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Lung cancer (LC) represents a major healthcare issue worldwide. It is the leading cause of cancer-related mortality in Slovakia and European Union. Data from multiple randomized controlled trials have shown significant evidence of a mortality benefit in LC using screening with low-dose computed tomography of the chest (LDCT). Therefore, European healthcare authorities, relevant expert societies, and professional organizations recommend implementing national LC screening (LCS) programs in their member countries. This article outlines the basic methodology, guidelines, and practical aspects of LCS implementation strategies in Slovakia. We describe fundamental principles to identify asymptomatic high-risk patients reduce false positive and false negative results, decrease benign resection rates, and avoid unnecessary invasive procedures. The efficacious utilization of public resources to secure the highest possible quality standards of LDCT plays a crucial role in successfully implementing a nationwide LCS program (Tab. 1, Fig. 4, Ref. 31). Text in PDF www.elis.sk. [ABSTRACT FROM AUTHOR]

Purpose: Despite the current guidelines supporting open communication about serious news, the evidence about the impact of prognostic awareness on the quality of life in cancer patients is not clear. The aim of this study was to assess the association between quality of life and prognostic awareness in patients with advanced cancer. Methods: This was a cross-sectional study which involved patients (n = 129) with incurable advanced cancer (estimated by oncologist using 12-month surprise question). Data were collected at oncology departments at 3 hospitals using structured interview in which patients were asked about their quality of life (using Integrated Palliative Outcome Scale—IPOS and a single-item global measure), prognostic awareness, information needs and demographics. Results: Only 16% of the sample was completely aware of prognosis and 57% was partially aware. Accurate prognostic awareness was significantly associated (p = 0.02) with lower level of quality of life between (when measured by both the IPOS and the single-item scale) patients with accurate prognostic awareness (M = 37.1; 10.4) and partially aware (M = 31.9; 9.1) and unaware patients (M = 30; 7.4). Detailed analysis showed that significant difference between groups was found only for physical symptoms subscales (p = 0.002), not for emotional and communication subscales. Conclusion: Prognostic awareness was found to be negatively associated with physical domain of quality of life, but not with emotional and communication domains. More research is needed on personality factors that might influence the development of prognostic awareness and quality of life. [ABSTRACT FROM AUTHOR]

In Russia's long-standing vision of organizing international relations, only the great powers enjoy full sovereignty. They are entitled to their security, which they ensure by maintaining a zone of influence around themselves, where they retain a degree of control over neighboring states. The great powers then respect each other's spheres of influence. This is, of course, completely incompatible with Western notions of world order and international law. The reliance of the EU and, indirectly, the UK on Russian gas supplies has intensified over the last decade. Over that period, natural gas consumption in the EU and the UK has not increased, but production has fallen by a third. Imports have met the shortfall. In 2021, Russian gas accounted for 32% of European demand, up from 25% in 2009. Meanwhile, the construction of additional transit corridors, such as Nord Stream piping Russian gas to the EU and the UK, has reduced Ukraine's importance as a transit country. As one of the authors of this article pointed out for the first time in 2017 (Polak, 2017), Russia can finance its current wars overseas mainly with profits from the extraction and sale of oil, coal, and natural gas. [ABSTRACT FROM AUTHOR]

The complex shape of embryonic cartilage represents a true challenge for phenotyping and basic understanding of skeletal development. X-ray computed microtomography (μCT) enables inspecting relevant tissues in all three dimensions; however, most 3D models are still created by manual segmentation, which is a time-consuming and tedious task. In this work, we utilised a convolutional neural network (CNN) to automatically segment the most complex cartilaginous system represented by the developing nasal capsule. The main challenges of this task stem from the large size of the image data (over a thousand pixels in each dimension) and a relatively small training database, including genetically modified mouse embryos, where the phenotype of the analysed structures differs from the norm. We propose a CNN-based segmentation model optimised for the large image size that we trained using a unique manually annotated database. The segmentation model was able to segment the cartilaginous nasal capsule with a median accuracy of 84.44% (Dice coefficient). The time necessary for segmentation of new samples shortened from approximately 8 h needed for manual segmentation to mere 130 s per sample. This will greatly accelerate the throughput of μCT analysis of cartilaginous skeletal elements in animal models of developmental diseases. [ABSTRACT FROM AUTHOR]

