it is important to choose the methodology that produces good results comparing to experimental results. To verify the prediction of second hyperpolarizability (γ) in oligomers of Trans-Polyacetylene (TPA) by theoretical calculations, a series of semi-empirical, Hartree-Fock (HF), and Density Functional Theory (DFT) calculations were performed and analysed through linear fitting statistical analysis to investigate the accuracy of such theoretical predictions in comparison to the experimental ones. The results showed that HF and DFT methodologies do not describe γ with good accuracy, but the use of diffuse and polarizability functions in HF methodology provided better results than 3-21G and 6-31G functions. It was concluded that RM1 methodology better agrees with γ experimental results for TPA oligomers, and linear fitting statistical analysis is a useful tool to compare experimental and theoretical results.
ABSTRACT
Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer susceptibility syndrome characterized by early-onset diffuse gastric cancer (DGC) and lobular breast cancer. E-cadherin (CDH1) heterozygous germline mutations and deletions are found in 40% of families. Independent of CDH1 alterations, most HDGC tumours display mislocalized or absent E-cadherin immunoexpression, therefore undetected defects at the CDH1 locus may still be involved. We aimed at determining whether CDH1 mutation-negative probands display germline CDH1 allele-specific expression (ASE) imbalance, using a single-nucleotide primer extension-based procedure and tried to uncover the underlying molecular defect. CDH1 ASE analysis was performed using three intragenic SNPs in RNA extracted from the blood of 21 cancer-free individuals and 22 HDGC probands (5 CDH1 mutation carriers and 17 CDH1 negative). Germline promoter methylation, deletions and haplotype-related susceptibility at the CDH1 locus were analysed. Both CDH1 alleles from cancer-free individuals displayed equivalent expression levels, whereas monoallelic CDH1 expression or high allelic expression imbalance (AI) was present in 80% of CDH1 mutant and 70.6% (n = 12) of CDH1-negative HDGC probands. Germline deletions and promoter hypermethylation were found in 25% of probands displaying high CDH1 AI. No particular haplotype was found to be associated with CDH1 high AI. Germline CDH1 AI is highly frequent among CDH1 mutation-negative probands but was not seen in cancer-free individuals. This implicates the CDH1 locus in the majority of mutation-negative HDGC families.
Subject(s)
Alleles , Cadherins/genetics , Down-Regulation , Genetic Predisposition to Disease , Stomach Neoplasms/genetics , Adult , Antigens, CD , Germ-Line Mutation , Haplotypes , Humans , Stomach Neoplasms/metabolismABSTRACT
Esta investigação tem como objectivo geral analisar a auto-eficácia, na pesquisa de informação escolar e profissional na internet, em alunos do 7º, 9º e 12º anos de escolaridade. Trata-se de um estudo com uma amostra de 187 estudantes (M=15,01; DP=2,142), de ambos os sexos, dos quais 33,2 por cento frequentam o 7º ano, 34,2 por cento o 9º ano e 32,6 por cento o 12º ano. Os resultados da análise da regressão linear múltipla (método stepwise) sugerem que a auto-eficácia na internet para a pesquisa de informação escolar e profissional prediz a actividade exploratória nesse domínio. À medida que se avança no ano de escolaridade, maior é o nível de auto-eficácia entre os estudantes, sendo que são os alunos do 12º ano os que mais confiantes se sentem para realizar as actividades inerentes ao comportamento exploratório na internet sobre carreiras.
The main goal of this study was to analyze the self-efficacy of students attending the last terms of school (7th and 9th) and high school (3rd) grade, in using the internet to do school and professional survey. The sample consisted of 187 students (M=15,01; SD=2,142) of both genders, of which 33,2 percent attended the 7th grade, 34,2 percent, the 9th grade and 32,6 percent the 3rd high school. Multiple regression analyses (stepwise method) indicated that high levels of internet self-efficacy in career information search predicts a wider exploratory activity. Moreover, it was observed that the level of self-efficacy increases with the level of schooling, and that the 3rd high school grade students were the most confident to do career exploration search on the internet.
Esta investigación tiene el objetivo general de analizar la autoeficacia, en la búsqueda de información escolar y profesional en internet, de alumnos de 7, 9 y 12 años de escolaridad. Se trata de un estudio con una muestra de 187 estudiantes (M=15,01; DP=2,142), de ambos sexos, de los cuales 33,2 por ciento frecuentan el 7º año, 34,2 por ciento el 9º año y 32,6 por ciento el 12º año. Los resultados del análisis de la regresión lineal múltiple (método stepwise) sugieren que la autoeficacia en internet para la búsqueda de información escolar y profesional predice la actividad exploratoria en el dominio. A medida que se avanza en años de escolaridad, mayor es el grado de autoeficacia entre los estudiantes, y son los alumnos del 12º año los que más confianza tienen para realizar las actividades inherentes al comportamiento exploratorio, en internet.
Subject(s)
Humans , Male , Female , Adolescent , Internet , Professional Practice , Resources for Research , Self Efficacy , Staff DevelopmentABSTRACT
Esta investigação tem como objectivo geral analisar a auto-eficácia, na pesquisa de informação escolar e profissional na internet, em alunos do 7º, 9º e 12º anos de escolaridade. Trata-se de um estudo com uma amostra de 187 estudantes (M=15,01; DP=2,142), de ambos os sexos, dos quais 33,2 por cento frequentam o 7º ano, 34,2 por cento o 9º ano e 32,6 por cento o 12º ano. Os resultados da análise da regressão linear múltipla (método stepwise) sugerem que a auto-eficácia na internet para a pesquisa de informação escolar e profissional prediz a actividade exploratória nesse domínio. À medida que se avança no ano de escolaridade, maior é o nível de auto-eficácia entre os estudantes, sendo que são os alunos do 12º ano os que mais confiantes se sentem para realizar as actividades inerentes ao comportamento exploratório na internet sobre carreiras.(AU)
The main goal of this study was to analyze the self-efficacy of students attending the last terms of school (7th and 9th) and high school (3rd) grade, in using the internet to do school and professional survey. The sample consisted of 187 students (M=15,01; SD=2,142) of both genders, of which 33,2 percent attended the 7th grade, 34,2 percent, the 9th grade and 32,6 percent the 3rd high school. Multiple regression analyses (stepwise method) indicated that high levels of internet self-efficacy in career information search predicts a wider exploratory activity. Moreover, it was observed that the level of self-efficacy increases with the level of schooling, and that the 3rd high school grade students were the most confident to do career exploration search on the internet.(AU)
Esta investigación tiene el objetivo general de analizar la autoeficacia, en la búsqueda de información escolar y profesional en internet, de alumnos de 7, 9 y 12 años de escolaridad. Se trata de un estudio con una muestra de 187 estudiantes (M=15,01; DP=2,142), de ambos sexos, de los cuales 33,2 por ciento frecuentan el 7º año, 34,2 por ciento el 9º año y 32,6 por ciento el 12º año. Los resultados del análisis de la regresión lineal múltiple (método stepwise) sugieren que la autoeficacia en internet para la búsqueda de información escolar y profesional predice la actividad exploratoria en el dominio. A medida que se avanza en años de escolaridad, mayor es el grado de autoeficacia entre los estudiantes, y son los alumnos del 12º año los que más confianza tienen para realizar las actividades inherentes al comportamiento exploratorio, en internet.(AU)
