VLBI imaging of the gravitational lens MGJ0414+0534

We observed the quadruple gravitationally lensed image of MGJ0414+0534 on 23 November 1997 with a global VLBI array at 8.4 GHz. We report wide-field imaging results of its four components at submilliarcsecond resolution, displaying complex core-like and jet-like extended structures. A simple model combining a singular isothermal ellipsoid to represent the main lens galaxy, external shear, and a singular isothermal sphere to represent an additional, nearby object accounts well for the core positions and flux densities of the VLBI images. This model predicts delays between the different lensed images of several weeks.Comment: 6 pages, 3 figures, accepted for publication in Astronomy & Astrophysic

A clean sightline to quiescence: multiwavelength observations of the high Galactic latitude black hole X-ray binary Swift J1357.2-0933

We present coordinated multiwavelength observations of the high Galactic latitude (b = +50°) black hole X-ray binary (BHXB) Swift J1357.2−0933 in quiescence. Our broad-band spectrum includes strictly simultaneous radio and X-ray observations, and near-infrared, optical, and ultraviolet data taken 1–2 d later. We detect Swift J1357.2−0933 at all wavebands except for the radio (f5 GHz < 3.9 μJy beam−1; 3σrms). Given current constraints on the distance (2.3–6.3 kpc), its 0.5–10 keV X-ray flux corresponds to an Eddington ratio LX/LEdd = 4 × 10−9–3 × 10−8 (assuming a black hole mass of 10 M⊙). The broad-band spectrum is dominated by synchrotron radiation from a relativistic population of outflowing thermal electrons, which we argue to be a common signature of short-period quiescent BHXBs. Furthermore, we identify the frequency where the synchrotron radiation transitions from optically thick-to-thin (νb ≈ 2–5 × 1014 Hz), which is the most robust determination of a ‘jet break’ for a quiescent BHXB to date. Our interpretation relies on the presence of steep curvature in the ultraviolet spectrum, a frequency window made observable by the low amount of interstellar absorption along the line of sight. High Galactic latitude systems like Swift J1357.2−0933 with clean ultraviolet sightlines are crucial for understanding black hole accretion at low luminosities

Leprosy Associated with Atypical Cutaneous Leishmaniasis in Nicaragua and Honduras

In Central America, few cases of leprosy have been reported, but the disease may be unrecognized. Diagnosis is based on clinical criteria and histology. Preliminary field work in Nicaragua and Honduras found patients, including many children, with skin lesions clinically suggestive of atypical cutaneous leishmaniasis or indeterminate leprosy. Histology could not distinguish these diseases although acid-fast organisms were visible in a few biopsies. Lesions healed after standard antimicrobial therapy for leprosy. In the present study, patients, family members, and other community members were skin-tested and provided nasal swabs and blood samples. Biopsies were taken from a subgroup of patients with clinical signs of infection. Two laboratories analyzed samples, using local in-house techniques. Mycobacterium leprae, Leishmania spp. and Leishmania infantum were detected using polymerase chain reactions. Mycobacterium leprae DNA was detected in blood samples and nasal swabs, including some cases where leprosy was not clinically suspected. Leishmania spp. were also detected in blood and nasal swabs. Most biopsies contained Leishmania DNA and coinfection of Leishmania spp. with M. leprae occurred in 33% of cases. Mycobacterium leprae DNA was also detected and sequenced from Nicaraguan and Honduran environmental samples. In conclusion, leprosy and leishmaniasis are present in both regions, and leprosy appears to be widespread. The nature of any relationship between these two pathogens and the epidemiology of these infections need to be elucidated

NTHL1 biallelic mutations seldom cause colorectal cancer, serrated polyposis or a multi-tumor phenotype, in absence of colorectal adenomas

