Arginase I in myeloid suppressor cells is induced by COX-2 in lung carcinoma

Myeloid suppressor cells (MSCs) producing high levels of arginase I block T cell function by depleting l-arginine in cancer, chronic infections, and trauma patients. In cancer, MSCs infiltrating tumors and in circulation are an important mechanism for tumor evasion and impair the therapeutic potential of cancer immunotherapies. However, the mechanisms that induce arginase I in MSCs in cancer are unknown. Using the 3LL mouse lung carcinoma, we aimed to characterize these mechanisms. Arginase I expression was independent of T cell–produced cytokines. Instead, tumor-derived soluble factors resistant to proteases induced and maintained arginase I expression in MSCs. 3LL tumor cells constitutively express cyclooxygenase (COX)-1 and COX-2 and produce high levels of PGE2. Genetic and pharmacological inhibition of COX-2, but not COX-1, blocked arginase I induction in vitro and in vivo. Signaling through the PGE2 receptor E-prostanoid 4 expressed in MSCs induced arginase I. Furthermore, blocking arginase I expression using COX-2 inhibitors elicited a lymphocyte-mediated antitumor response. These results demonstrate a new pathway of prostaglandin-induced immune dysfunction and provide a novel mechanism that can help explain the cancer prevention effects of COX-2 inhibitors. Furthermore, an addition of arginase I represents a clinical approach to enhance the therapeutic potential of cancer immunotherapies

Mini Subcritical Nuclear Reactor

A mini subcritical nuclear reactor was designed using Monte Carlo methods. The reactor has light water as moderator, natural uranium as fuel, and a 239PuBe neutron source. In the design uranium fuel was modeled in an arrangement of concentric rings: 8.5, 14.5, 20.5 26.5, 32.5 cm-inner radius, 3 cm-thick, and 36 cm-high. Different models were made from a single ring of natural uranium to five rings. For each case, the neutron spectra, the neutron fluence distribution, the effective multiplication factor, the amplification factor, and the reactor power were estimated. The ambient dose equivalent rate outside the mini reactor was also estimated. The maximum value for the keff (0.78) was obtained when five rings of fuel were used; this value is close to 0.86 which belongs to a Nuclear Chicago subcritical reactor which requires almost twice the amount of uranium than the mini subcritical reactor

Repair of a Mutation Disrupting the Guinea Pig Cytomegalovirus Pentameric Complex Acquired during Fibroblast Passage Restores Pathogenesis in Immune-Suppressed Guinea Pigs and in the Context of Congenital Infection

ABSTRACT Guinea pig cytomegalovirus (GPCMV) provides a valuable model for congenital cytomegalovirus transmission. Salivary gland (SG)-passaged stocks of GPCMV are pathogenic, while tissue culture (TC) passage in fibroblasts results in attenuation. Nonpathogenic TC-derived virus N13R10 (cloned as a bacterial artificial chromosome [BAC]) has a 4-bp deletion that disrupts GP129 , which encodes a subunit of the GPCMV pentameric complex (PC) believed to govern viral entry into select cell types, and GP130 , an overlapping open reading frame (ORF) of unknown function. To determine if this deletion contributes to attenuation of N13R10, markerless gene transfer in Escherichia coli was used to construct virus r129, a variant of N13R10 in which the 4-bp deletion is repaired. Virions from r129 were found to contain GP129 as well as two other PC subunit proteins, GP131 and GP133, whereas these three PC subunits were absent from N13R10 virions. Replication of r129 in fibroblasts appeared unaltered compared to that of N13R10. However, following experimental challenge of immunocompromised guinea pigs, r129 induced significant weight loss, longer duration of viremia, and dramatically higher (up to 1.5 × 10 6 -fold) viral loads in blood and end organs compared to N13R10. In pregnant guinea pigs, challenge with doses of r129 virus of ≥5 × 10 6 PFU resulted in levels of maternal viremia, congenital transmission, pup viral loads, intrauterine growth restriction, and pup mortality comparable to that induced by pathogenic SG virus, although higher doses of r129 were required. These results suggest that the GP129-GP130 mutation is a significant contributor to attenuation of N13R10, likely by abrogating expression of a functional PC. IMPORTANCE Tissue culture adaptation of cytomegaloviruses rapidly selects for mutations, deletions, and rearrangements in the genome, particularly for viruses passaged in fibroblast cells. Some of these mutations are focused in the region of the genome encoding components of the pentameric complex (PC), in particular homologs of human cytomegalovirus (HCMV) proteins UL128, UL130, and UL131A. These mutations can attenuate the course of infection when the virus is reintroduced into animals for vaccine and pathogenesis studies. This study demonstrates that a deletion that arose during the process of tissue culture passage can be repaired, with subsequent restoration of pathogenicity, using BAC-based mutagenesis. Restoration of pathogenicity by repair of a frameshift mutation in GPCMV gene GP129 using this approach provides a valuable genetic platform for future studies using the guinea pig model of congenital CMV infection