Purpose: Approximately 1–2% of chronic myeloid leukemia (CML) patients harbor atypical BCR-ABL1 transcripts that cannot be monitored by real-time quantitative PCR (RT-qPCR) using standard methodologies. Within the European Treatment and Outcome Study (EUTOS) for CML we established and validated robust RT-qPCR methods for these patients. Methods: BCR-ABL1 transcripts were amplified and sequenced to characterize the underlying fusion. Residual disease monitoring was carried out by RT-qPCR with specific primers and probes using serial dilutions of appropriate BCR-ABL1 and GUSB plasmid DNA calibrators. Results were expressed as log reduction of the BCR-ABL1/GUSB ratio relative to the patient-specific baseline value and evaluated as an individual molecular response (IMR). Results: In total, 330 blood samples (2–34 per patient, median 8) from 33 CML patients (19 male, median age 62 years) were analyzed. Patients expressed seven different atypical BCR-ABL1 transcripts (e1a2, n = 6; e6a2, n = 1; e8a2, n = 2; e13a3, n = 4; e14a3, n = 6; e13a3/e14a3, n = 2; e19a2, n = 12). Most patients (61%) responded well to TKI therapy and achieved an IMR of at least one log reduction 3 months after diagnosis. Four patients relapsed with a significant increase of BCR-ABL1/GUSB ratios. Conclusions: Characterization of atypical BCR-ABL1 transcripts is essential for adequate patient monitoring and to avoid false-negative results. The results cannot be expressed on the International Scale (IS) and thus the common molecular milestones and guidelines for treatment are difficult to apply. We, therefore, suggest reporting IMR levels in these cases as a time-dependent log reduction of BCR-ABL1 transcript levels compared to baseline prior to therapy. [ABSTRACT FROM AUTHOR]

Neutralizing antibodies that target the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein are among the most promising approaches against COVID-191,2. A bispecific IgG1-like molecule (CoV-X2) has been developed on the basis of C121 and C135, two antibodies derived from donors who had recovered from COVID-193. Here we show that CoV-X2 simultaneously binds two independent sites on the RBD and, unlike its parental antibodies, prevents detectable spike binding to the cellular receptor of the virus, angiotensin-converting enzyme 2 (ACE2). Furthermore, CoV-X2 neutralizes wild-type SARS-CoV-2 and its variants of concern, as well as escape mutants generated by the parental monoclonal antibodies. We also found that in a mouse model of SARS-CoV-2 infection with lung inflammation, CoV-X2 protects mice from disease and suppresses viral escape. Thus, the simultaneous targeting of non-overlapping RBD epitopes by IgG-like bispecific antibodies is feasible and effective, and combines the advantages of antibody cocktails with those of single-molecule approaches.The bispecific IgG1-like CoV-X2 prevents SARS-CoV-2 spike binding to ACE2, neutralizes SARS-CoV-2 and its variants of concern, protects against disease in a mouse model, whereas the parental monoclonal antibodies generate viral escape. [ABSTRACT FROM AUTHOR]

