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Mitotic cell division is tightly monitored by checkpoints that safeguard the genome from instability. Failures in accurate chromosome segregation during mitosis can cause numerical aneuploidy, which was hypothesized by Theodor Boveri over a century ago to promote tumorigenesis. Recent interrogation of pan-cancer genomes has identified unexpected classes of chromosomal abnormalities, including complex rearrangements arising through chromothripsis. This process is driven by mitotic errors that generate abnormal nuclear structures that provoke extensive yet localized shattering of mis-segregated chromosomes. Here, we discuss emerging mechanisms underlying chromothripsis from micronuclei and chromatin bridges, as well as highlight how this mutational cascade converges on the DNA damage response. A fundamental understanding of these catastrophic processes will provide insight into how initial errors in mitosis can precipitate rapid cancer genome evolution. Chromothripsis drives rapid genome evolution through the extensive shattering of mis-segregated chromosomes. This review discusses the cell cycle checkpoints that protect against mitotic errors, how mis-segregated chromosomes entrapped in abnormal nuclear structures undergo shattering, and the DNA damage response mechanisms that reassemble shattered chromosomes to generate complex cancer genome rearrangements. [ABSTRACT FROM AUTHOR]

This article explores the relationship between the Catholic Church and animal magnetism. At the beginning of the nineteenth century, the Catholic Church had first tried to stem the rise of animal magnetism in a vague manner, but after a few decades, it eventually put a genuine veto in place. This measure was founded upon the dangers to morality and faith arising from the progressive polarization of the original doctrine in forms related to esotericism. Among the causes of the condemnation by the Congregation of the Holy Office, the primary ones were the naturalist interpretation of the miracles described in the Gospels and in the New Testament, and the possibility of falling under the control of a demonic spirit. [ABSTRACT FROM AUTHOR]

Objective: Noise-induced hearing loss is the most prevalent occupational disease worldwide and is historically associated with the Industrial Revolution. This study analyses early descriptions of this disorder during the pre-industrial period in the work of the Italian physician Bernardino Ramazzini (1633–1714). Method: Primary and secondary historical literature were reviewed. Results: Ramazzini described hearing loss in corn millers and in coppersmiths and recognised that this disorder is irreversible and progressive when exposure to noise continues. He also seemed to describe tinnitus. He further suggested the use of earplugs as a preventive measure for these classes of workers. Ramazzini's anatomical and pathological knowledge appears to be based on ancient authors; he did not discuss contemporaneous medical authors' work on hearing function. Conclusion: Despite some limitations, Ramazzini's work appears pioneering for his time and represents an important milestone in the history of otolaryngology. [ABSTRACT FROM AUTHOR]

Aim: Cardiac arrest (CA) survival has diverse psychosocial outcomes for both survivors and their close family, with little known regarding long-term adjustment and recovery experiences. We explored the psychological adjustment and experiential perspectives of survivors and families in the second year after out-of-hospital cardiac arrest (OHCA).Methods: A prospective, mixed-methods study of adult OHCA survivors in Victoria, Australia was conducted. Eighteen survivors and 12 family members completed semi-structured interviews 14-19 months post-arrest. Survivors' cognition, anxiety, depression and post-traumatic stress symptoms were measured using a battery of psychological assessments. A thematic content analysis approach was applied to qualitative interview data by two independent investigators, with data coded and categorised into themes and sub-themes.Results: Survivors' cognition, depression, anxiety and post-traumatic stress symptoms were not clinically elevated in the second year post-arrest. Subjective cognitive failures were associated with increased anxiety but not with mental state. Depression was significantly correlated with post-traumatic symptoms. Six primary themes emerged from survivors' recovery stories, focused on: awakening and realisation, barriers to adjustment, psychosocial difficulties, integration, protective factors and unmet needs. Family perspectives revealed four primary themes focused on trauma exposure, survivor adjustment problems, family impact, and areas for service improvement.Conclusion: Survivors and their family members describe complex recovery journeys characterised by a range of psychosocial adjustment challenges, which are not adequately captured by common psychological measures. Post-arrest care systems are perceived by survivors and their families as inadequate due to a lack of accurate information regarding post-arrest sequalae, limited follow-up and inconsistent access to allied health care. [ABSTRACT FROM AUTHOR]

