Search

Copyright of Gesunde Pflanzen is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: The aim of this study was to investigate the contribution of chromosomal microarray analysis (CMA) and next‐generation sequencing (NGS) to genetic diagnosis in fetuses with normal karyotype who underwent invasive testing for different indications. Methods: The results of invasive genetic testing performed at a tertiary center between September 2020 and March 2022 were retrospectively analyzed. Indications for invasive tests were classified as fetal structural malformation, presence of soft markers, and high risk in screening tests. CMA results were classified as pathogenic or likely pathogenic (pCNVs), benign (bCNVs), and variants of unknown clinical significance (VOUS). Results: A total of 830 invasive tests were performed and aneuploidy was detected in 11.2% of the fetuses. CMA was performed in 465 fetuses with normal karyotype, and pCNVs were detected in 6.9%. pCNVs were detected in 8.2% of fetuses with structural malformations, 6.5% in soft markers, and 4.7% in high risk in screening tests. Pathogenic variants were detected by NGS in 33.8% of fetuses with bCNVs. Conclusions: pCNVs can be significantly detected not only in fetuses with structural malformations, but also in invasive testing with other indications. NGS significantly contributes to genetic diagnosis in fetuses with structural malformations. [ABSTRACT FROM AUTHOR]

The safe disposal of pulp and paper mill effluent is still a threat to the environment due to the presence of several unknown organic pollutants. The comparative physico-chemical analysis of pulp and paper mill effluent-contaminated sediment (PPECS) of site 1 and site 2 showed that the sediment had an alkaline nature and was loaded with several organic pollutants and heavy metals. SEM-EDX examination showed a porous structure with a heterogeneous distribution of particles, allowing the adsorption of metal and other complex organic ions. FTIR analysis depicted the presence of a variety of functional groups, i.e., alkyl halides, phenolics, and lignin, in the contaminated sediment. GC-MS analysis showed the major presence of organic pollutants, i.e., 2-methyl-4-keto-2-pentan-2-ol and 3,7-dioxa-2,8-disilanonane,2,2,8,8-tetramethyl-5-[(trimethylsilyl)oxy], in the site 1 sediment contaminated with pulp and paper mill waste, while 2-methyl-4-keto-2-trimethylsiloxypentane, 4-ethyl-2-methoxyphenol, ethyl-2-octynoate, cis-9-hexadecenoic acid, and octadecenoic acid were detected in the site 2 sediment contaminated with pulp and paper mill waste. The genotoxicity of PPECS determined by examining Allium cepa root cell division showed chromosomal aberration. In this study, several compounds that have not been reported before were identified. [ABSTRACT FROM AUTHOR]

t(11;18)(q21;q21) is the most frequent chromosomal aberration specifically associated with mucosa-associated lymphoid tissue (MALT) lymphoma. The translocation fuses the API2 gene to the MALT1 gene and generates a functional API2-MALT1 transcript. The breakpoint of the fusion gene is well characterized at the transcript level but poorly understood at the genomic level and the mechanism underlying the translocation is unknown. We identified the genomic breakpoint in 19 t(11;18)-positive MALT lymphoma cases by polymerase chain reaction and sequencing and analysed the junctional sequences. The breakpoints were scattered in intron 7 and exon  8 of the API2 gene, and introns  4, 6, 7 and 8 of the MALT1 gene. Comparative sequence analysis between the API2-MALT1 fusion on der(11) and the MALT1-API2 fusion on der(18) showed extensive alterations including deletions, duplications and non-template-based insertions at the fusion junctions in all cases examined. An extensive sequence search failed to reveal any known sequence motifs that might be associated with chromosomal recombination or any novel consensus sequences at or near the breakpoints on both der(11) and der(18) except in one case, in which Alu repeats spanned the breakpoint of the MALT1-API2 fusion. Our results suggest that t(11;18) may result from illegitimate non-homologous end joining following double strand breaks. [ABSTRACT FROM AUTHOR]

Comments on the article by A.A. Edwards published in the 2002 issue of the International Journal of Radiation Biology,' about modelling radiation-induced chromosome aberrations. Lesion/non-lesion interaction for the formation of chromosomal aberrations; Claim that the model cannot predict the relatively common three-way exchange complex rearrangement.

Simple Summary: Much research has been conducted on the causes of childhood cancer, but many areas of uncertainty remain. We conducted a detailed search of recent studies investigating the causes of childhood cancer. Our findings, based on publications from 2014 to 2021, are summarized by topic in three separate papers: factors acting during childhood (Paper 1), factors relating to the parents and pregnancy (Paper 2), and factors relating to the environment (Paper 3). In this first paper, we summarize convincing evidence from studies that show increased childhood cancer risk associated with genetic cancer predisposition, birth defects, prior cancer, medical ionizing radiation, organ transplantation and exposure to cancer-causing viruses, and a reduced risk associated with some childhood vaccinations. Other factors discussed in this paper include the impact of the child's diet, allergies, medications, and body mass index. This review of factors associated with childhood cancer may help evidence-based efforts to reduce cancer in our pediatric populations. Purpose: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). Methods: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. Results: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy. [ABSTRACT FROM AUTHOR]

Introduction and aim. Structural chromosome aberrations result from the breakage of one or more chromosomes and the abnormal joining of their fragments during cell division. Unbalanced chromosome aberrations lead to a loss or gain of genetic material. The incidence of chromosome aberrations among live-born children is estimated at 0.5%. Chromosome aberrations can occur spontaneously or under the influence of mutagenic agents such as ionizing radiation, ultraviolet radiation or high temperature. Duplication is the doubling of a chromosome fragment, while deletion is the loss of a chromosome fragment. Description of the case. This report discusses a case of an 11-year-old boy, who was referred to a genetic clinic, after a multi-specialist consultation. The patient was found to have an unbalanced translocation associated with a duplication of a fragment of the long arm of chromosome 3 in the q26.3 region and a deletion of a fragment of the short arm of chromosome 8, region p23.1. The aberration is the result of a balanced translocation in the mother. The analyzed karyotype of the father is normal. Chromosome analysis using whole-genome microarray with oligonucleotide probes revealed a duplication involving 111 OMIM genes and a deletion involving 16 OMIM genes. The identified aberration, in the form of deletion and duplication, is responsible for the patient's abnormalities as delayed motor development and speech, autism, motor stereotypy and dysmorphic features. The child requires especially attentive care of parents and constant stimulation of psychomotor development under the professional care of relevant specialists. Conclusion. Further studies to understand the genetic basis of the abnormalities and the resulting phenotypic symptoms of patients with an unbalanced chromosomal aberration in the form of der(8)t(3;8)(q26.3;p23.1), will identify more patients and allow for an improvement in the treatment regimens. [ABSTRACT FROM AUTHOR]

