Genetic analysis of the Replication Protein A large subunit family in Arabidopsis reveals unique and overlapping roles in DNA repair, meiosis and DNA replication

Replication Protein A (RPA) is a heterotrimeric protein complex that binds single-stranded DNA. In plants, multiple genes encode the three RPA subunits (RPA1, RPA2 and RPA3), including five RPA1-like genes in Arabidopsis. Phylogenetic analysis suggests two distinct groups composed of RPA1A, RPA1C, RPA1E (ACE group) and RPA1B, RPA1D (BD group). ACE-group members are transcriptionally induced by ionizing radiation, while BD-group members show higher basal transcription and are not induced by ionizing radiation. Analysis of rpa1 T-DNA insertion mutants demonstrates that although each mutant line is likely null, all mutant lines are viable and display normal vegetative growth. The rpa1c and rpa1e single mutants however display hypersensitivity to ionizing radiation, and combination of rpa1c and rpa1e results in additive hypersensitivity to a variety of DNA damaging agents. Combination of the partially sterile rpa1a with rpa1c results in complete sterility, incomplete synapsis and meiotic chromosome fragmentation, suggesting an early role for RPA1C in promoting homologous recombination. Combination of either rpa1c and/or rpa1e with atr revealed additive hypersensitivity phenotypes consistent with each functioning in unique repair pathways. In contrast, rpa1b rpa1d double mutant plants display slow growth and developmental defects under non-damaging conditions. We show these defects in the rpa1b rpa1d mutant are likely the result of defective DNA replication leading to reduction in cell division

Best Practices for Cataloging Objects Using RDA and MARC 21

This best practices document is intended to assist catalogers in creating bibliographic records for objects, which RDA refers to as three dimensional forms, according to RDA instructions. This document provides guidance for the most common object situations encountered in libraries. Each section includes examples that reflect the RDA instructions. A list of resources and a selection of full MARC record examples illustrating common situations encountered in cataloging objects (of various types) completes the document. The Objects Task Force especially worked on the examples to provide a variety of materials that fall bibliographically under Objects. The Task Force found at least one example of Realia, Toy, Model, Art Original, Game, Microscope Slide, Diorama, and Tactile Three-Dimensional Form. This document is intended for use with Resource Description and Access (RDA) and the MARC21 Format for Bibliographic Data. This document does not replace the use of RDA, but it works in tandem with RDA to provide best practices guidance in cataloging objects. This document is also not a step-by-step guide on how to catalog objects. The best practice recommendations and cataloging examples presented in the document are intended to clarify RDA principles and instructions used in cataloging objects. These guidelines assume some familiarity with RDA. Subject analysis is not fully covered in this best practices guide. Classification is not covered. Name and topical subject access points, as well as genre/form information, are not covered fully in this document, although we do provide a section to discuss access points on a very practical level, and certainly, they do appear in the MARC record examples

Cytogenetic analysis of adult T-Cell leukemia/ lymphoma: evaluation of a Caribbean cohort

Adult T-cell leukemia/lymphoma (ATLL) is a rare and highly aggressive type of peripheral T-cell lymphoma associated with human T-lymphotropic virus, type I (HTLV-I) infection. ATLL has a long latency and only a small percentage of HTLV-I infected individuals develop ATLL, suggesting the requirement of additional genetic events for neoplastic transformation of HTLV-I infected lymphocytes. The disease is endemic in several regions of the world, in particular, southwestern Japan and the Caribbean basin. The clinical features of Caribbean ATLL have been reported to differ from Japanese cases, includ- ing a younger age at diagnosis, higher frequency of the lymphomatous subtype, and a more aggressive clinical course [1–7]. A number of publications have described the cytogenetic profile of Japanese ATLL [8–11]; however, cytogenetic data on Caribbean ATLL are limited [5,6]. In this study, we assessed the cytogenetic alterations in a large series of Caribbean ATLL cases to investigate whether the differences in the types and frequencies of karyotype abnormalities account for the reported differ- ences in clinical presentation and outcome between Japanese and Caribbean patients

Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract.

Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract are rare clonal T-cell diseases that more commonly occur in the intestines and have a protracted clinical course. Different immunophenotypic subsets have been described, but the molecular pathogenesis and cell of origin of these lymphocytic proliferations is poorly understood. Hence, we performed targeted next-generation sequencing and comprehensive immunophenotypic analysis of ten indolent T-cell lymphoproliferative disorders of the gastrointestinal tract, which comprised CD4 <sup>+</sup> (n=4), CD8 <sup>+</sup> (n=4), CD4 <sup>+</sup> /CD8 <sup>+</sup> (n=1) and CD4 <sup>-</sup> /CD8 <sup>-</sup> (n=1) cases. Genetic alterations, including recurrent mutations and novel rearrangements, were identified in 8/10 (80%) of these lymphoproliferative disorders. The CD4 <sup>+</sup> , CD4 <sup>+</sup> /CD8 <sup>+</sup> , and CD4 <sup>-</sup> /CD8 <sup>-</sup> cases harbored frequent alterations of JAK-STAT pathway genes (5/6, 82%); STAT3 mutations (n=3), SOCS1 deletion (n=1) and STAT3-JAK2 rearrangement (n=1), and 4/6 (67%) had concomitant mutations in epigenetic modifier genes (TET2, DNMT3A, KMT2D). Conversely, 2/4 (50%) of the CD8 <sup>+</sup> cases exhibited structural alterations involving the 3' untranslated region of the IL2 gene. Longitudinal genetic analysis revealed stable mutational profiles in 4/5 (80%) cases and acquisition of mutations in one case was a harbinger of disease transformation. The CD4 <sup>+</sup> and CD4 <sup>+</sup> /CD8 <sup>+</sup> lymphoproliferative disorders displayed heterogeneous Th1 (T-bet <sup>+</sup> ), Th2 (GATA3 <sup>+</sup> ) or hybrid Th1/Th2 (T-bet <sup>+</sup> /GATA3 <sup>+</sup> ) profiles, while the majority of CD8 <sup>+</sup> disorders and the CD4 <sup>-</sup> /CD8 <sup>-</sup> disease showed a type-2 polarized (GATA3 <sup>+</sup> ) effector T-cell (Tc2) phenotype. Additionally, CD103 expression was noted in 2/4 CD8 <sup>+</sup> cases. Our findings provide insights into the pathogenetic bases of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract and confirm the heterogeneous nature of these diseases. Detection of shared and distinct genetic alterations of the JAK-STAT pathway in certain immunophenotypic subsets warrants further mechanistic studies to determine whether therapeutic targeting of this signaling cascade is efficacious for a proportion of patients with these recalcitrant diseases

Frame Theory for Signal Processing in Psychoacoustics

This review chapter aims to strengthen the link between frame theory and signal processing tasks in psychoacoustics. On the one side, the basic concepts of frame theory are presented and some proofs are provided to explain those concepts in some detail. The goal is to reveal to hearing scientists how this mathematical theory could be relevant for their research. In particular, we focus on frame theory in a filter bank approach, which is probably the most relevant view-point for audio signal processing. On the other side, basic psychoacoustic concepts are presented to stimulate mathematicians to apply their knowledge in this field

Diversity of SCCmec Elements in Methicillin-Resistant Coagulase-Negative Staphylococci Clinical Isolates

in MR-CoNS can generate useful information on the mobilization and evolution of this element.). in MR-CoNS

Tomorrow’s Digital Worker : A Critical Review and Agenda for Building Digital Competency Models

In competency management studies, scholars call for the importance of digital savviness to hire, train, and develop new digital workers. Yet, the knowledge about the development of such a competence is still scarce. For this endeavor, we followed a systematic literature review to identify a sample of 103 published scientific articles and book chapters dealing with the development and implementation of competency tools in the past 10 years. To our surprise, our review suggests that the landscape of competency tools is surprisingly obsolete and that contemporary requirements of digitization have not yet been incorporated into updated usable competency tools. Through this review our hope is to provide competency managers and researchers with a framework to advance and upgrade their competency tools to address the gap between existing know how and the needed expertise of the digital world.© 2020 Springer. This is a post-peer-review, pre-copyedit version of an article published in Advances in Human Factors, Business Management and Leadership Proceedings of the AHFE 2020 Virtual Conferences on Human Factors, Business Management and Society, and Human Factors in Management and Leadership, July 16-20, 2020, USA. The final authenticated version is available online at: https://doi.org/10.1007/978-3-030-50791-6_14fi=vertaisarvioitu|en=peerReviewed

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Operation Allelopathy: An Experiment Investigating an Alternative to Synthetic Agrochemicals

Synthetic herbicides represent a serious problem in modern agriculture because they are not biodegradable and can accumulate in the soil and in the groundwater, a situation that allows them to enter the trophic chain and ultimately leads to human exposure. Allelopathic chemicals offer an effective alternative to the synthetic compounds. The aim of this experiment is to highlight the differences between chemical and biological control of diseases in crops and to demonstrate the use of natural fungicides and herbicides as alternatives to synthetic chemicals. The experiment involves an evaluation by students of the potential of plant extracts as an alternative to synthetic agrochemicals to identify new ecological farming techniques that could be applied in agriculture. In an effort to encourage 1800 students in high school (14 to 16 years old) to have an interest in science, technology, and innovation, the third edition of the Summer Science Campus was organized by the Spanish Foundation for Science and Technology and the Ministry of Education, Culture, and Sports with support from the foundation Obra Social “la Caixa”