Movies could provide unexpected information on the state of medical knowledge in different historical periods. The first centenary of the German silent horror movie Das Cabinet des Dr. Caligari (The Cabinet of Dr. Caligari) by Robert Wiene (1873–1938) could be a timely occasion to reflect on the scientific debate of hypnosis and its legal implications between the 19th and the 20th century. In particular, this article describes the positions of the School of Salpêtrière (Charcot) and the School of Nancy (Bernheim) on the possibility of crimes committed by subjects under hypnosis and the influence of these theories on medical community and public opinion of Germany in the interwar period. [ABSTRACT FROM AUTHOR]

Background: The centromere is the specialized locus required for correct chromosome segregation during cell division. The DNA of most eukaryotic centromeres is composed of extended arrays of tandem repeats (satellite DNA). In the horse, we previously showed that, although the centromere of chromosome 11 is completely devoid of tandem repeat arrays, all other centromeres are characterized by the presence of satellite DNA. We isolated three horse satellite DNA sequences (37cen, 2P1 and EC137) and described their chromosomal localization in four species of the genus Equus. Results: In the work presented here, using the ChIP-seq methodology, we showed that, in the horse, the 37cen satellite binds CENP-A, the centromere-specific histone-H3 variant. The 37cen sequence bound by CENP-A is GC-rich with 221 bp units organized in a head-to-tail fashion. The physical interaction of CENP-A with 37cen was confirmed through slot blot experiments. Immuno-FISH on stretched chromosomes and chromatin fibres demonstrated that the extension of satellite DNA stretches is variable and is not related to the organization of CENP-A binding domains. Finally, we proved that the centromeric satellite 37cen is transcriptionally active. Conclusions: Our data offer new insights into the organization of horse centromeres. Although three different satellite DNA families are cytogenetically located at centromeres, only the 37cen family is associated to the centromeric function. Moreover, similarly to other species, CENP-A binding domains are variable in size. The transcriptional competence of the 37cen satellite that we observed adds new evidence to the hypothesis that centromeric transcripts may be required for centromere function. [ABSTRACT FROM AUTHOR]

The article investigates how the protein p62/SQSTM1 (sequestosome 1) influences micronuclear integrity and chromosome rearrangements in cancer cells. Topics discussed include the role of p62 in stabilizing micronuclei through oxidation-driven oligomerization, the impact of reactive oxygen species (ROS) from mitochondria on p62 localization, and the mechanisms leading to micronuclear envelope rupture and subsequent deoxyribonucleic acid (DNA) damage.

The article explores oxidative damage causes micronuclear collapse, focusing on reactive oxygen species (ROS) disrupting nuclear membrane repair via the endosomal sorting complex required for transport III (ESCRT-III). It details how ROS affect charged multivesicular body protein 7 (CHMP7) and Lamina-Associated Polypeptide 2 (LEM) domain nuclear envelope protein 2 (LEMD2) interactions and highlights the implications for chromosomal rearrangements in tumors, especially under hypoxic conditions.

The typical vertebrate centromeres contain long stretches of highly repeated DNA sequences (satellite DNA). We previously demonstrated that the karyotypes of the species belonging to the genus Equus are characterized by the presence of satellite-free and satellite-based centromeres and represent a unique biological model for the study of centromere organization and behavior. Using horse primary fibroblasts cultured in vitro, we compared the segregation fidelity of chromosome 11, whose centromere is satellite-free, with that of chromosome 13, which has similar size and a centromere containing long stretches of satellite DNA. The mitotic stability of the two chromosomes was compared under normal conditions and under mitotic stress induced by the spindle inhibitor, nocodazole. Two independent molecular-cytogenetic approaches were used—the interphase aneuploidy analysis and the cytokinesis-block micronucleus assay. Both assays were coupled to fluorescence in situ hybridization with chromosome specific probes in order to identify chromosome 11 and chromosome 13, respectively. In addition, we tested if the lack of centromeric satellite DNA affected chromatid cohesion under normal and stress conditions. We demonstrated that, in our system, the segregation fidelity of a chromosome is not influenced by the presence of long stretches of tandem repeats at its centromere. To our knowledge, the present study is the first analysis of the mitotic behavior of a natural satellite-free centromere. [ABSTRACT FROM AUTHOR]

