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Extensive abdominal wall ulceration as a late manifestation of antiphospholipid syndrome: a case report
Get PDFThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background
Antiphospholipid syndrome is an autoimmune disorder characterized by the presence of antiphospholipid antibodies and commonly presents with vascular thromboembolic phenomena, thrombocytopenia, and obstetric complications. Antiphospholipid syndrome can be classified as either primary or secondary to other connective tissue diseases. Dermatologic manifestations are common; however, non-vasculitic skin ulceration is an uncommon manifestation of antiphospholipid syndrome with limited treatment options.
Case presentation
In this paper we report the case of a 58-year-old white woman who developed necrotic abdominal wall ulcers 27 years after a diagnosis of secondary antiphospholipid syndrome associated with systemic lupus erythematosus. The ulcers developed despite our patient being on therapeutic anticoagulation with warfarin and were resistant to further increases in the intensity of anticoagulation. Management was further complicated due to reluctance on the part of our patient to switch over to injectable heparin.
Conclusions
This case highlights a rare late dermatologic presentation of antiphospholipid syndrome, which responded poorly to conventional anticoagulation with warfarin. Current management is limited to experimental therapies and the role of newer anticoagulants is still unknown.There is no funding to declare
Neurocranial anatomy of an enigmatic Early Devonian fish sheds light on early osteichthyan evolution
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permits unrestricted use and
redistribution provided that the
original author and source are
credited.The skull of ‘Ligulalepis’ from the Early Devonian of Australia (AM-F101607) has significantly expanded our knowledge of early osteichthyan anatomy, but its phylogenetic position has remained uncertain. We herein describe a second skull of ‘Ligulalepis’ and present micro-CT data on both specimens to reveal novel anatomical features, including cranial endocasts. Several features previously considered to link ‘Ligulalepis’ with actinopterygians are now considered generalized osteichthyan characters or of uncertain polarity. The presence of a lateral cranial canal is shown to be variable in its development between specimens. Other notable new features include the presence of a pineal foramen, the some detail of skull roof sutures, the shape of the nasal capsules, a placoderm-like hypophysial vein, and a chondrichthyan-like labyrinth system. New phylogenetic analyses place ‘Ligulalepis’ as a stem osteichthyan, specifically as the sister taxon to ‘psarolepids’ plus crown osteichthyans. The precise position of ‘psarolepids’ differs between parsimony and Bayesian analyses.This work was supported by the
Australian Research Council: JAL, AMC, GCY and BK acknowledge support from ARC DP
140101461, BC acknowledges ARC DE 160100247. SG was supported by a Junior Research Fellow-
ship (Christ Church, Oxford) and a Royal Society Dorothy Hodgkin Research Fellowship, and PEA
acknowledges the support of the Knut and Alice Wallenberg Foundation
Tetramerization of MADS family transcription factors SEPALLATA3 and AGAMOUS is required for floral meristem determinacy in Arabidopsis
Get PDFPublished by Oxford University Press on behalf of Nucleic Acids Research.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License
(http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work
is properly cited. For commercial re-use, please contact [email protected] MADS transcription factors (TF) constitute an ancient family of TF found in all eukaryotes that bind DNA as obligate dimers. Plants have dramatically expanded the functional diversity of the MADS family during evolution by adding protein–protein interaction domains to the core DNA-binding domain, allowing the formation of heterotetrameric complexes. Tetramerization of plant MADS TFs is believed to play a central role in the evolution of higher plants by acting as one of the main determinants of flower formation and floral organ specification. The MADS TF, SEPALLATA3 (SEP3), functions as a central protein–protein interaction hub, driving tetramerization with other MADS TFs. Here, we use a SEP3 splice variant, SEP3Δtet, which has dramatically abrogated tetramerization capacity to decouple SEP3 tetramerization and DNA-binding activities. We unexpectedly demonstrate that SEP3 heterotetramer formation is required for correct termination of the floral meristem, but plays a lesser role in floral organogenesis. The heterotetramer formed by SEP3 and the MADS protein, AGAMOUS, is necessary to activate two target genes, KNUCKLES and CRABSCLAW, which are required for meristem determinacy. These studies reveal unique and highly specific roles of tetramerization in flower development and suggest tetramerization may be required to activate only a subset of target genes in closed chromatin regions.Action Thematique et Incitative sur Programme (ATIP)-
Avenir (to C.Z.); Grenoble Alliance for Integrated
Structural Cell Biology (ANR-10-LABX-49-01 to V.H.,
A.J., C.Z., Q.C., A.S., V.C., F.P.); Agence Nationale de
la Recherche (project Flopinet to C.Z., V.H., A.J., F.P., C.C.) and Centre National de la Recherche Scientifique
(to S.J.C.). Funding for open access charge: ATIP-Avenir,
ANR
miR-200/375 control epithelial plasticity-associated alternative splicing by repressing the RNA-binding protein Quaking
