Star Formation Under the Outflow: The Discovery of a Non-Thermal Jet from OMC-2 FIR 3 and its Relationship to the Deeply Embedded FIR 4 Protostar

We carried out multiwavelength (0.7-5 cm), multiepoch (1994-2015) Very Large Array (VLA) observations toward the region enclosing the bright far-IR sources FIR 3 (HOPS 370) and FIR 4 (HOPS 108) in OMC-2. We report the detection of 10 radio sources, seven of them identified as young stellar objects. We image a well-collimated radio jet with a thermal free-free core (VLA 11) associated with the Class I intermediate-mass protostar HOPS 370. The jet presents several knots (VLA 12N, 12C, 12S) of non-thermal radio emission (likely synchrotron from shock-accelerated relativistic electrons) at distances of ~7,500-12,500 au from the protostar, in a region where other shock tracers have been previously identified. These knots are moving away from the HOPS 370 protostar at ~ 100 km/s. The Class 0 protostar HOPS 108, which itself is detected as an independent, kinematically decoupled radio source, falls in the path of these non-thermal radio knots. These results favor the previously proposed scenario where the formation of HOPS 108 has been triggered by the impact of the HOPS 370 outflow with a dense clump. However, HOPS 108 presents a large proper motion velocity of ~ 30 km/s, similar to that of other runaway stars in Orion, whose origin would be puzzling within this scenario. Alternatively, an apparent proper motion could result because of changes in the position of the centroid of the source due to blending with nearby extended emission, variations in the source shape, and /or opacity effects.Comment: 16 pages, 4 figures, accepted for publication in The Astrophysical Journa

Ig-Like Transcript 2 (ILT2) Blockade and Lenalidomide Restore NK Cell Function in Chronic Lymphocytic Leukemia

One of the cardinal features of chronic lymphocytic leukemia (CLL) is its association with a profound immunosuppression. NK cell function is markedly impaired in CLL patients, who show a significant dysregulation of the expression of activating and inhibitory receptors. Here, we analyzed the role of the novel inhibitory receptor Ig-like transcript 2 (ILT2, also termed LIR-1, LILRB1) in the regulation of NK cells in CLL. Our results show that ILT2 expression was significantly decreased on leukemic cells and increased on NK cells of CLL patients, particularly in those with advanced disease and with bad prognostic features, such as those carrying chromosome del(11q). The immunomodulatory drug lenalidomide may regulate the expression of ILT2 and its ligands in CLL since it significantly increased the expression of ILT2 and partially reestablished the expression of its ligands on leukemic cells. Furthermore, lenalidomide significantly increased the activation and proliferation of NK cells, which was strongly enhanced by ILT2 blockade. Combining ILT2 blockade and lenalidomide activated NK cell cytotoxicity resulting in increased elimination of leukemic cells from CLL patients. Overall, we describe herein the role of an inhibitory receptor involved in the suppression of NK cell activity in CLL, which is restored by ILT2 blockade in combination with lenalidomide, suggesting that it may be an interesting therapeutic strategy to be explored in this disease

New constraints on protostellar jet collimation from high-density gas UV tracers

The analysis of high-resolution profiles of the semiforbidden UV lines of C III](1908) and Si III](1892) in the spectra of T Tauri stars (TTSs) shows the following : (1) There is C III](1908) and Si III](1892) emission at velocities that are similar to those observed in the optical forbidden lines formed in the TTSs jets. The luminosity of the UV lines is comparable to that of the optical lines. (2) The comparison between the optical and UV light curves indicates that the C III](1908) and Si III](1892) emission of RY Tau is not associated with accretion shocks, but it is produced farther than 2 R-* from the star. (3) The profiles of the UV semiforbidden lines are significantly broader than those of the optical forbidden lines. These profiles cannot be produced in a narrow collimated beam, and they are most likely produced in a bow-shaped shock wave formed at the base of the optical jet, where the hot gas emits in a broad range of projected radial velocities. (4) The atmosphere of RU Lup contributes significantly to the Si III](1892) emission. (5) A puzzling narrow feature is observed close to the C III](1908) line. The feature is blueshifted by -260 km s(-1), which corresponds to the wind terminal velocity measured in the P Cygni profile of the Mg II (UV1) lines. Moreover, constraints are derived on the characteristics of the C III](1908) and Si III](1892) emitting region in RY Tau. It is shown that 4.7 less than or equal to log T-e less than or equal to 5.0 and 10(9) cm(-3) less than or equal to N-e less than or equal to 10(11) cm(-3) provided that the emission is produced in a collisional plasma and that the 1665 Angstrom feature observed in low-dispersion International Ultraviolet Explorer (IUE) spectra is confirmed to be O III](1665) emission produced in the wind. These very high densities are difficult to generate in the shocks produced by the magnetic pinching of centrifugally driven magnetized disk winds. The data also suggest that the shocked layer has a radius of some few stellar radii and it is closer than similar to 38 R-* to the star

The RNA Binding Protein Csx1 Promotes Sexual Differentiation in Schizosaccharomyces pombe

