Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy

Chronic Chagas disease cardiomyopathy (CCC) affects millions in endemic areas and is presenting in growing numbers in the USA and European countries due to migration currents. Clinical progression, length of survival and overall prognosis are significantly worse in CCC patients when compared to patients with dilated cardiomyopathy of non-inflammatory etiology. Impairment of energy metabolism seems to play a role in heart failure due to cardiomyopathies. Herein, we have analyzed energy metabolism enzymes in myocardium samples of CCC patients comparing to other non-inflammatory cardiomyopathies. We found that myocardial tissue from CCC patients displays a significant reduction of both myocardial protein levels of ATP synthase alpha and creatine kinase enzyme activity, in comparison to control heart samples, as well as idiopathic dilated cardiomyopathy and ischemic cardiomyopathy. Our results suggest that CCC myocardium displays a selective energetic deficit, which may play a role in the reduced heart function observed in such patients

Polarized blazar X-rays imply particle acceleration in shocks

Most of the light from blazars, active galactic nuclei with jets of magnetized plasma that point nearly along the line of sight, is produced by high-energy particles, up to around 1 TeV. Although the jets are known to be ultimately powered by a supermassive black hole, how the particles are accelerated to such high energies has been an unanswered question. The process must be related to the magnetic field, which can be probed by observations of the polarization of light from the jets. Measurements of the radio to optical polarization—the only range available until now—probe extended regions of the jet containing particles that left the acceleration site days to years earlier1,2,3, and hence do not directly explore the acceleration mechanism, as could X-ray measurements. Here we report the detection of X-ray polarization from the blazar Markarian 501 (Mrk 501). We measure an X-ray linear polarization degree ΠX of around 10%, which is a factor of around 2 higher than the value at optical wavelengths, with a polarization angle parallel to the radio jet. This points to a shock front as the source of particle acceleration and also implies that the plasma becomes increasingly turbulent with distance from the shock

Magnetic Field Properties inside the Jet of Mrk 421: Multiwavelength Polarimetry Including the Imaging X-ray Polarimetry Explorer

We conducted a polarimetry campaign from radio to X-ray wavelengths of the high-synchrotron-peak (HSP) blazar Mrk 421, including Imaging X-ray Polarimetry Explorer (IXPE) measurements on 2022 December 6-8. We detected X-ray polarization of Mrk 421 with a degree of $\Pi_{\rm X}$=14$\pm$1$\%$ and an electric-vector position angle $\psi_{\rm X}$=107$\pm$3$^{\circ}$ in the 2-8 keV band. From the time variability analysis, we find a significant episodic variation in $\psi_{\rm X}$. During 7 months from the first IXPE pointing of Mrk 421 in 2022 May, $\psi_{\rm X}$ varied across the range of 0$^{\circ}$ to 180$^{\circ}$, while $\Pi_{\rm X}$ maintained similar values within $\sim$10-15$\%$. Furthermore, a swing in $\psi_{\rm X}$ in 2022 June was accompanied by simultaneous spectral variations. The results of the multiwavelength polarimetry show that the X-ray polarization degree was generally $\sim$2-3 times greater than that at longer wavelengths, while the polarization angle fluctuated. Additionally, based on radio, infrared, and optical polarimetry, we find that rotation of $\psi$ occurred in the opposite direction with respect to the rotation of $\psi_{\rm X}$ over longer timescales at similar epochs. The polarization behavior observed across multiple wavelengths is consistent with previous IXPE findings for HSP blazars. This result favors the energy-stratified shock model developed to explain variable emission in relativistic jets. The accompanying spectral variation during the $\psi_{\rm X}$ rotation can be explained by a fluctuation in the physical conditions, e.g., in the energy distribution of relativistic electrons. The opposite rotation direction of $\psi$ between the X-ray and longer-wavelength polarization accentuates the conclusion that the X-ray emitting region is spatially separated from that at longer wavelengths.Comment: 17 pages, 13 figures, 4 tables; Accepted for publication in A&