Background: Genome Mapping Technologies (optical and electronic) use ultra-high molecular weight DNA to detect structural variation and have application in constitutional genetic disorders, hematological neoplasms, and solid tumors. Genome mapping can detect balanced and unbalanced structural variation, copy number changes, and haplotypes. The technique is analogous to chromosomal microarray analysis, although genome mapping has the added benefit of being able to detect and ascertain the nature of more abnormalities in a single assay than array, karyotyping, or FISH alone. Key Messages: This paper describes a specific nomenclature for genome mapping that can be used by diagnostic and research centers to report their findings accurately. An international nomenclature is essential for patient results to be understood by different healthcare providers as well as for clear communication in publications and consistency in databases. Summary: Genome mapping can detect aneuploidy, balanced and unbalanced structural variation, as well as copy number changes. The Standing Committee for the International System for Human Cytogenomic Nomenclature (ISCN) recognised there was a need for a specific nomenclature for genome mapping that encompasses the range of abnormalities detected by this technique. This paper explains the general principles of the nomenclature as well as giving specific ISCN examples for the different types of numerical and structural rearrangements. [ABSTRACT FROM AUTHOR]

This article considers a problem of chromosomal pathologies detection. Chromosomal pathologies are dangerous and pose a great threat for family planning. To address them, the karyotyping process is conducted. Currently this process is manual or semimanual, despite high effort and error cost. So, there is a need for automation of the process. This process (and automation algorithm) can be separated into different stages with various objectives. However, the shared element among these stages is format that allows to store and manage data efficiently. The goal of this paper is to propose such format. The paper revises peculiarities of karyotyping process and briefly describes steps of the pathology detection algorithm. It also considers common formats for bioinformatics data. However, their efficiency is debatable, since data stored in these formats is redundant for the task at hand. After that, a new custom data format is proposed. This format represents main entities involved in the process of anomaly recognition. Several fragments of algorithm are considered, and their complexity is estimated combined with proposed data format. As a result, this paper proposes a new data storage format used in a chromosome abnormalities recognition algorithm, and metrics that can be used to make measurable improvement over the proposed format. [ABSTRACT FROM AUTHOR]

Background: Non-invasive prenatal testing (NIPT) has had an incomparable triumph in prenatal diagnostics in the last decade. Over 1400 research articles have been published, predominantly praising the advantages of this test. Methods: The present study identified among the 1400 papers 24 original and one review paper, which were suited to re-evaluate the efficacy of > 750,000 published NIPT-results. Special attention was given to false-positive and false-negative result-rates. Those were discussed under different aspects—mainly from a patient-perspective. Results: A 27: 1 rate of false-positive compared to false-negative NIPT results was found. Besides, according to all reported, real-positive, chromosomally aberrant NIPT cases, 90% of those would have been aborted spontaneously before birth. These findings are here discussed under aspects like (i) How efficient is NIPT compared to first trimester screening? (ii) What are the differences in expectations towards NIPT from specialists and the public? and (iii) There should also be children born suffering from not by NIPT tested chromosomal aberrations; why are those never reported in all available NIPT studies? Conclusions: Even though much research has been published on NIPT, unbiased figures concerning NIPT and first trimester screening efficacy are yet not available. While false positive rates of different NIPT tests maybe halfway accurate, reported false-negative rates are most likely too low. The latter is as NIPT-cases with negative results for tested conditions are yet not in detail followed up for cases with other genetic or teratogenic caused disorders. This promotes an image in public, that NIPT is suited to replace all invasive tests, and also to solve the problem of inborn errors in humans, if not now then in near future. Overall, it is worth discussing the usefulness of NIPT in practical clinical application. Particularly, asking for unbiased figures concerning the efficacy of first trimester-screening compared to NIPT, and for really comprehensive data on false-positive and false-negative NIPT results. [ABSTRACT FROM AUTHOR]

The field of preimplantation genetic testing (PGT) is evolving fast, and best practice advice is essential for regulation and standardisation of diagnostic testing. The previous ESHRE guidelines on best practice for PGD, published in 2005 and 2011, are considered outdated, and the development of new papers outlining recommendations for good practice in PGT was necessary. The current paper provides recommendations on the technical aspects of PGT for chromosomal structural rearrangements (PGT-SR) and PGT for aneuploidies (PGT-A) and covers recommendations on array-based comparative genomic hybridisation (aCGH) and next-generation sequencing (NGS) for PGT-SR and PGT-A and on fluorescence in situ hybridisation (FISH) and single nucleotide polymorphism (SNP) array for PGT-SR, including laboratory issues, work practice controls, pre-examination validation, preclinical work-up, risk assessment and limitations. Furthermore, some general recommendations on PGT-SR/PGT-A are formulated around training and general risk assessment, and the examination and post-examination process. This paper is one of a series of four papers on good practice recommendations on PGT. The other papers cover the organisation of a PGT centre, embryo biopsy and tubing and the technical aspects of PGT for monogenic/single-gene defects (PGT-M). Together, these papers should assist everyone interested in PGT in developing the best laboratory and clinical practice possible. [ABSTRACT FROM AUTHOR]

Multi-layer Complex networks are commonly used for modeling and analysing biological entities. This paper presents the advantage of using COMBO (Combining Multi Bio Omics) to suggest a new role of the chromosomal aberration as a cancer driver factor. Exploiting the heterogeneous multi-layer networks, COMBO integrates gene expression and DNA-methylation data in order to identify complex bilateral relationships between transcriptome and epigenome. We evaluated the multi-layer networks generated by COMBO on different TCGA cancer datasets (COAD, BLCA, BRCA, CESC, STAD) focusing on the effect of a specific chromosomal numerical aberration, broad gain in chromosome 20, on different cancer histotypes. In addition, the effect of chromosome 8q amplification was tested in the same TCGA cancer dataset. The results demonstrate the ability of COMBO to identify the chromosome 20 amplification cancer driver force in the different TCGA Pan Cancer project datasets. [ABSTRACT FROM AUTHOR]

The study discusses a new approach to parental agency in pediatric palliative care based on an active form of caregiving. It also explores the possibility of a positive conceptualization of parental agency in its relational context. The paper begins with an illustrative case study based on a clinical situation. This is followed by an analysis of various aspects of parental agency based on empirical studies that disclose the insufficiencies of the traditional approach to parental agency. In the next step, parental agency is analyzed from a reality‐based perspective as an activity focused on relationships and the cognitive capacity of parents vis‐a‐vis their seriously ill children. The paper also considers the importance of the cultural and social contexts in which parental agency and decision‐making take place. This agency is addressed not as individualistic in form, and nor is it exercised in terms of fixed choices. Rather, the focus is on its dynamic and future‐oriented aspects. Consequently, parental agency should be comprehended not only as a form of proxy agency representing the child's best interests but also as a complex decision‐making process in which the parents learn from their child how to become good, compassionate caregivers and at the same time good parents. [ABSTRACT FROM AUTHOR]

