Validation of the Thai version of the family reported outcome measure (FROM-16)© to assess the impact of disease on the partner or family members of patients with cancer

© The Author(s). 2019Background: Cancer not only impairs a patient's physical and psychosocial functional behaviour, but also contributes to negative impact on family members' health related quality of life. Currently, there is an absence of a relevant tool in Thai with which to measure such impact. The aim of this study was to translate and validate the Family Reported Outcome Measure (FROM-16) in Thai cancer patients' family members. Methods: Thai version of FROM-16 was generated by interactive forward-backward translation process following standard guidelines. This was tested for psychometric properties including reliability and validity, namely content validity, concurrent validity, known group validity, internal consistency, exploratory and confirmatory factor analysis. Construct validity was examined by comparing the Thai FROM-16 version with the WHOQOL-BREF-THAI. Results: The internal consistency reliability was strong (Cronbach's alpha = 0.86). A Negative moderate correlation between the Thai FROM-16 and WHOQOL-BREF-THAI was observed (r = - 0.4545, p < 0.00), and known group validity was proved by a statistically significant higher score in family members with high burden of care and insufficient income. The factor analysis supported both 3-factor and 2-factor loading model with slight difference when compared with the original version. Conclusions: The Thai FROM-16 showed good reliability and validity in Thai family members of patients with cancer. A slight difference in factor analysis results compared to the original version could be due to cross-culture application.Peer reviewedFinal Published versio

Parallel Imaging of Thickness Variations and Disbonding of Thermal Barrier Coatings by Time-Resolved Infrared Radiometry (TRIR)

Pulsed photothermal radiometry has been shown to be a useful thermally-based nondestructive evaluation technique for various thin films and layered specimens [1,2]. In this method the time development of the surface temperature is studied for both heating and cooling, during and after the application of a step heating pulse of duration, T. In this paper, we show that the method gives quantitative information about layered materials including measurement of coating thickness and the detection and characterization of disbonding between layers. Since all times are monitored, it is not necessary to know the thickness of the coating provided the heating pulse is set longer than the thermal transit time of the coating. As a result, both coating thickness and the integrity of the coating-substrate bond can be determined simultaneously

Methods designed for the identification and characterization of in vitro and in vivo chromatin assembly mutants in Saccharomyces cerevisiae

Assembly of DNA into chromatin allows for the formation of a barrier that protects naked DNA from protein and chemical agents geared to degrade or metabolize DNA. Chromatin assembly occurs whenever a length of DNA becomes exposed to the cellular elements, whether during DNA synthesis or repair. This report describes tools to study chromatin assembly in the model system Saccharomyces cerevisiae. Modifications to an in vitro chromatin assembly assay are described that allowed a brute force screen of temperature sensitive (ts) yeast strains in order to identify chromatin assembly defective extracts. This screen yielded mutations in genes encoding two ubiquitin protein ligases (E3s): RSP5, and a subunit of the Anaphase Promoting Complex (APC), APC5. Additional modifications are described that allow for a rapid analysis and an in vivo characterization of yeast chromatin assembly mutants, as well as any other mutant of interest. Our analysis suggests that the in vitro and in vivo chromatin assembly assays are responsive to different cellular signals, including cell cycle cues that involve different molecular networks

Selective Estrogen Receptor Down-Regulator and Selective Estrogen Receptor Modulators Differentially Regulate Lactotroph Proliferation

occupation, differentially modulates the biological outcome of anti-estrogens. expression and release, as well as ERE-mediated transcriptional activity. expression

The Intracellular Localization of ID2 Expression Has a Predictive Value in Non Small Cell Lung Cancer

ID2 is a member of a subclass of transcription regulators belonging to the general bHLH (basic-helix-loophelix) family of transcription factors. In normal cells, ID2 is responsible for regulating the balance between proliferation and differentiation. More recent studies have demonstrated that ID2 is involved in tumor progression in several cancer types such as prostate or breast

The Polycomb Repressive Complex 2 Is a Potential Target of SUMO Modifications

The Polycomb Repressive Complex 2 (PRC2) functions as a transcriptional repressor through a mechanism that involves methylation of Histone H3 at lysine 27. The PRC2 complex activity is essential for cellular proliferation, development, and cell fate decisions. PRC2 target genes include important regulators of development and proliferation as well as tumor suppressor genes. Consistent with this, the activity of several Polycomb group (PcG) proteins is deregulated in human cancer suggesting an important role for PcGs in tumor development. Whereas the downstream functions of PcGs are well characterized, the mechanisms of their recruitment to target genes and the regulation of their activity are not fully understood.Here we show that the two PRC2 components SUZ12 and EZH2 are sumoylated in vitro and in vivo. Among several putative sumoylation sites we have mapped the major site of SUZ12 sumoylation. Furthermore, we show that SUZ12 interacts with the E2-conjugating enzyme UBC9 both in vitro and in vivo and that mutation of the SUZ12 sumoylation site does not abolish this binding. Finally, we provide evidence that the E3-ligase PIASXbeta interacts and enhances the sumoylation of SUZ12 in vivo suggesting that PIASXbeta could function as an E3-ligase for SUZ12.Taken together, our data identify sumoylation as a novel post-translational modification of components of the PRC2 complex, which could suggest a potential new mechanism to modulate PRC2 repressive activity. Further work aimed to identify the physiological conditions for these modifications will be required to understand the role of SUZ12 and EZH2 sumoylation in PcG-mediated epigenetic regulation of transcription

