The role of atrial natriuretic peptide to attenuate inflammation in a mouse skin wound and individually perfused rat mesenteric microvessels.

We tested the hypothesis that the anti-inflammatory actions of atrial natriuretic peptide (ANP) result from the modulation of leukocyte adhesion to inflamed endothelium and not solely ANP ligation of endothelial receptors to stabilize endothelial barrier function. We measured vascular permeability to albumin and accumulation of fluorescent neutrophils in a full-thickness skin wound on the flank of LysM-EGFP mice 24 h after formation. Vascular permeability in individually perfused rat mesenteric microvessels was also measured after leukocytes were washed out of the vessel lumen. Thrombin increased albumin permeability and increased the accumulation of neutrophils. The thrombin-induced inflammatory responses were attenuated by pretreating the wound with ANP (30 min). During pretreatment ANP did not lower permeability, but transiently increased baseline albumin permeability concomitant with the reduction in neutrophil accumulation. ANP did not attenuate acute increases in permeability to histamine and bradykinin in individually perfused rat microvessels. The hypothesis that anti-inflammatory actions of ANP depend solely on endothelial responses that stabilize the endothelial barrier is not supported by our results in either individually perfused microvessels in the absence of circulating leukocytes or the more chronic skin wound model. Our results conform to the alternate hypothesis that ANP modulates the interaction of leukocytes with the inflamed microvascular wall of the 24 h wound. Taken together with our previous observations that ANP reduces deformability of neutrophils and their strength of attachment, rolling, and transvascular migration, these observations provide the basis for additional investigations of ANP as an anti-inflammatory agent to modulate leukocyte-endothelial cell interactions

Categories of First-Order Quantifiers

One well known problem regarding quantifiers, in particular the 1storder quantifiers, is connected with their syntactic categories and denotations. The unsatisfactory efforts to establish the syntactic and ontological categories of quantifiers in formalized first-order languages can be solved by means of the so called principle of categorial compatibility formulated by Roman Suszko, referring to some innovative ideas of Gottlob Frege and visible in syntactic and semantic compatibility of language expressions. In the paper the principle is introduced for categorial languages generated by the Ajdukiewicz’s classical categorial grammar. The 1st-order quantifiers are typically ambiguous. Every 1st-order quantifier of the type k \u3e 0 is treated as a two-argument functorfunction defined on the variable standing at this quantifier and its scope (the sentential function with exactly k free variables, including the variable bound by this quantifier); a binary function defined on denotations of its two arguments is its denotation. Denotations of sentential functions, and hence also quantifiers, are defined separately in Fregean and in situational semantics. They belong to the ontological categories that correspond to the syntactic categories of these sentential functions and the considered quantifiers. The main result of the paper is a solution of the problem of categories of the 1st-order quantifiers based on the principle of categorial compatibility

Conformation of Polypyrimidine Tract Binding Protein in Solution

SummaryThe polypyrimidine tract binding protein (PTB) is an RNA binding protein that normally functions as a regulator of alternative splicing but can also be recruited to stimulate translation initiation by certain picornaviruses. High-resolution structures of the four RNA recognition motifs (RRMs) that make up PTB have previously been determined by NMR. Here, we have used small-angle X-ray scattering to determine the low-resolution structure of the entire protein. Scattering patterns from full-length PTB and deletion mutants containing all possible sequential combinations of the RRMs were collected. All constructs were found to be monomeric in solution. Ab initio analysis and rigid-body modeling utilizing the high-resolution models of the RRMs yielded a consistent low-resolution model of the spatial organization of domains in PTB. Domains 3 and 4 were found to be in close contact, whereas domains 2 and especially 1 had loose contacts with the rest of the protein

Molecular and morphometric variation in European populations of the articulate brachiopod <i>Terebeatulina retusa</i>

Molecular and morphometric variation within and between population samples of the articulate brachiopod &lt;i&gt;Terebratulina&lt;/i&gt; spp., collected in 1985-1987 from a Norwegian fjord, sea lochs and costal sites in western Scotland, the southern English Channel (Brittany) and the western Mediterranean, were measured by the analysis of variation in the lengths of mitochondrial DNA (mtDNA) fragments produced by digestion with nine restriction endonucleases and by multivariate statistical analysis of six selected morphometric parameters. Nucleotide difference within each population sample was high. Nucleotide difference between population samples from the Scottish sites, both those that are tidally contiguous and those that appear to be geographically isolated, were not significantly different from zero. Nucleotide differences between the populations samples from Norway, Brittany, Scotland and the western Mediterranean were also very low. Morphometric analysis confirmed the absence of substantial differentiation

Consequences of sexual harassment in sport for female athletes

Sexual harassment research was first undertaken in the workplace and educational settings. Research on sexual harassment in sport is scarce but has grown steadily since the mid-1980s. Even so, very little is known about the causes and/or characteristics and/or consequences of sexual harassment in sport settings. This article reports on the findings from interviews with 25 elite female athletes in Norway who indicated in a prior survey (N =572) that they had experienced sexual harassment from someone in sport. The consequences of the incidents of sexual harassment that were reported were mostly negative, but some also reported that their experiences of sexual harassment had had no consequences for them. “Thinking about the incidents”, a “destroyed relationship to the coach”, and “more negative view of men in general” were the most often negative consequences mentioned. In addition, a surprising number had chosen to move to a different sport or to drop out of elite sport altogether because of the harassment