Borrelia Chilensis, a New Member of the Borrelia Burgdorferi Sensu Lato Complex That Extends the Range of This Genospecies in the Southern Hemisphere

Borrelia burgdorferi sensu lato (s.l.), transmitted by Ixodes spp. ticks, is the causative agent of Lyme disease. Although Ixodes spp. ticks are distributed in both Northern and Southern Hemispheres, evidence for the presence of B. burgdorferi s.l. in South America apart from Uruguay is lacking. We now report the presence of culturable spirochetes with flat-wave morphology and borrelial DNA in endemic Ixodes stilesi ticks collected in Chile from environmental vegetation and long-tailed rice rats (Oligoryzomys longicaudatus). Cultured spirochetes and borrelial DNA in ticks were characterized by multilocus sequence typing and by sequencing five other loci (16S and 23S ribosomal genes, 5S-23S intergenic spacer, flaB, ospC). Phylogenetic analysis placed this spirochete as a new genospecies within the Lyme borreliosis group. Its plasmid profile determined by polymerase chain reaction and pulsed-field gel electrophoresis differed from that of B. burgdorferi B31A3. We propose naming this new South American member of the Lyme borreliosis group B. chilensis VA1 in honor of its country of origin

Colposcopy in the Primary Health Care: A Scoping Review

Aim: Low- and middle-income countries represent nearly 85% of all cervical cancer cases worldwide; thereby, it is extremely important to identify methods to improve the screening process. Therefore, this study aimed to summarize the primary characteristics of studies on accessibility, coverage, patient preferences, and factors associated with patient satisfaction or acceptance of colposcopy in primary healthcare. Methods: A search strategy, based on MeSH, Emtree, and free terms, was run through 5 databases (PubMed, Scopus, Embase, Ovid/Medline, and Web of Science). EndNote 20.1 © and Rayyan QCRI © were used for screening. A preset datasheet was used for data extraction. Results: The systematic search retrieved 1127 references, and after removing duplicates, screening the titles and abstracts, and reviewing the full text, 7 studies were included. The interrater reliability was 77.73% (kappa statistic = 0.1842). Most studies estimated the proportion of women that sought for colposcopy after a previous screening test for human papilloma virus. One study identifies barriers to colposcopy examination in women at risk of developing cervical cancer. Three studies assessed the decentralization of colposcopy from a tertiary healthcare center to a primary care center. Pap smear was the most common first-line screening test, followed by liquid-based cytology sample and visual inspection with acetic acid. Conclusion: Only a few countries have investigated the use of colposcopy in primary care. Thus, barriers and the care structure for this implementation to be successful in reducing cervical cancer incidence and mortality should be identified.Revisión por pare

Recent increase of ulcerative lesions caused by Anisakis spp. in cetaceans from the north-east Atlantic

Species of Anisakis typically infect the stomach of cetaceans worldwide, often causing ulcerative lesions that may compromise the host’s health. These nematodes also cause anisakiasis or allergic reactions in humans. To assess the risks of this emerging zoonosis, data on long-term changes in Anisakis infections in cetaceans are necessary. Here, we compare the prevalence and severity of ulcerative lesions caused by Anisakis spp. in five cetacean species stranded along the north-west Spanish coast in 2017–2018 with published data from 1991–1996. Open ulcers were found in 32/ 43 short-beaked common dolphins, Delphinus delphis; 3/5 striped dolphins, Stenella coeruleoalba; 1/7 bottlenose dolphins, Tursiops truncatus; and 1/3 harbour porpoises, Phocoena phocoena mer- idionalis; a single individual of long-finned pilot whale, Globicephala melas, was found unin- fected. In common dolphins, the mean abundance of open ulcers per host was 1.1 (95% confidence interval: 0.8–1.3), with a maximum diameter (mean ± standard deviation) of 25.4 ± 16.9 mm. Stomachs with scars or extensive fibrosis putatively associated with Anisakis were detected in 14 and five animals, respectively. A molecular analysis based on the mitochondrial cytochrome c oxidase II gene using 18 worms from three cetacean species revealed single or mixed infections ofAnisakis simplex sensu stricto and Anisakis pegreffii. Compared with the per- iod 1991–1996, we found a strong increase of prevalence, abundance and extension of ulcerative lesions in most cetacean species. Anisakis populations could have increased in the study area over the last decades, although we cannot rule out that a higher environmental stress has also boosted the pathological effects of these parasites.En prens

