Is the C-terminal flanking peptide of rat cholecystokinin double sulphated?

AbstractA specific radioimmunoassay was developed to the predicted nine amino acid C-terminal flanking peptide of cholecystokinin (peptide serine serine, PSS). In aqueous extracts of rat brain, PSS was undetectable unless the extracts were first treated with arylsulphatase, which also resulted in desulphation of cholecystokinin. The reverse-phase HPLC analysis of partially desulphated extracts showed the presence of two peaks intermediate to the naturally occurring and the completely desulphated forms. It is therefore proposed that the CCK-flanking peptide PSS has both tyrosine residues sulphated

Haptoglobin genotype-dependent anti-inflammatory signaling in CD163(+) macrophages

Intraplaque hemorrhage causes adaptive remodelling of macrophages towards a protective phenotype specialized towards handling iron and lipid overload, denoted Mhem. The Mhem phenotype expresses elevated levels of hemoglobin (Hb) scavenger receptor, CD163, capable of endocytosing pro-oxidant free Hb complexed to acute phase protein haptoglobin (Hp). It is notable that individuals homozygous for the Hp 2 allele (a poorer antioxidant) are at increased risk of cardiovascular disease compared to the Hp 1 allele. In this study, we examined whether scavenging of polymorphic Hp:Hb complexes differentially generated downstream anti-inflammatory signals in cultured human macrophages culminating in interleukin (IL)-10 secretion. We describe an anti-inflammatory signalling pathway involving phosphatidylinositol-3-kinase activation upstream of Akt phosphorylation (pSer473Akt) and IL-10 secretion. The pathway is mediated specifically through CD163 and is blocked by anti-CD163 antibody or phagocytosis inhibitor. However, levels of pSer473Akt and IL-10 were significantly diminished when scavenging polymorphic Hp2-2:Hb complexes compared to Hp1-1:Hb complexes (P < 0.05). Impaired anti-inflammatory macrophage signaling through a CD163/pAkt/IL-10 axis may thus represent a possible Hp2-2 disease mechanism in atherosclerosis

Structural Alterations in the Corpus Callosum Are Associated with Suicidal Behavior in Women with Borderline Personality Disorder

Structural alterations in the corpus callosum (CC), the major white matter tract connecting functionally related brain regions in the two hemispheres, have been shown to be associated with emotional instability, impulsivity and suicidality in various mental disorders. To explore whether structural alterations of the CC would be similarly associated with emotional instability, impulsivity and suicidality in borderline personality disorder (BPD), we used diffusion tensor imaging (DTI) to assess the structural integrity of the CC in 21 BPD and 20 healthy control (HC) participants. Our hypothesis-driven analyses revealed a positive correlation between BPD participants’ suicidal behavior and fractional anisotropy (FA) in the splenium and genu of the CC and a negative correlation between BPD participants’ suicidal behavior and mean diffusivity (MD) in the splenium of CC. Our exploratory analyses suggested that suicidal BPD participants showed less FA and more MD in these regions than HC participants but that non-suicidal BPD participants showed similar FA and MD in these regions as HC participants. Taken together, our findings suggest an association between BPD participants’ suicidal behavior and structural alterations in regions of the CC that are connected with brain regions implicated in emotion regulation and impulse control. Structural alterations of the CC may, thus, account for deficits in emotion regulation and impulse control that lead to suicidal behavior in BPD. However, these findings should be considered as preliminary until replicated and extended in future studies that comprise larger samples of suicidal and non-suicidal BPD participants

The Single State Dominance Hypothesis and the Two-Neutrino Double Beta Decay of Mo100

The hypothesis of the single state dominance (SSD) in the calculation of the two-neutrino double beta decay of Mo100 is tested by exact consideration of the energy denominators of the perturbation theory. Both transitions to the ground state as well as to the 0+ and 2+ excited states of the final nucleus Ru100 are considered. We demonstrate, that by experimental investigation of the single electron energy distribution and the angular correlation of the outgoing electrons, the SSD hypothesis can be confirmed or ruled out by a precise two-neutrino double beta decay measurement (e.g. by NEMO III collaboration).Comment: 13 pages, RevTex, 1 figur

EVALUATION OF CONDITIONS CONCERNING THE DEVELOPMENT OF TOURISM. INVESTIGATION INTO THE BASIN OF THE PARSĘTA RIVER

DOI: 10.2478/v10089-008-0021-7 Available on-line at: http://www.bulletinofgeography.umk.pl http://versita.com/bgssThe article presents the results of multidimensional evaluation of conditions concerning the development of tourism in rural areas of Parsęta basin. For the purpose the synthetic measure has been applied in reference to 27 variables divided into two groups: suitable for tourism or investing. Having conducted the analysis of the selected variables, the investigated area was divided into three regions: the seaside at the North with very good conditions for the development of the touristic function as its core function, the central region, highly diversified with only moderate touristic capabilities, and finally the southern region, the lake district, with adequate features for the development of tourism

