Duodenal intraepithelial lymphocytes of children with cow milk allergy preferentially bind the glycan-binding protein galectin-3

A breakdown in intestinal homeostasis results in inflammatory bowel diseases including coeliac disease and allergy. Galectins, evolutionarily conserved beta-galactoside-binding proteins, can modulate immune-epithelial cell interactions by influencing immune cell fate and cytokine secretion. In this study we investigated the glycosylation signature, as well as the regulated expression of galectin-1 and -3 in human duodenal samples of allergic and non-allergic children. Whereas galectin-1 was predominantly localized in the epithelial compartment (epithelial cells and intraepithelial lymphocytes) and the underlying lamina propria (T cells, macrophages and plasma cells), galectin-3 was mainly expressed by crypt epithelial cells and macrophages in the lamina propria. Remarkably, expression of these galectins was not significantly altered in allergic versus non-allergic patients. Investigation of the glycophenotype of the duodenal inflammatory microenvironment revealed substantial alpha2-6-linked sialic acid bound to galactose in lamina propria plasma cells, macrophages and intraepithelial lymphocytes and significant levels of asialo core 1 O-glycans in CD68+ macrophages and enterocytes. Galectin-1 preferentially bound to neutrophils, plasma cells and enterocytes, while galectin-3 binding sites were mainly distributed on macrophages and intraepithelial lymphocytes. Notably, galectin-3, but not galectin-1 binding, was substantially increased in intraepithelial gut lymphocytes of allergic patients compared to non-allergic subjects, suggesting a potential role of galectin-3-glycan interactions in shaping epithelial-immune cell connections during allergic inflammatory processes.Fil: Mercer, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata; ArgentinaFil: Guzman, Luciana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Cueto Rua, Eduardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Drut, Ricardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Ahmed, H.. University of Maryland; Estados UnidosFil: Vasta, G. R.. University of Maryland; Estados UnidosFil: Toscano, Marta Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Rabinovich, Gabriel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de La Plata; Argentin

A case of double cystic esophageal duplication in VACTERL syndrome: the first case report and a review of the literature

BackgroundAn esophageal duplication cyst (EDC) is a rare malformation resulting from the embryonic foregut. VACTERL syndrome is a genetic disorder affecting many systems of the human body. We report the first case of VACTERL syndrome associated to asymptomatic double EDC.Case reportA girl with anorectal malformation and rectovestibular fistula, kidney malformation, and various vertebral defects came to our attention at the time of birth. VACTERL disease was diagnosed. She underwent Peña anoplasty at 4 months of life without complications. MRI was conducted at the age of 2. It accidentally showed a double esophageal duplication (12 mm × 35 mm × 10 mm) at the D7–D9 level. We planned a thoracoscopy; previous intraoperative esophagogastroduodenoscopy showed an external compression of the native esophagus. Two duplicated esophageal lesions were removed. The patient made an uneventful recovery and was completely asymptomatic at long-term follow-up.ConclusionsVACTERL syndrome is still a not well-defined disease. Based on the current literature, this is the first case of a double esophageal duplication in a patient affected by VACTERL syndrome. According to us, the thoracoscopic approach of esophageal duplications can be followed by experts. Complete surgical excision is possible even if the cyst shares a common muscular wall with the esophagus. For this reason, we suggest to close the muscular wall by a simple interrupted suture

Enhanced GRK2 expression and desensitization of betaAR vasodilatation in hypertensive patients.

Increased levels of G protein coupled receptor kinase GRK2 appear to participate in hypertension presumably through the desensitization of beta adrenergic receptors (betaARs) that mediate vasodilatation. There are contrasting data on the occurrence of betaAR desensitization in the vasculature, we therefore investigated betaAR vasodilatation and desensitization in normotensives and in hypertensive humans. In blood lymphocytes, we assessed betaAR signaling and GRK2 expression and found betaAR signaling alterations and, consistent with desensitization, ncreased GRK2 levels in hypertensives. We studied in vivo vasodilatation to the betaAR agonist isoproterenol (ISO) injected in the brachia artery in control conditions and during the concomitant infusion of heparin, a known in vitro nonspecific GRK inhibitor. ISO induced a dose-dependent vasorelaxation that was attenuated in hypertensives indicating a loss of betaAR signaling. Intra-arterial infusion of heparin nhibited lymphocyte GRK2 activity and prevented desensitization of betaAR vasodilatation in normotensives. In hypertensives, heparin restored vasodilatation to ISO, to levels observed in normotensives. Our results suggest that betaAR desensitization does indeed occur at the vascular levels in vivo, and that heparin by acting as a GRK inhibitor prevents this in normotensives and restores impaired betaAR vasodilation in hypertensives. We conclude that desensitization participates to impaired betaAR vasodilation in hypertension