Background: In mammals, an important source of genomic variation is insertion polymorphism of retrotransposons. These may acquire a functional role when inserted inside genes or in their proximity. The aim of this work was to carry out a genome wide analysis of ERE1 retrotransposons in the horse and to analyze insertion polymorphism in relation to evolution and function. The effect of an ERE1 insertion in the promoter of the myostatin gene, which is involved in muscle development, was also investigated. Results: In the horse population, the fraction of ERE1 polymorphic loci is related to the degree of similarity to their consensus sequence. Through the analysis of ERE1 conservation in seven equid species, we established that the level of identity to their consensus is indicative of evolutionary age of insertion. The position of ERE1s relative to genes suggests that some elements have acquired a functional role. Reporter gene assays showed that the ERE1 insertion within the horse myostatin promoter affects gene expression. The frequency of this variant promoter correlates with sport aptitude and racing performance. Conclusions: Sequence conservation and insertion polymorphism of ERE1 elements are related to the time of their appearance in the horse lineage, therefore, ERE1s are a useful tool for evolutionary and population studies. Our results suggest that the ERE1 insertion at the myostatin locus has been unwittingly selected by breeders to obtain horses with specific racing abilities. Although a complex combination of environmental and genetic factors contributes to athletic performance, breeding schemes may take into account ERE1 insertion polymorphism at the myostatin promoter. [ABSTRACT FROM AUTHOR]

The centromere directs the segregation of chromosomes during mitosis and meiosis. It is a distinct genetic locus whose identity is established through epigenetic mechanisms that depend on the deposition of centromere-specific centromere protein A (CENP-A) nucleosomes. This important chromatin domain has so far escaped comprehensive molecular analysis due to its typical association with highly repetitive satellite DNA. In previous work, we discovered that the centromere of horse chromosome 11 is completely devoid of satellite DNA; this peculiar feature makes it a unique model to dissect the molecular architecture of mammalian centromeres. Here, we exploited this native satellite-free centromere to determine the precise localization of its functional domains in five individuals: We hybridized DNA purified from chromatin immunoprecipitated with an anti CENP-A antibody to a high resolution array (ChIP-on-chip) of the region containing the primary constriction of horse chromosome 11. Strikingly, each individual exhibited a different arrangement of CENP-A binding domains. We then analysed the organization of each domain using a single nucleotide polymorphism (SNP)-based approach and single molecule analysis on chromatin fibres. Examination of the ten instances of chromosome 11 in the five individuals revealed seven distinct 'positional alleles', each one extending for about 80-160 kb, were found across a region of about 500 kb. Our results demonstrate that CENP-A binding domains are autonomous relative to the underlying DNA sequence and are characterized by positional instability causing the sliding of centromere position. We propose that this dynamic behaviour may be common in mammalian centromeres and may determine the establishment of epigenetic alleles. [ABSTRACT FROM AUTHOR]

Centromeres are the sites of kinetochore assembly and spindle fiber attachment and consist of protein-DNA complexes in which the DNA component is typically characterized by the presence of extended arrays of tandem repeats called satellite DNA. Here, we describe the isolation and characterization of a 137-bp-long new satellite DNA sequence from the horse genome (EC137), which is also present, even if less abundant, in the domestic donkey, the Grevy's zebra and the Burchelli's zebra. We investigated the chromosomal distribution of the EC137 sequence in these 4 species. Moreover, we analyzed its architectural organization by high-resolution FISH. The position of this sequence with respect to the primary constriction and in relation to the 2 major horse satellite tandem repeats (37cen and 2PI) on horse chromosomes suggests that the new centromeric equine satellite is an accessory DNA element, presumably contributing to the organization of pericentromeric chromatin. FISH on combed DNA fibers reveals that the EC137 satellite is organized in relatively short stretches (2-8 kb) which are strictly intermingled within 37cen or 2PI arrays. This arrangement suggests that interchanges between satellite families are a frequent occurrence in the horse genome. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]