366 research outputs found

    The relation of C - reactive protein to chronic kidney disease in African Americans: the Jackson Heart Study

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    <p>Abstract</p> <p>Background</p> <p>African Americans have an increased incidence and worse prognosis with chronic kidney disease (CKD - estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m<sup>2</sup>) than their counterparts of European-descent. Inflammation has been related to renal disease in non-Hispanic whites, but there are limited data on the role of inflammation in renal dysfunction in African Americans in the community.</p> <p>Methods</p> <p>We examined the cross-sectional relation of log transformed C-reactive protein (CRP) to renal function (eGFR by Modification of Diet and Renal Disease equation) in African American participants of the community-based Jackson Heart Study's first examination (2000 to 2004). We conducted multivariable linear regression relating CRP to eGFR adjusting for age, sex, body mass index, systolic and diastolic blood pressure, diabetes, total/HDL cholesterol, triglycerides, smoking, antihypertensive therapy, lipid lowering therapy, hormone replacement therapy, and prevalent cardiovascular disease events. In a secondary analysis we assessed the association of CRP with albuminuria (defined as albumin-to-creatinine ratio > 30 mg/g).</p> <p>Results</p> <p>Participants (n = 4320, 63.2% women) had a mean age ± SD of 54.0 ± 12.8 years. The prevalence of CKD was 5.2% (n = 228 cases). In multivariable regression, CRP concentrations were higher in those with CKD compared to those without CKD (mean CRP 3.2 ± 1.1 mg/L vs. 2.4 ± 1.0 mg/L, respectively p < 0.0001). CRP was significantly associated with albuminuria in sex and age adjusted model however not in the multivariable adjusted model (p > 0.05).</p> <p>Conclusion</p> <p>CRP was associated with CKD however not albuminuria in multivariable-adjusted analyses. The study of inflammation in the progression of renal disease in African Americans merits further investigation.</p

    A dual specificity kinase, DYRK1A, as a potential therapeutic target for head and neck squamous cell carcinoma

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    Despite advances in clinical management, 5-year survival rate in patients with late-stage head and neck squamous cell carcinoma (HNSCC) has not improved significantly over the past decade. Targeted therapies have emerged as one of the most promising approaches to treat several malignancies. Though tyrosine phosphorylation accounts for a minority of total phosphorylation, it is critical for activation of signaling pathways and plays a significant role in driving cancers. To identify activated tyrosine kinase signaling pathways in HNSCC, we compared the phosphotyrosine profiles of a panel of HNSCC cell lines to a normal oral keratinocyte cell line. Dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) was one of the kinases hyperphosphorylated at Tyr-321 in all HNSCC cell lines. Inhibition of DYRK1A resulted in an increased apoptosis and decrease in invasion and colony formation ability of HNSCC cell lines. Further, administration of the small molecular inhibitor against DYRK1A in mice bearing HNSCC xenograft tumors induced regression of tumor growth. Immunohistochemical labeling of DYRK1A in primary tumor tissues using tissue microarrays revealed strong to moderate staining of DYRK1A in 97.5% (39/40) of HNSCC tissues analyzed. Taken together our results suggest that DYRK1A could be a novel therapeutic target in HNSCC

    Gene content evolution in the arthropods

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    Arthropods comprise the largest and most diverse phylum on Earth and play vital roles in nearly every ecosystem. Their diversity stems in part from variations on a conserved body plan, resulting from and recorded in adaptive changes in the genome. Dissection of the genomic record of sequence change enables broad questions regarding genome evolution to be addressed, even across hyper-diverse taxa within arthropods. Using 76 whole genome sequences representing 21 orders spanning more than 500 million years of arthropod evolution, we document changes in gene and protein domain content and provide temporal and phylogenetic context for interpreting these innovations. We identify many novel gene families that arose early in the evolution of arthropods and during the diversification of insects into modern orders. We reveal unexpected variation in patterns of DNA methylation across arthropods and examples of gene family and protein domain evolution coincident with the appearance of notable phenotypic and physiological adaptations such as flight, metamorphosis, sociality, and chemoperception. These analyses demonstrate how large-scale comparative genomics can provide broad new insights into the genotype to phenotype map and generate testable hypotheses about the evolution of animal diversity

    Energetic Particles of Cosmic Accelerators II: Active Galactic Nuclei and Gamma-ray Bursts

