Alternative Lengthening of Telomeres (ALT) is a telomere maintenance pathway utilised in 15% of cancers. ALT cancers are strongly associated with inactivating mutations in ATRX; yet loss of ATRX ...alone is insufficient to trigger ALT, suggesting that additional cooperating factors are involved. We identify H3.3
and IDH1/2 mutations as two such factors in ATRX-mutated glioblastomas. Both mutations are capable of inactivating histone demethylases, and we identify KDM4B as the key demethylase inactivated in ALT. Mouse embryonic stem cells inactivated for ATRX, TP53, TERT and KDM4B (KDM4B knockout or H3.3
) show characteristic features of ALT. Conversely, KDM4B over-expression in ALT cancer cells abrogates ALT-associated features. In this work, we demonstrate that inactivation of KDM4B, through H3.3
or IDH1/2 mutations, acts in tandem with ATRX mutations to promote ALT in glioblastomas.
The present study investigated the kinetics of heat pump drying of cocoa beans under stepwise drying conditions and the heat and mass transfer analysis carried out using 3-D computer simulation. The ...fermented cocoa beans were subject to drying at constant temperature (56 °C), step up temperature (30.7 °C–43.6°C–56.9 °C) and step down temperature (54.9 °C–43.9 °C) drying profiles. Shrinkage factor was incorporated into the heat and mass transfer models. Simulation results showed that the mean relative errors determined ranged from 3.1% to 12.1% in the predicted moisture ratio profiles in both models with and without shrinkage factor. In the bean temperature profiles, results showed excellent agreement between the predicted and experimental data with mean relative errors less than 5%. The present study showed that shrinkage played a lesser role in the analysis due to the small shrinkage ratio observed before and after drying.
► Heat and mass transfer analyses were carried out using a 3-D cocoa bean model under stepwise drying condition. ► Results showed good agreement between the experimental and predicted data. ► Shrinkage could be insignificant in the model due to the mild drying conditions.
Eph receptors interact with ephrin ligands on adjacent cells to facilitate tissue patterning during normal and oncogenic development, in which unscheduled expression and somatic mutations contribute ...to tumor progression. EphA and B subtypes preferentially bind A- and B-type ephrins, respectively, resulting in receptor complexes that propagate via homotypic Eph-Eph interactions. We now show that EphA and B receptors cocluster, such that specific ligation of one receptor promotes recruitment and cross-activation of the other. Remarkably, coexpression of a kinase-inactive mutant EphA3 with wild-type EphB2 can cause either cross-activation or cross-inhibition, depending on relative expression. Our findings indicate that cellular responses to ephrin contact are determined by the EphA/EphB receptor profile on a given cell rather than the individual Eph subclass. Importantly, they imply that in tumor cells coexpressing different Ephs, functional mutations in one subtype may cause phenotypes that are a result of altered signaling from heterotypic rather from homotypic Eph clusters.
► The moisture content profile of the cotyledon and testa of cocoa was investigated. ► The moisture content of the testa was higher than the cotyledon at the end of drying. ► The heat pump dryer ...could preserve greater amount of polyphenols during drying. ► Hardness was found comparable to commercial products.
Investigation was carried out to study the drying kinetics of the individual layer of cocoa beans, namely the testa and cotyledon, during heat pump drying. The cocoa beans were dried in thin layer using dehumidified air at 28.2°C, 40.4°C and 56°C. Moisture contents of the bean, testa and cotyledon were recorded during drying. Reduction in moisture content was relatively fast at the testa as compared to the cotyledon in the initial two hours of drying. Subsequent drying showed a crossover region where the moisture content of the testa was higher than the cotyledon. The final moisture content of the testa was found to be higher than the inner cotyledon at the end of drying. This showed that moisture migrated from the cotyledon (lower moisture content) to the testa (higher moisture content) during drying. Although such transfer mechanism seems contradict but this can be further explained by the mass transfer potential concept as postulated by Luikov where the transfer of moisture is due to moisture potential difference instead of moisture content difference. Product quality analyses showed percent retention of cocoa polyphenols ranged from 44% to 73% as compared to freeze dried sample. Bean hardness was found reasonably comparable to the commercial sample and increased with decreasing moisture content.
