6,622 research outputs found

    Altered expression of caspases-4 and -5 during inflammatory bowel disease and colorectal cancer : diagnostic and therapeutic potential

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    Caspases are a group of proteolytic enzymes involved in the co-ordination of cellular processes, including cellular homeostasis, inflammation and apoptosis. Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC). However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation. Furthermore, we found a clear correlation between stromal caspase-4 and -5 expression levels, inflammation and disease activity in ulcerative colitis patients. Deregulated intestinal inflammation in IBD patients is associated with an increased risk of developing CRC. We found robust expression of caspases-4 and -5 within intestinal epithelial cells, exclusively within neoplastic tissue, of colorectal tumours. An examination of adjacent normal, inflamed and tumour tissue from patients with colitis-associated CRC confirmed that stromal expression of caspases-4 and -5 is increased in inflamed and dysplastic tissue, while epithelial expression is restricted to neoplastic tissue. In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC

    PrimPol is required for replicative tolerance of G quadruplexes in vertebrate cells

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    G quadruplexes (G4s) can present potent blocks to DNA replication. Accurate and timely replication of G4s in vertebrates requires multiple specialized DNA helicases and polymerases to prevent genetic and epigenetic instability. Here we report that PrimPol, a recently described primase-polymerase (PrimPol), plays a crucial role in the bypass of leading strand G4 structures. While PrimPol is unable to directly replicate G4s, it can bind and reprime downstream of these structures. Disruption of either the catalytic activity or zinc-finger of PrimPol results in extreme G4-dependent epigenetic instability at the BU-1 locus in avian DT40 cells, indicative of extensive uncoupling of the replicative helicase and polymerase. Together, these observations implicate PrimPol in promoting restart of DNA synthesis downstream of, but closely coupled to, G4 replication impediments

    Biomarker Discovery in Animal Health and Disease: The Application of Post-Genomic Technologies

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    The causes of many important diseases in animals are complex and multifactorial, which present unique challenges. Biomarkers indicate the presence or extent of a biological process, which is directly linked to the clinical manifestations and outcome of a particular disease. Identifying biomarkers or biomarker profiles will be an important step towards disease characterization and management of disease in animals. The emergence of post-genomic technologies has led to the development of strategies aimed at identifying specific and sensitive biomarkers from the thousands of molecules present in a tissue or biological fluid. This review will summarize the current developments in biomarker discovery and will focus on the role of transcriptomics, proteomics and metabolomics in biomarker discovery for animal health and disease

    Kenyan palliative care providers’ and leaders’ perceptions of palliative care research needs and support to facilitate rigorous research

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    Background: Palliative care (PC) can reduce symptom distress and improve quality of life for patients and their families experiencing life-threatening illness. While the need for PC in Kenya is high, PC service delivery and research is limited. Qualitative research is needed to explore potential areas for PC research and support needed to enable that research. This insight is critical for informing a national PC research agenda and mobilizing limited resources for conducting rigorous PC research in Kenya. Objectives: To explore perceptions of priority areas for PC research and support needed to facilitate rigorous research from the perspective of Kenyan PC providers and leaders. Methods: Focus groups (FGs) were conducted in November and December of 2018 using a semi-structured interview guide. FGs were audio-recorded, transcribed, and analyzed using a thematic content analysis approach. Results: Three FGs were conducted (n = 22 participants). Ten themes related to PC research emerged, including research on: 1) beliefs about death, disease, and treatment to inform PC; 2) awareness about PC, 3) integration of PC within the health system; 4) understanding caregiver experiences and needs; 5) community health volunteers (CHVs) and volunteer programs; 6) evaluation of costs and benefits of PC; 7) treatment approaches, including complementary and alternative medicine (CAM) and advanced diagnostics at end of life; 8) other suggestions for research, 9) populations in need of PC research; and 10) resources for enabling research. Conclusions: Kenyan PC providers and leaders identified key areas requiring increased scientific inquiry and critical resources needed to enable this research. These findings can help to focus future PC research in Kenya and encourage funding agencies to prioritize the issues identified

    The Pan-STARRS1 Photometric System

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    The Pan-STARRS1 survey is collecting multi-epoch, multi-color observations of the sky north of declination -30 deg to unprecedented depths. These data are being photometrically and astrometrically calibrated and will serve as a reference for many other purposes. In this paper we present our determination of the Pan-STARRS photometric system: gp1, rp1, ip1, zp1, yp1, and wp1. The Pan-STARRS photometric system is fundamentally based on the HST Calspec spectrophotometric observations, which in turn are fundamentally based on models of white dwarf atmospheres. We define the Pan-STARRS magnitude system, and describe in detail our measurement of the system passbands, including both the instrumental sensitivity and atmospheric transmission functions. Byproducts, including transformations to other photometric systems, galactic extinction, and stellar locus are also provided. We close with a discussion of remaining systematic errors.Comment: 39 pages, 9 figures, machine readable table of bandpasses, accepted for publication in Ap

    Infrared Spectroscopy of a Massive Obscured Star Cluster in the Antennae Galaxies (NGC 4038/4039) with NIRSPEC

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    We present infrared spectroscopy of the Antennae Galaxies (NGC 4038/4039) with NIRSPEC at the W. M. Keck Observatory. We imaged the star clusters in the vicinity of the southern nucleus (NGC 4039) in 0.39" seeing in K-band using NIRSPEC's slit-viewing camera. The brightest star cluster revealed in the near-IR (M_K(0) = -17.9) is insignificant optically, but coincident with the highest surface brightness peak in the mid-IR (12-18 micron) ISO image presented by Mirabel et al. (1998). We obtained high signal-to-noise 2.03 - 2.45 micron spectra of the nucleus and the obscured star cluster at R ~ 1900. The cluster is very young (4 Myr old), massive (16e6 M_sun), and compact (density ~ 115 M_sun pc^(-3) within a 32 pc half-light radius), assuming a Salpeter IMF (0.1 - 100 M_sun). Its hot stars have a radiation field characterized by T_eff ~ 39,000 K, and they ionize a compact H II region with n_e ~ 1e4 cm^(-3). The stars are deeply embedded in gas and dust (A_V ~ 9-10 mag), and their strong FUV field powers a clumpy photodissociation region with densities n_H >= 1e5 cm^(-3) on scales of up to 200 pc, radiating L[H_2 1-0 S(1)] = 9600 L_sun.Comment: 4 pages, 5 embedded figures. To appear in proceedings of 33d ESLAB Symposium: Star Formation from the Small to the Large Scale, held in Noordwijk, The Netherlands, Nov. 1999. Also available at http://astro.berkeley.edu/~agilber

    Polarized thermal emission from dust in a galaxy at redshift 2.6

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    Magnetic fields are fundamental to the evolution of galaxies, playing a key role in the astrophysics of the interstellar medium and star formation. Large-scale ordered magnetic fields have been mapped in the Milky Way and nearby galaxies, but it is not known how early in the Universe such structures form. Here we report the detection of linearly polarized thermal emission from dust grains in a strongly lensed, intrinsically luminous galaxy that is forming stars at a rate more than a thousand times that of the Milky Way at redshift 2.6, within 2.5 Gyr of the Big Bang. The polarized emission arises from the alignment of dust grains with the local magnetic field. The median polarization fraction is of order one per cent, similar to nearby spiral galaxies. Our observations support the presence of a 5 kiloparsec-scale ordered magnetic field with a strength of around 500uG or lower, orientated parallel to the molecular gas disk. This confirms that such structures can be rapidly formed in galaxies, early in cosmic history.Comment: Published in Nature. Online version available at https://www.nature.com/articles/s41586-023-06346-
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