Emerging roles of telomeric chromatin alterations in cancer

Telomeres, the nucleoprotein structures that cap the ends of eukaryotic chromosomes, play important and multiple roles in tumorigenesis. Functional telomeres need the establishment of a protective chromatin structure based on the interplay between the specific complex named shelterin and a tight nucleosomal organization. Telomere shortening in duplicating somatic cells leads eventually to the destabilization of the telomere capping structure and to the activation of a DNA damage response (DDR) signaling. The final outcome of this process is cell replicative senescence, which constitute a protective barrier against unlimited proliferation. Cells that can bypass senescence checkpoint continue to divide until a second replicative checkpoint, crisis, characterized by chromosome fusions and rearrangements leading to massive cell death by apoptosis. During crisis telomere dysfunctions can either inhibit cell replication or favor tumorigenesis by the accumulation of chromosomal rearrangements and neoplastic mutations. The acquirement of a telomere maintenance mechanism allows fixing the aberrant phenotype, and gives the neoplastic cell unlimited replicative potential, one of the main hallmarks of cancer. Despite the crucial role that telomeres play in cancer development, little is known about the epigenetic alterations of telomeric chromatin that affect telomere protection and are associated with tumorigenesis. Here we discuss the current knowledge on the role of telomeric chromatin in neoplastic transformation, with a particular focus on H3.3 mutations in alternative lengthening of telomeres (ALT) cancers and sirtuin deacetylases dysfunctions

Experimental study of internal gravity waves over a slope

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution September, 1970A series of laboratory experiments were conducted in a glass wave tank to investigate the propagation of internal gravity waves up a sloping bottom in a fluid with constant Brunt-Vaisala frequency. Measurements of the wave motion in the fluid interior were primarily taken with electrical conductivity probes; measurements in the boundary layer were made with dye streaks and neutrally buoyant particles. The results indicate that, outside of the breaking zone, the amplitude and horizontal wave number of the high-frequency waves increase lineariy with decreasing depth; this is shown to agree with existing linear, inviscid solutions. A zone of breaking or runup is induced by these high-frequency waves well upslope. Shadowgraph observations show that, if the wave characteristics are coincident, or nearly so, with the bottom slope, the upslope propagation of the low-frequency waves causes a line of regularly spaced vortices to form along the slope. Subsequent mixing in the vortex cells creates thin horizontal laminae that are more homogeneous than the adjacent layers. These laminae slowly penetrate the fluid interior, creating a step-like vertical density structure. Available linear theoretical solutions for the velocity in the viscous boundary layer, determined to be valid for certain experimental conditions, are used to develop a criterion for incipient motion of bottom sediment induced by shoaling internal waves. The maximum sediment sizes that can be placed into motion, according to this criterion, are larger than certain mean sediment sizes on the continental margin off New England. This suggests that internal waves might induce initial sediment movement. Speculation about the geological effects of breaking and vortex instabilities is also given. These processes, not definitely measured in the field as yet, might also be conducive to sediment movement.This work was supported by the Office of Naval Research

MLB Rule IV Draft: Valuing Draft Pick Slots

This study explored the Net Present Value (NPV) in dollar terms of draft pick slots in the Major League Rule IV Draft. In order to accomplish this, the cumulative performance of players selected in each slot within the draft was evaluated and brought to the Present Value of the time they were selected using a discount rate. The performance of the players was determined using the baseball-reference Wins Above Replacement (WAR) metric. It is intuitive that earlier draft picks are the most valuable; however, it is unclear how quickly the value of draft picks decline. This research demonstrates that the decline in NPV is rapid for the first 40 draft selections before the pace slows. Around the 116th selection, draft pick slots level off and experience little decline, as teams are less able to determine the value of the players’ talents. There is substantial difference between the top 5 picks in the draft and the draft picks following the 116th selection, as the top 5 picks are worth in excess of $28 million each, while the later selections level off around$2 million each

Knowledge and Attitudes After Using Videos to Educate a Non-Clinical Cohort About Prenatal Cell-Free DNA Screening