Trauma induced coagulopathy is limited to only one out of four shock induced endotheliopathy (SHINE) phenotypes among moderate-severely injured trauma patients: an exploratory analysis

Background: Trauma induced coagulopathy remains to be an important cause of high transfusion requirements and mortality and shock induced endotheliopathy (SHINE) has been implicated. Methods: European multicenter observational study of adult trauma patients with injury severity score ≥ 16 arriving within 2 h from injury to the trauma centers. Admission blood samples obtained were used for analysis of the SHINE biomarkers (syndecan-1, soluble thrombomodulin, adrenaline) and extensive analysis of coagulation, -and fibrinolytic factors together with collection of clinical data. Hierarchical clustering of the SHINE biomarkers was used to identify the SHINE phenotypes. Results: The 313 patients clustered into four SHINE phenotypes. Phenotype 2, having the highest glycocalyx shedding, encompassing 22% of the whole cohort, had severe coagulopathy with lower levels of prothrombin, FV, IX, X, XI and severe hyperfibrinolysis with higher plasmin – alpha 2-antiplasmin (PAP) – and tPA levels and lower alpha2 – antiplasmin levels. This phenotype had significantly higher transfusion requirements and higher mortality (39% vs. 23%, 15% and 14%) but similar injury severity score (ISS) compared to the others phenotypes. Conclusions: Hierarchical clustering identified four SHINE phenotype in a cohort of trauma patients. Trauma induced coagulopathy was confined to only one of the SHINE phenotypes, encompassing 22% of the total cohort. This phenotype was characterized by severe hypocoagulability and hyperfibrinolysis, which translated to significantly higher transfusion requirements and higher mortality compared to the other SHINE phenotypes with similar injury severity, warranting further investigation

First detection of NH3 (1,0 - 0,0) from a low mass cloud core: On the low ammonia abundance of the rho Oph A core

Odin has successfully observed the molecular core rho Oph A in the 572.5 GHz rotational ground state line of ammonia, NH3 (J,K = 1,0 - 0,0). The interpretation of this result makes use of complementary molecular line data obtained from the ground (C17O and CH3OH) as part of the Odin preparatory work. Comparison of these observations with theoretical model calculations of line excitation and transfer yields a quite ordinary abundance of methanol, X(CH3OH) = 3e-9. Unless NH3 is not entirely segregated from C17O and CH3OH, ammonia is found to be significantly underabundant with respect to typical dense core values, viz. X(NH3) = 8e-10.Comment: 4 pages, 2 figures, 2 tables, to appear in Astron. Astrophys. Letter

GNA11 brain somatic pathogenic variant in an individual with phacomatosis pigmentovascularis

Objective: To describe the findings of histopathology and genotyping studies in affected brain tissue from an individual with phacomatosis pigmentovascularis (PPV). / Methods: A retrospective chart review of a 2-year 10-month-old male with a clinical diagnosis of PPV cesiomarmorata (or type V) was performed. Clinical features, brain imaging and histopathology findings, and genotyping studies in his affected brain tissue are summarized. / Results: The proband had a clinically severe neurologic phenotype characterized by global developmental delay, generalized hypotonia, and recurrent episodes of cardiac asystole in the setting of status epilepticus. A somatic pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys) was detected in his skin tissue but not in blood (previously published). He underwent an urgent left posterior quadrantectomy for his life-threatening seizures. Histopathology of resected brain tissue showed an increase in leptomeningeal melanocytes and abnormal vasculature, and the exact pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys), previously isolated from his skin tissue but not blood, was detected in his resected brain tissue. / Conclusions: The finding of this variant in affected skin and brain tissue of our patient with PPV supports a unifying genetic diagnosis of his neurocutaneous features

Submillimeter Emission from Water in the W3 Region

We have mapped the submillimeter emission from the 1(10)-1(01) transition of ortho-water in the W3 star-forming region. A 5'x5' map of the W3 IRS4 and W3 IRS5 region reveals strong water lines at half the positions in the map. The relative strength of the Odin lines compared to previous observations by SWAS suggests that we are seeing water emission from an extended region. Across much of the map the lines are double-peaked, with an absorption feature at -39 km/s; however, some positions in the map show a single strong line at -43 km/s. We interpret the double-peaked lines as arising from optically thick, self-absorbed water emission near the W3 IRS5, while the narrower blue-shifted lines originate in emission near W3 IRS4. In this model, the unusual appearance of the spectral lines across the map results from a coincidental agreement in velocity between the emission near W3 IRS4 and the blue peak of the more complex lines near W3 IRS5. The strength of the water lines near W3 IRS4 suggests we may be seeing water emission enhanced in a photon-dominated region.Comment: Accepted to A&A Letters as part of the special Odin issue; 4 page