Premature ovarian insufficiency (POI) due to early depletion of ovarian follicles leads to primary amenorrhea or premature menopause. The causes can be genetic or secondary to infection, metabolic disease, autoimmune disorders, radiation, chemotherapy or physical damage to the ovary. Here in this paper we discuss the genetic causes of POI. The causes could be chromosomal disorders such as Turner syndrome (45, X) or structural X chromosomal abnormalities such as deletions/duplications/ring chromosome/X:autosome translocations. The causes could be single gene disorders with various inheritance patterns being possible such as autosomal dominant, autosomal recessive, X-linked dominant or X linked recessive We describe a panel of 157 genes which can be analysed on next generation sequencing panel and FMR1 gene which can be analysed on triple primer polymerase chain reaction method. [ABSTRACT FROM AUTHOR]

Background: A variation in the number of chromosomes can lead to chromosomal disorders. These chromosomal aberrations might be related to autosomes or sex chromosomes. The most common chromosomal aberrations that are sex-linked and autosomal are Klinefelter syndrome and Down syndrome, respectively. However, the worldwide occurrence of double chromosomal aneuploidy in a single individual is relatively exceptional event and random meiotic nondisjunction events result in double aneuploidy, which causes trisomy of two distinct chromosomes. The clinical manifestations vary depending on whether aneuploidy is dominant or an amalgam of both. Moreover, double aneuploidy including autosome and sex chromosome is not often documented. In this paper, we document a case of Down–Klinefelter double aneuploidy syndrome in an Indian infant hospitalized to the neonatal care unit. Case presentation: A full-term 9-month-old male infant born to a 36-year-old female with classical clinical signs of Down syndrome like epicanthus, a depressed nasal bridge, a flat face, small ears, an open mouth, thick lower lip vermilion, a protruding tongue, and a short neck was referred for cytogenetic examination, revealing a rare karyotype of 48, XXY, + 21. Conclusion: Down–Klinefelter syndrome is a rare chromosomal anomaly with unique characteristics, often displaying only Down syndrome-like traits at birth. Early diagnosis can be challenging due to the lack of noticeable symptoms until puberty. Early cytogenetic investigation can detect double aneuploidy, improving the affected person's quality of life and educating family members about potential medical and psychosocial difficulties. [ABSTRACT FROM AUTHOR]

This study reviews global trends in the publication of papers on the micronucleus test of the exfoliated cells of the oral mucosa in mammals as an approach for environmental biomonitoring. This test has been widely used due to its precision for the detection of chromosome damage. Our temporal analysis showed a significant increase ( p < 0.05) in the publication of papers on the oral mucosa over the past 33 years. Brazil was the country that published most papers (24% of the total), followed by India (16%), the USA (10%), Mexico (7%), and Turkey (6%). A further 30 countries contributed the other 37% of the papers. Overall, 99% of the micronucleus studies involved human subjects, and only 1% involved other mammals. As many wild mammals are subject to the same environmental pressures as humans, in particular chemical pollution, it seems likely that many species are equally susceptible to genotoxicogical damage. We emphasize the importance of applying this technique to the analysis of the oral mucosa of wild mammals, as well as the evaluation of its effectiveness, as observed in humans, and the expansion of the available approaches to the monitoring of environmental quality. [ABSTRACT FROM AUTHOR]

Copy number variants (CNVs) found in individuals with communication deficits provide a valuable window to the genetic causes of problems with language and, more generally, to the genetic foundation of the human-specific ability to learn and use languages. This paper reports on the language and communication problems of a patient with a microduplication in 22q11.23 and a microdeletion in 7q31.1-q1.33 encompassing FOXP2. The proband exhibits severe speech problems and moderate comprehension deficits, whereas her pragmatic abilities are a relative strength, as she uses gestures quite competently to compensate for her expressive issues. This profile is compatible with the deficiencies found in patients with similar CNVs, particularly with people bearing microdeletions in 7q31.1-q31.33. [ABSTRACT FROM AUTHOR]

Currently, there is much interest in the sales and study of consumable Cannabis sativa L. products that contain relatively high levels of cannabidiol (CBD) and low levels of Δ‐9‐tetrahydrocannabinol. While there are published safety evaluations for extracts containing low concentrations of CBD, toxicological assessments for those with higher concentrations are still scant in the public domain. In this paper, genotoxicity tests and a 90‐day repeated‐dose toxicity study of an ethanolic extract of C. sativa containing ~85% CBD were performed following relevant OECD guidelines. No increased gene mutations were observed in a bacterial reverse mutation assay compared to controls up to the maximum recommended concentration of the guideline. An in vitro chromosomal aberration assay showed no positive findings in the short‐term (3 h) treatment assays. Long‐term treatment (20 h) showed an increased number of cells containing aberrations at the highest dose of 2 μg/mL, which was outside of historical control levels, but not statistically significantly different from the controls. An in vivo micronucleus study showed no genotoxic potential of the test item in mice. A 90‐day repeated‐dose gavage study using 0, 75, 125, and 175 mg/kg bw/day showed several slight findings that were considered likely to be related to an adaptive response to consumption of the extract by the animals but were not considered toxicologically relevant. These included increases in liver and adrenal weights compared to controls. The NOAEL was determined as 175 mg/kg bw/day, the highest dose tested (equivalent to approximately 150 mg/kg bw/day of CBD). A toxicological assessment of an ethanolic Cannabis sativa extract containing ~85% CBD was performed. Genotoxicity concern based on a bacterial reverse mutation assay, an in vitro chromosomal aberration assay, and an in vivo mouse micronucleus assay was considered low. A 90‐day repeated dose study in rats showed some adaptive responses but no toxicological concern. The NOAEL was 175 mg/kg bw/day, the highest dose tested. [ABSTRACT FROM AUTHOR]

Simple Summary: Intestinal parasites are among the main causes of hidden economic losses in livestock farming. This study reports the results of chromosome instability analyses in Esperia ponies with different intestinal strongyles fecal egg counts. Interestingly, animals with higher fecal egg counts showed increased levels of chromosome instability. If this condition is confirmed in other horse breeds and livestock species, it will be important to understand the causes in order to implement therapeutic strategies for the management of intestinal parasites. The Pony of Esperia is an Italian autochthonous horse breed reared in the wild on the Aurunci and Ausoni Mountains. Currently, it is considered an endangered breed, as its population consists of 1623 animals. It is therefore essential to identify all aspects that can improve the management and economy of its breeding, favoring its diffusion. In this paper, the effects of intestinal strongyle infection on the chromosome stability of peripheral blood lymphocytes (PBLs) was evaluated through aneuploidy and chromosome aberration (gap, chromatid and chromosome breaks, and the number of abnormal cells) test. Statistical difference in the mean values of aneuploidy, cells with chromosome abnormalities, and chromosome and chromatid breaks were observed between ponies with high fecal egg counts (eggs per gram > 930) and those with undetectable intestinal strongylosis. The causes of this phenomenon and possible repercussions on the management of Pony of Esperia are discussed in the paper. [ABSTRACT FROM AUTHOR]

