Types Of Aberrations Research Articles

Relationship Between Aberration Coefficients of an Optical Device and Its Focusing Property

The best focus point of a focused Gaussian beam subject to a phase aberration is generally shifted with respect to the focal plane of the focusing lens. This focus shift is attributed to a lensing effect that belongs to the phase aberration, which mean focal length can be determined from the aberration coefficients determined in the framework of a Zernike polynomial decomposition. In this paper, we have checked the validity of this procedure, already available in literature, applied to three aberration types: a pure primary spherical aberration, the Kerr effect induced by a Gaussian beam, and an axicon illuminated by a Gaussian beam. Note that usually, the mean focal length of an aberrated lens is based on the relation between the effective radius of curvature of the wavefront before and after the lens. However, in this paper, the focal length associated with the phase aberration under study is defined from the point of the best focus, where the diffracted intensity on the axis is the maximum.

Biological effects of radiation exposure in patients treated with X-ray guided endovascular aortic repair

Abstract Background X-ray guided cardiovascular interventions such as endovascular aortic repair (EVAR) expose patients and operators to significant amounts of repeated ionising radiation over a long period of time. The biological effect of such protracted radiation exposure is poorly understood. We have previously demonstrated a higher incidence of dicentric chromosome (DC) aberrations in high-volume endovascular interventionalists and differences in acute DNA damage in lymphocytes between individuals following in vitro irradiation. Studies suggested a higher incidence of cancer in patients who underwent EVAR compared with those who have had open aneurysm repair, but the evidence is inconclusive. Further work is required to evaluate the biological radiation risk of X-ray guided cardiovascular interventions. Purposes We aimed to examine radiation-induced genome instability from patients after complex EVAR. We also aimed to investigate the intrinsic response of each patient to radiation using biomarkers of acute DNA damage following in vitro irradiation of their blood and to correlate this response to the expression of radiation-responsive genes. Methods Lymphocytes were isolated from patients after complex (branched/fenestrated) EVAR and non-irradiated controls. DC, a type of chromosomal aberration caused by radiation exposure were enumerated. γ-H2AX, a marker of acute DNA damage/repair, was measured by immunofluorescence after in vitro irradiation at 0.2 Gy and 1 Gy, along with the expression of the radiation-responsive genes FDXR, CCNG1, P21 and PHPT1 using qPCR. Results 17 patients (82% male, median age 73[59 – 85years]) and 16 controls (56% male, median age 68[53 – 83years]) were recruited. The mean incidence of DC was 3.782 (95% CI 3.13 - 4.43) and 0.898 (95% CI 0.48 -1.32) per 1000 cells for patients and controls, respectively (P<0.0001). Patients had higher background of γ-H2AX foci than unexposed controls, (0.7056, 95% CI 0.316 - 1.10) vs (0.241 95% CI 0.077 - 0.405) per cell, P<0.05. FDXR expression was most increased following irradiation (P<0.0001), reaching a mean 13.1-fold and 11.4-fold increase at 4-hour and 24-hour time-point, respectively, but this upregulation was not significantly different between the two groups. Conclusion We have shown an increased frequency of chromosomal aberrations in patients after complex EVAR, a biological finding that may support a propensity to developing malignancies. Patients also have higher basal DNA damage/repair (γ-H2AX) activity. Expression of ferredoxin reductase, FDXR gene could be a potential radio-responsive biomarker to provide personalised biological dosimetry information for clinical monitoring. Our study further underlines the long-term radiation risk of X-ray guided cardiovascular interventions and the potential of biological assays that may guide personalised care.

