The six main minichromosome maintenance proteins (Mcm2-7), which presumably constitute the core of the replicative DNA helicase, are present in chromatin in large excess relative to the number of ...active replication forks. To evaluate the relevance of this apparent surplus of Mcm2-7 complexes in human cells, their levels were down-regulated by using RNA interference. Interestingly, cells continued to proliferate for several days after the acute (>90%) reduction of Mcm2-7 concentration. However, they became hypersensitive to DNA replication stress, accumulated DNA lesions, and eventually activated a checkpoint response that prevented mitotic division. When this checkpoint was abrogated by the addition of caffeine, cells quickly lost viability, and their karyotypes revealed striking chromosomal aberrations. Single-molecule analyses revealed that cells with a reduced concentration of Mcm2-7 complexes display normal fork progression but have lost the potential to activate "dormant" origins that serve a backup function during DNA replication. Our data show that the chromatin-bound "excess" Mcm2-7 complexes play an important role in maintaining genomic integrity under conditions of replicative stress.
The genome of proliferating cells must be precisely duplicated in each cell division cycle. Chromosomal replication entails risks such as the possibility of introducing breaks and/or mutations in the ...genome. Hence, DNA replication requires the coordinated action of multiple proteins and regulatory factors, whose deregulation causes severe developmental diseases and predisposes to cancer. In recent years, the concept of “replicative stress” (RS) has attracted much attention as it impinges directly on genomic stability and offers a promising new avenue to design anticancer therapies. In this review, we summarize recent progress in three areas: (1) endogenous and exogenous factors that contribute to RS, (2) molecular mechanisms that mediate the cellular responses to RS, and (3) the large list of diseases that are directly or indirectly linked to RS.
Lichen planus pigmentosus (LPP) is considered a rare variant of lichen planus (LP). It is characterized by acquired dark brown to gray macular pigmentation located on sun‐exposed areas of the face, ...neck, and flexures, commonly found in dark‐skinned patients. In patients with LPP, an inflammatory lichenoid response results in marked pigmentary incontinence. It has been associated with hepatitis C virus, sun exposure, and contactants such as mustard oil and nickel. LPP‐inversus affects fair and dark skin, predominantly involving flexural and intertriginous areas, while sun‐exposed areas are spared; friction is an associated trigger. LPP along Blaschko's lines has been associated with susceptibility to genetic mosaicisms. LPP can present concomitantly with other variants of LP such as frontal fibrosing alopecia, as well as endocrinopathies, and autoimmune diseases. Treatment is difficult and consists of avoidance of triggers and topical and systemic medications in order to stop the inflammatory reaction and reduce pigmentation, improving aesthetic appearance and quality of life.
The visualization of medical images with advanced techniques, such as augmented reality and virtual reality, represent a breakthrough for medical professionals. In contrast to more traditional ...visualization tools lacking 3D capabilities, these systems use the three available dimensions. To visualize medical images in 3D, the anatomical areas of interest must be segmented. Currently, manual segmentation, which is the most commonly used technique, and semi-automatic approaches can be time consuming because a doctor is required, making segmentation for each individual case unfeasible. Using new technologies, such as computer vision and artificial intelligence for segmentation algorithms and augmented and virtual reality for visualization techniques implementation, we designed a complete platform to solve this problem and allow medical professionals to work more frequently with anatomical 3D models obtained from medical imaging. As a result, the Nextmed project, due to the different implemented software applications, permits the importation of digital imaging and communication on medicine (dicom) images on a secure cloud platform and the automatic segmentation of certain anatomical structures with new algorithms that improve upon the current research results. A 3D mesh of the segmented structure is then automatically generated that can be printed in 3D or visualized using both augmented and virtual reality, with the designed software systems. The Nextmed project is unique, as it covers the whole process from uploading dicom images to automatic segmentation, 3D reconstruction, 3D visualization, and manipulation using augmented and virtual reality. There are many researches about application of augmented and virtual reality for medical image 3D visualization; however, they are not automated platforms. Although some other anatomical structures can be studied, we focused on one case: a lung study. Analyzing the application of the platform to more than 1000 dicom images and studying the results with medical specialists, we concluded that the installation of this system in hospitals would provide a considerable improvement as a tool for medical image visualization.
Cell division cycle 6 (CDC6) is an essential regulator of DNA replication in eukaryotic cells. Its best-characterized function is the assembly of prereplicative complexes at origins of replication ...during the G1 phase of the cell division cycle. However, CDC6 also plays important roles in the activation and maintenance of the checkpoint mechanisms that coordinate S phase and mitosis, and recent studies have unveiled its proto-oncogenic activity. CDC6 overexpression interferes with the expression of INK4/ARF tumor suppressor genes through a mechanism involving the epigenetic modification of chromatin at the INK4/ARF locus. In addition, CDC6 overexpression in primary cells may promote DNA hyperreplication and induce a senescence response similar to that caused by oncogene activation. These findings indicate that deregulation of CDC6 expression in human cells poses a serious risk of carcinogenesis.
The increasing growth of mobile technology in our Society has become a reality. This paper was designed to research about the different factors and drivers that could influence students’ behaviour ...into the usage of mobile technologies for learning.
The methodology was based on a quantitative survey grounded on the Technology Acceptance Model and the Unified Theory of Acceptance and Use of Technology. Data were collected from medical students in University of Coimbra.
This model pointed to a behaviour pattern based on the experience and application by medical students, correlating with a strong attitude towards using mobile technology for learning (57%) and willingness to recommend it (40.5%).
