An ASCA Study of the High Luminosity SNR G349.7+0.2

We present ASCA observations of supernova remnant (SNR) G349.7+0.2. The remnant has an irregular shell morphology and is interacting with a molecular cloud, evident from the presence of OH(1720 MHz) masers and shocked molecular gas. The X-ray morphology is consistent with that at radio wavelengths, with a distinct enhancement in the south. The X-ray emission from the SNR is well described by a model of a thermal plasma which has yet to reach ionization equilibrium. The hydrogen column of ~6.0 X 10^{22} cm^{-2} is consistent with the large distance to the remnant of ~22 kpc estimated from the maser velocities. We derive an X-ray luminosity of L_x(0.5-10.0 keV)= 1.8 X 10^{37} d_{22}^2 erg/s, which makes G349.7+0.2 one of the most X-ray luminous shell-type SNRs known in the Galaxy. The age of the remnant is estimated to be about 2800 yrs. The ambient density and pressure conditions appear similar to those inferred for luminous compact SNRs found in starburst regions of other galaxies, and provides support for the notion that these may be the result of SNR evolution in the vicinity of dense molecular clouds.Comment: 5 pages, 3 figures. Accepted for publication in Ap

Saudi service users’ perceptions and experiences of the quality of their mental health care provision in the Kingdom of Saudi Arabia (KSA): A qualitative inquiry

© 2020 The Authors. International Journal of Mental Health Nursing published by John Wiley & Sons Australia, Ltd on behalf of Australian College of Mental Health Nurses Inc This paper presents, as part of a larger mixed-methods design, a study generating a theoretical understanding of issues pertinent to the quality of mental health care in the KSA from the perspective of those using services. Semi-structured interviews were undertaken with thirty service users admitted to inpatient psychiatric wards, using an interview guide developed by the researchers, based on relevant literature. Findings from the thematic analysis showed five themes: (1) The hospital as a prison: a custody versus care dilemma, (2) quality of interactions between staff and service users, (3) quality of services, (4) staff qualities and (5) suggestions for achieving quality of care. A theoretical model drawing upon Donabedian Health Care Model for Evaluating quality of care and the Andersen Behavioural Model of Health Service Use is evident from the data. Structural aspects of care include staff experience and qualifications and key enablers around social and financial support, service users’ health needs and status and the physical infrastructure and ward rules. These drive processes of care based upon robust rates of interaction between staff and service users and appear central to quality of mental health care in KSA. Quality of mental health care in KSA is manifested by a therapeutic ethos with a high degree of interaction between professional carers and service users, with the former being highly educated, competent, compassionate, with a high degree of self-awareness, and specialized in mental health. We have uncovered elements of Fanon and Azoulay’s ‘Cultural Originality’ as well as contemporary examples of Goffman’s mortification of the self

αvβ3 and α5β1 integrin recycling pathways dictate downstream Rho kinase signaling to regulate persistent cell migration

Accumulating evidence suggests that integrin recycling regulates cell migration. However, the lack of reagents to selectively target the trafficking of individual heterodimers, as opposed to endocytic transport as a whole, has made it difficult to define the contribution made by particular recycling pathways to directional cell movement. We show that autophosphorylation of protein kinase D1 (PKD1) at Ser916 is necessary for its association with αvβ3 integrin. Expression of PKD1916A or the use of mutants of β3 that do not bind to PKD1 selectively inhibits short-loop, Rab4-dependent recycling of αvβ3, and this suppresses the persistence of fibroblast migration. However, we report that short-loop recycling does not directly contribute to fibroblast migration by moving αvβ3 to the cell front, but by antagonizing α5β1 recycling, which, in turn, influences the cell's decision to migrate with persistence or to move randomly

Actin-Based Cell Protrusion in a 3D Matrix

Cell migration has been well studied in 2D, but how this relates to movement in physiological 3D tissues and matrix is not clear, particularly in vertebrate interstitial matrix. In 3D matrix cells actin polymerisation directly contributes to the formation of lamellipodia to facilitate migration and invasion (mesenchymal movement), analogous to 2D migration; actomyosin contractility promotes bleb formation to indirectly promote protrusion (amoeboid movement). Mesenchymal migration can be characterised by polymerisation of actin to form filopodial protrusions, in the absence of lamellipodia. Translocation of the nucleus is emerging as a critical step due to the constrictive environment of 3D matrices, and the mechanisms that transmit force to the nucleus and allow movement are beginning to be uncovered. Cell migration controls developmental processes (gastrulation and tissue patterning), tissue homeostasis (wound repair and inflammatory responses), and the pathobiology of diseases (cancer metastasis and inflammation). Understanding how cells move in physiologically relevant environments is of major importance, and the molecular machinery behind cell movement has been well studied on 2D substrates, beginning over half a century ago. Studies over the past decade have begun to reveal the mechanisms that control cell motility within 3D microenvironments – some similar to, and some highly divergent from those found in 2D. In this review we focus on migration and invasion of cells powered by actin, including formation of actin-rich protrusions at the leading edge, and the mechanisms that control nuclear movement in cells moving in a 3D matrix

Rab-coupling protein coordinates recycling of α5β1 integrin and EGFR1 to promote cell migration in 3D microenvironments

