Genomic Organization, Splice Variants and Expression of CGMl, a CD66-related Member of the Carcinoembryonic Antigen Gene Family

The tumor marker carcinoembryonic antigen (CEA) belongs to a family of proteins which are composed of one immunogiobulin variable domain and a varying number of immunoglobulin constant-like domains. Most of the membrane-bound members, which are anchored either by a glycosylphosphatidylinositol moiety or a transmembrane domain, have been shown to convey cell adhesion in vitro. Here we describe two splice variants of CGMI. a transmembrane member of the CEA family without immunoglobulin constant.like domains. CGM1a and CGM1c contain cytopiasmic domains of 71 and 31 amino acids, respectively, The cytoplasmic region of CGM1a is encoded by four exons (Cyt1-Cyt4). Differential splicing of the Cyt1 exon (53 bp)..

Geological archive of the onset of plate tectonics

© 2018 The Author(s) Published by the Royal Society. All rights reserved. Plate tectonics, involving a globally linked system of lateral motion of rigid surface plates, is a characteristic feature of our planet, but estimates of how long it has been the modus operandi of lithospheric formation and interactions range from the Hadean to the Neoproterozoic. In this paper, we review sedimentary, igneous and metamorphic proxies along with palaeomagnetic data to infer both the development of rigid lithospheric plates and their independent relative motion, and conclude that significant changes in Earth behaviour occurred in the mid- to late Archaean, between 3.2 Ga and 2.5 Ga. These data include: sedimentary rock associations inferred to have accumulated in passive continental margin settings, marking the onset of seafloor spreading; the oldest foreland basin deposits associated with lithospheric convergence; a change from thin, new continental crust of mafic composition to thicker crust of intermediate composition, increased crustal reworking and the emplacement of potassic and peraluminous granites, indicating stabilization of the lithosphere; replacement of dome and keel structures in granite-greenstone terranes, which relate to vertical tectonics, by linear thrust imbricated belts; the commencement of temporally paired systems of intermediate and high dT/dP gradients, with the former interpreted to represent subduction to collisional settings and the latter representing possible hinterland back-arc settings or ocean plateau environments. Palaeomagnetic data from the Kaapvaal and Pilbara cratons for the interval 2780-2710Ma and from the Superior, Kaapvaal and Kola-Karelia cratons for 2700-2440Ma suggest significant relative movements. We consider these changes in the behaviour and character of the lithosphere to be consistent with a gestational transition from a non-plate tectonic mode, arguably with localized subduction, to the onset of sustained plate tectonics

Faculty members engaging in transformative PETE: a feminist perspective

The purpose of this study was to describe sport pedagogy faculty members’ (FMs) efforts at engaging in transformative physical education teacher education (T-PETE). T-PETE stresses the importance of FMs creating social change through their pedagogical approach and begins by asking preservice teachers (PTs) to reflect on their perspectives and practices (Tinning, 2017 Tinning, R. (2017). Transformative pedagogies and physical education. In C. Ennis (Ed.), The Routledge handbook of physical education pedagogies (pp. 295–306). New York: Taylor & Francis. [Google Scholar]. Transformative pedagogies and physical education. In C. Ennis (Ed.), The Routledge handbook of physical education pedagogies (pp. 295–306). New York: Taylor & Francis; Ukpokodu, 2009. The practice of transformative pedagogy. Journal on Excellence in College Teaching, 20(2), 43–67.). Participants were three white, female, able-bodied, lesbian/gay sport pedagogy FMs. The study was conducted in the United States. Feminist theory and feminist pedagogy drove data collection and analysis. Data were collected by employing a series of qualitative methods. An inductive and deductive analysis revealed that FMs had specific T-PETE goals, content, and pedagogies. Furthermore, several factors served to facilitate and limit the FMs’ effectiveness when engaging in T-PETE. The findings suggest that program-wide PETE reform is necessary in the United States for creating social change, and influencing PTs perspectives and practices. In addition, they suggest that American PETE programs might benefit from greater diversity among the FMs who staff them

LSD1 activation promotes inducible EMT programs and modulates the tumour microenvironment in breast cancer