Beamion LUNG-1, a Phase Ia/Ib trial of the HER2-specific tyrosine kinase inhibitor, zongertinib (BI 1810631), in patients with HER2-driven tumors: outcomes according to HER2 aberration type

Abstract Introduction/Objective Beamion LUNG-1 (NCT04886804) is an ongoing, Phase Ia/Ib trial evaluating the novel HER2- specific tyrosine kinase inhibitor, zongertinib, in patients with HER2 aberration-positive solid tumors (Phase Ia) and HER2 mutation-positive NSCLC (Phase Ib). Here, we report data from Phase Ia according to HER2 aberration type. Methods/Case Report Phase Ia enrolled patients with HER2 aberration-positive (by local assessment: gene mutations, rearrangements, amplification, or overexpression) advanced/metastatic solid tumors. Patients received escalating doses of zongertinib BID (≥15 mg) or QD (≥60 mg), guided by a Bayesian model with overdose control. The primary endpoint of Phase Ia was maximum tolerated dose (MTD) based on dose-limiting toxicities (DLTs). Results (if a Case Study enter NA) At data cut-off (January 29, 2024), 83 patients received zongertinib (BID n=17; QD n=66). Three patients had DLTs during the MTD evaluation period (G3 decreased platelets, G3 diarrhea, G4 neutropenia); the MTD was not reached. Treatment-related adverse events (TRAEs; all/G3/G4/G5) were reported in 76%/8%/1%/0% of patients. Confirmed investigator-assessed ORR/DCR rates in evaluable patients/patients with NSCLC (n=74/n=41) were 35%/85% and 44%/93%; median duration of response was 12.7/15.8 months, respectively. Based on preliminary data, 43 patients were HER2 mutation-positive (TKD/non-TKD/unknown n=36/n=6/n=1; A775_G776insYVMA n=16; G778dupGSP insertions n=3; S310F n=2); 23 patients overexpressed HER2 (2+/3+); 17 had HER2 amplification; 3 patients had NRG1 fusions. ORR/DCR rates (regardless of confirmation) in patients with TKD mutation-positive, A775_G776insYVMA-positive, non-TKD mutation-positive, G778dupGSP-positive and S310F- positive tumors were 64%/97%, 69%/94%, 20%/100%, 33%/100% and 50%/100%, respectively. ORR/DCR rates (regardless of confirmation) in patients with HER2 overexpressing tumors (+/- amplification) were 39%/83%. Of the 3 patients with NRG1 fusions, one had a partial response and two had stable disease. Conclusion In this preliminary analysis, zongertinib showed promising activity across a broad range of tumor types with different HER2 aberrations, including aberrations that have historically been difficult to treat. Updated data will be presented.

Chromosomal aberrations and early mortality in a non-mammalian vertebrate: example from pressure-induced triploid Atlantic salmon.

In commercial aquaculture, the production of triploid fish is currently the most practical approach to prevent maturation and farm-to-wild introgression following escapes. However, triploids often exhibit poor welfare, and the underlying mechanisms remain unclear. Inheritance issues associated with sub-optimal hydrostatic pressure treatments used to induce triploidy, or the genetic background of parental fish, have been speculated to contribute. We tested this by quantifying the frequency and type of chromosomal aberrations in Atlantic salmon subjected to a gradient of sub-optimal pressure treatments (Experiment 1) and from multiple mothers (Experiment 2). From these experiments, we genotyped a subsample of ~900 eyed eggs and all ~3300 surviving parr across ~20 microsatellites. In contrast to the low frequency of chromosomal aberrations in the diploid (no hydrostatic pressure) and triploid (full 9500 PSI treatment) controls, eyed eggs subjected to sub-optimal pressure treatments (6500-8500 PSI) had a higher incidence of chromosomal aberrations such as aneuploidy and uniparental disomy, corresponding to lower triploidization success and higher egg mortality rates. We also observed maternal effects on triploidization success and incidence of chromosomal aberrations, with certain half-sibling families exhibiting more aberrations than others. Chromosomal aberrations were rare among surviving parr, suggesting a purge of maladapted individuals during early development. This study demonstrates that sub-optimal hydrostatic pressure treatments and maternal effects not only influence the success of triploidization treatments, but may also affect the incidence of chromosomal aberrations and early mortality. The results have important implications for aquaculture breeding programs and their efforts to prevent farm-to-wild introgression.