In 2015 Weren et al. described a hereditary cancer syndrome caused by biallelic mutations in the DNA base excision repair gene NTHL1, characterized by attenuated adenomatous polyposis and increased colorectal cancer (CRC) risk, largely resembling the recessive syndrome caused by MUTYH mutations1. To date, 33 homozygous or compound heterozygous NTHL1 mutation carriers have been reported (21 families)1,2,3,4,5,6,7,8. More than 5 colonic adenomas (range: 6 to >50) were identified in 24 of the 28 (85%) mutation carriers who underwent colonoscopy screening, and CRC was diagnosed in 19 (68%) of them. Noteworthy, 17 carriers (57%) were diagnosed with multiple primary malignant tumors in extracolonic locations, being the most recurrently found breast and endometrial tumors, head neck squamous cell carcimomas, meningiomas, and bladder and basal cell carcinomas, suggesting that the NTHL1-associated syndrome is a multi-tumor disease rather than a solely CRC syndrome. On the other hand, the fact that at least ¼ (7/28) of the reported biallelic mutation carriers who underwent colonoscopy screening had ≤10 adenomas, and that ≥5 hyperplastic polyps were detected in five carriers (polyp number range: 5->30), lead us to suspect a possible association of NTHL1 mutations with nonpolyposis CRC and serrated/hyperplastic polyposis. Based on previous evidence and with the aim of refining the phenotypic characteristics of the NTHL1-associated syndrome, here we evaluated the implication of NTHL1 biallelic mutations in the predisposition to personal or familial history of multiple tumor types, familial/early-onset nonpolyposis CRC, and serrated/hyperplastic polyposis

MYC activation impairs cell-intrinsic IFNγ signaling and confers resistance to anti-PD1/PD-L1 therapy in lung cancer

Elucidating the adaptive mechanisms that prevent host immune response in cancer will help predict efficacy of anti-programmed death-1 (PD1)/L1 therapies. Here, we study the cell-intrinsic response of lung cancer (LC) to interferon-y (IFNy), a cytokine that promotes immunoresponse and modulates programmed death-ligand 1 (PD-L1) levels. We report complete refractoriness to IFNy in a subset of LCs as a result of JAK2 or IFNGR1 inactivation. A submaximal response affects another subset that shows constitutive low levels of IFNy-stimulated genes (IySGs) coupled with decreased H3K27ac (histone 3 acetylation at lysine 27) depo-sition and promoter hypermethylation and reduced IFN regulatory factor 1 (IRF1) recruitment to the DNA on IFNy stimulation. Most of these are neuroendocrine small cell LCs (SCLCs) with oncogenic MYC/MYCL1/ MYCN. The oncogenic activation of MYC in SCLC cells downregulates JAK2 and impairs IySGs stimulation by IFNy. MYC amplification tends to associate with a worse response to anti-PD1/L1 therapies. Hence alterations affecting the JAK/STAT pathway and MYC activation prevent stimulation by IFNy and may predict anti-PD1/L1 efficacy in LC

Multi-Wavelength Observations of the Blazar 1ES 1011+496 in Spring 2008

The BL Lac object 1ES 1011+496 was discovered at Very High Energy gamma-rays by MAGIC in spring 2007. Before that the source was little studied in different wavelengths. Therefore a multi-wavelength (MWL) campaign was organized in spring 2008. Along MAGIC, the MWL campaign included the Metsahovi radio observatory, Bell and KVA optical telescopes and the Swift and AGILE satellites. MAGIC observations span from March to May, 2008 for a total of 27.9 hours, of which 19.4 hours remained after quality cuts. The light curve showed no significant variability. The differential VHE spectrum could be described with a power-law function. Both results were similar to those obtained during the discovery. Swift XRT observations revealed an X-ray flare, characterized by a harder when brighter trend, as is typical for high synchrotron peak BL Lac objects (HBL). Strong optical variability was found during the campaign, but no conclusion on the connection between the optical and VHE gamma-ray bands could be drawn. The contemporaneous SED shows a synchrotron dominated source, unlike concluded in previous work based on nonsimultaneous data, and is well described by a standard one zone synchrotron self Compton model. We also performed a study on the source classification. While the optical and X-ray data taken during our campaign show typical characteristics of an HBL, we suggest, based on archival data, that 1ES 1011+496 is actually a borderline case between intermediate and high synchrotron peak frequency BL Lac objects.Comment: 13 pages, accepted for publication in MNRA