Discovery of X-ray polarization angle rotation in active galaxy Mrk 421

The magnetic field conditions in astrophysical relativistic jets can be probed by multiwavelength polarimetry, which has been recently extended to X-rays. For example, one can track how the magnetic field changes in the flow of the radiating particles by observing rotations of the electric vector position angle $\Psi$. Here we report the discovery of a $\Psi_{\mathrm x}$ rotation in the X-ray band in the blazar Mrk 421 at an average flux state. Across the 5 days of Imaging X-ray Polarimetry Explorer (IXPE) observations of 4-6 and 7-9 June 2022, $\Psi_{\mathrm x}$ rotated in total by $\geq360^\circ$. Over the two respective date ranges, we find constant, within uncertainties, rotation rates ($80 \pm 9$ and $91 \pm 8 ^\circ/\rm day$) and polarization degrees ($\Pi_{\mathrm x}=10\%\pm1\%$). Simulations of a random walk of the polarization vector indicate that it is unlikely that such rotation(s) are produced by a stochastic process. The X-ray emitting site does not completely overlap the radio/infrared/optical emission sites, as no similar rotation of $\Psi$ was observed in quasi-simultaneous data at longer wavelengths. We propose that the observed rotation was caused by a helical magnetic structure in the jet, illuminated in the X-rays by a localized shock propagating along this helix. The optically emitting region likely lies in a sheath surrounding an inner spine where the X-ray radiation is released

X-ray Polarization Observations of BL Lacertae

Blazars are a class of jet-dominated active galactic nuclei with a typical double-humped spectral energy distribution. It is of common consensus the Synchrotron emission to be responsible for the low frequency peak, while the origin of the high frequency hump is still debated. The analysis of X-rays and their polarization can provide a valuable tool to understand the physical mechanisms responsible for the origin of high-energy emission of blazars. We report the first observations of BL Lacertae performed with the Imaging X-ray Polarimetry Explorer ({IXPE}), from which an upper limit to the polarization degree $\Pi_X<$12.6\% was found in the 2-8 keV band. We contemporaneously measured the polarization in radio, infrared, and optical wavelengths. Our multiwavelength polarization analysis disfavors a significant contribution of proton synchrotron radiation to the X-ray emission at these epochs. Instead, it supports a leptonic origin for the X-ray emission in BL Lac.Comment: 17 pages, 5 figures, accepted for publication in ApJ

Prevalência e achados epidemiológicos, anatomopatológicos e imuno-histoquímicos dos tumores hepáticos malignos primários de cães da Região Central do Rio Grande do Sul (1965-2012)

A prevalência e os aspectos epidemiológicos, anatomopatológicos e imuno-histoquímicos dos tumores hepáticos malignos primários (THMP) em cães foram estudados. De 7.373 cães necropsiados em 48 anos (1965-2012), 64 morreram de THMP, o que corresponde a 0,9% do total de cães que morreram por qualquer causa, 7,8% do total de cães que morreram por tumores em geral e 33,5% do total de cães que morreram por tumores hepáticos. Desses 64 casos de THMP, 51 foram revistos histologicamente, avaliados imuno-histoquimicamente e reclassificados como carcinomas (colangiocarcinomas [n=36], carcinomas hepatocelulares [n=9] e hepatocolangiocarcinoma [n=1]) e sarcomas (hemangiossarcomas [n=5]). Dos cães com colangiocarcinomas e carcinomas hepatocelulares em que a idade estava disponível nos protocolos, 64,7% e 77,8% eram idosos, respectivamente. Na necropsia, colangiocarcinomas caracterizaram-se principalmente por ocorrerem em um padrão multinodular (83,3%), enquanto carcinomas hepatocelulares ocorreram tanto de forma massiva (44,4%) quanto nodular (44,4%). Metástases extra-hepáticas foram vistas em 77,8% e 33,3% dos casos de colangiocarcinomas e carcinomas hepatocelulares, respectivamente, e em relação aos colangiocarcinomas afetaram principalmente pulmões (52,8%), linfonodos (50%) e peritônio (19,4%). Ascite (22,2%) e icterícia (22,2%) foram achados associados ocasionalmente com ambos os tumores. Na histologia, a maior parte dos colangiocarcinomas (86,1%) e dos carcinomas hepatocelulares (55,6%) tinha padrão tubular e trabecular, respectivamente. Na imuno-histoquímica, a maioria (63,9%) dos colangiocarcinomas demonstrou imunomarcação para CK7 e nenhum imunomarcou para Hep Par 1. A maioria (55,6%) dos carcinomas hepatocelulares demonstrou imunomarcação para Hep Par 1 e nenhum imunomarcou para CK7. Os resultados aqui apresentados demonstram uma altíssima prevalência de THMP, principalmente colangiocarcinomas, e servem para auxiliar, através dos achados de necropsia, histologia e imuno-histoquímica, patologistas veterinários no diagnóstico dessa tão comum forma de câncer em cães da Região Central do RS, Brasil

Prevalência e achados epidemiológicos, anatomopatológicos e imuno-histoquímicos dos tumores hepáticos malignos primários de cães da Região Central do Rio Grande do Sul (1965-2012) Prevalence and epidemiological, pathological and immunohistochemical aspects of primary canine malignant hepatic tumors in Rio Grande do Sul, Brazil (1965-2012)