Characterization of novel wheat-Thinopyrum ponticum introgression lines derived from partial amphiploid AUS6770 for resistance to stripe rust

The wild decaploid species Thinopyrum ponticum (Podp.) Barkworth & D.R. Dewey is an important source of genes against biotic and abiotic stresses affecting wheat. The wheat–Th. ponticum partial amphiploid AUS6770 shows resistance to multiple diseases, including stripe rust, stem rust, and powdery mildew. Mitotic chromosomes of AUS6770 were characterized by non-denaturing-fluorescence in situ hybridization (ND-FISH), and the individual Th. ponticum chromosomes 1Ae to 7Ae were karyotypically distinguished by Oligo-FISH painting using bulked oligo pools based on wheat-barley collinear regions. A novel stripe rust resistant line A155, derived from AUS6770, was found to have 44 chromosomes, including a pair of 2Ae chromosomes and a pair of 6B-6Ae translocations. To detect plants with transfer of resistance genes from A155 to wheat chromosomes, 1770 plants were developed from F2–F5 progenies of A155 crossed with the susceptible wheat cultivar MY11 and characterized with ND-FISH using multiple probes. A high frequency of transmission of chromosome 2Ae was observed, and 31 types of 2Ae chromosomal aberrations were identified using ND-FISH. Ten chromosomal bins on the 2Ae chromosome were determined from the deletion and translocation lines based on genome-based PCR markers. In combination with the evaluation of disease resistance, the gene(s) for stripe rust resistance was located on the FL0.79–1.00 of 2AeS and covers the corresponding region of 0–58.26 Mb in the reference genome of Th. elongatum. The newly identified wheat-Th. ponticum 2Ae translocation lines can be exploited as potential germplasm in wheat breeding for stripe rust resistance

Practical guidelines for cell segmentation models under optical aberrations in microscopy

Cell segmentation is essential in biomedical research for analyzing cellular morphology and behavior. Deep learning methods, particularly convolutional neural networks (CNNs), have revolutionized cell segmentation by extracting intricate features from images. However, the robustness of these methods under microscope optical aberrations remains a critical challenge. This study evaluates cell image segmentation models under optical aberrations from fluorescence and bright field microscopy. By simulating different types of aberrations, including astigmatism, coma, spherical aberration, trefoil, and mixed aberrations, we conduct a thorough evaluation of various cell instance segmentation models using the DynamicNuclearNet (DNN) and LIVECell datasets, representing fluorescence and bright field microscopy cell datasets, respectively. We train and test several segmentation models, including the Otsu threshold method and Mask R-CNN with different network heads (FPN, C3) and backbones (ResNet, VGG, Swin Transformer), under aberrated conditions. Additionally, we provide usage recommendations for the Cellpose 2.0 Toolbox on complex cell degradation images. The results indicate that the combination of FPN and SwinS demonstrates superior robustness in handling simple cell images affected by minor aberrations. In contrast, Cellpose 2.0 proves effective for complex cell images under similar conditions. Furthermore, we innovatively propose the Point Spread Function Image Label Classification Model (PLCM). This model can quickly and accurately identify aberration types and amplitudes from PSF images, assisting researchers without optical training. Through PLCM, researchers can better apply our proposed cell segmentation guidelines. This study aims to provide guidance for the effective utilization of cell segmentation models in the presence of minor optical aberrations and pave the way for future research directions.

Measurement precision bounds on aberrated single-molecule emission patterns

Single-molecule localization microscopy (SMLM) has revolutionized the study of biological phenomena by providing exquisite nanoscale spatial resolution. However, optical aberrations induced by sample and system imperfections distort the single-molecule emission patterns (i.e. PSFs), leading to reduced precision and resolution of SMLM, particularly in three-dimensional (3D) applications. While various methods, both analytical and instrumental, have been employed to mitigate these aberrations, a comprehensive analysis of how different types of commonly encountered aberrations affect single-molecule experiments and their image formation remains missing. In this study, we addressed this gap by conducting a quantitative study of the theoretical precision limit for position and wavefront distortion measurements in the presence of aberrations. Leveraging Fisher information and Cramér-Rao lower bound (CRLB), we quantitively analyzed and compared the effects of different aberration types, including index mismatch aberrations, on localization precision in both biplane and astigmatism 3D modalities as well as 2D SMLM imaging. Furthermore, we studied the achievable wavefront estimation precision from aberrated single-molecule emission patterns, a pivot step for successful adaptive optics in SMLM through thick specimens. This analysis lays a quantitative foundation for the development and application of SMLM in whole-cells, tissues and with a large field of view, providing in-depth insights into the behavior of different aberration types in single-molecule imaging and thus generating theoretical guidelines for developing highly efficient aberration correction strategies and enhancing the precision and reliability of 3D SMLM.

