97 research outputs found

    The Extraordinary Infrared Spectrum of NGC 1222 (Mkn 603)

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    The infrared spectra of starburst galaxies are dominated by the low-excitation lines of [NeII] and [SIII], and the stellar populations deduced from these spectra appear to lack stars larger than about 35 Msun. The only exceptions to this result until now were low metallicity dwarf galaxies. We report our analysis of the mid-infrared spectra obtained with IRS on Spitzer of the starburst galaxy NGC 1222 (Mkn 603). NGC 1222 is a large spheroidal galaxy with a starburst nucleus that is a compact radio and infrared source, and its infrared emission is dominated by the [NeIII] line. This is the first starburst of solar or near-solar metallicity, known to us, which is dominated by the high-excitation lines and which is a likely host of high mass stars. We model the emission with several different assumptions as to the spatial distibution of the high- and low-excitation lines and find that the upper mass cutoff in this galaxy is 40-100 Msun.Comment: accepted, Astronomical Journal. 29 pp, 4 figures. In replacement version an acknowledgment to NRAO is adde

    Could an Impairment in Local Translation of mRNAs in Glia be Contributing to Pathogenesis in ALS?

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    One of the key pathways implicated in amyotrophic lateral sclerosis (ALS) pathogenesis is abnormal RNA processing. Studies to date have focussed on defects in RNA stability, splicing, and translation, but this review article will focus on the largely overlooked RNA processing mechanism of RNA trafficking, with particular emphasis on the importance of glia. In the central nervous system (CNS), oligodendrocytes can extend processes to myelinate and metabolically support up to 50 axons and astrocytes can extend processes to cover up to 100,000 synapses, all with differing local functional requirements. Furthermore, many of the proteins required in these processes are large, aggregation-prone proteins which would be difficult to transport in their fully translated, terminally-folded state. This, therefore, highlights a critical requirement in these cells for local control of protein translation, which is achieved through specific trafficking of mRNAs to each process and local translation therein. Given that a large number of RNA-binding proteins have been implicated in ALS, and RNA-binding proteins are essential for trafficking mRNAs from the nucleus to glial processes for local translation, RNA misprocessing in glial cells is a likely source of cellular dysfunction in ALS. To date, neurons have been the focus of ALS research, but an intrinsic deficit in glia, namely astrocytes and oligodendrocytes, could have an additive effect on declining neuronal function in ALS. This review article aims to highlight the key evidence that supports the contention that RNA trafficking deficits in astrocytes and oligodendrocytes may contribute to in ALS

    Restoring mucosal barrier function and modifying macrophage phenotype with an extracellular matrix hydrogel: potential therapy for ulcerative colitis

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    Background & Aims: Despite advances in therapeutic options, more than half of all patients with ulcerative colitis (UC) do not achieve long-term remission, many require colectomy, and the disease still has a marked negative impact on quality of life. Extracellular matrix (ECM) bioscaffolds facilitate the functional repair of many soft tissues by mechanisms that include mitigation of pro-inflammatory macrophage phenotype and mobilization of endogenous stem/progenitor cells. The aim of the present study was to determine if an ECM hydrogel therapy could influence outcomes in an inducible rodent model of UC. Methods: The dextran sodium sulfate (DSS)-colitis model was used in male Sprague Dawley rats. Animals were treated via enema with an ECM hydrogel and the severity of colitis was determined by clinical and histologic criteria. Lamina propria cells were isolated and the production of inflammatory mediators was quantified. Mucosal permeability was assessed in-vivo by administering TRITC-dextran and in-vitro using transepithelial electrical resistance (TEER). Results: ECM hydrogel therapy accelerated healing and improved outcome. The hydrogel was adhesive to colonic tissue, which allowed for targeted delivery of the therapy, and resulted in a reduction in clinical and histologic signs of disease. ECM hydrogel facilitated functional improvement of colonic epithelial barrier function and the resolution of the pro-inflammatory state of tissue macrophages. Conclusions: The present study shows that a nonsurgical and nonpharmacologic ECM-based therapy can abate DSS-colitis not by immunosuppression but by promoting phenotypic change in local macrophage phenotype and rapid replacement of the colonic mucosal barrie