The incident of Chernobyl Nuclear Power Plant (CNPP) explosion has pioneered a plethora of studies unfolding various biological effects of radiation stress on several living systems. Determining radiation dose rates at which both acute and chronic biological effects occur in different biological systems will aid in the ex-situ generation of radiation-tolerant organisms. So far, the accumulation of data on different radiation doses from Chernobyl area demonstrating various biological impacts has not been documented altogether vastly. Therefore, this review aims to document the recorded doses in CNPP over the years at which different biological changes have been observed in plants, soil, aquatic organisms, birds, and animals. A total of 72 peer-reviewed papers obtained from PubMed, Google Scholar, Scopus, and Research4life were included in this review. A few factors have come under attention in this review. Firstly, plant and soil systems combinedly showed the most published studies after the catastrophe where plants showed a higher frequency of DNA methylation in their genome to resist radiation stress. Secondly, reduced species abundance, chromosomal aberrations, increased sterility, and mortality were mostly observed in the aftermath of Chernobyl catastrophe among plants, soil, aquatic organisms, birds, and small mammals. Furthermore, major scares of data after 2018 were prominently observed. Very few studies on radiation dose levels after 2018 are available. Hence, a major research area has emerged for radiation biologists to study present radiation levels and any genetic changes in the recent generation of the original victim species. This will help provide a standard dataset that can act as a reference resource for radiation biologists and future research on the impact of both acute and chronic radiation on the different biological systems. [ABSTRACT FROM AUTHOR]

Presents papers to be published in the periodical "British Journal of Haematology." Advances in the molecular and serological diagnosis of invasive fungal infection in hemato-oncology patients; Serum free light chains for monitoring multiple myeloma; Complex chromosomal abnormalities in utero.

Background: Intellectual disability (ID) consists of a broad range of disorders characterized by low general intellectual functioning (IQ below 70). ID etiologic causes are heterogeneous, ranging from environmental to chromosomal and monogenic conditions. Although many autosomal genes responsible for ID are expected, only a small number of these have been identified, and up to now most progress has been made in X-linked translocation ID area; but many autosomal genes play a crucial role in the development of a central nervous system. Any change which leads to lose or reduce the function or changes the expression of them; high or low, even have a damaging effect on the functional protein might lead to different phenotypes like developmental delay, growth retardation, or intellectual disabilities. Result & conclusion: In this paper, we discuss the importance of balanced chromosomal translocations in the cause of newborn intellectual disabilities. Balanced translocation is the result of breaking off two chromosomes and reattaching in a way that the sections of two chromosomes have switched places. These rearrangements are found as de novo events in 1/2000 live births and give rise to some congenital anomalies which are the product of submicroscopic deletions, duplications, inversion or disruption, activation, or inactivation of a gene or different genes located at or near the breakpoints in the basepair level. These apparently balanced translocations due to positional effect lead to abnormal phenotype. Conclusion: Cryptic genomic imbalances which cause mentality are very rare conditions but new technologies like NGS long-read genome sequencing could detect breakpoint effects on live birth health and discover a new way for prenatal diagnosis. [ABSTRACT FROM AUTHOR]

Background: Scholars agree that Torbjörn Caspersson's lab at the Institute of Medical Cell Research and Genetics at the Karolinska Institute, Sweden, played a key role in the first description of the so-called Q-banding technique. It laid the foundation for a new era of cytogenetic diagnostics and had a lasting impact in several areas of biology and medicine. Methods: Based on a mixed-method approach, essential aspects of the history of human cytogenetics are considered via primary and secondary analysis of biographical interviews as well as the qualitative evaluation of bibliometrics. Drawing on interviews with colleagues of lab member Lore Zech (1923–2013) and contemporary publications, this paper illuminates the role of and contribution by Zech: To what extent is the discovery attached to her and what does her legacy look like today? Results: The analysis of the contemporary witness interviews with colleagues, students and junior researchers shows that Lore Zech was a committed member of Caspersson's research group. In addition, memoirs by contemporary colleagues describe her outstanding skills in microscopy. The different sources paint a multifaceted picture. In addition to the historians' patterns of interpretation, different legacies can also be found within the peer group. Conclusions: We argue that Zech represent the type of scientist who, although her research was acknowledged with several prizes, so far has not been part of the canon of pioneers of international cytogenetics. [ABSTRACT FROM AUTHOR]

Noninvasive prenatal testing (NIPT) has become widely available in recent years. While initially used to screen for trisomies 21, 18, and 13, the test has expanded to include a range of other conditions and will likely expand further. This paper addresses the ethical issues that arise from one particularly controversial potential use of NIPT: screening for adult‐onset conditions (AOCs). We report data from our quantitative survey of Australian NIPT users' views on the ethical issues raised by NIPT for AOCs. The survey ascertained support for NIPT for several traits and conditions including AOCs. Participants were then asked about their level of concern around implications of screening for AOCs for the future child and parent(s). Descriptive and comparative data analyses were conducted. In total, 109 respondents were included in data analysis. The majority of respondents expressed support for NIPT screening for preventable (70.9%) and nonpreventable AOCs (80.8%). Most respondents indicated concern around potential harmful impacts associated with NIPT for AOCs, including the psychological impact on the future child and on the parent(s). Despite this, the majority of participants thought that continuation of a pregnancy known to be predisposed to an AOC is ethically acceptable. The implications of these data are critically discussed and used to inform the normative claim that prospective parents should be given access to NIPT for AOCs. The study contributes to a body of research debating the ethical acceptability and regulation of various applications of NIPT as screening panels expand. [ABSTRACT FROM AUTHOR]