Naturally occurring horse model of miscarriage reveals temporal relationship between chromosomal aberration type and point of lethality

Chromosomal abnormalities are a common cause of human miscarriage but rarely reported in any other species. As a result, there are currently inadequate animal models available to study this condition. Horses present one potential model since mares receive intense gynecological care. This allowed us to investigate the prevalence of chromosomal copy number aberrations in 256 products of conception (POC) in a naturally occurring model of pregnancy loss (PL). Triploidy (three haploid sets of chromosomes) was the most common aberration, found in 42% of POCs following PL over the embryonic period. Over the same period, trisomies and monosomies were identified in 11.6% of POCs and subchromosomal aberrations in 4.2%. Whole and subchromosomal aberrations involved 17 autosomes, with chromosomes 3, 4, and 20 having the highest number of aberrations. Triploid fetuses had clear gross developmental anomalies of the brain. Collectively, data demonstrate that alterations in chromosome number contribute to PL similarly in women and mares, with triploidy the dominant ploidy type over the key period of organogenesis. These findings, along with highly conserved synteny between human and horse chromosomes, similar gestation lengths, and the shared single greatest risk for PL being advancing maternal age, provide strong evidence for the first animal model to truly recapitulate many key features of human miscarriage arising due to chromosomal aberrations, with shared benefits for humans and equids.

Comparative analysis of the yields of dicentrics and chromosomal translocations

Purpose Chromosomal dicentrics and translocations are commonly employed as biomarkers to estimate radiation doses. The main goal of this article is to perform a comparative analysis of yields of both types of aberrations. The objective is to determine if there are relevant distinctions between both yields, allowing for a comprehensive assessment of their respective suitability and accuracy in the estimation of radiation doses. Materials and methods The analysis involved data from a partial-radiation simulation study with the calibration data obtained through two scoring methods: conventional and PAINT modified. Subsequently, a Bayesian bivariate zero-inflated Poisson model was employed to compare the posterior marginal density of the mean of dicentrics and translocations and assess the differences between them. Results When employing the conventional method of scoring, the findings indicate that there is no notable disparity between the yield of observed translocations and dicentrics. However, when utilizing the PAINT modified method, a notable discrepancy is observed for higher doses, indicating a relevant difference in the mean number of the two types of aberrations. Conclusions The choice of scoring method significantly influences the analysis of radiation-induced aberrations, especially when distinguishing between complex and simple chromosomal formations. Further research and analysis are necessary to gain a deeper understanding of the factors and mechanisms impacting the formation of dicentrics and translocations.

The influence of heavy metals on cytotoxicity in Tilapia zillii

The present study was designed to investigate the cytotoxic effects and bioaccumulation of heavy metals iron (Fe), zinc (Zn), copper (Cu), cadmium (Cd), lead (Pb), manganese (Mn), nickel (Ni), and chromium (Cr) in different parts (muscle, gills, and liver) of Tilapia zillii occurring in polluted drainage canal and fish farm, which is located in Abiece region in front of village number 10, Alexandria governorate, Egypt. Results of water analysis revealed the concentration of Cd, Pb, Mn, Ni, and Cr exceeded the limits defined by the American Public Health Association (APHA) in the polluted drainage canal. In addition, the concentration of Ni elevated to the standard limits of APHA and Cu was not detected in the fish farm. Different types of chromosomal aberrations were recorded (e.g., stickiness, fragmented chromosomes, centromeric gaps, chromatid break, chromatid deletion, and tetraploid). Micronucleus frequency was found to be 5.58 in the polluted drainage canal group and 0.32 in the fish farm group. Other nuclear abnormalities such as blebbed nucleus, segmented nucleus, enucleated erythrocyte, kidney-shaped nucleus, heart-shaped nucleus, polymorphic irregular nuclei, binucleated cell, nuclear fragmented erythrocyte, long nucleus, putative fragmented notched nucleus, lobed nuclei, fused erythrocytes, necrotic erythrocyte, and vacuolated nucleus were recorded. The total of erythrocytes nuclear morphological abnormalities was 70.33% in the polluted drainage canal and 1.78% in the fish farm.