A prevalência e os aspectos epidemiológicos, anatomopatológicos e imuno-histoquímicos dos tumores hepáticos malignos primários (THMP) em cães foram estudados. De 7.373 cães necropsiados em 48 anos (1965-2012), 64 morreram de THMP, o que corresponde a 0,9% do total de cães que morreram por qualquer causa, 7,8% do total de cães que morreram por tumores em geral e 33,5% do total de cães que morreram por tumores hepáticos. Desses 64 casos de THMP, 51 foram revistos histologicamente, avaliados imuno-histoquimicamente e reclassificados como carcinomas (colangiocarcinomas [n=36], carcinomas hepatocelulares [n=9] e hepatocolangiocarcinoma [n=1]) e sarcomas (hemangiossarcomas [n=5]). Dos cães com colangiocarcinomas e carcinomas hepatocelulares em que a idade estava disponível nos protocolos, 64,7% e 77,8% eram idosos, respectivamente. Na necropsia, colangiocarcinomas caracterizaram-se principalmente por ocorrerem em um padrão multinodular (83,3%), enquanto carcinomas hepatocelulares ocorreram tanto de forma massiva (44,4%) quanto nodular (44,4%). Metástases extra-hepáticas foram vistas em 77,8% e 33,3% dos casos de colangiocarcinomas e carcinomas hepatocelulares, respectivamente, e em relação aos colangiocarcinomas afetaram principalmente pulmões (52,8%), linfonodos (50%) e peritônio (19,4%). Ascite (22,2%) e icterícia (22,2%) foram achados associados ocasionalmente com ambos os tumores. Na histologia, a maior parte dos colangiocarcinomas (86,1%) e dos carcinomas hepatocelulares (55,6%) tinha padrão tubular e trabecular, respectivamente. Na imuno-histoquímica, a maioria (63,9%) dos colangiocarcinomas demonstrou imunomarcação para CK7 e nenhum imunomarcou para Hep Par 1. A maioria (55,6%) dos carcinomas hepatocelulares demonstrou imunomarcação para Hep Par 1 e nenhum imunomarcou para CK7. Os resultados aqui apresentados demonstram uma altíssima prevalência de THMP, principalmente colangiocarcinomas, e servem para auxiliar, através dos achados de necropsia, histologia e imuno-histoquímica, patologistas veterinários no diagnóstico dessa tão comum forma de câncer em cães da Região Central do RS, Brasil.The prevalence and epidemiological and immunohistochemical aspects of primary hepatic malignant tumors (PHMT) were reviewed in dogs necropsied in a 48-year period (1965-2012). Out of those7,373 dogs, 64 died due to PHMT, which corresponds to 0.9% of the dogs dying from any cause in the period; 7.8% of dogs which deaths were caused by tumors in general; and 33.5% of all dogs dying from hepatic tumors (primary and metastatic). Out of the 64 cases of PHMT, 51 were reviewed histologically and evaluated by immunohistochemistry; they were diagnosed as carcinomas (36 cholangiocarcinomas, 9 hepatocellular carcinomas and one hepatocholangiocarcinoma) and sarcomas (5 hemangiosarcomas). In those dogs in which the age was possible determined, 64.7% (cholangiocarcinomas) and 77.8% (hepatocellular carcinomas) were old. At necropsy examination cholangiocarcinomas were characterized mainly by a multinodular pattern (83.3%) while hepatocellular carcinomas occurred both as massive (44.4%) or nodular (44.4%) distribution. Extra-hepatic metastasis occurred respectively in 77.8% and 33.3% of the cases of cholangiocarcinomas and hepatocellular carcinomas; metastatic cholangiocarcinomas affected mainly the lungs (52.8%), lymph nodes (50%) and peritoneum (19.4%). Ascites (22.2%) and icterus (22.2%) were observed frequently associated to both tumors. Histologically, most part of the cholangiocarcinomas (86.1%) and of the hepatocellular carcinomas (55.6%) presented respectively a tubular or trabecular type. Immunohistochemistry revealed that the majority (63.9%) of cholangiocarcinomas was positive for CK7 and none was marked for Hep Par 1. The majority (55.6%) of the hepatocellular carcinomas revealed positive reaction for Hep Par 1 and none was marked for CK7. The results presented here demonstrated a very high prevalence of PHMT, especially cholangiocarcinomas, in the dog. The necropsy, histological and immunohistochemical findings reported might be useful to help veterinary pathologists in the diagnosis of this common form of cancer in dogs of the Rio Grande do Sul, Brazil