The Herschel HIFI water line survey in the low-mass proto-stellar outflow L1448

As part of the WISH (Water In Star-forming regions with Herschel) key project, we report on the observations of several ortho- and para-H2O lines performed with the HIFI instrument towards two bright shock spots (R4 and B2) along the outflow driven by the L1448 low-mass proto-stellar system, located in the Perseus cloud. These data are used to identify the physical conditions giving rise to the H2O emission and infer any dependence with velocity. These observations provide evidence that the observed water lines probe a warm (T_kin~400-600 K) and very dense (n 10^6 - 10^7 cm^-3) gas, not traced by other molecules, such as low-J CO and SiO, but rather traced by mid-IR H2 emission. In particular, H2O shows strong differences with SiO in the excitation conditions and in the line profiles in the two observed shocked positions, pointing to chemical variations across the various velocity regimes and chemical evolution in the different shock spots. Physical and kinematical differences can be seen at the two shocked positions. At the R4 position, two velocity components with different excitation can be distinguished, with the component at higher velocity (R4-HV) being less extended and less dense than the low velocity component (R4-LV). H2O column densities of about 2 10^13 and 4 10^14 cm^-2 have been derived for the R4-LV and the R4-HV components, respectively. The conditions inferred for the B2 position are similar to those of the R4-HV component, with H2O column density in the range 10^14 - 5 10^14 cm^-2, corresponding to H2O/H2 abundances in the range 0.5 - 1 10^-5. The observed line ratios and the derived physical conditions seem to be more consistent with excitation in a low velocity J-type shock with large compression rather than in a stationary C-shock, although none of these stationary models seems able to reproduce all the characteristics of the observed emission.Comment: Accepted for publication in A&

Duodenal intraepithelial lymphocytes of children with cow milk allergy preferentially bind the glycan-binding protein galectin-3

A breakdown in intestinal homeostasis results in inflammatory bowel diseases including coeliac disease and allergy. Galectins, evolutionarily conserved beta-galactoside-binding proteins, can modulate immune-epithelial cell interactions by influencing immune cell fate and cytokine secretion. In this study we investigated the glycosylation signature, as well as the regulated expression of galectin-1 and -3 in human duodenal samples of allergic and non-allergic children. Whereas galectin-1 was predominantly localized in the epithelial compartment (epithelial cells and intraepithelial lymphocytes) and the underlying lamina propria (T cells, macrophages and plasma cells), galectin-3 was mainly expressed by crypt epithelial cells and macrophages in the lamina propria. Remarkably, expression of these galectins was not significantly altered in allergic versus non-allergic patients. Investigation of the glycophenotype of the duodenal inflammatory microenvironment revealed substantial alpha2-6-linked sialic acid bound to galactose in lamina propria plasma cells, macrophages and intraepithelial lymphocytes and significant levels of asialo core 1 O-glycans in CD68+ macrophages and enterocytes. Galectin-1 preferentially bound to neutrophils, plasma cells and enterocytes, while galectin-3 binding sites were mainly distributed on macrophages and intraepithelial lymphocytes. Notably, galectin-3, but not galectin-1 binding, was substantially increased in intraepithelial gut lymphocytes of allergic patients compared to non-allergic subjects, suggesting a potential role of galectin-3-glycan interactions in shaping epithelial-immune cell connections during allergic inflammatory processes.Laboratorio de Investigaciones del Sistema Inmun

Emerging Marine Diseases: Climate Links and Anthropogenic Factors

Mass mortalities due to disease outbreaks have recently affected major taxa in the oceans. For closely monitored groups like corals and marine mammals, reports of the frequency of epidemics and the number of new diseases have increased recently. A dramatic global increase in the severity of coral bleaching in 1997-98 is coincident with high El Niño temperatures. Such climate-mediated, physiological stresses may compromise host resistance and increase frequency of opportunistic diseases. Where documented, new diseases typically have emerged through host or range shifts of known pathogens. Both climate and human activities may have also accelerated global transport of species, bringing together pathogens and previously unexposed host populations

