Cell adhesion molecules involved in the leukocyte recruitment induced by venom of the snake Bothrops jararaca.

It has been shown that Bothrops jararaca venom (BjV) induces a significant leukocyte accumulation, mainly neutrophils, at the local of tissue damage. Therefore, the role of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), LECAM-1, CD18, leukocyte function-associated antigen-1 (LFA-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) on the BjV-induced neutrophil accumulation and the correlation with release of LTB4, TXA2, tumor necrosis factor-alpha, interleukin (IL)-1 and IL-6 have been investigated. Anti-mouse LECAM-1, LFA-1, ICAM-1 and PECAM-1 monoclonal antibody injection resulted in a reduction of 42%, 80%, 66% and 67%, respectively, of neutrophil accumulation induced by BjV (250 microg/kg, intraperitoneal) injection in male mice compared with isotype-matched control injected animals. The anti-mouse CD18 monoclonal antibody had no significant effect on venom-induced neutrophil accumulation. Concentrations of LTB(4), TXA(2), IL-6 and TNF-alpha were significant increased in the peritoneal exudates of animals injected with venom, whereas no increment in IL-1 was detected. This results suggest that ICAM-1, LECAM-1, LFA-1 and PECAM-1, but not CD18, adhesion molecules are involved in the recruitment of neutrophils into the inflammatory site induced by BjV. This is the first in vivo evidence that snake venom is able to up-regulate the expression of adhesion molecules by both leukocytes and endothelial cells. This venom effect may be indirect, probably through the release of the inflammatory mediators evidenced in the present study

ALMA Fragmented Source Catalogue in Orion (FraSCO) I. Outflow interaction within an embedded cluster in OMC-2/FIR3, FIR4, and FIR5

We present a high angular resolution ($\sim1"$) and wide-field ($2'.9 \times 1'.9$) image of the 1.3-mm continuum, CO($J$ = 2--1) line, and SiO($J$ = 5--4) line emissions toward an embedded protocluster, FIR3, FIR4, and FIR5, in the Orion Molecular Cloud 2 obtained from the Atacama Large Millimeter/submillimeter Array (ALMA). We identify 51 continuum sources, 36 of which are newly identified in this study. Their dust masses, projected sizes, and $\mathrm{H_2}$ gas number densities are estimated to be $3.8 \times 10^{-5}$--$1.1 \times 10^{-2} \mathrm{M_{\odot}}$, 290--2000 au, and $6.4 \times 10^{6}$--$3.3 \times 10^{8}\,\mathrm{cm^{-3}}$, respectively. The results of a Jeans analysis show that $\sim80\,\%$ of the protostellar sources and $\sim15\,\%$ of the prestellar sources are gravitationally bound. We identify 12 molecular outflows traced in the CO($J$ = 2--1) emission, six of which are newly detected. We spatially resolve shocked gas structures traced by the SiO($J$ = 5--4) emission in this region for the first time. We identify shocked gas originating from outflows and other shocked regions. These results provide direct evidence of an interaction between a dust condensation, FIR4, and an energetic outflow driven by HOPS-370 located within FIR3. A comparison of the outflow dynamical timescales, fragmentation timescales, and protostellar ages shows that the previously proposed triggered star-formation scenario in FIR4 is not strongly supported. We also discuss the spatial distribution of filaments identified in our continuum image by comparing it with a previously identified hub-fiber system in the $\mathrm{N_2H^+}$ line.Comment: 45 pages, 24 figures, 2 figure sets, 2 animations, Accepted for publication in Ap

ALMA Fragmented Source Catalog in Orion (FraSCO). I. Outflow interaction within an embedded cluster in OMC-2/FIR 3, FIR 4, and FIR 5

Funding: This work was supported by NAOJ ALMA Scientific Research grant No. 2022-22B. The present study was supported by JSPS KAKENHI grants (JP17H06360, JP17K05387, JP17KK0096, JP21H00046, JP21K03617: MNM, 20K04034: SI). L.A.Z. acknowledges financial support from CONACyT-280775 and UNAM-PAPIIT IN110618 grants, México. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. 851435).We present a high-angular resolution (∼1″) and wide-field ( 2.′9×1.′9 ) image of the 1.3 mm continuum, CO(J = 2–1) and SiO(J = 5–4) line emissions toward an embedded protocluster, FIR 3, FIR 4, and FIR 5, in the Orion Molecular Cloud 2 obtained from the Atacama Large Millimeter/submillimeter Array. We identify 51 continuum sources, 36 of which are newly identified in this study. Their dust masses, projected sizes, and H2 gas number densities are estimated to be 3.8 × 10−5–1.1 × 10−2 M⊙, 290–2000 au, and 6.4 × 106–3.3 × 108 cm−3, respectively. The results of a Jeans analysis show that ∼80% of the protostellar sources and ∼15% of the prestellar sources are gravitationally bound. We identify 12 molecular outflows traced in the CO(J = 2–1) emission, six of which are newly detected. We spatially resolve shocked gas structures traced by the SiO(J = 5–4) emission in this region for the first time. We identify shocked gas originating from outflows and other shocked regions. These results provide direct evidence of an interaction between dust condensation, FIR 4, and an energetic outflow driven by HOPS-370 located within FIR 3. A comparison of the outflow dynamical timescales, fragmentation timescales, and protostellar ages shows that the previously proposed triggered star formation scenario in FIR 4 is not strongly supported. We also discuss the spatial distribution of filaments identified in our continuum image by comparing it with a previously identified hub-fiber system in the N2H+ line.Publisher PDFPeer reviewe