p53 is the most frequently mutated tumor-suppressor gene in human cancers. Unlike other tumor-suppressor genes, p53 mutations mainly occur as missense mutations within the DNA-binding domain, leading ...to the expression of full-length mutant p53 protein. Mutant p53 proteins not only lose their tumor-suppressor function, but may also gain new oncogenic functions and promote tumorigenesis. Here, we showed that silencing of endogenous p53-R273H contact mutant, but not p53-R175H conformational mutant, reduced AKT phosphorylation, induced BCL2-modifying factor (BMF) expression, sensitized BIM dissociation from BCL-XL and induced mitochondria-dependent apoptosis in cancer cells. Importantly, cancer cells harboring endogenous p53-R273H mutant were also found to be inherently resistant to anoikis and lack BMF induction following culture in suspension. Underlying these activities is the ability of p53-R273H mutant to suppress BMF expression that is dependent on constitutively active PI3K/AKT signaling. Collectively, these findings suggest that p53-R273H can specifically drive AKT signaling and suppress BMF expression, resulting in enhanced cell survivability and anoikis resistance. These findings open the possibility that blocking of PI3K/AKT will have therapeutic benefit in mutant p53-R273H expressing cancers.
A new semi-theoretical thin layer model for modeling the air drying of cocoa beans with overnight tempering at ambient temperature was developed. The new model was a combination of the Page and ...two-term drying model. Results showed that the new model was found best described the drying process under the conditions tested (60, 70 and 80
°C). Effective diffusivities were found between 7.46
×
10
−11 and 1.87
×
10
−10
m
2/s. The Arrhenius constant and activation energy were estimated at 8.43
×
10
−4
m
2/s and 44.92
KJ/mol, respectively. Analyses of pH and cut test for bean quality showed that beans dried at 60
°C had lower acidity and good flavour quality as compared to other drying treatments.
From an analysis of the distributions of measures of transmission rates among hosts, we identify an empirical relationship suggesting that, typically, 20% of the host population contributes at least ...80% of the net transmission potential, as measured by the basic reproduction number, R0. This is an example of a statistical pattern known as the 20/80 rule. The rule applies to a variety of disease systems, including vector-borne parasites and sexually transmitted pathogens. The rule implies that control programs targeted at the ``core'' 20% group are potentially highly effective and, conversely, that programs that fail to reach all of this group will be much less effective than expected in reducing levels of infection in the population as a whole.
This research investigated the effects of convective air drying on the quality of raw and cooked chicken breast meats at 60, 70, and 80°C. Raw samples were cut into sizes of 20 mm × 20 mm × 7 mm and ...cooked samples were precooked in hot water and cut into similar sizes. It was observed that cooked samples had a lower initial moisture content and dried faster than the raw samples. The thicknesses of raw samples were observed to increase in the first 2 h due to internal water vapor generation. The rigid structure of the cooked samples resulted in a lower degree of shrinkage compared to the raw samples. Rehydration capacity was lower in the cooked samples, which could be due to the rigid structure resulting from the precooking process. This further reduced the imbibition of water into the sample. Effective diffusivity values were determined in the order of magnitude of 10
−11
m
2
/s and comparable to those from the literature. Hardness values of dried cooked samples were significantly higher (p < 0.05) than the dried raw samples, whereas elasticity was significantly lower (p < 0.05).
In this study fermented cocoa beans were dried in a direct solar dryer at three levels of loading (20, 30 and 60 kg). Surface mouldiness was found to be heavy in the 60 kg treatment, with beans ...appearing blackish. All the dried beans were reasonably acceptable in terms of vinegary odour and weak in alcohol odour. Weak odour was also detected for the faecal, rancid and cheesy odours. The 60 kg treatment was rated strong for wet sock odour due to poor drying condition. A significant difference (P < 0.05) was found between the 60 kg treatment and the lower loading treatments for pH and titratable acidity. A cut test showed that the lower loading treatments resulted in a higher percentage of brown beans. The 20 kg treatment showed the highest cut test score, which is significantly different (P < 0.05) from the 60 kg treatment. Fermentation index also showed a tendency for lower loading treatments to have a higher index. No significant difference (P > 0.05) was found among the treatments in terms of cocoa, astringency, bitterness and sourness flavour notes. However, better flavour was observed for beans from the 20 kg treatment. No mouldy off flavour was found in any of the dried beans. Overall quality assessment showed that the 20 kg treatment was able to produce reasonably good-quality beans as compared to other loadings and therefore is recommended for the direct solar dryer.
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