Charming penguins in B => K* pi, K (rho,omega,phi) decays

We evaluate the decays B => K* pi, K (rho,omega,phi) adding the long distance charming penguin contributions to the short distance: Tree+Penguin amplitudes. We estimate the imaginary part of the charming penguin by an effective field theory inspired by the Heavy Quark Effective Theory and parameterize its real part. The final results for branching ratios depend on only two real parameters and show a significant role of the charming penguins. The overall agreement with the available experimental data is satisfactory.Comment: 13 pages, 1 figur

Response to Neutrons and γ-rays of Two Liquid Scintillators

UltimaGoldTM AB and OptiphaseTrisafe are two liquid scintillators made by Perkin Elmer and EG & G Company respectively. Both are commercially promoted as scintillation detectors for α and β particles. In this work, the responses to γ-rays and neutrons of UltimaGoldTM AB and OptiphaseTriSafe liquid scintillators, without and with reflector, have been measured aiming to use these scintillators as γ-rays and neutron detectors. Responses to γ-rays and neutrons were measured as pulse shape spectra in a multichannel analyzer. Scintillators were exposed to gamma rays produced by 137Cs, 54Mn, 22Na and 60Co sources. The response to neutrons was obtained with a 241AmBe neutron source that was measured to 25 and 50 cm from the scintillators. The pulse height spectra due to gamma rays are shifted to larger channels as the photon energy increases and these responses are different from the response due to neutrons. Thus, UltimaGoldTM AB and OptiphaseTrisafe can be used to detect γ-rays and neutrons

Ameliorating Systematic Uncertainties in the Angular Clustering of Galaxies: A Study using SDSS-III

We investigate the effects of potential sources of systematic error on the angular and photometric redshift, z_phot, distributions of a sample of redshift 0.4 < z < 0.7 massive galaxies whose selection matches that of the Baryon Oscillation Spectroscopic Survey (BOSS) constant mass sample. Utilizing over 112,778 BOSS spectra as a training sample, we produce a photometric redshift catalog for the galaxies in the SDSS DR8 imaging area that, after masking, covers nearly one quarter of the sky (9,913 square degrees). We investigate fluctuations in the number density of objects in this sample as a function of Galactic extinction, seeing, stellar density, sky background, airmass, photometric offset, and North/South Galactic hemisphere. We find that the presence of stars of comparable magnitudes to our galaxies (which are not traditionally masked) effectively remove area. Failing to correct for such stars can produce systematic errors on the measured angular auto-correlation function, w, that are larger than its statistical uncertainty. We describe how one can effectively mask for the presence of the stars, without removing any galaxies from the sample, and minimize the systematic error. Additionally, we apply two separate methods that can be used to correct the systematic errors imparted by any parameter that can be turned into a map on the sky. We find that failing to properly account for varying sky background introduces a systematic error on w. We measure w, in four z_phot slices of width 0.05 between 0.45 < z_phot < 0.65 and find that the measurements, after correcting for the systematic effects of stars and sky background, are generally consistent with a generic LambdaCDM model, at scales up to 60 degrees. At scales greater than 3 degrees and z_phot > 0.5, the magnitude of the corrections we apply are greater than the statistical uncertainty in w.Comment: Accepted by MNRA

Galaxy evolution in compact groups I: Revealing a transitional galaxy population through a multiwavelength approach

Compact groups of galaxies (CGs) show members with morphological disturbances, mainly products of galaxy-galaxy interactions, thus making them ideal systems to study galaxy evolution, in high-density environment. To understand how this environment affects the properties of galaxies, we select a sample of 340 CGs in the Stripe 82 region, for a total of 1083 galaxies, and a sample of 2281 field galaxies as a control sample. By performing a multi-wavelength morphological fitting process using S-PLUS data, we divide our sample into early-type (ETG), late-type (LTG), and transition galaxies using the r-band S\'ersic index and the colour (u-r). We find a bimodal distribution in the plane of the effective radius-S\'ersic index, where a secondary "peculiar" galaxy population of smaller and more compact galaxies is found in CGs, which is not observed in the control sample. This indicates that galaxies are undergoing a morphological transformation in CGs. In addition, we find significant statistical differences in the distribution of specific Star Formation Rate (sSFR) when we compare both environments for LTGs and ETGs. We also find a higher fraction of quenched galaxies and a lower median sSFR in CGs than in the control sample, suggesting the existence of environmental effects favoring the cessation of star formation, regardless of galaxy type. Our results support the notion that CGs promote morphological and physical transformations, highlighting their potential as ideal systems for galaxy pre-processing.Comment: 17 pages, 15 figures. Accepted for publication in MNRA