Genomic imbalances are confined to non-proliferating cells in paediatric patients with acute myeloid leukaemia and a normal or incomplete karyotype

Copyright @ 2011 Ballabio et al.Leukaemia is often associated with genetic alterations such as translocations, amplifications and deletions, and recurrent chromosome abnormalities are used as markers of diagnostic and prognostic relevance. However, a proportion of acute myeloid leukaemia (AML) cases have an apparently normal karyotype despite comprehensive cytogenetic analysis. Based on conventional cytogenetic analysis of banded chromosomes, we selected a series of 23 paediatric patients with acute myeloid leukaemia and performed whole genome array comparative genome hybridization (aCGH) using DNA samples derived from the same patients. Imbalances involving large chromosomal regions or entire chromosomes were detected by aCGH in seven of the patients studied. Results were validated by fluorescence in situ hybridization (FISH) to both interphase nuclei and metaphase chromosomes using appropriate bacterial artificial chromosome (BAC) probes. The majority of these copy number alterations (CNAs) were confirmed by FISH and found to localize to the interphase rather than metaphase nuclei. Furthermore, the proliferative states of the cells analyzed by FISH were tested by immunofluorescence using an antibody against the proliferation marker pKi67. Interestingly, these experiments showed that, in the vast majority of cases, the changes appeared to be confined to interphase nuclei in a non-proliferative status.This work was supported by a grant from Leukaemia Research UK (grant no. 0253). SJLK and RR were supported by the NIHR Biomedical Research Centre, Oxford, with funding from the Department of Health’s NIHR Biomedical Research Centres funding schemeThis article is available through the Brunel Open Access Publishing Fund

MicroRNA expression in lymphocyte development and malignancy

This article is available open access through the publisher’s website. Copyright @ 2008 Macmillan Publishers Limited.No abstract available.The Leukemia Research Fund, the Julian Starmer-Smith Memorial Fund, and the Medical Research Council

Bold Frogs or Shy Toads? How Did the COVID-19 Closure of Zoological Organisations Affect Amphibian Activity?

This is the final version. Available on open access from MDPI via the DOI in this recordData Availability Statement: Data are available upon reasonable request from the corresponding authors.Amphibians are an understudied group in the zoo-focussed literature. Whilst commonly housed in specialist exhibits and of real conservation value due to the global extinction crisis, amphibian welfare is not often investigated empirically in zoo settings. The limited research that is available suggests that enclosure design (structure, planting and naturalistic theming) has a positive impact on the time that amphibians will be on show to visitors. However, the categorisation of any “visitor effect” (i.e., influences of visitor presence on amphibian activity and time on display) is hard to find. The COVID-19 pandemic forced the closure of zoological organisations in the UK for several months from March 2020, with gradual re-openings from the summer into autumn and winter. This event provided a unique opportunity to study the effect of the lack of visitors, the presence of essential zoo staff only, the wider return of organisational staff, and then the return of visitors over a prolonged period. This project at WWT Slimbridge Wetlands Centre assessed the number of individuals of six species of amphibian—common toad (Bufo bufo), common frog (Rana temporaria), smooth newt (Lissotriton vulgaris), pool frog (Pelophylax lessonae), golden mantella (Mantella aurantiaca) and golden poison dart frog (Phyllobates terribilis)—visible to observers under different conditions. All amphibians were housed in a purpose-built indoor exhibit of individual enclosures and were recorded when visible (as a proportion of the total population of the enclosure) during closure, the return of extra centre staff and visitor periods. The results showed species-specific differences in visibility, with some species of amphibian being more likely to be on view when the presence of people at their enclosure was less likely or in smaller numbers. Such differences are likely related to the specific camouflage or anti-predation tactics in these focal species. Further study to quantify amphibian sensitivity to, and perception of, environmental change caused by public presence (e.g., light levels and sound) would be useful welfare-themed research extensions. Our results can help inform husbandry, collection planning and amphibian enclosure design to reduce any noticeable visitor effects, and provide a useful benchmark for further, more complex, welfare assessment measures

Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'

We combined large-scale mRNA expression analysis and gene mapping to identify genes and loci that control hematopoietic stem cell (HSC) function. We measured mRNA expression levels in purified HSCs isolated from a panel of densely genotyped recombinant inbred mouse strains. We mapped quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts. By comparing the physical transcript position with the location of the controlling QTL, we identified polymorphic cis-acting stem cell genes. We also identified multiple trans-acting control loci that modify expression of large numbers of genes. These groups of coregulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of candidate genes involved with HSC turnover. We compared expression QTLs in HSCs and brain from the same mice and identified both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of coregulated transcripts.

