Li-Fraumeni syndrome (LFS) is one of the most serious hereditary cancer syndromes with high risk of malignancy already in childhood. Adrenocortical carcinoma, brain tumor, leukemia, sarcoma are the most frequent malignancies in children. Early breast cancer, brain tumor, sarcoma, skin cancer, gastrointestinal, lung, gynecological, hematological and other malignancies can be seen in adults. Predictive testing in families with detected LFS and TP53 mutation is offered from the age of 18 for various reasons. One of the most important reasons is a very limited effectivity of prevention especially in children, also the possible risk of psychological harm to the child and his family caused by the diagnosis of this syndrome. Progress in diagnostic methods, especially total body MRI, enables to propose preventive care for early cancer diagnoses for children and adults. Biochemical tests, ultrasound, MRI may improve survival of these high risk individuals and support the possibility of predictive testing in children.

• MeSH
• celotělové zobrazování * MeSH
• geny p53 genetika   MeSH
• heterozygot * MeSH
• lidé MeSH
• Liův-Fraumeniho syndrom diagnóza   genetika   prevence a kontrola   MeSH
• magnetická rezonanční tomografie * MeSH
• mutace * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Li can find itself a wide range of applications since it is the lightest metal. However, Li detection by microscopy-based techniques is problematic because of the highly susceptible nature during electron beam irradiation. ToF-SIMS is a versatile technique to detect Li but the detection of light materials is also problematic due to the large ion contaminated zone and low sputtering yield. By combining ToF-SIMS with a recently launched Xe ion source FIB-SEM, which has small ion contamination and high sputtering yield features, can produce more realistic data at near surface and below the surface region especially for the detection of lightweight materials such as Li. In this study, Li detection and mapping capabilities of ToF-SIMS attached to the FIB-SEM with Ga and Xe ion sources were discussed for Al incorporated Li7 La3 Zr2 O12 solid electrolyte sample that contains Li and Al rich regions at triple junctions. In spite of smoother milling from Ga source, Xe performs more precisely in Li mapping. Low ion contaminated zone, high sputtering yield and low straggling obtained from Monte Carlo simulations are the main advantages of Xe ion sources. The Li detection efficiency for Xe is higher than Ga source discriminating the LiAlO2 phase placed at the triple junctions of grains and La2 Zr2 O7 regions placed at the outer side of LLZO neighbouring the LiAlO2 phase. LAY DESCRIPTION: Li can find itself a wide range of applications since it is the lightest metal. However, Li detection by microscopy-based techniques is problematic because of the highly susceptible nature during electron beam irradiation. ToF-SIMS is a versatile technique to detect Li but the detection of light materials is also problematic due to the large ion contaminated zone and low sputtering yield. By combining ToF-SIMS with a recently launched Xe ion source FIB-SEM, which has small ion contamination and high sputtering yield features, can produce more realistic data at near surface and below the surface region especially for the detection of lightweight materials such as Li. In this study, Li detection and mapping capabilities of ToF-SIMS attached to the FIB-SEM with Ga and Xe ion sources were discussed for Al incorporated Li7 La3 Zr2 O12 solid electrolyte sample that contains Li and Al rich regions at triple junctions. In spite of smoother milling from Ga source, Xe performs more precisely in Li mapping. Results were also supported from Monte Carlo simulations of ion-atom interactions. The Li detection resolution of xenon is much higher than gallium source discriminating the LiAlO2 phase placed at the triple junctions of grains and La2 Zr2 O7 regions placed at the outer side of LLZO neighbouring the LiAlO2 phase.

• Klíčová slova
• FIB-SEM, Ga ion source, Li detection, ToF-SIMS, Xe ion source,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The tumour suppressor gene p53 is exhibits somatic mutations in a high proportion of human tumours. In addition, there are cancer families suffering from the Li-Fraumeni syndrome, the members of which carry germ line mutations in this gene. The carriers of the p53 germ line mutations have a high risk of developing tumours. The genetic diagnosis of carriership of the mutation in the tumour family members is important for preventive measures and for eventual tumour therapy modification. METHODS AND RESULTS: We have developed a method for the detection of germ line mutations in the p53 gene based on non-radioactive SSCP and direct sequencing of PCR products. We have proved the efficiency of the method by finding known mutations in eight tumour cell lines. In our collection of tumour families we have detected polymorphisms in exons 4 and 6 of the p53 gene. In one family which conformed to the criteria of the Li-Fraumem syndrome we have found a novel germ line mutation in exon 5. CONCLUSIONS: The method developed by us is very simple and sensitive. The germ line mutations in the p53 gene are very rare.