O-030 The impact of aneuploidy on human peri-implantation development: findings from the extended in vitro culture of 191 human embryos

Abstract Study question How does aneuploidy affect lineage specification and the developmental potential of human embryos cultured up to 12 days post fertilization (D12)? Summary answer While distinct types of aberrations carry their own risk of embryonic arrest, prevailing aneuploidies appear to compromise lineage specification beyond the blastocyst stage of development. What is known already Chromosomal instability is a hallmark of human preimplantation development, with up to 50% of embryos diagnosed as aneuploid following preimplantation genetic testing (PGT). Aneuploidies are a major cause of implantation failure, pregnancy loss and human congenital defects. Yet despite their clinical relevance, the impact of distinct aberrations on early human development remains poorly understood. Innovative platforms for culturing human embryos up to D12 provide an important opportunity for investigating chromosomal instability. Understanding the effects of specific aneuploidies on human peri-implantation development will be key for advancing human embryo research and improving the interpretation of findings from in vitro embryo models. Study design, size, duration A total of 191 PGT blastocysts obtained from 103 patients were included in the study. Blastocysts were selected based on their original diagnosis, including embryos with single whole-chromosome aneuploidies (single trisomies, n = 37 and single monosomies, n = 71), single segmental aberrations (n = 22), embryos with complex chromosomal constitutions (two or more abnormalities, n = 44), as well as control euploid embryos (n = 17). Participants/materials, setting, methods Vitrified blastocysts were warmed and cultured up to D12 using an optimized protocol to generate embryo outgrowths. We correlated the original PGT diagnoses to developmental outcomes, including outgrowth viability, morphology and outgrowth size. We evaluated blastocyst quality using the Gardner grading system. Following culture, we immunostained 38 viable outgrowths for lineage-specific markers, including OCT4 (epiblast), GATA6 (hypoblast) and CK-7 (trophoblast). Fisher’s exact test was used for statistical analysis (p < 0.05 was considered significant). Main results and the role of chance Following extended culture, 43.5% of embryos remained viable and attached, while 56.5% degenerated and detached. No significant correlation was found between embryo grade and attachment rate. Euploid embryos exhibited the highest attachment rate, with 88.2% (15/17) forming viable outgrowths. Euploid embryos also generated significantly larger outgrowths than trisomic and monosomic embryos (p = 0.01). Embryos diagnosed with trisomies and segmental aberrations exhibited attachment rates comparable to euploid embryos, at 70.3% (p = 0.18) and 68.2% (p = 0.25), respectively. However, embryos with monosomies and complex chromosomal constitutions arrested more readily (28.2% and 15.9% viable, <0.00001, respectively). All euploid embryos (6/6) retained a discernible OCT4+ epiblast-like structure. This was similar to embryos with segmental aberrations and trisomies, with 75% (3/4) and 53.8% (7/13) of outgrowths containing OCT4+ cells, respectively. Nonetheless, distinct trisomies exerted varying effects on peri-implantation development in vitro. For instance, viable trisomies (13, 18, 21) developed similarly to euploid embryos, while outgrowths carrying a trisomy 22 had fewer OCT4+ cells (p = 0.02) and a higher number of GATA6+ cells (p < 0.01), suggesting a potential lineage proliferation defect. Monosomies had the most profound effects on development. Compared to euploid embryos, monosomic embryos formed significantly fewer OCT4+ outgrowths (28.6%, p = 0.02) and contained fewer epiblast (p < 0.0001) and hypoblast-like (p = 0.003) cells. Limitations, reasons for caution The limited number of embryos in certain groups warrants careful interpretation. The central drawback of the models is that embryo outgrowths are predominately flattened, which confounds identification of three-dimensional structures formed during normal embryogenesis. Future studies should encompass additional lineage specification markers and potential culture refinements to enhance our interpretation. Wider implications of the findings Our findings underscore the critical importance of reporting the chromosomal composition of human embryos utilized for research. This practice will enable a more nuanced interpretation of results from in vitro embryo models and ultimately advance our capabilities in human embryo research. Trial registration number not applicable