Background: The Freezing of Gait Questionnaire (FoG-Q) is a fast and sensitive assessment tool for freezing (FoG).Objective: The objective of the study is for validation of a Czech version of FoG-Q. A further, explorative aim was to examine what FoG-Q indicates about the presence and severity of gait impairment in patients treated with DBS in their full OFF state.Design: The study was a cross-sectional validation study.Methods: We translated FoG-Q following standardized validation protocol. We assessed 35 patients with PD and STN DBS using history taking, UPDRS, Hoehn and Yahr staging, Mini Mental State Examination, Frontal Assessment Battery, FoG-Q, Short Falls Efficacy Scale International, and Beck Depression Inventory, Second Edition. UPDRS III, clinical and instrumental gait assessment, was repeated OFF MED/DBS OFF and OFF MED/DBS ON.Results: Internal consistency of FoG-Q was excellent (α = 0.91) as well as convergent (significant correlations with UPDRS II item 14, UPDRS III item 29, several TUG parameters, and FoG Score) and divergent validity (no association with UPDRS I). OFF MED/DBS OFF, the total FoG-Q score correlated with UPDRS III items 29, 30, and PIGD subscore, step time variability, and negatively with step length and velocity.Limitations: Limitation of the study is a relatively small sample size.Conclusions: In conclusion, the Czech translation of FoG-Q is valid. With respect to gait and balance, FoG-Q does, to a certain extent, reflect the native state of the disease in patients treated with high frequency STN DBS. [ABSTRACT FROM AUTHOR]

Purpose: The advent of tyrosine kinase inhibitor (TKI) therapies has revolutionized the treatment of chronic myeloid leukemia (CML). The European LeukemiaNet (ELN) recommends quantification of BCR–ABL1 transcripts by real-time quantitative PCR every 3 months during TKI treatment. Since a proportion of patients in deep molecular response (DMR: MR4, MR4.5, MR5) maintain remission after treatment stop, assessment of DMR is crucial. However, systematically collected molecular data, monitored with sensitive standardized assays, are not available outside clinical trials. Methods: Data were collected on the standardized assessment of molecular response in the context of real-life practice. BCR–ABL1 transcript levels after > 2 years of TKI therapy were evaluated for DMR by local laboratories as well as standardized EUTOS laboratories. Since standardized molecular monitoring is a prerequisite for treatment discontinuation, central surveillance of the performance of the participating laboratories was carried out. Results: Between 2014 and 2017, 3377 peripheral blood samples from 1117 CML patients were shipped to 11 standardized reference laboratories in six European countries. BCR–ABL1 transcript types were b3a2 (41.63%), b2a2 (29.99%), b2a2/b3a2 (3.58%) and atypical (0.54%). For 23.72% of the patients, the initial transcript type had not been reported. Response levels (EUTOS laboratory) were: no MMR, n = 197 (6.51%); MMR, n = 496 (16.40%); MR4, n = 685 (22.64%); MR4.5, n = 937 (30.98%); MR5, n = 710 (23.47%). With a Cohen's kappa coefficient of 0.708, a substantial agreement between EUTOS-certified and local laboratories was shown. Conclusions: Multicenter DMR assessment is feasible in the context of real-life clinical practice in Europe. Information on the BCR–ABL1 transcript type at diagnosis is crucial to accurately monitor patients' molecular response during or after TKI therapy. [ABSTRACT FROM AUTHOR]

In the last few years, magnetically labeled cells have been intensively explored, and non-invasive cell tracking and magnetic manipulation methods have been tested in preclinical studies focused on cell transplantation. For clinical applications, it is desirable to know the intracellular pathway of nanoparticles, which can predict their biocompatibility with cells and the long-term imaging properties of labeled cells. Here, we quantified labeling efficiency, localization, and fluorescence properties of Rhodamine derivatized superparamagnetic maghemite nanoparticles (SAMN-R) in mesenchymal stromal cells (MSC). We investigated the stability of SAMN-R in the intracellular space during a long culture (20 days). Analyses were based on advanced confocal microscopy accompanied by atomic absorption spectroscopy (AAS) and magnetic resonance imaging. SAMN-R displayed excellent cellular uptake (24 h of labeling), and no toxicity of SAMN-R labeling was found. 83% of SAMN-R nanoparticles were localized in lysosomes, only 4.8% were found in mitochondria, and no particles were localized in the nucleus. On the basis of the MSC fluorescence measurement every 6 days, we also quantified the continual decrease of SAMN-R fluorescence in the average single MSC during 18 days. An additional set of analyses showed that the intracellular SAMN-R signal decrease was minimally caused by fluorophore degradation or nanoparticles extraction from the cells, main reason is a cell division. The fluorescence of SAMN-R nanoparticles within the cells was detectable minimally for 20 days. These observations indicate that SAMN-R nanoparticles have a potential for application in transplantation medicine. [ABSTRACT FROM AUTHOR]

