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- Abeysekara, A. U., et al.
(författare)
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VERITAS and Fermi-LAT Observations of TeV Gamma-Ray Sources Discovered by HAWC in the 2HWC Catalog
- 2018
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Ingår i: Astrophysical Journal. - : Institute of Physics Publishing. - 0004-637X .- 1538-4357. ; 866:1
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Tidskriftsartikel (refereegranskat)abstract
- The High Altitude Water Cherenkov (HAWC) collaboration recently published their 2HWC catalog, listing 39 very high energy (VHE; >100 GeV) gamma-ray sources based on 507 days of observation. Among these, 19 sources are not associated with previously known teraelectronvolt (TeV) gamma-ray sources. We have studied 14 of these sources without known counterparts with VERITAS and Fermi-LAT. VERITAS detected weak gamma-ray emission in the 1 TeV-30 TeV band in the region of DA 495, a pulsar wind nebula coinciding with 2HWC J1953+294, confirming the discovery of the source by HAWC. We did not find any counterpart for the selected 14 new HAWC sources from our analysis of Fermi-LAT data for energies higher than 10 GeV. During the search, we detected gigaelectronvolt (GeV) gamma-ray emission coincident with a known TeV pulsar wind nebula, SNR G54.1+0.3 (VER J1930+188), and a 2HWC source, 2HWC J1930+188. The fluxes for isolated, steady sources in the 2HWC catalog are generally in good agreement with those measured by imaging atmospheric Cherenkov telescopes. However, the VERITAS fluxes for SNR G54.1+0.3, DA 495, and TeV J2032+4130 are lower than those measured by HAWC, and several new HAWC sources are not detected by VERITAS. This is likely due to a change in spectral shape, source extension, or the influence of diffuse emission in the source region.
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- Mora, Ana M., et al.
(författare)
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Pesticide exposure and cortical brain activation among farmworkers in Costa Rica
- 2022
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Ingår i: NeuroToxicology. - : Elsevier BV. - 0161-813X. ; 93, s. 200-210
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Tidskriftsartikel (refereegranskat)abstract
- Background: Previous epidemiological studies have reported associations of pesticide exposure with poor cognitive function and behavioral problems. However, these findings have relied primarily on neuropsychological assessments. Questions remain about the neurobiological effects of pesticide exposure, specifically where in the brain pesticides exert their effects and whether compensatory mechanisms in the brain may have masked pesticide-related associations in studies that relied purely on neuropsychological measures. Methods: We conducted a functional neuroimaging study in 48 farmworkers from Zarcero County, Costa Rica, in 2016. We measured concentrations of 13 insecticide, fungicide, or herbicide metabolites or parent compounds in urine samples collected during two study visits (approximately 3–5 weeks apart). We assessed cortical brain activation in the prefrontal cortex during tasks of working memory, attention, and cognitive flexibility using functional near-infrared spectroscopy (fNIRS). We estimated associations of pesticide exposure with cortical brain activation using multivariable linear regression models adjusted for age and education level. Results: We found that higher concentrations of insecticide metabolites were associated with reduced activation in the prefrontal cortex during a working memory task. For example, 3,5,6-trichloro-2-pyridinol (TCPy; a metabolite of the organophosphate chlorpyrifos) was associated with reduced activation in the left dorsolateral prefrontal cortex (β = −2.3; 95% CI: −3.9, −0.7 per two-fold increase in TCPy). Similarly, 3-phenoxybenzoic acid (3-PBA; a metabolite of pyrethroid insecticides) was associated with bilateral reduced activation in the dorsolateral prefrontal cortices (β = −3.1; 95% CI: −5.0, −1.2 and −2.3; 95% CI: −4.5, −0.2 per two-fold increase in 3-PBA for left and right cortices, respectively). These associations were similar, though weaker, for the attention and cognitive flexibility tasks. We observed null associations of fungicide and herbicide biomarker concentrations with cortical brain activation during the three tasks that were administered. Conclusion: Our findings suggest that organophosphate and pyrethroid insecticides may impact cortical brain activation in the prefrontal cortex – neural dynamics that could potentially underlie previously reported associations with cognitive and behavioral function. Furthermore, our study demonstrates the feasibility and utility of fNIRS in epidemiological field studies.
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- Oikonomou, Vasileios, et al.
(författare)
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The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1.
- 2024
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Ingår i: The New England journal of medicine. - 1533-4406. ; 390:20, s. 1873-1884
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune polyendocrine syndrome type 1 (APS-1) is a life-threatening, autosomal recessive syndrome caused by autoimmune regulator (AIRE) deficiency. In APS-1, self-reactive T cells escape thymic negative selection, infiltrate organs, and drive autoimmune injury. The effector mechanisms governing T-cell-mediated damage in APS-1 remain poorly understood.We examined whether APS-1 could be classified as a disease mediated by interferon-γ. We first assessed patients with APS-1 who were participating in a prospective natural history study and evaluated mRNA and protein expression in blood and tissues. We then examined the pathogenic role of interferon-γ using Aire-/-Ifng-/- mice and Aire-/- mice treated with the Janus kinase (JAK) inhibitor ruxolitinib. On the basis of our findings, we used ruxolitinib to treat five patients with APS-1 and assessed clinical, immunologic, histologic, transcriptional, and autoantibody responses.Patients with APS-1 had enhanced interferon-γ responses in blood and in all examined autoimmunity-affected tissues. Aire-/- mice had selectively increased interferon-γ production by T cells and enhanced interferon-γ, phosphorylated signal transducer and activator of transcription 1 (pSTAT1), and CXCL9 signals in multiple organs. Ifng ablation or ruxolitinib-induced JAK-STAT blockade in Aire-/- mice normalized interferon-γ responses and averted T-cell infiltration and damage in organs. Ruxolitinib treatment of five patients with APS-1 led to decreased levels of T-cell-derived interferon-γ, normalized interferon-γ and CXCL9 levels, and remission of alopecia, oral candidiasis, nail dystrophy, gastritis, enteritis, arthritis, Sjögren's-like syndrome, urticaria, and thyroiditis. No serious adverse effects from ruxolitinib were identified in these patients.Our findings indicate that APS-1, which is caused by AIRE deficiency, is characterized by excessive, multiorgan interferon-γ-mediated responses. JAK inhibition with ruxolitinib in five patients showed promising results. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
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