Experimental validation of numerical point spread function calculation including aberration estimation

Image reconstruction in fluorescence microscopy is highly sensitive to the accuracy of the impulse response, defined as the point spread function (PSF), of the optical system under which the image to reconstruct was acquired. In our previous work, we developed a MATLAB toolbox for accurately calculating realistic vector Fourier-based PSF accounting for any type of aberrations [arXiv, arXiv:2301.13515 (2023)10.48550/arXiv.2301.13515]. In this work, we present a fundamental experimental validation of these numerical methods. The simulated results are found to fit experimental data under different image acquisition conditions at an accuracy higher than 0.97 in normalized cross-correlation. These methods enable a relative contrast of up to 95%.

Exploring the Impact of Cytogenetic Abnormalities on Treatment Responses and Survival Outcomes in Multiple Myeloma: A Single-Centre Experience of 13 Years of Follow-Up.

(1) Background: The introduction of novel therapies has led to a considerable evolution in the management of Multiple Myeloma, and chromosomal abnormalities predict the success of treatment. We aimed to characterize cytogenetic abnormalities for risk stratification in the patient population and to evaluate the predictive and prognostic value of the specified abnormalities in distinct treatment modalities. (2) Methods: This study included patients with Multiple Myeloma who applied to the Internal Medicine Clinic of the Cukurova University Faculty of Medicine. Between 2010 and 2023, 98 cases with cytogenetic abnormality data were identified. We analysed the effects of cytogenetic abnormalities on survival and response rates to first chemotherapies. (3) Results: P53 del was the most prevalent abnormality, and t(11;14) was the most common translocation. There was no significant difference in the mean survival and treatment response rates for specific cytogenetic abnormalities. When chemotherapies based on lenalidomide were initiated, patients' life-death statuses differed significantly from those of treatments without lenalidomide. Regardless of the type of chromosomal aberration, lenalidomide-based treatments independently enhanced average survival 14-fold, while there was no significant difference in overall survival among treatments. (4) Conclusions: In individuals with cytogenetic abnormalities, lenalidomide-based treatments should be started regardless of the chemotherapy to be used for the condition.

Impact of the presence and number of chromosomal abnormalities on the clinical outcome in Waldenström Macroglobulinemia: a monocentric experience.

The prognostic and predictive role of specific gene mutations in Waldenström Macroglobulinemia (WM) is well-ascertained whereas the clinical impact of chromosome aberrations is far less known. Recent work has provided initial evidence for an adverse prognostic impact of some aberrations, such as del(6q), while other studies suggest a possible relationship between some clinical features (e.g. advanced age and/or inflammatory status) and specific cytogenetic abnormalities. To add to the still limited knowledge on WM cytogenetics and its clinical implications, we herein report our experience in a cohort of WM patients across 23years. Based on our retrospective study, we found that abnormal karyotype was more represented in older patients and maintained a statistically significant independence from other molecular, clinical, and biological features related to WM. The presence and number of cytogenetic aberrations correlated with inferior overall and progression-free survival outcomes regardless of the type of single chromosome aberration. Our data suggests that the role of the altered karyotype deserves to be further clarified especially in elderly WM patients, in whom cytogenetic abnormalities and disease biology appear to be characterized by a higher degree of complexity.