Cheaters allow cooperators to prosper

Cooperation based on the production of costly common goods is observed throughout nature. This is puzzling, as cooperation is vulnerable to exploitation by defectors which enjoy a fitness advantage by consuming the common good without contributing fairly. Depletion of the common good can lead to population collapse and the destruction of cooperation. However, population collapse implies small population size, which, in a structured population, is known to favor cooperation. This happens because small population size increases variability in cooperator frequency across different locations. Since individuals in cooperator-dominated locations (which are most likely cooperators) will grow more than those in defector-dominated locations (which are most likely defectors), cooperators can outgrow defectors globally despite defectors outgrowing cooperators in each location. This raises the possibility that defectors can lead to conditions that sometimes rescue cooperation from defector-induced destruction. We demonstrate multiple mechanisms through which this can occur, using an individual-based approach to model stochastic birth, death, migration, and mutation events. First, during defector-induced population collapse, defectors occasionally go extinct before cooperators by chance, which allows cooperators to grow. Second, empty locations, either preexisting or created by defector-induced population extinction, can favor cooperation because they allow cooperator but not defector migrants to grow. These factors lead to the counterintuitive result that the initial presence of defectors sometimes allows better survival of cooperation compared to when defectors are initially absent. Finally, we find that resource limitation, inducible by defectors, can select for mutations adaptive to resource limitation. When these mutations are initially present at low levels or continuously generated at a moderate rate, they can favor cooperation by further reducing local population size. We predict that in a structured population, small population sizes precipitated by defectors provide a "built-in" mechanism for the persistence of cooperation

The frequency-dependent Wright-Fisher model: diffusive and non-diffusive approximations

We study a class of processes that are akin to the Wright-Fisher model, with transition probabilities weighted in terms of the frequency-dependent fitness of the population types. By considering an approximate weak formulation of the discrete problem, we are able to derive a corresponding continuous weak formulation for the probability density. Therefore, we obtain a family of partial differential equations (PDE) for the evolution of the probability density, and which will be an approximation of the discrete process in the joint large population, small time-steps and weak selection limit. If the fitness functions are sufficiently regular, we can recast the weak formulation in a more standard formulation, without any boundary conditions, but supplemented by a number of conservation laws. The equations in this family can be purely diffusive, purely hyperbolic or of convection-diffusion type, with frequency dependent convection. The particular outcome will depend on the assumed scalings. The diffusive equations are of the degenerate type; using a duality approach, we also obtain a frequency dependent version of the Kimura equation without any further assumptions. We also show that the convective approximation is related to the replicator dynamics and provide some estimate of how accurate is the convective approximation, with respect to the convective-diffusion approximation. In particular, we show that the mode, but not the expected value, of the probability distribution is modelled by the replicator dynamics. Some numerical simulations that illustrate the results are also presented

Fine Tuning of Globin Gene Expression by DNA Methylation

Expression patterns in the globin gene cluster are subject to developmental regulation in vivo. While the γ(A) and γ(G) genes are expressed in fetal liver, both are silenced in adult erythrocytes. In order to decipher the role of DNA methylation in this process, we generated a YAC transgenic mouse system that allowed us to control γ(A) methylation during development. DNA methylation causes a 20-fold repression of γ(A) both in non-erythroid and adult erythroid cells. In erythroid cells this modification works as a dominant mechanism to repress γ gene expression, probably through changes in histone acetylation that prevent the binding of erythroid transcription factors to the promoter. These studies demonstrate that DNA methylation serves as an elegant in vivo fine-tuning device for selecting appropriate genes in the globin locus. In addition, our findings provide a mechanism for understanding the high levels of γ-globin transcription seen in patients with Hereditary Persistence of Fetal Hemoglobin, and help explain why 5azaC and butyrate compounds stimulate γ-globin expression in patients with β-hemoglobinopathies

A Novel OxyR Sensor and Regulator of Hydrogen Peroxide Stress with One Cysteine Residue in Deinococcus radiodurans

In bacteria, OxyR is a peroxide sensor and transcription regulator, which can sense the presence of reactive oxygen species and induce antioxidant system. When the cells are exposed to H2O2, OxyR protein is activated via the formation of a disulfide bond between the two conserved cysteine residues (C199 and C208). In Deinococcus radiodurans, a previously unreported special characteristic of DrOxyR (DR0615) is found with only one conserved cysteine. dr0615 gene mutant is hypersensitive to H2O2, but only a little to ionizing radiation. Site-directed mutagenesis and subsequent in vivo functional analyses revealed that the conserved cysteine (C210) is necessary for sensing H2O2, but its mutation did not alter the binding characteristics of OxyR on DNA. Under oxidant stress, DrOxyR is oxidized to sulfenic acid form, which can be reduced by reducing reagents. In addition, quantitative real-time PCR and global transcription profile results showed that OxyR is not only a transcriptional activator (e.g., katE, drb0125), but also a transcriptional repressor (e.g., dps, mntH). Because OxyR regulates Mn and Fe ion transporter genes, Mn/Fe ion ratio is changed in dr0615 mutant, suggesting that the genes involved in Mn/Fe ion homeostasis, and the genes involved in antioxidant mechanism are highly cooperative under extremely oxidant stress. In conclusion, these findings expand the OxyR family, which could be divided into two classes: typical 2-Cys OxyR and 1-Cys OxyR