Changing landscape configuration, a component of landscape heterogeneity, due to varying arable field size represents an attribute of farmland intensification with potentially grave consequences for biodiversity. We recorded butterflies in an intensively farmed region along the border of two European countries with contrasting socioeconomic heritage, one with small farms (Poland), the other with huge farmed units (Czech Republic). Although only the most common generalist species occurred in our records, we observed 2.3× more individuals and 1.9× more species in Poland, and the differences withstood robust statistical controls. Different socioeconomic heritage-in this case, different policies of two communist regimes, one tolerating small family farms and the other expropriating them-influence biodiversity long after the policies that shaped the respective landscapes had been abandoned. [ABSTRACT FROM AUTHOR]

Purpose: Here, we studied whether amplicon next-generation deep sequencing (NGS) could improve the detection of emerging BCR- ABL1 kinase domain mutations in chronic phase chronic myeloid leukemia (CML) patients under tyrosine kinase inhibitor (TKI) treatment and discussed the clinical relevance of such sensitive mutational detection. Methods: For NGS data evaluation including extraction of biologically relevant low-level variants from background error noise, we established and applied a robust and versatile bioinformatics approach. Results: Results from a retrospective longitudinal analysis of 135 samples of 15 CML patients showed that NGS could have revealed emerging resistant mutants 2-11 months earlier than conventional sequencing. Interestingly, in cases who later failed first-line imatinib treatment, NGS revealed that TKI-resistant mutations were already detectable at the time of major or deeper molecular response. Identification of emerging mutations by NGS was mirrored by BCR- ABL1 transcript level expressed either fluctuations around 0.1 % or by slight transcript level increase. NGS also allowed tracing mutations that emerged during second-line TKI therapy back to the time of switchover. Compound mutants could be detected in three cases, but were not found to outcompete single mutants. Conclusions: This work points out, that next-generation deep sequencing, coupled with a robust bioinformatics approach for mutation calling, may be just in place to ensure reliable detection of emerging BCR- ABL1 mutations, allowing early therapy switch and selection of the most appropriate therapy. Further, prospective assessment of how to best integrate NGS in the molecular monitoring and clinical decision algorithms is warranted. [ABSTRACT FROM AUTHOR]

Treatment of chronic myeloid leukemia (CML) with tyrosine kinase inhibitors has advanced to a stage where many patients achieve very low or undetectable levels of disease. Remarkably, some of these patients remain in sustained remission when treatment is withdrawn, suggesting that they may be at least operationally cured of their disease. Accurate definition of deep molecular responses (MRs) is therefore increasingly important for optimal patient management and comparison of independent data sets. We previously published proposals for broad standardized definitions of MR at different levels of sensitivity. Here we present detailed laboratory recommendations, developed as part of the European Treatment and Outcome Study for CML (EUTOS), to enable testing laboratories to score MR in a reproducible manner for CML patients expressing the most common BCR-ABL1 variants. [ABSTRACT FROM AUTHOR]

Extra-pair copulation without apparent direct benefits is an evolutionary puzzle that requires indirect fitness benefits to females to explain its ubiquity in socially monogamous mating systems. Using wild scarlet rosefinches ( Carpodacus erythrinus), we tested if genetic benefits in the form of global (microsatellite) heterozygote advantage, adaptive genes (major histocompatibility complex), or complementary genes (using both markers) were responsible for female extra-pair mate choice, while considering that the benefits of mate choice may be conditional on female genotype. We found no evidence for assortative or relatedness-based mating (complementary genes), but higher MHC diversity, microsatellite heterozygosity, and condition were significantly related to male extra-pair paternity (EPP) success. In contrast, female probability of having extra-pair offspring decreased with increasing heterozygosity. Interestingly, extra-pair and within-pair males had higher heterozygosity than their female mates and extra-pair males had higher MHC supertype diversity. The only genetic difference between extra-pair and within-pair offspring was lower variance in MHC allelic diversity within extra-pair offspring, providing limited support for indirect genetic fitness benefits for the markers tested. Offspring had both higher neutral heterozygosity and number of MHC supertypes than adults, as well as significant identity disequilibrium, potentially suggesting that mates are chosen to increase offspring diversity in the period of the present study. Overall, our results point to an EPP heterozygote advantage for males, especially when involving less heterozygous females, and suggest that heterozygosity effects on reproduction may differ between the sexes. [ABSTRACT FROM AUTHOR]