The advantages of UK Biobank's open access strategy for health research

Ready access to health research studies is becoming more important as researchers, and their funders, seek to maximize the opportunities for scientific innovation and health improvements. Large‐scale population‐based prospective studies are particularly useful for multidisciplinary research into the causes, treatment and prevention of many different diseases. UK Biobank has been established as an open‐access resource for public health research, with the intention of making the data as widely available as possible in an equitable and transparent manner. Access to UK Biobank's unique breadth of phenotypic and genetic data has attracted researchers worldwide from across academia and industry. As a consequence, it has enabled scientists to perform world‐leading collaborative research. Moreover, open access to an already deeply characterized cohort has encouraged both public and private sector investment in further enhancements to make UK Biobank an unparalleled resource for public health research and an exemplar for the development of open‐access approaches for other studies

Rhodium(II)-catalyzed stereocontrolled synthesis of dihydrofuran-3-imines from 1-Tosyl-1,2,3-triazoles

Rhodium(II) acetate catalyzes the denitrogenative transformation of 5-substituted and 4,5-disubstituted 1-sulfonyl-1,2,3-triazoles with pendent allyl and propargyl ether motifs to oxonium ylides that undergo [2,3]-sigmatropic rearrangement to give substituted dihydrofuran-3-imines in high yield and diastereoselectivity

MicroRNA expression in multiple myeloma is associated with genetic subtype, isotype and survival

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited - Copyright @ 2011 Chi et al.Background: MicroRNAs are small RNA species that regulate gene expression post-transcriptionally and are aberrantly expressed in many cancers including hematological malignancies. However, the role of microRNAs in the pathogenesis of multiple myeloma (MM) is only poorly understood. We therefore used microarray analysis to elucidate the complete miRNome (miRBase version 13.0) of purified tumor (CD138+) cells from 33 patients with MM, 5 patients with monoclonal gammopathy of undetermined significance (MGUS) and 9 controls. Results: Unsupervised cluster analysis revealed that MM and MGUS samples have a distinct microRNA expression profile from control CD138+ cells. The majority of microRNAs aberrantly expressed in MM (109/129) were up-regulated. A comparison of these microRNAs with those aberrantly expressed in other B-cell and T-cell malignancies revealed a surprising degree of similarity (~40%) suggesting the existence of a common lymphoma microRNA signature. We identified 39 microRNAs associated with the pre-malignant condition MGUS. Twenty-three (59%) of these were also aberrantly expressed in MM suggesting common microRNA expression events in MM progression. MM is characterized by multiple chromosomal abnormalities of varying prognostic significance. We identified specific microRNA signatures associated with the most common IgH translocations (t(4;14) and t(11;14)) and del(13q). Expression levels of these microRNAs were distinct between the genetic subtypes (by cluster analysis) and correctly predicted these abnormalities in > 85% of cases using the support vector machine algorithm. Additionally, we identified microRNAs associated with light chain only myeloma, as well as IgG and IgA-type MM. Finally, we identified 32 microRNAs associated with event-free survival (EFS) in MM, ten of which were significant by univariate (logrank) survival analysis. Conclusions: In summary, this work has identified aberrantly expressed microRNAs associated with the diagnosis, pathogenesis and prognosis of MM, data which will prove an invaluable resource for understanding the role of microRNAs in this devastating disease.This work was funded by grants from Leukaemia and Lymphoma Research (JC, EB, X-HC, DT, JB and JSW) and the Julian Starmer-Smith Memorial Fund (CHL). The authors acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Oxford Radcliffe NHS Trust

Modeling of Acoustic Emission Failure Mechanism Data from a Unidirectional Fiberglass/Epoxy Tensile Test Specimen

The purpose of this work was to model the acoustic emission (AE) flaw growth data that resulted from the tensile test of a unidirectional fiberglass/epoxy specimen. The data collected and stored during the test were the six standard AE quantification parameters for each event. A classification neural network was used to sort the data into five failure mechanism clusters. The resulting frequency histograms of the sorted data were then mathematically modeled herein using the three types of Johnson distributions: bounded, lognormal, and unbounded. These provided a reasonably good fit for all six AE parameter distributions for each of the five failure mechanisms

A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.

The identification of the genes associated with chromosomal translocation breakpoints has fundamentally changed understanding of the molecular basis of hematological malignancies. By contrast, the study of chromosomal deletions has been hampered by the large number of genes deleted and the complexity of their analysis. We report the generation of a mouse model for human 5q- syndrome using large-scale chromosomal engineering. Haploinsufficiency of the Cd74-Nid67 interval (containing Rps14, encoding the ribosomal protein S14) caused macrocytic anemia, prominent erythroid dysplasia and monolobulated megakaryocytes in the bone marrow. These effects were associated with defective bone marrow progenitor development, the appearance of bone marrow cells expressing high amounts of the tumor suppressor p53 and increased bone marrow cell apoptosis. Notably, intercrossing with p53-deficient mice completely rescued the progenitor cell defect, restoring common myeloid progenitor and megakaryocytic-erythroid progenitor, granulocyte-monocyte progenitor and hematopoietic stem cell bone marrow populations. This mouse model suggests that a p53-dependent mechanism underlies the pathophysiology of the 5q- syndrome