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    The high-energy universe has revealed that energetic particles are ubiquitous in the cosmos and play a vital role in the cultivation of cosmic environments on all scales. Though they play a key role in cultivating the cosmological environment and/or enabling our studies of it, there is still much we do not know about AGNs and GRBs, particularly the avenue in which and through which they supply radiation and energetic particles, namely their jets. This White Paper is the second of a two-part series highlighting the most well-known high-energy cosmic accelerators and contributions that MeV gamma-ray astronomy will bring to understanding their energetic particle phenomena. The focus of this white paper is active galactic nuclei and gamma-ray bursts.Comment: 11 pages (including references), 2 figures; Submitted to the Astro2020 call for science white paper

    Energetic Particles of Cosmic Accelerators I: Galactic Accelerators

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    The high-energy universe has revealed that energetic particles are ubiquitous in the cosmos and play a vital role in the cultivation of cosmic environments on all scales. Our pursuit of more than a century to uncover the origins and fate of these cosmic energetic particles has given rise to some of the most interesting and challenging questions in astrophysics. Energetic particles in our own galaxy, galactic cosmic rays (GCRs), engage in a complex interplay with the interstellar medium and magnetic fields in the galaxy, giving rise to many of its key characteristics. For instance, GCRs act in concert with galactic magnetic fields to support its disk against its own weight. GCR ionization and heating are essential ingredients in promoting and regulating the formation of stars and protostellar disks. GCR ionization also drives astrochemistry, leading to the build up of complex molecules in the interstellar medium. GCR transport throughout the galaxy generates and maintains turbulence in the interstellar medium, alters its multi-phase structure, and amplifies magnetic fields. GCRs could even launch galactic winds that enrich the circumgalactic medium and alter the structure and evolution of galactic disks. As crucial as they are for many of the varied phenomena in our galaxy, there is still much we do not understand about GCRs. While they have been linked to supernova remnants (SNRs), it remains unclear whether these objects can fully account for their entire population, particularly at the lower (approximately less than 1 GeV per nucleon) and higher (~PeV) ends of the spectrum. In fact, it is entirely possible that the SNRs that have been found to accelerate CRs merely re-accelerate them, leaving the origins of the original GCRs a mystery. The conditions for particle acceleration that make SNRs compelling source candidates are also likely to be present in sources such as protostellar jets, superbubbles, and colliding wind binaries (CWBs), but we have yet to ascertain their roles in producing GCRs. For that matter, key details of diffusive shock acceleration (DSA) have yet to be revealed, and it remains to be seen whether DSA can adequately explain particle acceleration in the cosmos. This White Paper is the first of a two-part series highlighting the most well-known high-energy cosmic accelerators and contributions that MeV gamma-ray astronomy will bring to understanding their energetic particle phenomena. For the case of GCRs, MeV astronomy will: 1) Search for fresh acceleration of GCRs in SNRs; 2) Test the DSA process, particularly in SNRs and CWBs; 3) Search for signs of CR acceleration in protostellar jets and superbubbles

    An unusual pulse shape change event in PSR J1713+0747 observed with the Green Bank Telescope and CHIME

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    The millisecond pulsar J1713+0747 underwent a sudden and significant pulse shape change between April 16 and 17, 2021 (MJDs 59320 and 59321). Subsequently, the pulse shape gradually recovered over the course of several months. We report the results of continued multi-frequency radio observations of the pulsar made using the Canadian Hydrogen Intensity Mapping Experiment (CHIME) and the 100-meter Green Bank Telescope (GBT) in a three-year period encompassing the shape change event, between February 2020 and February 2023. As of February 2023, the pulse shape had returned to a state similar to that seen before the event, but with measurable changes remaining. The amplitude of the shape change and the accompanying TOA residuals display a strong non-monotonic dependence on radio frequency, demonstrating that the event is neither a glitch (the effects of which should be independent of radio frequency, ν\nu) nor a change in dispersion measure (DM) alone (which would produce a delay proportional to ν2\nu^{-2}). However, it does bear some resemblance to the two previous "chromatic timing events" observed in J1713+0747 (Demorest et al. 2013; Lam et al. 2016), as well as to a similar event observed in PSR J1643-1224 in 2015 (Shannon et al. 2016).Comment: 19 pages, 8 figures. Submitted to ApJ. Data available at https://doi.org/10.5281/zenodo.723645
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