In line with previous studies, Social Influence raised to be an important factor towards the Attitude and Behavioural Intention of using Mobile Learning. In addition, according to the results, the student’s ease of perception seems to be the main factor affecting the Social Influence (31.9%) and the reliability for recommending this technology for learning was the main factor that affected the Behavioural Intention. Findings provide support for Technology Acceptance Model and the implications of these findings are discussed within the context of Innovation in Education.
•We analyse the factors that affect the students’ behaviour towards the use of mobile technologies.•We used the TAM and UTAUT model to design the survey distributed to the medical students.•This research used a component-based SEM technique (Partial Least Square).•Medical students have a strong attitude towards using mobile technologies for learning.•Medical students have a medium willing to adopt the mobile technologies for learning.
Mexican apple production suffers high losses due to poor handling in processing. Implementation of a straightforward, low cost method to sort apples by their ripening stage is required. A set of ...Golden Delicious apples was used to monitor their physicochemical properties and external colour, a second set of apples was used to validate the method. To classify the stages, a ripening index (RPI) was proposed, in which three stages were identified; unripe, ripe and senescent. Weibull model was applied to the physicochemical parameters in order to describe their kinetic behaviour. The three RPI stages were compared with colour variability using the CIELab colour space, chroma (C∗) and hue angle (h∗), allowing the identification of the three ripening stages. Principal component analysis was used to evaluate the correlation between variables. A first correlation was performed between physicochemical and colour parameters and variables correlated correctly between each other except for L∗, but both described the samples variability with 91.05% reliability. Using only colour parameters, the samples were described accurately with 95.06% reliability. Multivariate discriminant analysis (MDA) was done in order to validate the method. A cross-validation was performed with an initial set of apples used as trial samples and a second set of apples for validation. MDA was capable of classifying apples in their correct ripening stage with 100% accuracy. A second analysis was carried out using four colour parameters (a∗, b∗, C and h∗), and results indicated that the ripening stages can be classified with 100% accuracy.
•Physicochemical and colour parameters describe well three stages of apple maturity.•The degree of ripeness in apples was an important feature to classify them.•Colour could be used instead of physicochemical analysis for ripening assay.•The multivariate analysis is a helpful tool to sorting apples by colour parameters.•CVS was efficient as a non-destructive method for sorting Golden Delicious apples.
The term hemicellulose groups different polysaccharides with heterogeneous structures, mannans, xyloglucans, mixed-linkage β-glucans and xylans, which differ in their backbone and branches, and in ...the type and distribution of glycosidic linkages. The enzymatic degradation of these complex polymers requires the concerted action of multiple hemicellulases and auxiliary enzymes. Most commercial enzymes are produced by Trichoderma and Aspergillus species, but recent studies have disclosed Penicillium and Talaromyces as promising sources of hemicellulases. In this review, we summarize the current knowledge on the hemicellulolytic system of these genera, and the role of hemicellulases in the disruption and synthesis of glycosidic bonds. In both cases, the enzymes from Penicillium and Talaromyces represent an interesting alternative for valorization of lignocellulosic biomass in the current framework of circular economy.
•We introduce an extension of the spatial ODT formulation (S-ODT), in order to study a variable density internal air flow.•S-ODT results are compared to the results of a traditional temporal ODT ...formulation (T-ODT) and to reference DNS data.•For bulk quantities, both the T-ODT and S-ODT formulations have a similar performance in comparison to DNSs.•For the evaluation of radial distributions, the S-ODT formulation clearly outperforms the T-ODT formulation.
A novel spatial formulation of the One-Dimensional Turbulence (ODT) model is applied to a vertical pipe-flow with heat transfer, analogous to the Direct Numerical Simulation (DNS) performed by Bae et al. Phys. Fluids 18, (075102) (2006). The framework presented here is an extension for radially confined domains of the cylindrical ODT spatial formulation for low Mach number flows with variable density. The variable density simulations for air (Prandtl number Pr=0.71) are performed at an initial bulk Reynolds number Reb,0,DNS=6000 and Grashof number Gr0,DNS=6.78×106. ODT results are presented for both the spatial formulation introduced in this work and the standard temporal formulation for cylindrical flows introduced by Lignell et al. Theor. Comput. Fluid Dyn. 32, 4 (2018), pp. 495–20. Streamwise bulk profiles and radial profiles at specific streamwise positions for the temporal and spatial formulations are in good agreement with the DNS results from Bae et al. For the present application, the spatial formulation yields physically better results in comparison to the temporal formulation. Overall, the findings in the original work of Bae et al. were corroborated with ODT. Although the framework proposed in this work is not a compressible framework and has some clear limitations regarding conservation properties, we suggest its use for future studies in the low Mach number variable density regime.
•Chia seed mucilage can emerge as a potential industrial additive.•Chia mucilage release can be studied by applying drug release mathematical models.•Microscopy and Image analysis can be used to ...model chia mucilage release process.
Chia seed mucilage could be used as industrial additive due to its outstanding physical properties. However, not many reports about this gel have been published, maybe due to it remains tightly bounded to the coat seed during processing. The aim of this work was to characterise the chia seed structure and the mucilage release by microscopy, spectroscopy and image analysis techniques. Results showed that the mucilage is excreted from the polygonal cells of the epidermis coat, being composed mainly by carbohydrates fibres (18–45nm width). It was observed from the kinetic modelling that the mucilage release follows a non Fickian process (0.5<n<1.0), presenting the best fitting the Peppas and Sahlin equation (R2=0.9984 and EDM %=0.8). Chia mucilage could be used for the controlled release of drugs, or, as a result of the size of its fibres, for the production of nanocomposites.
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