Cas9-directed long-read sequencing to resolve optical genome mapping findings in leukemia diagnostics

Leukemias are genetically heterogeneous and diagnostics therefore includes various standard-of-care (SOC) techniques, including karyotyping, SNP-array and FISH. Optical genome mapping (OGM) may replace these as it detects different types of structural aberrations simultaneously and additionally detects much smaller aberrations (500 bp vs 5–10 Mb with karyotyping). However, its resolution may still be too low to define clinical relevance of aberrations when they are located between two OGM labels or when labels are not distinct enough. Here, we test the potential of Cas9-directed long-read sequencing (LRS) as an additional technique to resolve such potentially relevant new findings. From an internal Bionano implementation study we selected ten OGM calls that could not be validated with SOC methods. Per variant we designed crRNAs for Cas9 enrichment, prepared libraries and sequenced them on a MinION/GridION device. We could confirm all aberrations and, importantly, the actual breakpoints of the OGM calls were located between 0.2 and 5.5 kb of the OGM-estimated breakpoints, confirming the high reliability of OGM. Furthermore, we show examples of redefinition of aberrations between labels that enable judgment of clinical relevance. Our results suggest that Cas9-directed LRS can be a relevant and flexible secondary technique in diagnostic workflows including OGM.

Genetic And Environmental Associations Of Nonspecific Chromosomal Aberrations.

Nonspecific structural chromosomal aberrations (CAs) are found in around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. CAs have been used in the monitoring of persons exposed to genotoxic agents and radiation. Previous studies on occupationally exposed individuals have shown associations between the frequency of CAs in peripheral blood lymphocytes and subsequent cancer risk. The cause for CA formation are believed to be unrepaired or insufficiently repaired DNA double-strand breaks or other DNA damage, and additionally telomere shortening. CAs include chromosome (CSAs) and chromatid type aberrations (CTAs). In the present review, we first describe the types of CAs, the conventional techniques used for their detection and some aspects of interpreting the results. We then focus on germline genetic variation in the frequency and type of CAs measured in a genome-wide association study (GWAS) in healthy individuals in relation to occupational and smoking-related exposure compared to non-exposed referents. The associations (at p<10-5) on 1473 healthy individuals were broadly classified in candidate genes from functional pathways related to DNA damage response/repair, including PSMA1, UBR5, RRM2B, PMS2P4, STAG3L4, BOD1, COPRS and FTO; another group included genes related to apoptosis, cell proliferation, angiogenesis and tumorigenesis, COPB1, NR2C1, COPRS, RHOT1, ITGB3, SYK, and SEMA6A; a third small group mapped to genes KLF7, SEMA5A and ITGB3 which were related to autistic traits, known to manifest frequent CAs. Dedicated studies on 153 DNA repair genes showed associations for some 30 genes, expression of which could be modified by the implicated variants. We finally point out that monitoring of CAs is so far the only method of assessing cancer risk in healthy human populations, and the use of the technology should be made more attractive by developing automated performance steps and incorporating artificial intelligence methods into the scoring.

The glutathione biosynthesis is involved in metamorphosis, antioxidant function, and insecticide resistance in Tribolium castaneum.

Reduced glutathione (GSH) synthesis is vital for redox homeostasis, cell-cycle regulation and apoptosis, and immune function. The glutamate-cysteine ligase catalytic subunit (Gclc) is the first and rate-limiting enzyme in GSH synthesis, suggesting the potential use of Gclc as a pesticide target. However, the functional characterization of Gclc, especially its contribution in metamorphosis, antioxidant status and insecticide resistance, is unclear in Tribolium castaneum. In this study, we identified and cloned Gclc from T. castaneum (TcGclc) and found that its expression began to increase significantly from the late larvae (LL) stage (3.491 ± 0.490-fold). Furthermore, RNA interference-mediated knockdown of TcGclc resulted in three types of aberration (100% total aberration rate) caused by the downregulation of genes related to the 20-hydroxyecdysone (20E) pathway. This deficiency was partially rescued by exogenous 20E treatment (53.1% ± 3.2%), but not by antioxidant. Moreover, in the TcGclc knockdown group, GSH content was decreased to 62.3%, and total antioxidant capacity, glutathione peroxidase and total superoxide dismutase activities were reduced by 14.6%, 83.6%, and 82.3%, respectively. In addition, treatment with different insecticides upregulated expression of TcGclc significantly compared with a control group during the late larval stage (P < 0.01). Our results indicate that TcGclc has an extensive role in metamorphosis, antioxidant function and insecticide resistance in T. castaneum, thereby expanding our understanding of GSH functions and providing a scientific basis for pest control. © 2024 Society of Chemical Industry.