Topographical expression of class IA and class II phosphoinositide 3-kinase enzymes in normal human tissues is consistent with a role in differentiation

BACKGROUND: Growth factor, cytokine and chemokine-induced activation of PI3K enzymes constitutes the start of a complex signalling cascade, which ultimately mediates cellular activities such as proliferation, differentiation, chemotaxis, survival, trafficking, and glucose homeostasis. The PI3K enzyme family is divided into 3 classes; class I (subdivided into IA and IB), class II (PI3K-C2α, PI3K-C2β and PI3K-C2γ) and class III PI3K. Expression of these enzymes in human tissue has not been clearly defined. METHODS: In this study, we analysed the immunohistochemical topographical expression profile of class IA (anti-p85 adaptor) and class II PI3K (PI3K-C2α and PI3K-C2β) enzymes in 104 formalin-fixed, paraffin embedded normal adult human (age 33–71 years, median 44 years) tissue specimens including those from the gastrointestinal, genitourinary, hepatobiliary, endocrine, integument and lymphoid systems. Antibody specificity was verified by Western blotting of cell lysates and peptide blocking studies. Immunohistochemistry intensity was scored from undetectable to strong. RESULTS: PI3K enzymes were expressed in selected cell populations of epithelial or mesenchymal origin. Columnar epithelium and transitional epithelia were reactive but mucous secreting and stratified squamous epithelia were not. Mesenchymal elements (smooth muscle and endothelial cells) and glomerular epithelium were only expressed PI3K-C2α while ganglion cells expressed p85 and PI3K-C2β. All three enzymes were detected in macrophages, which served as an internal positive control. None of the three PI3K isozymes was detected in the stem cell/progenitor compartments or in B lymphocyte aggregates. CONCLUSIONS: Taken together, these data suggest that PI3K enzyme distribution is not ubiquitous but expressed selectively in fully differentiated, non-proliferating cells. Identification of the normal in vivo expression pattern of class IA and class II PI3K paves the way for further analyses which will clarify the role played by these enzymes in inflammatory, neoplastic and other human disease conditions

Neutrino statistics and big bang nucleosynthesis

Neutrinos may possibly violate the spin-statistics theorem, and hence obey Bose statistics or mixed statistics despite having spin half. We find the generalized equilibrium distribution function of neutrinos which depends on a single fermi-bose parameter, \kappa, and interpolates continuously between the bosonic and fermionic distributions when \kappa changes from -1 to +1. We consider modification of the Big Bang Nucleosynthesis (BBN) in the presence of bosonic or partly bosonic neutrinos. For pure bosonic neutrinos the abundances change (in comparison with the usual Fermi-Dirac case) by -3.2% for 4He (which is equivalent to a decrease of the effective number of neutrinos by \Delta N_\nu = - 0.6), +2.6% for 2H and -7% for 7Li. These changes provide a better fit to the BBN data. Future BBN studies will be able to constrain the fermi-bose parameter to \kappa > 0.5, if no deviation from fermionic nature of neutrinos is found. We also evaluate the sensitivity of future CMB and LSS observations to the fermi-bose parameter.Comment: 11 pages, 3 figures, matches version in JCAP, discussion and references extended slightl

The role of left hemispheric structures for emotional processing as a monitor of bodily reaction and felt chill: A case-control functional imaging study

Background: The particular function of the left anterior human insula on emotional arousal has been illustrated with several case studies. Only after left hemispheric insula lesions, patients lose their pleasure in habits such as listening to joyful music. In functional magnetic resonance imaging studies (fMRI) activation in the left anterior insula has been associated with both processing of emotional valence and arousal. Tight interactions with different areas of the prefrontal cortex are involved in bodily response monitoring and cognitive appraisal of a given stimulus. Therefore, a large left hemispheric lesion including the left insula should impair the bodily response of chill experience (objective chill response) but leave the cognitive aspects of chill processing (subjective chill response) unaffected. Methods: We investigated a patient (MC) with a complete left hemispheric media cerebral artery stroke, testing fMRI representation of pleasant (music) and unpleasant (harsh sounds) chill response. Results: Although chill response to both pleasant and unpleasant rated sounds was confirmed verbally at passages also rated as chilling by healthy participants, skin conductance response was almost absent in MC. For a healthy control (HC) objective and subjective chill response was positively associated. Bilateral prefrontal fMRI-response to chill stimuli was sustained in MC whereas insula activation restricted to the right hemisphere. Diffusion imaging together with lesion maps revealed that left lateral tracts were completely damaged but medial prefrontal structures were intact. Conclusion: With this case study we demonstrate how bodily response and cognitive appraisal are differentially participating in the internal monitor of chill response