Simple Summary: Uveal melanoma (UM) is a rare eye cancer with a high mortality rate due to metastases, leading to death in up to 50% of patients within 10 years from UM diagnosis. Moreover, patients show a median survival of 6 to 12 months after metastasis diagnosis. UM and cutaneous melanoma (CM) have the same melanocytic origin; however, they are very different in terms of molecular alterations and biological behavior. In this review, we will discuss the complex genetic and non-coding RNA-based epigenetic landscapes underlying the transformation, progression, and dissemination of UM. This knowledge will pave the way for the future identification of new biomarkers of the pathology and therapeutic targets. Uveal melanoma (UM) is the most common intraocular malignant tumor and the most frequent melanoma not affecting the skin. While the rate of UM occurrence is relatively low, about 50% of patients develop metastasis, primarily to the liver, with lethal outcome despite medical treatment. Notwithstanding that UM etiopathogenesis is still under investigation, a set of known mutations and chromosomal aberrations are associated with its pathogenesis and have a relevant prognostic value. The most frequently mutated genes are BAP1, EIF1AX, GNA11, GNAQ, and SF3B1, with mutually exclusive mutations occurring in GNAQ and GNA11, and almost mutually exclusive ones in BAP1 and SF3B1, and BAP1 and EIF1AX. Among chromosomal aberrations, monosomy of chromosome 3 is the most frequent, followed by gain of chromosome 8q, and full or partial loss of chromosomes 1 and 6. In addition, epigenetic mechanisms regulated by non-coding RNAs (ncRNA), namely microRNAs and long non-coding RNAs, have also been investigated. Several papers investigating the role of ncRNAs in UM have reported that their dysregulated expression affects cancer-related processes in both in vitro and in vivo models. This review will summarize current findings about genetic mutations, chromosomal aberrations, and ncRNA dysregulation establishing UM biology. [ABSTRACT FROM AUTHOR]

Deletions and duplications of the distal region of the long arm of chromosome 1 are associated with brain abnormalities and developmental delay. Because duplications are less frequent than deletions, no detailed account of the cognitive profile of the affected people is available, particularly, regarding their language (dis)abilities. In this paper we report on the cognitive and language capacities of a girl with one of the smallest interstitial duplications ever described in this region, affecting to 1q42.3q43 (arr[hg19] 1q42.3q43(235,963,632–236,972,276)x3), and advance potential candidate genes for the observed deficits. The proband's speech is severely impaired, exhibiting dysarthric-like features, with speech problems also resulting from a phonological deficit boiling down to a verbal auditory memory deficit. Lexical and grammatical knowledge are also impaired, impacting negatively on both expressive and receptive abilities, seemingly as a consequence of the phonological deficit. Still, her pragmatic abilities seem to be significantly spared, granting her a good command on the principles governing conversational exchanges. Genetic analyses point to several genes of interest. These include one gene within the duplicated region (LYST), one predicted functional partner (CMIP), and three genes outside the 1q42.3q43 region, which are all highly expressed in the cerebellum: DDIT4 and SLC29A1, found strongly downregulated in the proband compared to her healthy parents, and CNTNAP3, found strongly upregulated. The genes highlighted in the paper emerge as potential candidates for the phonological and speech deficits exhibited by the proband and ultimately, for her problems with language. [ABSTRACT FROM AUTHOR]

This systematic review, conducted according to the PRISMA guidelines, focuses on genotoxicity of oxidative hair dye precursors. The search for original papers published from 2000 to 2021 was performed in Medline, Web of Science, Cochrane registry, Scientific Committee on Consumer Safety of the European Commission and German MAK Commission opinions. Nine publications on genotoxicity of p -phenylenediamine (PPD) and toluene-2,5-diamine (p -toluylenediamine; PTD) were included, reporting results of 17 assays covering main genotoxicity endpoints. PPD and PTD were positive in bacterial mutation in vitro assay, and PPD tested positive also for somatic cell mutations in the Rodent Pig-a assay in vivo. Clastogenicity of PPD and PTD was revealed by in vitro chromosomal aberration assay. The alkaline comet assay in vitro showed DNA damage after PPD exposure, which was not confirmed in vivo , where PTD exhibited positive results. PPD induced micronucleus formation in vitro, and increased micronucleus frequencies in mice erythrocytes following high dose oral exposure in vivo. Based on the results of a limited number of data from the classical genotoxicity assay battery, this systematic review indicates genotoxic potential of hair dye precursors PPD and PTD, which may present an important health concern for consumers and in particular for professional hairdressers. [ABSTRACT FROM AUTHOR]

This is the fourth in a series of papers. The previous papers inform midwifery practice by providing insight into whether, to what extent and how cognitive status influences understanding of Down syndrome screening information, the importance of tailoring information, and highlighting areas of communication that are effective in facilitating understanding. These findings led to the development of recommendations to inform a 'best practice' model for midwifery communication of screening information within a conceptual framework that recognises the importance of accurate facts, empathic communication and support for decision-making in a woman-centred approach. These recommendations may have wider relevance beyond midwife communication of Down syndrome screening and may impact upon the communication of other screening information provided within antenatal and neonatal screening. It is important that screening information is communicated effectively in light of changes to screening programmes, such as the introduction of non-invasive prenatal testing. [ABSTRACT FROM AUTHOR]

The fluorescent tracer, MB-102, has been designed for the direct, real-time measurement of glomerular filtration rate. Previous studies, both in vitro and in vivo (rats, rabbits and dogs), were conducted to assess potential toxicity including single dose toxicity, mutation assay, chromosomal aberration assay, phototoxicity, local tolerance study, micronuclease assay, hERG channel changes, CNS and cardiovascular safety. The results of these studies led to a safety/toxicology profile for this agent deemed sufficient by the FDA to conduct Phase I and Phase II human clinical studies. In this paper we report on maternal toxicity and the potential effects on embryo-fetal development and the toxicokinetics of MB-102 administered daily via intravenous (bolus) injection into pregnant rabbits during the period of organogenesis gestation day 7-19. Assessment of toxicity was based on mortality, clinical observations, body weight, food consumption, reproductive performance and necropsy and cesarean section findings. Blood samples were collected for toxicokinetic evaluation. No test article findings were noted in any of these studies. The only clinical findings observed were the discoloration of skin, eyes or pelage in the 2 higher dose groups, which were considered related to the color and fluorescent properties of MB-102 and were deemed non-adverse. Exposure, as assessed by Cmax and AUC(0-6) increased in a dose dependent manner from 4.5 to 113 mg/kg/day. No accumulation of the test article was noted after multiple doses were administered. Thus, intravenous administration of MB-102 was not associated with any adverse developmental or reproductive toxicities in pregnant rabbits. [ABSTRACT FROM AUTHOR]

Cherubism also known as familial fibrous dysplasia is a rare, non neoplastic, self-limiting fibro-osseous disorder commonly affecting the jaws in children and young adults. It is also described as familial multilocular cystic disease and familial benign giant cell tumor of the jaw. It is characterised by bilateral, painless swelling involving the mandible giving a cherubic (angel like) appearance. As it is a rare disorder, it is challenging to determine the disease frequency. A familial disorder like cherubism is more likely to be of autosomal dominant trait and shows 100% male sex predilection compared to female which is 50-70%. Although cherubism becomes noticeable in childhood (2-7 years of age), the treatment is however contentious as the disorder is believed to regress gradually after the onset of puberty and surgical intervention is to be decided based on aesthetics or functional difficulties. Numerous researches have been conducted to prove that cherubism is a genetically mediated disorder and the chromosome mapped is 4q16.3. This paper describes a case of an 11-year-old girl with cherubism and also encountered in two subsequent generations of a family, the father and his three children. The genetic and pedigree analysis carried out in this family proves hereditary basis in better understanding the genetic association related with the disorder. All the patients were educated about the disorder and were advised for surgical management after the onset of puberty. [ABSTRACT FROM AUTHOR]