M-FISH evaluation of chromosome aberrations to examine for historical exposure to ionising radiation due to participation at British nuclear test sites

Veterans of the British nuclear testing programme represent a population of ex-military personnel who had the potential to be exposed to ionising radiation through their participation at nuclear testing sites in the 1950s and 1960s. In the intervening years, members of this population have raised concerns about the status of their health and that of their descendants, as a consequence. Radiation dose estimates based on film badge measurements of external dose recorded at the time of the tests suggest any exposure to be limited for the majority of personnel, however, only ∼20% of personnel were monitored and no measurement for internalised exposure are on record. Here, to in-part address families concerns, we assay for chromosomal evidence of historical radiation exposure in a group of aged nuclear test (NT) veterans, using multiplex in situ hybridisation (M-FISH), for comparison with a matched group of veterans who were not present at NT sites. In total, we analysed 9379 and 7698 metaphase cells using M-FISH (24-colour karyotyping) from 48 NT and 38 control veteran samples, representing veteran servicemen from the army, Royal Airforce and Royal Navy. We observed stable and unstable simple- and complex-type chromosome aberrations in both NT and control veterans’ samples, however find no significant difference in yield of any chromosome aberration type between the two cohorts. We do observe higher average frequencies of complex chromosome aberrations in a very small subset of veterans previously identified as having a higher potential for radiation exposure, which may be indicative of internalised contamination to long-lived radionuclides from radiation fallout. By utilising recently published whole genome sequence analysis data of a sub-set of the same family groups, we examined for but found no relationship between paternal chromosome aberration burden, germline mutation frequency and self-reported concerns of adverse health in family members, suggesting that the previously reported health issues by participants in this study are unlikely to be associated with historical radiation exposure. We did observe a small number of families, representing both control and NT cohorts, showing a relationship between paternal chromosome aberrations and germline mutation sub-types which should be explored in future studies. In conclusion, we find no cytogenetic evidence of historical radiation exposure in the cohort of nuclear veterans sampled here, offering reassurance that attendance at NTs sites by the veterans sampled here, was not associated with significant levels of exposure to radiation.

Evaluation of cytotoxicity and genotoxicity of the upstream Citarum River using Allium cepa assay

Citarum River is the longest and largest river in West Java, and its existence greatly influences the lives of surrounding communities. Many industries are built around the area. It is important to assess the quality of the water, because certain heavy metal might leak to the body of water. This research aimed to investigate the mitotic index (MI), root length, frequency and types of chromosomal aberration which determined the cytotoxicity and genotoxicity by using Allium cepa L. as biomarker. The Completely randomized design with seven treatments and four replications were used. Observation was done 96 hours after onion bulb soaked in water. Data was analysed using Analysis of Variance and continued with Duncan post-hoc. Results showed that root length was not affected. Water samples were affecting the MI, frequency, and types of chromosomal aberration. The highest number of chromosome aberrations was recorded on Dayeuh Kolot stations and the most common type of aberration was stickiness. The chromosome aberrations observed were; stickiness, chromosome loss, chromosome bridge, chromosome break, binucleated cells, multipolar, micronuclei, and c-mitosis. Based on the results, Allium assay is beneficial to evaluate the level of cytotoxicity and genotoxicity in the upstream Citarum River.

Aberracje wyższego rzędu jako coraz istotniejszy parametr podczas kwalifikacji pacjenta do operacji usunięcia zaćmy

Higher order aberrations are complex optical errors that affect the quality of vision, especially in low light conditions. The article discusses the impact of higher order aberrations on the choice of intraocular lens during cataract removal surgery. These aberrations affect the patient’s vision quality after the surgery, and their analysis allows for a more precise selection of intraocular lens, increasing the chances of achieving better clinical outcomes. The article covers the main types of higher order aberrations and their impact on the choice of intraocular lens. The number of higher order aberrations changes with the patient’s age and can be the cause of suboptimal outcomes after the implantation of multifocal IOLs. Preoperative examination of the patient, taking into account higher order aberrations, is crucial for obtaining satisfactory postoperative results. Further research on higher order aberrations is essential for the development of technologically advanced intraocular lenses.