    Senescence and cancer : a review of clinical implications of senescence and senotherapies

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    Cellular senescence is a key component of human aging that can be induced by a range of stimuli, including DNA damage, cellular stress, telomere shortening, and the activation of oncogenes. Senescence is generally regarded as a tumour suppressive process, both by preventing cancer cell proliferation and suppressing malignant progression from pre-malignant to malignant disease. It may also be a key effector mechanism of many types of anticancer therapies, such as chemotherapy, radiotherapy, and endocrine therapies, both directly and via bioactive molecules released by senescent cells that may stimulate an immune response. However, senescence may contribute to reduced patient resilience to cancer therapies and may provide a pathway for disease recurrence after cancer therapy. A new group of drugs, senotherapies, (drugs which interact with senescent cells to interfere with their pro-aging impacts by either selectively destroying senescent cells (senolytic drugs) or inhibiting their function (senostatic drugs)) are under active investigation to determine whether they can enhance the efficacy of cancer therapies and improve resilience to cancer treatments. Senolytic drugs include quercetin, navitoclax, and fisetin and preclinical and early phase clinical data are emerging of their potential role in cancer treatments, although none are yet in routine use clinically. This article provides a review of these issues

    Eddy covariance flux observations at a semi-natural grassland on the Indo-Gangetic Plain

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    A new network of eddy covariance (EC) stations was established at a variety of semi-natural and managed ecosystems located across India during the INCOMPASS project. These new stations were installed to monitor surface-atmosphere fluxes of water, energy and carbon dioxide (CO2) and to provide supporting micrometeorological and soil physics observations. In this presentation, EC flux observations obtained at a semi-natural Phragmites-Saccharum-Imperata grassland on the Indo-Gangetic Plain are presented. The poster presents flux observations captured over two complete annual cycles. The grassland was characterised by a distinct seasonality. Latent heat dominated the turbulent energy flux during Monsoon, whereas sensible heat was the dominant turbulent flux during winter. The site experienced periodic flooding by waters from an adjacent irrigation canal as well as the removal of aboveground biomass during a wildfire in May 2017. Additional flood waters did not have a large influence on turbulent energy fluxes during inundation periods. Wildfire influenced fluxes in the period after the burn. Latent heat and net carbon gain recovered to pre-disturbance levels within a month of the wildfire

    Grandi Byen-supporting child growth and development through integrated, responsive parenting, nutrition and hygiene: Study protocol for a randomized controlled trial

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    BACKGROUND: Poor child growth and development outcomes stem from complex relationships encompassing biological, behavioral, social, and environmental conditions. However, there is a dearth of research on integrated approaches targeting these interwoven factors. The Grandi Byen study seeks to fill this research gap through a three-arm longitudinal randomized controlled trial which will evaluate the impact of an integrated nutrition, responsive parenting, and WASH (water, sanitation and hygiene) intervention on holistic child growth and development. METHODS: We will recruit 600 mother-infant dyads living in Cap-Haitien, Haiti and randomize them equally into one of the following groups: 1) standard well-baby care; 2) nutritional intervention (one egg per day for 6 months); and 3) multicomponent Grandi Byen intervention (responsive parenting, nutrition, WASH + one egg per day for 6 months). Primary outcomes include child growth as well as cognitive, language, motor, and social-emotional development. The study also assesses other indicators of child health (bone maturation, brain growth, diarrheal morbidity and allergies, dietary intake, nutrient biomarkers) along with responsive parenting as mediating factors influencing the primary outcomes. An economic evaluation will assess the feasibility of large-scale implementation of the interventions. DISCUSSION: This study builds on research highlighting the importance of responsive parenting interventions on overall child health, as well as evidence demonstrating that providing an egg daily to infants during the complementary feeding period can prevent stunted growth. The multicomponent Grandi Byen intervention may provide evidence of synergistic or mediating effects of an egg intervention with instruction on psychoeducational parenting and WASH on child growth and development. Grandi Byen presents key innovations with implications for the well-being of children living in poverty globally. TRIAL REGISTRATION: NCT04785352 . Registered March 5, 2021 at https://clinicaltrials.gov/