Complex regulatory networks control epithelial-to-mesenchymal transition (EMT) but the underlying epigenetic control is poorly understood. Lysine-specific demethylase 1 (LSD1) is a key histone demethylase that alters the epigenetic landscape. Here we explored the role of LSD1 in global epigenetic regulation of EMT, cancer stem cells (CSCs), the tumour microenvironment, and therapeutic resistance in breast cancer. LSD1 induced pan-genomic gene expression in networks implicated in EMT and selectively elicits gene expression programs in CSCs whilst repressing non-CSC programs. LSD1 phosphorylation at serine-111 (LSD1-s111p) by chromatin anchored protein kinase C-theta (PKC-θ), is critical for its demethylase and EMT promoting activity and LSD1-s111p is enriched in chemoresistant cells in vivo. LSD1 couples to PKC-θ on the mesenchymal gene epigenetic template promotes LSD1-mediated gene induction. In vivo, chemotherapy reduced tumour volume, and when combined with an LSD1 inhibitor, abrogated the mesenchymal signature and promoted an innate, M1 macrophage-like tumouricidal immune response. Circulating tumour cells (CTCs) from metastatic breast cancer (MBC) patients were enriched with LSD1 and pharmacological blockade of LSD1 suppressed the mesenchymal and stem-like signature in these patient-derived CTCs. Overall, LSD1 inhibition may serve as a promising epigenetic adjuvant therapy to subvert its pleiotropic roles in breast cancer progression and treatment resistance.T. Boulding, R.D. McCuaig, A. Tan, K. Hardy, F. Wu, J. Dunn, M. Kalimutho, C.R. Sutton, J.K. Forwood, A.G. Bert, G.J. Goodall, L. Malik, D. Yip, J.E. Dahlstrom, A. Zafar, K.K. Khanna, S. Ra

Stress and psychological health: testing the mediating role of cognitive appraisal

This study tested the mediating role of primary (e.g., threat and challenge perceptions) and secondary (e.g., coping potential and control perception) cognitive appraisal in the relationship between occupational stress and psychological health. This mediation was tested using a cross-sectional study based on self-reported measures. The total sample consisted of 2,302 nurses, 1,895 females (82.3%) and 407 males (17.7%), who completed an evaluation protocol with measures of occupational stress, cognitive appraisal, and psychological health. To test the mediating role of cognitive appraisal in the relationship between cognitive appraisal and psychological health, we used Structural Equation Modeling (SEM). The results confirmed that primary and secondary cognitive appraisals partially mediated the relationship between occupational stress and psychological health; however, the direct effects of stress on psychological health cannot be ignored. The findings indicated that cognitive appraisal is an important underlying mechanism in explaining adaptation at work.This study was conducted at Psychology Research Centre (UID/PSI/01662/2013), University of MInho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653)

Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice

Trichothiodystrophy (TTD) is a rare, autosomal recessive nucleotide excision repair (NER) disorder caused by mutations in components of the dual functional NER/basal transcription factor TFIIH. TTD mice, carrying a patient-based point mutation in the Xpd gene, strikingly resemble many features of the human syndrome and exhibit signs of premature aging. To examine to which extent TTD mice resemble the normal process of aging, we thoroughly investigated the bone phenotype. Here, we show that female TTD mice exhibit accelerated bone aging from 39 weeks onwards as well as lack of periosteal apposition leading to reduced bone strength. Before 39 weeks have passed, bones of wild-type and TTD mice are identical excluding a developmental defect. Albeit that bone formation is decreased, osteoblasts in TTD mice retain bone-forming capacity as in vivo PTH treatment leads to increased cortical thickness. In vitro bone marrow cell cultures showed that TTD osteoprogenitors retain the capacity to differentiate into osteoblasts. However, after 13 weeks of age TTD females show decreased bone nodule formation. No increase in bone resorption or the number of osteoclasts was detected. In conclusion, TTD mice show premature bone aging, which is preceded by a decrease in mesenchymal stem cells/osteoprogenitors and a change in systemic factors, identifying DNA damage and repair as key determinants for bone fragility by influencing osteogenesis and bone metabolism

Severe traumatic injury during long duration spaceflight: Light years beyond ATLS

Traumatic injury strikes unexpectedly among the healthiest members of the human population, and has been an inevitable companion of exploration throughout history. In space flight beyond the Earth's orbit, NASA considers trauma to be the highest level of concern regarding the probable incidence versus impact on mission and health. Because of limited resources, medical care will have to focus on the conditions most likely to occur, as well as those with the most significant impact on the crew and mission. Although the relative risk of disabling injuries is significantly higher than traumatic deaths on earth, either issue would have catastrophic implications during space flight. As a result this review focuses on serious life-threatening injuries during space flight as determined by a NASA consensus conference attended by experts in all aspects of injury and space flight