In DNA vaccination, CD4+ T-cell help can be enhanced by fusion of a gene encoding an immunization protein with a foreign gene or its part providing Th epitopes. To study the effect of helper epitope localization in a protein molecule, the influence of the vicinity of the helper epitope, and the impact of chimeric protein cellular localization, we fused the helper epitope p30 from tetanus toxin (TT, aa 947-967) with the N- or C-terminus of the mutated E7 oncoprotein (E7GGG) of human papillomavirus type 16, enlarged the p30 epitope with the flanking residues containing potential protease-sensitive sites and altered the cellular localization of the fusion constructs by signal sequences. The p30 epitope enhanced the E7-specific response, but only in constructs without added signal sequences. After localization of the fusion proteins into the endoplasmic reticulum and endo/lysosomal compartment, the TT-specific Th2 response was increased. The synthetic Pan DR epitope (PADRE) induced a stronger E7-specific response than the p30 epitope and its stimulatory effect was not limited to nuclear/cytoplasmic localization of the E7 antigen. These results suggest that in the optimization of immune responses by adding helper epitopes to DNA vaccines delivered by the gene gun, the cellular localization of the antigen needs to be taken into account. [ABSTRACT FROM AUTHOR]

Altered expression and methylation pattern of tumor suppressor and DNA repair genes, in particular involved in mismatch repair (MMR) pathway, frequently occur in primary colorectal (CRC) tumors. However, little is known about (epi)genetic changes of these genes in precancerous and early stages of CRC. The aim of this pilot study was to analyze expression profile and promoter methylation status of important tumor suppressor and DNA repair genes in the early stages of experimentally induced colorectal carcinogenesis. Rats were treated with azoxymethane (AOM), dextran sodium sulphate (DSS) or with their combination, and sacrificed 1 or 4 months post-treatment period. The down-regulation of Apc expression in left colon, detectable in animals treated with DSS-AOM and sacrificed 1 month after the end of treatment, represents most early marker of the experimental colorectal carcinogenesis. Significantly reduced gene expressions were also found in 5 out of 7 studied MMR genes ( Mlh1, Mlh3, Msh3 Pms1, Pms2), regarding the sequential administration of DSS-AOM at 4 months since the treatment. Strong down-regulation was also discovered for Apc, Apex1, Mgmt and TP53. Tumors developed in rectum-sigmoid region displayed significantly lower Apc and Pms2 expressions. The decreased expression of studied genes was not in any case associated with aberrant methylation of promoter region. Present data suggest that down-regulation of Apc and MMR genes are prerequisite for the development of CRC. In this study we addressed for the first time early functional alterations of tumor suppressor genes with underlying epigenetic mechanisms in experimentally induced CRC in rats. [ABSTRACT FROM AUTHOR]