Get PDFThis is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Members of the miR‐200 family are critical gatekeepers of the epithelial state, restraining expression of pro‐mesenchymal genes that drive epithelial–mesenchymal transition (EMT) and contribute to metastatic cancer progression. Here, we show that miR‐200c and another epithelial‐enriched miRNA, miR‐375, exert widespread control of alternative splicing in cancer cells by suppressing the RNA‐binding protein Quaking (QKI). During EMT, QKI‐5 directly binds to and regulates hundreds of alternative splicing targets and exerts pleiotropic effects, such as increasing cell migration and invasion and restraining tumour growth, without appreciably affecting mRNA levels. QKI‐5 is both necessary and sufficient to direct EMT‐associated alternative splicing changes, and this splicing signature is broadly conserved across many epithelial‐derived cancer types. Importantly, several actin cytoskeleton‐associated genes are directly targeted by both QKI and miR‐200c, revealing coordinated control of alternative splicing and mRNA abundance during EMT. These findings demonstrate the existence of a miR‐200/miR‐375/QKI axis that impacts cancer‐associated epithelial cell plasticity through widespread control of alternative splicing.Department of Health | National Health and Medical Research Council (NHMRC) GNT1068773, GNT1128479, GNT1083961
Cancer Council South Australia Beat Cancer Fellowship
Prostate Cancer Foundation Foundation 1
Family quality of life and nurturing the sibling relationship
Get PDFCopyright (c) 2018 Nicole Kyrkou
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.Research that gauges family quality of life in families that include a child with a disability has often focused on the relationship between parents and the child, but in doing so they underestimate the importance of the sibling relationship: siblings are in each other’s lives generally for a much longer period of time than parents are. The sibling relationship is not intrinsically positive or negative, but it is a dynamic and critical bond; from it children can learn to understand and advocate for themselves and each other in the context of the disability. The sibling relationship is a lifelong one. Nurturing it in the early stages of development will not only support family quality of life, but will set the foundation for healthy adult sibling relationships that can create positive outcomes for all members of the family. The important aspects of nurturing the sibling relationship are considered from the viewpoint of both sibling and parent. The assumptions that inform sibling relationships are discussed, and suggestions for nurturing them are provided
Review of Faithfully, I Wait by Jaydeep Sarangi
Get PDFReview of Faithfully, I Wait by Jaydeep Sarang
On Pacification and Perspective: The International Referents of an Australian Artwork and a Novel
No full textThis is a piece of creative non-fiction merging art commentary, literary analysis, and a personal account of the writer’s research. Changes across time in the writer’s understanding of an Australian painting – Breakfast Piece (1936) by Herbert Badham – are examined, with the writer’s slowness to comprehend the painting’s overt allusion to the Italian invasion of Ethiopia (Abyssinia) highlighted. The writer’s discovery that Breakfast Piece was reproduced on the covers of a 1985 edition of Eleanor Dark’s 1945 novel The Little Company and a 1991 edition of Elizabeth Harrower’s 1966 novel The Watch Tower provokes an analysis of these authors’ treatment of international geopolitical affairs and local gender relations
Electrical remodelling post cardiac resynchronization therapy in patients with ischemic and non-ischemic heart failure
Get PDFCrown Copyright © 2018 Published by Elsevier Inc. This manuscript version is made available under the CC-BYNC-ND 4.0 license:
http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (December 2018) in accordance with the publisher’s archiving policyBackground
The beneficial effects of cardiac resynchronization therapy (CRT) in heart failure are largely considered to be due to improved mechanical contractility. The contributory role of electrical remodelling is less clear. We sought to evaluate the impact of electrical remodelling in these patients.
Methods
33 patients with conventional indications for CRT and with ischemic (ICM) (n = 17) and non-ischemic (NICM) (n = 16) aetiologies for heart failure were prospectively recruited. Functional parameters of peak exercise oxygen consumption (VO2max) and Minnesota quality of life (QOL) score, echocardiographic measures of LV functions and parameters of electrical remodelling, e.g. intrinsic QRS duration (iQRSD), intracardiac conduction times of LV pacing to RV electrocardiogram (LVp-RVegm), were measured at CRT implant and after 6 months.
Results
Only two electrical parameters predicted functional or symptomatic improvement. LVp-RVegm reduction significantly correlated with improvement in VO2max (r = −0.42, p = 0.03 while reduction in iQRSD significantly correlated with improvement in QOL score (r = 0.39, p = 0.04). The extent of changes in LVp-RVegm and iQRSD was significantly greater in NICM than in ICM patients (p = 0.017 and p = 0.042 for heterogeneity). There was also significant differential impact on QOL score in the NICM relative to the ICM group (p = 0.003) but none with VO2max. On multivariate analysis, only non-ischemic aetiology was a significant determinant of reduction in iQRSD.
Conclusion
CRT induces potentially beneficial reduction in LVp-RVegm and iQRSD, which are seen selectively in NICM rather than ICM patients. The extent of improvement in these markers is associated with some functional and symptomatic measures of CRT efficacy