Background Approximately 50% of spontaneous miscarriages are associated with chromosome abnormalities. Identification of these karyotypic abnormalities helps to estimate recurrence risks in future pregnancies. Chromosomal microarray analysis ( CMA) is transforming clinical cytogenetic practice with its ability to examine the human genome at increasingly high resolution. Objectives The aim of this study was to determine whether CMA testing on the products of conception following miscarriage provides better diagnostic information compared with conventional karyotyping. Search strategy MEDLINE (from 1996 to December 2012), EMBASE (from 1974 to December 2012), and CINAHL (from 1996 to December 2012) databases were searched electronically. Selection criteria Studies were selected if CMA was used on products of conception following miscarriage, alongside conventional karyotyping. Data collection and analysis Nine papers were included in the systematic review and meta-analysis. All statistical analyses were performed using stata 11.0 ( Stata Corp., College Station, TX, USA). Main results There was agreement between CMA and karyotyping in 86.0% of cases (95% CI 77.0-96.0%). CMA detected 13% (95% CI 8.0-21.0) additional chromosome abnormalities over conventional full karyotyping. In addition, traditional, full karyotyping detected 3% (95% CI 1.0-10.0%) additional abnormalities over CMA. The incidence of a variant of unknown significance ( VOUS) being detected was 2% (95% CI 1.0-10.0%). Author's conclusions Compared with karyotyping, there appears to be an increased detection rate of chromosomal abnormalities when CMA is used to analyse the products of conception; however, some of these abnormalities are VOUS, and this information should be provided when counselling women following miscarriage and when taking consent for the analysis of miscarriage products by CMA. [ABSTRACT FROM AUTHOR]

Rainer Kurt Sachs, a Professor of Mathematics and Physics at UC Berkeley, passed away in April 2024. He had two successful careers in science, one in general relativity and cosmology, and the other in the mathematics of radiation biology and carcinogenesis. Sachs made significant contributions to the analysis of gravitational waves and the prediction of minute angular fluctuations in the cosmic microwave background radiation. In his later career, he focused on understanding radiation-induced chromosome aberrations and modeling radiation carcinogenesis. Sachs was known for his modesty, attentiveness, and supportiveness as a mentor. A Memorial Colloquium will be held in his honor in October 2024. [Extracted from the article]

An adverse outcome pathway (AOP) is a conceptual construct of causally and sequentially linked events, which occur during exposure to stressors, with an adverse outcome relevant to risk assessment. The development of an AOP is a means of identifying knowledge gaps in order to prioritize research assessing the health risks associated with exposure to physical or chemical stressors. In this paper, a review of knowledge was proposed, examining experimental and epidemiological data, in order to identify relevant key events and potential key event relationships in an AOP for renal impairment, relevant to stressors such as uranium (U). Other stressors may promote similar pathways, and this review is a necessary step to compare and combine knowledge reported for nephrotoxicants. U metal ions are filtered through the glomerular membrane of the kidneys, then concentrate in the cortical and juxtaglomerular areas, and bind to the brush border membrane of the proximal convoluted tubules. U uptake by epithelial cells occurs through endocytosis and the sodium-dependent phosphate co-transporter (NaPi-IIa). The identified key events start with the inhibition of the mitochondria electron transfer chain and the collapse of mitochondrial membrane potential, due to cytochrome b5/cytochrome c disruption. In the nucleus, U directly interacts with negatively charged DNA phosphate, thereby inducing an adduct formation, and possibly DNA strand breaks or cross-links. U also compromises DNA repair by inhibiting zing finger proteins. Thereafter, U triggers the Nrf2, NF-κB, or endoplasmic reticulum stress pathways. The resulting cellular key events include oxidative stress, DNA strand breaks and chromosomal aberrations, apoptosis, and pro-inflammatory effects. Finally, the main adverse outcome is tubular damage of the S2 and S3 segments of the kidneys, leading to tubular cell death, and then kidney failure. The attribution of renal carcinogenesis due to U is controversial, and specific experimental or epidemiological studies must be conducted. A tentative construction of an AOP for uranium-induced kidney toxicity and failure was proposed. [ABSTRACT FROM AUTHOR]

In this paper, we have studied the role of chromosomal abnormalities in the expression of small nucleolar RNAs (snoRNAs) of radioresistant (K562) and radiosensitive (HL-60) leukemia cell line. Cells were exposed to an X-ray dose of 4 Gy. SnoRNA expression was investigated using NGS sequencing. The distribution of expressed snoRNAs on chromosomes has been found to be different for two cell lines. The most significant differences in the expression of snoRNAs were found in the K562 cell line based on the analysis of the dynamics of log2fc values. The type of clustering, the number and type of snoRNAs slightly differed in the chromosomes with trisomy and monosomy and had a pronounced difference in pairs with marker chromosomes in both cell lines. In this study, we have demonstrated that chromosomal abnormalities alter the expression of snoRNA after irradiation. Trisomies and monosomies do not have such a noticeable effect on the expression of snoRNAs as the presence of marker chromosomes. [ABSTRACT FROM AUTHOR]

An effective synthetic protocol towards the oxidation of sumanene–ferrocene conjugates bearing one to four ferrocene moieties has been established. The oxidation protocol was based on the transformation of FeII from ferrocene to FeIII-containing ferrocenium cations by means of the treatment of the title organometallic buckybowls with a mild oxidant. Successful isolation of these ferrocenium-tethered sumanene derivatives 5–7 gave rise to the biological evaluation of the first, buckybowl-based anticancer agents, as elucidated by in vitro assays with human breast adenocarcinoma cells (MDA-MB-231) and embryotoxicity trials in zebrafish embryos supported with in silico toxicology studies. The designed ferrocenium-tethered sumanene derivatives featured attractive properties in terms of their use in cancer treatments in humans. The tetra-ferrocenium sumanene derivative 7 featured especially beneficial biological features, elucidated by low (<40% for 10 μM) viabilities of MDA-MB-231 cancer cells together with a 1.4–1.7-fold higher viability of normal cells (human mammary fibroblasts, HMF) for respective concentrations. Compound 7 featured significant cytotoxicity against cancer cells thanks to the presence of sumanene and ferrocenium moieties; the latter motif also provided the selectivity of anticancer action. The biological properties of 7 were also improved in comparison with those of native building blocks, which suggested the effects of the presence of the sumanene skeleton towards the anticancer action of this molecule. Ferrocenium-tethered sumanene derivatives exhibited potential towards the generation of reactive oxygen species (ROS), responsible for biological damage to the cancer cells, with the most efficient generation of the tetra-ferrocenium sumanene derivative 7. Derivative 7 also did not show any embryotoxicity in zebrafish embryos at the tested concentrations, which supports its potential as an effective and cancer-specific anticancer agent. In silico computational analysis also showed no chromosomal aberrations and no mutation with AMES tests for the compound 7 tested with and without microsomal rat liver fractions, which supports its further use as a potent drug candidate in detailed anticancer studies. [ABSTRACT FROM AUTHOR]