• MeSH
• detekce genetických nosičů MeSH
• genetické markery MeSH
• genetické techniky * MeSH
• geny p53 genetika   MeSH
• lidé MeSH
• Liův-Fraumeniho syndrom diagnóza   genetika   MeSH
• polymerázová řetězová reakce MeSH
• polymorfismus konformace jednovláknové DNA MeSH
• prenatální diagnóza MeSH
• rodokmen MeSH
• zárodečné mutace * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• genetické markery MeSH

We describe two Li-Fraumeni syndrome families. Family A was remarkable for two early childhood cases of adrenocortical tumours, family B for a high incidence of many characteristic cancers, including a childhood case of choroid plexus tumour. Using direct sequencing, we analysed exons 5-9 of the p53 gene in constitutional DNA of individuals from both families and found two novel germline mutations in exon 5. In family A, we detected a point substitution in codon 138 (GCC to CCC), which resulted in the replacement of the alanine by a proline residue. Family B harboured a single-base pair deletion in codon 178 (CAC to -AC), resulting in a frameshift and premature chain termination. Three out of six tumours examined from both families, a renal cell carcinoma, a rhabdomyosarcoma and a breast cancer, showed loss of heterozygosity and contained only the mutant p53 allele. The remaining three neoplasms, both adrenocortical tumours and the choroid plexus tumour retained heterozygosity. Immunohistochemistry with anti-p53 antibody confirmed accumulation of p53 protein in tumours with loss of heterozygosity, while the remaining tumours were p53 negative. These results support the view that complete loss of activity of the wild-type p53 need not be the initial event in the formation of all tumours in Li-Fraumeni individuals.

• MeSH
• alely MeSH
• dítě MeSH
• dospělí MeSH
• geny p53 genetika   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• Liův-Fraumeniho syndrom genetika   MeSH
• mladiství MeSH
• polymerázová řetězová reakce MeSH
• předškolní dítě MeSH
• rodokmen MeSH
• senioři MeSH
• zárodečné mutace genetika   MeSH
• ztráta heterozygozity MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Germline TP53 mutations are found in only 70% of families with the Li-Fraumeni syndrome (LFS), and with an even lower frequency in families suggestive of LFS but not meeting clinical criteria of the syndrome. Despite intense efforts, to date, no other genes have been associated with the disorder in a significant number of TP53 mutation-negative families. A search for defects in TP53 other than heterozygous missense mutations showed that neither intron variants nor sequence variants in the TP53 promoter are frequent in LFS, and multiexon deletions have been found to be responsible for LFS only in several cases. Another cancer predisposition syndrome, hereditary non-polyposis colon cancer, has been associated with epigenetic silencing of one allele of the MLH1 or MSH2 genes. This prompted us to test the methylation of the TP53 gene promoter in a set of 14 families suggestive of LFS using bisulphite sequencing of three DNA fragments from the 5' region of the gene. We found no detectable methylation at any of the CG dinucleotides tested. Thus, epigenetic silencing of the TP53 promoter is not a frequent cause of the disorder in families suggestive of LFS but with no germline mutations in the coding part of the gene.

• MeSH
• geny p53 * MeSH
• lidé MeSH
• Liův-Fraumeniho syndrom genetika   MeSH
• metylace DNA * MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory genetika   MeSH
• polymerázová řetězová reakce MeSH
• promotorové oblasti (genetika) genetika   MeSH
• rodina MeSH
• sekvenční analýza DNA MeSH
• zárodečné mutace * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• nádorový supresorový protein p53 MeSH
• TP53 protein, human MeSH Prohlížeč

BACKGROUND: A decrease in the age at cancer onset and increase in cancer incidence in successive generations in Li-Fraumeni syndrome (LFS) families with germline TP53 mutations have been previously described. In the current study a possible relation was analyzed between telomere length and cancer onset in TP53 mutation carriers. METHODS: Telomere length was measured using real-time quantitative polymerase chain reaction (PCR) in 20 carriers of germline TP53 mutations and in 83 unrelated healthy individuals. According to the age at blood sampling, patients and controls were divided into 2 age groups, children and adults. Telomere length was correlated to TP53 mutation status and telomere shortening in patients to the age at cancer onset. A t-test and linear regression were used to analyze the data. RESULTS: Compared with healthy controls, telomere length was significantly shorter both in the child (P = .001) and adult (P = .034) germline T53 mutation carriers. Although a statistically significant correlation between telomere shortening and the age at cancer onset was not observed, there was a trend of shorter telomeres in mutation carriers affected in childhood compared with those affected later in life. Neither cancer therapy nor sex differences were likely to affect the results. CONCLUSIONS: The findings suggest a possible link between the carriership of a germline TP53 mutation, telomere length, predisposition to early-onset cancer, and anticipation in LFS.