Here we show that blocking the adhesive function of αvβ3 integrin with soluble RGD ligands, such as osteopontin or cilengitide, promoted association of Rab-coupling protein (RCP) with α5β1 integrin and drove RCP-dependent recycling of α5β1 to the plasma membrane and its mobilization to dynamic ruffling protrusions at the cell front. These RCP-driven changes in α5β1 trafficking led to acquisition of rapid/random movement on two-dimensional substrates and to a marked increase in fibronectin-dependent migration of tumor cells into three-dimensional matrices. Recycling of α5β1 integrin did not affect its regulation or ability to form adhesive bonds with substrate fibronectin. Instead, α5β1 controlled the association of EGFR1 with RCP to promote the coordinate recycling of these two receptors. This modified signaling downstream of EGFR1 to increase its autophosphorylation and activation of the proinvasive kinase PKB/Akt. We conclude that RCP provides a scaffold that promotes the physical association and coordinate trafficking of α5β1 and EGFR1 and that this drives migration of tumor cells into three-dimensional matrices

The βI domain promotes active β1 integrin clustering into mature adhesion sites

Modulation of integrin function is required in many physiological and pathological settings, such as angiogenesis and cancer. Integrin allosteric changes, clustering, and trafficking cooperate to regulate cell adhesion and motility on extracellular matrix proteins via mechanisms that are partly defined. By exploiting four monoclonal antibodies recognizing distinct conformational epitopes, we show that in endothelial cells (ECs), the extracellular βI domain, but not the hybrid or I-EGF2 domain of active β1 integrins, promotes their FAK-regulated clustering into tensin 1–containing fibrillar adhesions and impairs their endocytosis. In this regard, the βI domain–dependent clustering of active β1 integrins is necessary to favor fibronectin-elicited directional EC motility, which cannot be effectively promoted by β1 integrin conformational activation alone

ASCA Observations of the Thermal Composite Supernova Remnant 3C 391

We present the results from ASCA observations of the centrally enhanced supernova remnant 3C 391 (G31.9+0.0). We use the ASCA SIS data to carry out an investigation of the spatial and spectral properties of the X-ray emission from this remnant. The collisional equilibrium ionization and non-equilibrium ionization spectral fits indicate that the hot gas within the remnant has basically reached ionization equilibrium. The variation of the hydrogen column density across the remnant is in agreement with the presence of a molecular cloud to the northwest. The comparisons of hydrogen column and X-ray hardness between the NW and SE portions of the remnant support a scenario in which the SNR has broken out of a dense region into an adjacent region of lower density. The mean density within the SNR is observed to be much lower than the immediate ambient cloud density. This and the centrally brightened X-ray morphology can be explained either by the evaporation of engulfed cloudlets or by a radiative stage of evolution for the remnant.Comment: 23 pages, 3 figures, accepted for the v563 ApJ 12/10/01 issu

α5β1 integrin recycling promotes Arp2/3-independent cancer cell invasion via the formin FHOD3

Invasive migration in 3D extracellular matrix (ECM) is crucial to cancer metastasis, yet little is known of the molecular mechanisms that drive reorganization of the cytoskeleton as cancer cells disseminate in vivo. 2D Rac-driven lamellipodial migration is well understood, but how these features apply to 3D migration is not clear. We find that lamellipodia-like protrusions and retrograde actin flow are indeed observed in cells moving in 3D ECM. However, Rab-coupling protein (RCP)-driven endocytic recycling of α5β1 integrin enhances invasive migration of cancer cells into fibronectin-rich 3D ECM, driven by RhoA and filopodial spike-based protrusions, not lamellipodia. Furthermore, we show that actin spike protrusions are Arp2/3-independent. Dynamic actin spike assembly in cells invading in vitro and in vivo is regulated by Formin homology-2 domain containing 3 (FHOD3), which is activated by RhoA/ROCK, establishing a novel mechanism through which the RCP–α5β1 pathway reprograms the actin cytoskeleton to promote invasive migration and local invasion in vivo

Ecological equivalence: a realistic assumption for niche theory as a testable alternative to neutral theory

Hubbell's 2001 neutral theory unifies biodiversity and biogeography by modelling steady-state distributions of species richness and abundances across spatio-temporal scales. Accurate predictions have issued from its core premise that all species have identical vital rates. Yet no ecologist believes that species are identical in reality. Here I explain this paradox in terms of the ecological equivalence that species must achieve at their coexistence equilibrium, defined by zero net fitness for all regardless of intrinsic differences between them. I show that the distinction of realised from intrinsic vital rates is crucial to evaluating community resilience. An analysis of competitive interactions reveals how zero-sum patterns of abundance emerge for species with contrasting life-history traits as for identical species. I develop a stochastic model to simulate community assembly from a random drift of invasions sustaining the dynamics of recruitment following deaths and extinctions. Species are allocated identical intrinsic vital rates for neutral dynamics, or random intrinsic vital rates and competitive abilities for niche dynamics either on a continuous scale or between dominant-fugitive extremes. Resulting communities have steady-state distributions of the same type for more or less extremely differentiated species as for identical species. All produce negatively skewed log-normal distributions of species abundance, zero-sum relationships of total abundance to area, and Arrhenius relationships of species to area. Intrinsically identical species nevertheless support fewer total individuals, because their densities impact as strongly on each other as on themselves. Truly neutral communities have measurably lower abundance/area and higher species/abundance ratios. Neutral scenarios can be parameterized as null hypotheses for testing competitive release, which is a sure signal of niche dynamics. Ignoring the true strength of interactions between and within species risks a substantial misrepresentation of community resilience to habitat los