ALMA Fragmented Source Catalog in Orion (FraSCO). I. Outflow Interaction within an Embedded Cluster in OMC-2/FIR 3, FIR 4, and FIR 5

We present a high-angular resolution (∼1'') and wide-field () image of the 1.3 mm continuum, CO(J = 2–1) and SiO(J = 5–4) line emissions toward an embedded protocluster, FIR 3, FIR 4, and FIR 5, in the Orion Molecular Cloud 2 obtained from the Atacama Large Millimeter/submillimeter Array. We identify 51 continuum sources, 36 of which are newly identified in this study. Their dust masses, projected sizes, and H2 gas number densities are estimated to be 3.8 × 10−5–1.1 × 10−2 M⊙, 290–2000 au, and 6.4 × 106–3.3 × 108 cm−3, respectively. The results of a Jeans analysis show that ∼80% of the protostellar sources and ∼15% of the prestellar sources are gravitationally bound. We identify 12 molecular outflows traced in the CO(J = 2–1) emission, six of which are newly detected. We spatially resolve shocked gas structures traced by the SiO(J = 5–4) emission in this region for the first time. We identify shocked gas originating from outflows and other shocked regions. These results provide direct evidence of an interaction between dust condensation, FIR 4, and an energetic outflow driven by HOPS-370 located within FIR 3. A comparison of the outflow dynamical timescales, fragmentation timescales, and protostellar ages shows that the previously proposed triggered star formation scenario in FIR 4 is not strongly supported. We also discuss the spatial distribution of filaments identified in our continuum image by comparing it with a previously identified hub-fiber system in the N2H+ line

Immunophenotypic features of tumor infiltrating lymphocytes from mammary carcinomas in female dogs associated with prognostic factors and survival rates

<p>Abstract</p> <p>Background</p> <p>The immune system plays an important role in the multifactorial biologic system during the development of neoplasias. However, the involvement of the inflammatory response in the promotion/control of malignant cells is still controversial, and the cell subsets and the mechanisms involved are poorly investigated. The goal of this study was to characterize the clinical-pathological status and the immunophenotyping profile of tumor infiltrating lymphocytes and their association with the animal survival rates in canine mammary carcinomas.</p> <p>Methods</p> <p>Fifty-one animals with mammary carcinomas, classified as carcinomas in mixed tumors-MC-BMT = 31 and carcinomas-MC = 20 were submitted to systematic clinical-pathological analysis (tumor size; presence of lymph node and pulmonary metastasis; clinical stage; histological grade; inflammatory distribution and intensity as well as the lymphocytic infiltrate intensity) and survival rates. Twenty-four animals (MC-BMT = 16 and MC = 8) were elected to the immunophenotypic study performed by flow cytometry.</p> <p>Results</p> <p>Data analysis demonstrated that clinical stage II-IV and histological grade was I more frequent in MC-BMT as compared to MC. Univariate analysis demonstrated that the intensity of inflammation (moderate/intense) and the proportion of CD4⁺(≥ 66.7%) or CD8⁺T-cells (<33.3%) were not associated with worse survival rate. Multivariate analysis demonstrated that only lymphocytic infiltrate intensity ≥ 600 (<it>P </it>= 0.02) remained as independent prognostic factor. Despite the clinical manifestation, the lymphocytes represented the predominant cell type in the tumor infiltrate. The percentage of T-cells was higher in animals with MC-BMT without metastasis, while the percentage of B-lymphocytes was greater in animals with metastasized MC-BMT (<it>P </it>< 0.05). The relative percentage of CD4⁺T-cells was significantly greater in metastasized tumors (both MC-BMT and MC), (<it>P </it>< 0.05) while the proportion of CD8⁺T-cells was higher in MC-BMT without metastasis. Consequently, the CD4⁺/CD8⁺ratio was significantly increased in both groups with metastasis. Regardless of the tumor type, the animals with high proportions of CD4⁺and low CD8⁺T-cells had decreased survival rates.</p> <p>Conclusion</p> <p>The intensity of lymphocytic infiltrate and probably the relative abundance of the CD4⁺and CD8⁺T-lymphocytes may represent important survival prognostic biomarkers for canine mammary carcinomas.</p

The Near Infrared Imager and Slitless Spectrograph for the James Webb Space Telescope. IV. Aperture Masking Interferometry