Sexual differentiation is a highly regulated process in the fission yeast Schizosaccharomyces pombe and is triggered by nutrient depletion, mainly nitrogen source

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n = 3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (pcombined  = 5.66 × 10-5 ; ORcombined  = 2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (pcombined  = 1.02 × 10-4 ; ORcombined  = 2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10DmRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p = 0.01 and p < 0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p = 0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC.This work was supported by the Spanish Society of Medical Oncology; Fundación SEOM and Fundación Salud 2000; and Government of Navarra.S

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC

The next phases of the Migrante Project: Study protocol to expand an observatory of migrant health on the Mexico—U.S. border

BackgroundMexican migrants traveling across the Mexico-United States (U.S.) border region represent a large, highly mobile, and socially vulnerable subset of Mexican nationals. Population-level health data for this group is hard to obtain given their geographic dispersion, mobility, and largely unauthorized status in the U.S. Over the last 14 years, the Migrante Project has implemented a unique migration framework and novel methodological approach to generate population-level estimates of disease burden and healthcare access for migrants traversing the Mexico-U.S. border. This paper describes the rationale and history of the Migrante Project and the protocol for the next phases of the project.Methods/designIn the next phases, two probability, face-to-face surveys of Mexican migrant flows will be conducted at key crossing points in Tijuana, Ciudad Juarez, and Matamoros (N = 1,200 each). Both survey waves will obtain data on demographics, migration history, health status, health care access, COVID-19 history, and from biometric tests. In addition, the first survey will focus on non-communicable disease (NCD), while the second will dive deeper into mental health and substance use. The project will also pilot test the feasibility of a longitudinal dimension with 90 survey respondents that will be re-interviewed by phone 6 months after completing the face-to-face baseline survey.DiscussionInterview and biometric data from the Migrante project will help to characterize health care access and health status and identify variations in NCD-related outcomes, mental health, and substance use across migration phases. The results will also set the basis for a future longitudinal extension of this migrant health observatory. Analyses of previous Migrante data, paired with data from these upcoming phases, can shed light on the impact of health care and immigration policies on migrants’ health and inform policy and programmatic responses to improve migrant health in sending, transit, and receiving communities

Sarcoma treatment in the era of molecular medicine

Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.Peer reviewe

LXR Deficiency Confers Increased Protection against Visceral Leishmania Infection in Mice

Leishmania spp. are protozoan single-cell parasites that are transmitted to humans by the bite of an infected sand fly, and can cause a wide spectrum of disease, ranging from self-healing skin lesions to potentially fatal systemic infections. Certain species of Leishmania that cause visceral (systemic) disease are a source of significant mortality worldwide. Here, we use a mouse model of visceral Leishmania infection to investigate the effect of a host gene called LXR. The LXRs have demonstrated important functions in both cholesterol regulation and inflammation. These processes, in turn, are closely related to lipid metabolism and the development of atherosclerosis. LXRs have also previously been shown to be involved in protection against other intracellular pathogens that infect macrophages, including certain bacteria. We demonstrate here that LXR is involved in susceptibility to Leishmania, as animals deficient in the LXR gene are much more resistant to infection with the parasite. We also demonstrate that macrophages lacking LXR kill parasites more readily, and make higher levels of nitric oxide (an antimicrobial mediator) and IL-1β (an inflammatory cytokine) in response to Leishmania infection. These results could have important implications in designing therapeutics against this deadly pathogen, as well as other intracellular microbial pathogens

Genomic characterization of individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced lung cancer

Single nucleotide polymorphisms (SNPs) may modulate individual susceptibility to carcinogens. We designed a genome-wide association study to characterize individuals presenting extreme phenotypes of high and low risk to develop tobacco-induced non-small cell lung cancer (NSCLC), and we validated our results. We hypothesized that this strategy would enrich the frequencies of the alleles that contribute to the observed traits. We genotyped 2.37 million SNPs in 95 extreme phenotype individuals, that is: heavy smokers that either developed NSCLC at an early age (extreme cases); or did not present NSCLC at an advanced age (extreme controls), selected from a discovery set (n=3631). We validated significant SNPs in 133 additional subjects with extreme phenotypes selected from databases including >39,000 individuals. Two SNPs were validated: rs12660420 (p(combined)=5.66x10(-5); ORcombined=2.80), mapping to a noncoding transcript exon of PDE10A; and rs6835978 (p(combined)=1.02x10(-4); ORcombined=2.57), an intronic variant in ATP10D. We assessed the relevance of both proteins in early-stage NSCLC. PDE10A and ATP10D mRNA expressions correlated with survival in 821 stage I-II NSCLC patients (p=0.01 and p<0.0001). PDE10A protein expression correlated with survival in 149 patients with stage I-II NSCLC (p=0.002). In conclusion, we validated two variants associated with extreme phenotypes of high and low risk of developing tobacco-induced NSCLC. Our findings may allow to identify individuals presenting high and low risk to develop tobacco-induced NSCLC and to characterize molecular mechanisms of carcinogenesis and resistance to develop NSCLC