Water emission from the chemically rich outflow L1157

In the framework of the Herschel-WISH key program, several ortho-H2O and para-H2O emission lines, in the frequency range from 500 to 1700 GHz, were observed with the HIFI instrument in two bow-shock regions (B2 and R) of the L1157 cloud. The primary aim is to analyse water emission lines as a diagnostic of the physical conditions in the blue (B2) and red-shifted (R) lobes to compare the excitation conditions. A total of 5 ortho- and para-H216O plus one o-H218O transitions were observed in B2 and R with a wide range of excitation energies (27 K<=Eu<=215 K). The H2O spectra, observed in the two shocked regions, show that the H2O profiles are markedly different in the two regions. In particular, at the bow-shock R, we observed broad (~30 km s-1 with respect to the ambient velocity) red-shifted wings where lines at different excitation peak at different red-shifted velocities. The B2 spectra are associated with a narrower velocity range (~6 km s-1), peaking at the systemic velocity. The excitation analysis suggests, for B2, low values of column density NH2O <=5{\times}1013 cm-2, a density range of 105 <=nH2 <=107 cm-3, and warm temperatures (>=300 K). The presence of the broad red-shifted wings and multiple peaks in the spectra of the R region, prompted the modelling of two components. High velocities are associated with relatively low temperatures (~100K),NH2O{\simeq}5{\times}1012-5{\times}1013 cm-2 and densities nH2{\simeq}106-108 cm-3.Lower velocities are associated with higher excitation conditions with Tkin>=300 K, very dense gas (nH2 ~108 cm-3) and low column density (NH2O<5{\times}1013 cm-2).Comment: 9 pages, 8 figures, A&A in pres

Classification and identification of Pfiesteria and Pfiesteria-like species.

Dinoflagellates can be classified both botanically and zoologically; however, they are typically put in the botanical division Pyrrhophyta. As a group they appear most related to the protistan ciliates and apicomplexans at the ultrastructure level. Within the Pyrrhophyta are both unarmored and armored forms of the dominant, motile flagellated stage. Unarmored dinoflagellates do not have thecal or wall plates arranged in specific series, whereas armored species have plates that vary in thickness but are specific in number and arrangement. In armored dinoflagellates, the plate pattern and tabulation is a diagnostic character at the family, subfamily, and even genus levels. In most cases, the molecular characterization of dinoflagellates confirms the taxonomy on the basis of external morphology; this has been demonstrated for several groups. Together, both genetic and morphological criteria are becoming increasingly important for the characterization, separation, and identification of dinoflagellates species. Pfiesteria and Pfiesteria-like species are thinly armored forms with motile dinospore stages characterized by their distinct plate formulae. Pfiesteria piscicida is the best-known member of the genus; however, there is at least one other species. Other genetically and morphologically related genera, now grouped under the common names of "Lucy," "Shepherd's crook," and cryptoperidiniopsoid, are being studied and described in separate works. All these other heterotrophic dinoflagellate groups, many of which are thought to be benign, co-occur in estuarine waters where Pfiesteria has been found

Herschel/PACS observations of young sources in Taurus: the far-infrared counterpart of optical jets

Observations of the atomic and molecular line emission associated with jets and outflows emitted by young stellar objects can be used to trace the various evolutionary stages they pass through as they evolve to become main sequence stars. To understand the relevance of atomic and molecular cooling in shocks, and how accretion and ejection efficiency evolves with the source evolutionary state, we will study the far-infrared counterparts of bright optical jets associated with Class I and II sources in Taurus (T Tau, DG Tau A, DG Tau B, FS Tau A+B, and RW Aur). We have analysed Herschel/PACS observations of a number of atomic ([OI]63um, 145um, [CII]158um) and molecular (high-J CO, H2O, OH) lines, collected within the OTKP GASPS. To constrain the origin of the detected lines we have compared the FIR emission maps with the emission from optical-jets and millimetre-outflows, and the line fluxes and ratios with predictions from shock and disk models. All of the targets are associated with extended emission in the atomic lines correlated with the direction of the optical jet/mm-outflow. The atomic lines can be excited in fast dissociative J-shocks. The molecular emission, on the contrary, originates from a compact region, that is spatially and spectrally unresolved. Slow C- or J- shocks with high pre-shock densities reproduce the observed H2O and high-J CO lines; however, the disk and/or UV-heated outflow cavities may contribute to the emission. While the cooling is dominated by CO and H2O lines in Class 0 sources, [OI] becomes an important coolant as the source evolves and the environment is cleared. The cooling and mass loss rates estimated for Class II and I sources are one to four orders of magnitude lower than for Class 0 sources. This provides strong evidence to indicate that the outflow activity decreases as the source evolves.Comment: 18 pages, 9 figures, accepted by A&