The James Webb Space Telescope’s Near Infrared Imager and Slitless Spectrograph (JWST-NIRISS) flies a 7-hole non-redundant mask (NRM), the first such interferometer in space, operating at 3-5 μm wavelengths, and a bright limit of ≃4 mag in W2. We describe the NIRISS Aperture Masking Interferometry (AMI) mode to help potential observers understand its underlying principles, present some sample science cases, explain its operational observing strategies, indicate how AMI proposals can be developed with data simulations, and how AMI data can be analyzed. We also present key results from commissioning AMI. Since the allied Kernel Phase Imaging (KPI) technique benefits from AMI operational strategies, we also cover NIRISS KPI methods and analysis techniques, including a new user-friendly KPI pipeline. The NIRISS KPI bright limit is ≃8 W2 (4.6 μm) magnitudes. AMI NRM and KPI achieve an inner working angle of ∼70 mas, which is well inside the ∼400 mas NIRCam inner working angle for its circular occulter coronagraphs at comparable wavelengths

The Near Infrared Imager and Slitless Spectrograph for the James Webb Space Telescope. IV. Aperture Masking Interferometry

The James Webb Space Telescope’s Near Infrared Imager and Slitless Spectrograph (JWST-NIRISS) flies a 7-hole non-redundant mask (NRM), the first such interferometer in space, operating at 3-5 μm wavelengths, and a bright limit of ≃4 mag in W2. We describe the NIRISS Aperture Masking Interferometry (AMI) mode to help potential observers understand its underlying principles, present some sample science cases, explain its operational observing strategies, indicate how AMI proposals can be developed with data simulations, and how AMI data can be analyzed. We also present key results from commissioning AMI. Since the allied Kernel Phase Imaging (KPI) technique benefits from AMI operational strategies, we also cover NIRISS KPI methods and analysis techniques, including a new user-friendly KPI pipeline. The NIRISS KPI bright limit is ≃8 W2 (4.6 μm) magnitudes. AMI NRM and KPI achieve an inner working angle of ∼70 mas, which is well inside the ∼400 mas NIRCam inner working angle for its circular occulter coronagraphs at comparable wavelengths

The JCMT Transient Survey: Four-year Summary of Monitoring the Submillimeter Variability of Protostars

We present the four-year survey results of monthly submillimeter monitoring of eight nearby (<500 pc) star-forming regions by the JCMT Transient Survey. We apply the Lomb–Scargle Periodogram technique to search for and characterize variability on 295 submillimeter peaks brighter than 0.14 Jy beam−1, including 22 disk sources (Class II), 83 protostars (Class 0/I), and 190 starless sources. We uncover 18 secular variables, all of them protostars. No single-epoch burst or drop events and no inherently stochastic sources are observed. We classify the secular variables by their timescales into three groups: Periodic, Curved, and Linear. For the Curved and Periodic cases, the detectable fractional amplitude, with respect to mean peak brightness, is ∼4% for sources brighter than ∼0.5 Jy beam−1. Limiting our sample to only these bright sources, the observed variable fraction is 37% (16 out of 43). Considering source evolution, we find a similar fraction of bright variables for both Class 0 and Class I. Using an empirically motivated conversion from submillimeter variability to variation in mass accretion rate, six sources (7% of our full sample) are predicted to have years-long accretion events during which the excess mass accreted reaches more than 40% above the total quiescently accreted mass: two previously known eruptive Class I sources, V1647 Ori and EC 53 (V371 Ser), and four Class 0 sources, HOPS 356, HOPS 373, HOPS 383, and West 40. Considering the full protostellar ensemble, the importance of episodic accretion on few years timescale is negligible—only a few percent of the assembled mass. However, given that this accretion is dominated by events on the order of the observing time window, it remains uncertain as to whether the importance of episodic events will continue to rise with decades-long monitoring

Genetic Interactions with Age, Sex, Body Mass Index, and Hypertension in Relation to Atrial Fibrillation: The AFGen Consortium

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10-5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10-8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk

The CHEK2 Variant C.349A>G Is Associated with Prostate Cancer Risk and Carriers Share a Common Ancestor.

The identification of recurrent founder variants in cancer predisposing genes may have important implications for implementing cost-effective targeted genetic screening strategies. In this study, we evaluated the prevalence and relative risk of the CHEK2 recurrent variant c.349A>G in a series of 462 Portuguese patients with early-onset and/or familial/hereditary prostate cancer (PrCa), as well as in the large multicentre PRACTICAL case-control study comprising 55,162 prostate cancer cases and 36,147 controls. Additionally, we investigated the potential shared ancestry of the carriers by performing identity-by-descent, haplotype and age estimation analyses using high-density SNP data from 70 variant carriers belonging to 11 different populations included in the PRACTICAL consortium. The CHEK2 missense variant c.349A>G was found significantly associated with an increased risk for PrCa (OR 1.9; 95% CI: 1.1-3.2). A shared haplotype flanking the variant in all carriers was identified, strongly suggesting a common founder of European origin. Additionally, using two independent statistical algorithms, implemented by DMLE+2.3 and ESTIAGE, we were able to estimate the age of the variant between 2300 and 3125 years. By extending the haplotype analysis to 14 additional carrier families, a shared core haplotype was revealed among all carriers matching the conserved region previously identified in the high-density SNP analysis. These findings are consistent with CHEK2 c.349A>G being a founder variant associated with increased PrCa risk, suggesting its potential usefulness for cost-effective targeted genetic screening in PrCa families