Effects of physiological saline (PS)-dissolved or Freund′s incomplete adjuvant (FIA)-emulsified sGnRHa on the induction and advancement of ovulation in brook char were assessed. Two-year-old females were randomly divided into 5 groups. Groups A and B received intraperitoneal injection of FIA-emulsified sGnRHa (sGnRHa-FIA) at dosages of 50 and 25 μg kg body weight (BW), respectively. Females in group C were treated with a double injection (DI) of PS-dissolved sGnRHa (sGnRHa-PS) at 25 μg kg BW spaced 3 days apart. Fish in group D received a 25 μg kg BW single injection (SI) of sGnRHa-PS. Group E was established as a control group. After stripping, ovarian plasma pH level was measured, and an egg sample was taken from each female to record egg weight and diameter and survival to the eyed stage. Females in the GnRHa-treated groups ovulated significantly earlier than did females in the control group ( P < 0.01). No significant differences were found among GnRHa-treated groups in ovulation dynamics and mean time to ovulation. Ovarian fluid pH was significantly higher in groups A, B, and C compared to control group E ( P < 0.05). Significantly lower egg weight was found only in group B ( P < 0.01), although all advanced groups tended to have lower egg weight than the control group. Egg diameters paralleled egg weight. Survival to the eyed stage was significantly higher in GnRHa-advanced groups compared to the control. A negative relationship was found between egg weight end eyed eggs percent ( R = 0.26). No pre-spawning or post-spawning mortality was observed during a 6-month period. Neither sGnRHa-PS nor sGnRHa-FIA are associated with negative influences on the health of females. The sGnRHa-FIA injections proved to exhibit the same efficacy as the DI protocol with sGnRHa-PS. Although no statistical differences were found in ovulation dynamics, we do not recommend the use of SI with sGnRHa-PS in brook char. [ABSTRACT FROM AUTHOR]

We analyzed 192 strains of the pathogenic yeast Candida glabrata from patients, mainly suffering from systemic infection, at Danish hospitals during 1985-1999. Our analysis showed that these strains were closely related but exhibited large karyotype polymorphism. Nine strains contained small chromosomes, which were smaller than 0.5 Mb. Regarding the year, patient and hospital, these C. glabrata strains had independent origin and the analyzed small chromosomes were structurally not related to each other (i.e. they contained different sets of genes). We suggest that at least two mechanisms could participate in their origin: (i) through a segmental duplication which covered the centromeric region, or (ii) by a translocation event moving a larger chromosome arm to another chromosome that leaves the centromere part with the shorter arm. The first type of small chromosomes carrying duplicated genes exhibited mitotic instability, while the second type, which contained the corresponding genes in only one copy in the genome, was mitotically stable. Apparently, in patients C. glabrata chromosomes are frequently reshuffled resulting in new genetic configurations, including appearance of small chromosomes, and some of these resulting 'mutant' strains can have increased fitness in a certain patient 'environment'. [ABSTRACT FROM AUTHOR]

Infection with Human papillomaviruses (HPVs) is linked to cervical cancer, which is one of the most common cancers found among women worldwide. Despite preventive immunization, a therapeutic vaccine, targeting infected individuals, is required. Vaccine strategies for treatment of HPV-induced cervical cancer are based on E7 and E6 oncoproteins. In this work we report the transient expression of chimeric particles containing the E6 oncoprotein from Human papillomavirus type 16 (HPV-16) in plants. We fused a mutagenized coding sequence of the E6 oncoprotein (E6GT) with the coding sequence of Potato virus X coat protein (PVX CP) both with the 5′- and 3′-terminus using linkers of different length (0, 4 or 15 amino acids). The expression in E. coli was performed to assess the characteristics of the recombinant protein prior to plant expression. The yield and immunological reactivity of the expressed proteins were screened with anti-PVX CP and E6 antibodies. The highest yields of chimeric particles were observed in the transgenic N. benthamiana expressing Potato virus A HC-Pro protein and the Tobacco mosaic virus movement protein. When inoculated on host plants, these recombinant viruses were not able to spread systemically. The obtained results revealed the new relations for design of expression cassettes for plant-based vaccine production. [ABSTRACT FROM AUTHOR]

The efficacy of therapeutic modalities in chronic myeloid leukemia (CML) depends on both genetic and epigenetic mechanisms. This review focuses on epigenetic mechanisms involved in the pathogenesis of CML and in resistance of tumor cells to tyrosine kinase inhibitors leading to the leukemic clone escape and propagation. Regulatory events at the levels of gene regulation by transcription factors and microRNAs are discussed in the context of CML pathogenesis and therapeutic modalities. [ABSTRACT FROM AUTHOR]