• MeSH
• detekce genetických nosičů MeSH
• dítě MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• lidé MeSH
• Liův-Fraumeniho syndrom krev   genetika   MeSH
• messenger RNA genetika   metabolismus   MeSH
• nádorový supresorový protein p53 genetika   MeSH
• nádory krev   genetika   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• telomery fyziologie   MeSH
• věk při počátku nemoci MeSH
• zárodečné mutace genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• messenger RNA MeSH
• nádorový supresorový protein p53 MeSH

Detection of NH3 at a trace level is nowadays of great importance. Here, we investigate the reactivity and sensitivity of a B36 borophene toward NH3 gas employing DFT calculations. The energetic results point out that the adsorption process strongly depends on the orientation of NH3 relative to the B36 sheet. An NH3 molecule preferentially interacts via its N-head with a B atom of the B36 with a change of enthalpy of - 90.5 kJ/mol at room temperature and 1 atm. Mulliken charges analysis results reveal that approximately 0.35 |e| transfers from NH3 to the B36, leaving partially positive NH3. We found that the B36 electronic properties are meaningfully sensitive to the NH3 gas, and it may be a sign of further usage of B36 as a potential NH3 gas sensor. The density of state analysis shows that the B36 gap is expressively decreased from 1.55 to 1.35 eV, increasing its electrical conductance.

• Klíčová slova
• Ammonia, B36 cluster, DFT calculations, Detection,
• Publikační typ
• časopisecké články MeSH

Brucellosis is a zoonosis caused by Brucella, which poses a great threat to human health and animal husbandry. Pathogen surveillance is an important measure to prevent brucellosis, but the traditional method is time-consuming and not suitable for field applications. In this study, a recombinase polymerase amplification-SYBR Green I (RPAS) assay was developed for the rapid and visualized detection of Brucella in the field by targeting BCSP31 gene, a conserved marker. The method was highly specific without any cross-reactivity with other common bacteria and its detection limit was 2.14 × 104 CFU/mL or g of Brucella at 40 °C for 20 min. It obviates the need for costly instrumentation and exhibits robustness towards background interference in serum, meat, and milk samples. In summary, the RPAS assay is a rapid, visually intuitive, and user-friendly detection that is highly suitable for use in resource-limited settings. Its simplicity and ease of use enable swift on-site detection of Brucella, thereby facilitating timely implementation of preventive measures.

• Klíčová slova
• BCSP31 gene, Brucella, Recombinase polymerase amplification, SYBR Green I, Visualization,
• MeSH
• Brucella * genetika   izolace a purifikace   MeSH
• brucelóza * diagnóza   mikrobiologie   MeSH
• DNA bakterií genetika   MeSH
• lidé MeSH
• limita detekce MeSH
• mléko mikrobiologie   MeSH
• rekombinasy * metabolismus   genetika   MeSH
• senzitivita a specificita MeSH
• skot MeSH
• techniky amplifikace nukleových kyselin * metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• skot MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA bakterií MeSH
• rekombinasy * MeSH

The early diagnosis of diseases plays a vital role in healthcare and the extension of human life. Graphene-based biosensors have boosted the early diagnosis of diseases by detecting and monitoring related biomarkers, providing a better understanding of various physiological and pathological processes. They have generated tremendous interest, made significant advances, and offered promising application prospects. In this paper, we discuss the background of graphene and biosensors, including the properties and functionalization of graphene and biosensors. Second, the significant technologies adopted by biosensors are discussed, such as field-effect transistors and electrochemical and optical methods. Subsequently, we highlight biosensors for detecting various biomarkers, including ions, small molecules, macromolecules, viruses, bacteria, and living human cells. Finally, the opportunities and challenges of graphene-based biosensors and related broad research interests are discussed.

• Klíčová slova
• biodevices, biomarker detection, circulating tumor cells, early diagnosis, electrochemical biosensors, field-effect transistors, functionalization, graphene, microfluidic system, optical biosensors,
• MeSH
• biologické markery MeSH
• biosenzitivní techniky * MeSH
• časná diagnóza MeSH
• grafit * MeSH
• lidé MeSH
• viry * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• grafit * MeSH

This article describes a fast and automatic reconstruction of the edge plasma electron density from the radiation of energetic Li atoms of the diagnostic beam on the COMPASS tokamak. Radiation is detected by using a CCD camera and by using an avalanche photo-diode system with a temporal resolution of 20 ms and 2 μs, respectively. Both systems are equipped with a 670.8 nm optical filter which corresponds to the lithium 1s22s1-1s22p1 transition. A theoretical model and a data processing procedure of a raw signal to obtain the density profile are described. The reconstruction algorithm provides the absolutely calibrated electron density profiles together with the measurement error estimated from relatively calibrated light profiles; the implementation is performed in Python. Time demanding operations of the code were optimized to provide reconstruction of a single profile within less than 10 ms which makes the code applicable for processing of a large amount of data. Thanks to this calculation speed, it is possible to reconstruct electron density profiles between two consecutive shots on the COMPASS tokamak with 2 μs time resolution.

• Publikační typ
• časopisecké články MeSH