Prenatal cell-free DNA (cfDNA) screening is now offered to pregnant women of all risk categories, creating a challenge in providing informed decision-making on a broad scale. Resources to support patient education, such as short educational videos, have been created to help ameliorate this issue but have not been formally evaluated. Thus, we sought to investigate the utility of videos in educating women about prenatal cfDNA screening and whether there were differences in knowledge and/or attitudes after viewing a video created by a non-profit genetics organization (Video A) versus a similar video created by a commercial testing company (Video B). Participants were asked to view one of the two videos and complete a survey assessing take-home messages, knowledge, attitudes, and demographics. A total of 207 individuals participated in the study; 106 viewed Video A (Group A) and 101 viewed Video B (Group B). Mean knowledge scores for both groups indicated sufficient education by their respective videos; however, Group A scored significantly higher (mean = 9.40) than Group B (mean = 8.99) (p

Chimpanzees ( Pan troglodytes ) and bonobos ( Pan paniscus ) quantify split solid objects

Recent research suggests that gorillas' and orangutans' object representations survive cohesion violations (e.g., a split of a solid object into two halves), but that their processing of quantities may be affected by them. We assessed chimpanzees' (Pan troglodytes) and bonobos' (Pan paniscus) reactions to various fission events in the same series of action tasks modelled after infant studies previously run on gorillas and orangutans (Cacchione and Call in Cognition 116:193-203, 2010b). Results showed that all four non-human great ape species managed to quantify split objects but that their performance varied as a function of the non-cohesiveness produced in the splitting event. Spatial ambiguity and shape invariance had the greatest impact on apes' ability to represent and quantify objects. Further, we observed species differences with gorillas performing lower than other species. Finally, we detected a substantial age effect, with ape infants below 6years of age being outperformed by both juvenile/adolescent and adult ape

The Private Side of Victorian Mourning Practices in Nineteenth-Century New England: The Cole’s Hill Memorial Cache

Excavated in downtown Plymouth, Massachusetts, a cache of 19th-century personal-adornment artifacts, daguerreotypes, ambrotypes, and organic materials provides an alternative view of mourning and memorialization practices in Victorian-era New England. The associated artifacts possess characteristics indicative of Victorian mourning symbols and material types. However, no other current examples of this mourning practice exist in the historical and archaeological records. Thus, this article will attempt to understand this discovery as an aspect of the private side of the traditionally public mourning practices and women’s efforts to create mourning customs that served in creating a feminine historical memory in the Victorian era

Silence at the End: How Drosophila Regulates Expression and Transposition of Telomeric Retroelements

The maintenance of chromosome ends in Drosophila is an exceptional phenomenon because it relies on the transposition of specialized retrotransposons rather than on the activity of the enzyme telomerase that maintains telomeres in almost every other eukaryotic species. Sequential transpositions of Het-A, TART, and TAHRE (HTT) onto chromosome ends produce long head-to-tail arrays that are reminiscent to the long arrays of short repeats produced by telomerase in other organisms. Coordinating the activation and silencing of the HTT array with the recruitment of telomere capping proteins favors proper telomere function. However, how this coordination is achieved is not well understood. Like other Drosophila retrotransposons, telomeric elements are regulated by the piRNA pathway. Remarkably, HTT arrays are both source of piRNA and targets of gene silencing thus making the regulation of Drosophila telomeric transposons a unique event among eukaryotes. Herein we will review the genetic and molecular mechanisms underlying the regulation of HTT transcription and transposition and will discuss the possibility of a crosstalk between piRNA mediated regulation, telomeric chromatin establishment and telomere protection

Desarrollo y futuro de la salud pública veterinaria

En la presente comunicación se analizan diferentes instancias de la gestión de la salud pública veterinaria y su evolución en el país.Academia Nacional de Agronomía y Veterinari

A role for Separase in telomere protection

Drosophila telomeres are elongated by transposition of specialized retroelements rather than telomerase activity and are assembled independently of the sequence. Fly telomeres are protected by the terminin complex that localizes and functions exclusively at telomeres and by non-terminin proteins that do not serve telomere-specific functions. We show that mutations in the Drosophila Separase encoding gene Sse lead not only to endoreduplication but also telomeric fusions (TFs), suggesting a role for Sse in telomere capping. We demonstrate that Separase binds terminin proteins and HP1, and that it is enriched at telomeres. Furthermore, we show that loss of Sse strongly reduces HP1 levels, and that HP1 overexpression in Sse mutants suppresses TFs, suggesting that TFs are caused by a HP1 diminution. Finally, we find that siRNA-induced depletion of ESPL1, the Sse human orthologue, causes telomere dysfunction and HP1 level reduction in primary fibroblasts, highlighting a conserved role of Separase in telomere protection