Wilms' tumor gene 1 (WT1) functions including some contradictory effects may be explained by the presence and interactions of its isoforms, however, their evaluation has been so far complicated by several technical problems. We designed unique quantitative PCR systems for direct quantification of the major WT1 isoforms A[EX5−/KTS−], B[+/−], C[−/+] and D[+/+] and verified their sensitivity, specificity and reproducibility in extensive testing. With this method we evaluated WT1 total and isoform expression in 23 normal bone marrow (BM) samples, 73 childhood acute myeloid leukemia (AML), 20 childhood myelodysplastic syndrome (MDS), 9 childhood severe aplastic anemia (SAA), 30 adult AML and 29 adult MDS patients. WT1 isoform patterns showed differences among these samples and clustered them into groups representing the specific diagnoses (P<0.0001). Isoform profiles were independent of total WT1 expression and possess certain common features-overexpression of isoform D and EX5[+] variants. The KTS[+]/KTS[−] ratio was less variable than the EX5[+]/EX5[−] ratio and differed between children and adults (P<0.001); the EX5[+]/EX5[−] ratio varied between diagnoses (AML vs MDS, P<0.001). These findings bring new insights into WT1 isoform function and suggest that the ratio of WT1 isoforms, particularly EX5 variants, is probably crucial for the process of malignant transformation. [ABSTRACT FROM AUTHOR]

Purpose: Welders have been chronically exposed to hexavalent chromium with potential consequences on chromosomal integrity. Our study is focused on the extent of any such chromosomal aberrations with respect to chromium levels in the blood of welders as well as on the tentative modulating role of polymorphisms in DNA repair genes XPD Lys751Gln, XPG Asn114His, XPC Lys939Gln, hOGG1 Ser326Cys and XRCC1 Arg399Gln on chromosomal damage. Methods: The study was conducted on 144 individuals consisting of 73 welders exposed to chromium for 10.2 ± 1.67 years and 71 control individuals without known exposures. Chromosomal aberrations, their chromatid-type and chromosome-type aberrations were detected by conventional cytogenetic analysis. XPD, XPG, XPC, hOGG1 and XRCC1 gene polymorphisms were assayed for by Taqman SNP genotyping assay ('Assay-by-Demand') using Real-Time allelic discrimination on AB 7500 equipment. Chromium concentration in the blood was determined by atomic absorption spectrophotometry. Results: The level of chromium in the blood of welders ranged between 0.032 and 0.182 μmol l and was significantly higher than that in controls (0.07 ± 0.04 μmol l vs. 0.03 ± 0.007 μmol l). Parameters of chromosomal damage were similar in both the exposed and the control individuals (1.89% vs. 1.70% for total chromosomal aberrations, 0.97% vs. 0.88% for chromosome-type and 0.92% vs. 0.80% for chromatid-type, respectively). Chromatid-type of aberrations positively correlated with the level of chromium in the blood ( r = 0.28; P = 0.02). Significantly higher total chromosomal aberrations were detected in individuals with homozygous variant polymorphism in XRCC1 Arg399Gln gene as compared to those with heterozygous and homozygous wild-type genotypes (2.20, 1.89 and 1.48%, respectively; P = 0.01). A similar tendency was found for chromatid-type aberrations (1.30% for homozygous variant genotype bearers, 0.94% for those with heterozygous genotype and 0.75% for carriers of homozygous wild-type genotype, respectively; P = 0.04). Conclusions: Although no apparent increase in chromosomal damage was recorded in chromium-exposed welders in comparison with controls, genetic make-up in DNA repair genes may increase susceptibility toward adverse effect of chromium. [ABSTRACT FROM AUTHOR]