    On-demand cell-autonomous gene therapy for brain circuit disorders

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    Several neurodevelopmental and neuropsychiatric disorders are characterized by intermittent episodes of pathological activity. Although genetic therapies offer the ability to modulate neuronal excitability, a limiting factor is that they do not discriminate between neurons involved in circuit pathologies and “healthy” surrounding or intermingled neurons. We describe a gene therapy strategy that down-regulates the excitability of overactive neurons in closed loop, which we tested in models of epilepsy. We used an immediate early gene promoter to drive the expression of Kv1.1 potassium channels specifically in hyperactive neurons, and only for as long as they exhibit abnormal activity. Neuronal excitability was reduced by seizure-related activity, leading to a persistent antiepileptic effect without interfering with normal behaviors. Activity-dependent gene therapy is a promising on-demand cell-autonomous treatment for brain circuit disorders

    Monitoring dryland energy and water dynamics in India: an analysis of COSMOS-India and flux tower observations

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    Small changes in precipitation and temperature can dramatically influence surface energy and water budgets in semi-arid regions. Quantifying land-atmosphere interactions and feedbacks in these areas is crucial to understanding global water and carbon cycles, for the development and testing of land surface, weather prediction and climate models, as well as for monitoring local water resources and agricultural output. We report the results of co-located observations of land surface water and energy fluxes and large-area soil moisture dynamics obtained at three study sites located across India. These sites were instrumented as part of the INCOMPASS (INteraction of Convective Organisation with Monsoon Precipitation, Atmosphere, Surface and Sea) and COSMOS-India projects. Two sites are located on contrasting red (Alfisols) and black (Vertisols) soils on the Deccan Plateau. A third site is installed on alluvial soils (Fluvisols) on the Indo-Gangetic Plain. Each site consists of an eddy covariance flux tower providing measurements of sensible (H) and latent heat (LE) fluxes, micrometeorology and soil physics, in combination with a COSMOS (COsmic-ray Soil Moisture Observing System) sensor that provides spatially-integrated measurements of soil water content at field scale. In this presentation, we report on feedbacks between the land surface and the atmosphere, with a specific focus on the evaporative fraction (EF=LE/LE+H), precipitation and time varying soil moisture dynamics. CEH: Ross Morrison, Jonathan Evans, Chris Taylor, Lucy Ball, Alan Jenkins, Hollie Cooper, Jenna Thornton. IISc (Indian Institute of Science): Sekhar Muddu. University of Agricultural Sciences, Dharwad: S.S. Angadi. Indian Institute of Technology, Kanpur: Sachi Tripathi, Mithun Krishnan, Geet George. University of Reading: Andrew G. Turner

    Yoga jam: remixing Kirtan in the Art of Living

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    Yoga Jam are a group of musicians in the United Kingdom who are active members of the Art of Living, a transnational Hindu-derived meditation group. Yoga Jam organize events—also referred to as yoga raves and yoga remixes—that combine Hindu devotional songs (bhajans) and chants (mantras) with modern Western popular musical genres, such as soul, rock, and particularly electronic dance music. This hybrid music is often played in a clublike setting, and dancing is interspersed with yoga and meditation. Yoga jams are creative fusions of what at first sight seem to be two incompatible phenomena—modern electronic dance music culture and ancient yogic traditions. However, yoga jams make sense if the Durkheimian distinction between the sacred and the profane is challenged, and if tradition and modernity are not understood as existing in a sort of inverse relationship. This paper argues that yoga raves are authenticated through the somatic experience of the modern popular cultural phenomenon of clubbing combined with therapeutic yoga practices and validated by identifying this experience with a reimagined Vedic tradition
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