This study set out to determine the impact of different storage temperatures and packing materials on storage fungi, genotoxic effect, germination rate, and chemical properties of three different cultivars of maize (SC131, TWC324, and Balady) that were stored for 0, 8, and 18 months. Data show that Fusarium verticilioides, was the most common fungus attacking maize grains and causing kernel rots in all tested maize cultivars and under all storage conditions. It was followed by Aspergillus niger, Aspergillus flavus and Penicillium spp. For storage conditions, keeping maize grains in refrigerators (at 10°C and -5°C) in high density polyethylene packing was the most effective technique to prevent kernel rot. Results for grain germination and chemical attributes showed that when grains were maintained in refrigerators (at 10oC, and at -5°C) in high density polyethylene packing, maize SC131 had the highest germination percentage, protein, carbs, oil, and fibre content. In contrast, the Balady cultivar that was held at room temperature in woven polyethylene containers had higher amounts of ash, free fatty acids, and acidity than normal. Increased storage periods were observed to significantly reduce germination percentage and chemical grain component, particularly at room temperature and in woven polyethylene packing. In terms of genotoxicity, maize grain cultivar SC131 had the lowest percentage of chromosomal aberrations (CA), the highest percentage of mitotic index (MI), and the lowest infection by kernel rot. [ABSTRACT FROM AUTHOR]

Klinefelter syndrome is the most common sex chromosome disorder, with a prevalence of 1 in every 660 males, and despite being so prevalent, less than 30% of cases do ever get diagnosed. This is due to the very heterogeneous phenotypic presentations of the patients; failure in early identification of these patients can have dire consequences on those individuals' overall health and life quality as it is a major cause of primary hypogonadism and subsequent infertility, in addition to the increased risk of neoplasms and a plethora of other systemic conditions. Our objective was to look into the literature concerning Klinefelter's: clinical features and management in the pediatric population. PubMed database was used for articles selection, from where the papers were obtained and reviewed. The clinical presentation of Klinefelter syndrome patients can vary dramatically based on the age and severity of the disease. Most cases have near-normal phenotypes during infancy except for extreme phenotypes that could present with micro-pen undescended testis. As the child grows and reaches puberty detection rate increases as signs of normal puberty such as virilization and increase in muscle mass are usually deficient or incomplete. Most cases only picked up during adulthood who presents complaining of infertility. The treatment approach consists of testosterone therapy, assisted fertility, and early detection and treatment of associated complications. [ABSTRACT FROM AUTHOR]

Copyright of Evidência is the property of Evidencia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Macedonian Pharmaceutical Bulletin / Makedonsko Farmacevtski Bilten is the property of Macedonian Pharmaceutical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Nanomaterials (NMs) present unique challenges in safety evaluation. An international working group, the Genetic Toxicology Technical Committee of the International Life Sciences Institute’s Health and Environmental Sciences Institute, has addressed issues related to the genotoxicity assessment of NMs. A critical review of published data has been followed by recommendations on methods alterations and best practices for the standard genotoxicity assays: bacterial reverse mutation (Ames); in vitro mammalian assays for mutations, chromosomal aberrations, micronucleus induction, or DNA strand breaks (comet); and in vivo assays for genetic damage (micronucleus, comet and transgenic mutation assays). The analysis found a great diversity of tests and systems used for in vitro assays; many did not meet criteria for a valid test, and/or did not use validated cells and methods in the Organization for Economic Co-operation and Development Test Guidelines, and so these results could not be interpreted. In vivo assays were less common but better performed. It was not possible to develop conclusions on test system agreement, NM activity, or mechanism of action. However, the limited responses observed for most NMs were consistent with indirect genotoxic effects, rather than direct interaction of NMs with DNA. We propose a revised genotoxicity test battery for NMs that includes in vitro mammalian cell mutagenicity and clastogenicity assessments; in vivo assessments would be added only if warranted by information on specific organ exposure or sequestration of NMs. The bacterial assays are generally uninformative for NMs due to limited particle uptake and possible lack of mechanistic relevance, and are thus omitted in our recommended test battery for NM assessment. Recommendations include NM characterization in the test medium, verification of uptake into target cells, and limited assay-specific methods alterations to avoid interference with uptake or endpoint analysis. These recommendations are summarized in a Roadmap guideline for testing. [ABSTRACT FROM AUTHOR]

Anthraquinone is a recently identified contaminant present in teas globally, and its potential teratogenic and genotoxic impacts have yet to be fully comprehended. Hence, this study's objective was to determine anthraquinone's genotoxicity using various studies such as the Ames test, Mammalian erythrocyte micronucleus test, and in-vitro mammalian chromosome aberration study. Additionally, the study assessed its effects on maternal gestational toxicity and the fetus's teratogenicity through prenatal developmental toxicity research in rats. Results indicated that anthraquinone did not manifest mutagenic effects on Salmonella typhimurium histidine-deficient, did not cause chromosomal aberrations in Chinese hamster ovary cell subclone CHO-K1, and did not exhibit a genotoxic effect on mouse bone marrow erythrocytes. However, in the prenatal developmental toxicity study, administering anthraquinone orally to pregnant rats from day 5 to day 19 of gestation resulted in decreased body weight and food consumption of pregnant rats, along with a higher number of visceral malformations in the fetuses in the highest dose group (217.6 mg/kg BW). Additionally, two pregnant rats died in this group. The study has established the no observed adverse effect level (NOAEL) as 21.76 mg/kg BW, while the lowest observed adverse effect level (LOAEL) was 217.6 mg/kg BW. [Display omitted] • This paper discusses the genotoxicity and teratotoxicity of anthraquinone. • Anthraquinone is not genotoxic. • The NOAEL for anthraquinone teratology was 21.76 mg/kg, the LOAEL was 217.6 mg/kg. • Data on genotoxicity and prenatal developmental toxicity of anthraquinone were added. • Provides a basis for chronic toxicity design and risk assessment of anthraquinones. [ABSTRACT FROM AUTHOR]