The crystal structure of 2-cyclohexylethyl α- d-mannopyranoside (CHO, Mr = 290.35) has been determined by single crystal X-ray diffraction analysis. The compound crystallizes in the monoclinic crystal system with space group C2 and unit cell parameters: a = 14.2420(2), b = 6.0320(1), c = 17.8065(3) Å, β = 102.131(2)° and Z = 4. The final reliability index is 0.0256 for 2,654 observed reflections. The one molecule of 2-cyclohexylethyl α- d-mannopyranoside is localized in independent part of unit cell. The molecules of 2-cyclohexylethyl α- d-mannopyranoside are linked through O-H···O hydrogen bond into bilayer. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Infection with high-risk types of human papillomavirus (HPV) can cause the development of malignant tumors. To study mechanisms responsible for immune escape of tumor cells infected with HPV16, we previously used mouse oncogenic TC-1 cells producing HPV16 E6 and E7 oncoproteins to derive TC-1 clones resistant to immunization against E7. We have found immunoresistance of the clones to correlate with the point mutation in the E7 oncogene, which resulted in the N53S substitution in the immunodominant epitope RAHYNIVTF (aa 49–57). Here, we have shown that this mutation reduced stabilization of H-2Db molecules on RMA-S cells and eliminated immunogenicity of E7. The resistance of TC-1 clones was E7-specific as immunization against E6 inhibited tumor growth. Transduction of the TC-1/F9 clone carrying the mutated epitope with the wild-type E7 gene restored susceptibility to immunization against E7. Our results suggest that mutagenesis of tumor antigens can lead to the escape of malignant cells and should be considered in the development and evaluation of cancer immunotherapy. [ABSTRACT FROM AUTHOR]

This article starts with a review of the current SISAK liquid-liquid extraction system, as used after the physical preseparator BGS at LBNL for chemical studies of transactinide elements. Emphasis will be on new additions and developments. Then the possibilities offered by the new TASCA separator at GSI and the use of actinide targets at both GSI and LBNL are discussed with respect to future SISAK transactinide experiments. Finally, current and future liquid-liquid extraction systems for studying elements Rf up to Hs are discussed. [ABSTRACT FROM AUTHOR]

Barley α-amylase variability influences the quality of barley grain in the brewing, feed and food industries. α-Amylase proteins are encoded by multigene families in cereals, and this study focused on the barley Amy32b gene. We identified coding region single nucleotide polymorphism (cSNP) and insertion/deletion variation in DNA sequences, which resulted in amino acid substitution and stop codon formation, respectively. The substitution affected the β1 strand in domain C, whereas the stop codon removed the β5 strand. Possible effects of these changes on the protein are discussed. A cSNP in the coding region of the Amy32b gene was used as a specific marker to map Amy32b loci on chromosome 7H. [ABSTRACT FROM AUTHOR]

β-Amylase is involved in the starch degradation process and therefore influences grain quality. Starch degradation efficiency is dependent on the enzyme thermostability during malting and mashing. Four alleles resulting in different enzyme thermostability are known. These alleles are distinguished by coding single nucleotide polymorphism (cSNP). Pyrosequencing was used for cSNP genotyping of β-amylase alleles in 79 spring barley varieties by using analyser PSQ MA96 System (Pyrosequencing, Biotage). A new cSNP was revealed by means of Pyrosequencing analysis of sequence flanking cSNP698, thus recognizing a fifth β-amylase allele. Pyrosequencing is a high-throughput, fast, and precise system for barley SNP genotyping. [ABSTRACT FROM AUTHOR]

Brefeldin A (BFA) induced a rapid redistribution of vesicular stomatitis virus G protein (VSV-G) to the endoplasmatic reticulum (ER) in interferon (IFN)-pretreated cells. This result is consistent with accumulation of VSV-G in the trans-Golgi (GC) complex in cells pretreated with IFN and implies that IFN does not interfere with the ability of BFA to induce redistribution of proteins from GC to ER. [ABSTRACT FROM AUTHOR]

A correction to the article "Small chromosomes among Danish Candida glabrata isolates originated through different mechanisms," by Khadija Mohamed and colleagues published in a 2013 issue of "Antonie van Leeuwenhoek."