It has long been known that the chiasmata are not independently distributed in most organisms, a phenomenon known as chiasma interference. In this paper, I suggest a model of chiasma interference that generalizes the Poisson model, the counting model, the Poissonskip model, and the two-pathway counting model into a single framework, and use it to derive infinite series expressions for the sterility and recombination pattern probabilities in inversion homo- and heterokaryotypes, and a closed-form expression for the special case of the two-pathway counting model in homokaryotypes. I then use these expressions to perform maximum likelihood parameter estimations for recombination and tetrad data from various species. The results imply that the simpler counting models perform well compared to more complex ones, that interference works in a similar way in homo- and heterokaryotypes, and that the model fits well with data for the latter as well as the former. I also find evidence that the interference signal is broken by the centromere in some species, but not others, suggestions of negative interference in Aspergillus nidulans, and no consistent support for the theory that a second noninterfering chiasma pathway exists only in organisms that require double-strand break for synapsis. I suggest that the latter finding is at least partly due to issues involved in analyzing aggregate data from different experiments and individuals. [ABSTRACT FROM AUTHOR]

Immunoglobulin light chain amyloidosis (AL) is an indolent plasma cell disorder characterized by free immunoglobulin light chain (FLC) misfolding and amyloid fibril deposition. The cytogenetic pattern of AL shows profound similarity with that of other plasma cell disorders but harbors distinct features. AL can be classified into two primary subtypes: non-hyperdiploidy and hyperdiploidy. Non-hyperdiploidy usually involves immunoglobulin heavy chain translocations, and t(11;14) is the hallmark of this disease. T(11;14) is associated with low plasma cell count but high FLC level and displays distinct response outcomes to different treatment modalities. Hyperdiploidy is associated with plasmacytosis and subclone formation, and it generally confers a neutral or inferior prognostic outcome. Other chromosome abnormalities and driver gene mutations are considered as secondary cytogenetic aberrations that occur during disease evolution. These genetic aberrations contribute to the proliferation of plasma cells, which secrete excess FLC for amyloid deposition. Other genetic factors, such as specific usage of immunoglobulin light chain germline genes and light chain somatic mutations, also play an essential role in amyloid fibril deposition in AL. This paper will propose a framework of AL classification based on genetic aberrations and discuss the amyloid formation of AL from a genetic aspect. [ABSTRACT FROM AUTHOR]

Variations in the intrinsic radiosensitivity of different cells to ionizing radiation is now widely believed to be a significant driver in differences in response to radiotherapy. While the mechanisms of radiosensitivity have been extensively studied in the laboratory, there are a lack of models which integrate this knowledge into a predictive framework. This paper presents an overview of the Medras model, which has been developed to provide a mechanistic framework in which different radiation responses can be modelled and individual responses predicted. This model simulates the repair of radiation-induced DNA damage, incorporating the overall kinetics of repair and its fidelity, to predict a range of biological endpoints including residual DNA damage, mutation, chromosome aberration, and cell death. Validation of this model against a range of exposure types is presented, including considerations of varying radiation qualities and dose-rates. This approach has the potential to inform new tools to deliver mechanistic predictions of radiation sensitivity, and support future developments in treatment personalization. [ABSTRACT FROM AUTHOR]

Hibakusha (atomic bomb survivors) are "witnesses" of the atomic bombings, not just in a standard sense but also in the instrumental sense. For medical and scientific experts, hibakusha are biological resources of unparalleled scientific value. Over the past seventy years, the hibakusha bodies have narrated what it means to be exposed to radiation. In this paper, I explore studies at the Atomic Bomb Casualty Commission (ABCC) that examined hibakusha bodies as sites where risk could be read. I focus on a period from the mid-1950s to 1975, during which new methods, practices, and technologies allowed ABCC scientists to investigate chromosomes as a way to study radiation exposure and human risk. By focusing on chromosomal aberrations, ABCC scientists connected their work directly to the emerging infrastructure for radiobiology at the time. ABCC administrators actively sought out such prestige, especially given their relationship with the Atomic Energy Commission (AEC). The shift in approach would also alleviate some public relations problems with which the institution was struggling. Launching a cytogenetics program required some older practices that had assumed American privilege and dominance to be abandoned. Eventually, the decision to let chromosomes speak of radiation exposure brought about fundamental changes in ABCC, which came to symbolize the model for future studies at the organization, especially as ABCC was transitioning to a US-Japan binational organization. More broadly, this case highlights the intricate scientific negotiation of radiation risk where uncertainties necessarily prevail. [ABSTRACT FROM AUTHOR]

Summary: Rivulidae comprises a family of fish largely distributed in Brazil that includes 201 species, of which 125 are considered endangered. This fact emphasizes the need for development of conservation strategies including studies on genetics and reproduction. In this paper, we describe aspects of biology and reproduction of the rivuliid species Hypsolebias sertanejo. We outline the reproductive behaviour of this species under laboratory conditions, analyze ploidy status by flow cytometry, describe reproductive behaviour and performance and test dry and wet incubation of eggs. Although H. sertanejo showed well known patterns of reproductive behaviour, we verified many peculiarities inherent to its reproductive biology. As expected, most individuals were diploid (87.71%), however 14.29% were considered mosaics. Although no sterility was observed within mosaics, infertility of these fish was not fully evaluated. Hatching rate of the eggs collected was very low following both dry and wet incubation (5.04 and 3.79%, respectively). These results provide interesting information regarding the reproductive success of this species, and suggest that chromosomal abnormalities described may reduce the survival of H. sertanejo under natural conditions, limiting the perpetuation of this species, and emphasizing the need for more preservation efforts, including artificial propagation and gene banking. [ABSTRACT FROM AUTHOR]

In Part I of this paper, we detected elements blocked by ribs during simulated and in vivo transcostal liver scans, and we turned those elements OFF to compensate for the loss in visibility of liver vasculature. Here, we apply blocked-element detection and adaptive compensation to large synthetic-aperture (SA) data collected through rib samples ex vivo, in order to reduce near-field clutter and to recover lateral resolution. To construct large synthetic transmit and receive apertures, we collected the individual-channel signals from a fully sampled matrix array at multiple and known array locations across the tissue samples. The blocked elements in SAs were detected using the method presented in Part I and retroactively turned OFF, while the subapertures covering intercostal spaces were either compounded, or coherently summed using uniform and adaptive element-weighting schemes. Turning OFF the blocked elements reduced the reverberation clutter by 5 dB on average. Adaptive weighing of the nonblocked elements to rescale the attenuated spatial frequencies reduced sidelobe levels by up to 5 dB for the transcostal acquisitions, and demonstrated a potential to restore lateral resolution to the nonblocked levels. In addition, the arrival-time surfaces were reconstructed to estimate the aberration from intercostal spaces and to offer further means to compensate for the loss of focus quality in transthoracic imaging. [ABSTRACT FROM AUTHOR]