Testing a Model of Sexual Minority Orientation in Individuals with Typical Development,the Broad Autism Phenotype,and Autism Spectrum Disorder

Journal of Autism and Developmental Disorders - Individuals with Autism Spectrum Disorder (ASD) and the Broad Autism Phenotype (BAP) are more likely than individuals with typical development (TD)...     

Quantitative sensory testing and norepinephrine levels in REM sleep behaviour disorder – a clue to early peripheral autonomic and sensory dysfunction?

Journal of Neurology - Studies have reported autonomic impairment in patients with idiopathic REM sleep behaviour disorder (iRBD), which is considered a prodromal stage of alpha-synucleinopathies....     

Real‐Time Visualization of Platelet Interaction With Micro Structured Surfaces

Improving the hemocompatibility of artificial implants by micro structuring their surfaces has shown promising results, but the mechanisms which lead to this improvement are not yet understood. Therefore, we built a test setup for real‐time visualization of platelet interaction with a plain and two micro structured surfaces. The micro structures, defined by the distance of the plain surface area between the structures, were chosen to be 3 and 30 μm, representing a positive and a negative effect on the hemocompatibility. The main part of the test setup was a flow chamber containing films of low density polyethylene (LDPE) with the differently structured surfaces. For different wall shear stresses, no considerable differences were observed in the platelet‐surface interaction for all surface types. Whereas, major differences in flow behavior were observed when comparing the surfaces to each other. The platelets “rolled” along the smooth surface, being in constant contact with the surface material. Although the platelets “rolled” over the surface with small structures as well, they were only in contact with the tips of the structure and therefore had less surface contact with the foreign material. The increased distance and height of the structures of the last surface led to a trapping of platelets between the structures. This resulted in a longer contact time with the foreign material as well as a larger contact area, which both increase the risk of platelet activation, adhesion, and finally clotting. Our results showed the mechanisms which lead to these effects and thus revealed why micro structuring of surfaces impacts the hemocompatibility. Furthermore, we established a test setup which can be used for future investigations on the platelet‐structure interactions.     

Opa proteins of pathogenic neisseriae initiate Src kinase-dependent or lipid raft-mediated uptake via distinct human carcinoembryonic antigen-related cell adhesion molecule isoforms

Several pathogenic bacteria exploit human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) for adhesion to and invasion into their host cells. CEACAM isoforms have characteristic expression patterns on epithelial, endothelial, or hematopoietic cells, providing bacteria with distinct sets of receptors on particular tissues. For example, while CEACAM1 and CEACAM6 have a wide tissue distribution, CEACAM3, CEACAM4, and CEACAM8 are uniquely expressed on primary human granulocytes, whereas CEA and CEACAM7 are limited to epithelia. By reconstitution of a CEACAM-deficient cell line with individual CEACAMs, we have analyzed the requirements for CEACAM-mediated internalization of Neisseria gonorrhoeae. Our results point to two mechanistically different uptake pathways triggered by either epithelial CEACAMs (CEACAM1, CEA, and CEACAM6) or the granulocyte-specific CEACAM3. In particular, CEACAM3-mediated uptake critically depends on Src family protein tyrosine kinase (PTK) activity, and CEACAM3 associates with the SH2 domains of several Src PTKs. In contrast, epithelial CEACAMs require the integrity of cholesterol-rich membrane microdomains and are affected by cholesterol depletion, whereas CEACAM3-mediated uptake by transfected cells or the opsonin-independent phagocytosis by human granulocytes is not altered in the presence of cholesterol chelators. These results allow the subdivision of all human CEACAMs known to be utilized as pathogen receptors into functional groups and point to important consequences for bacterial engagement of distinct CEACAM isoforms.     

Expression of transforming growth factor-beta receptor type 1 and type 2 in human sporadic vestibular Schwannoma

Expression of the transforming growth factor-beta (TGF-beta) protein family in the peripheral nervous system is well established, but the role of their cognate receptors TGF-beta receptor type 1 (R1) and type 2 (R2) has been less well studied. TGF-beta plays an essential role in Schwann cell proliferation and differentiation, and is involved in neurotrophic effects of several neurotrophic substances. TGF-beta is also expressed in benign peripheral nervous system tumors such as vestibular schwannomas. In the present study, we aimed to detect TGF-beta R1 and R2 in a total of 40 sporadic vestibular schwannomas using immunohistochemistry, and correlated the findings to essential clinicopathologic data. TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA was further analyzed by RT-PCR in six vestibular schwannomas. TGF-beta R1 immunoexpression was found in about 95% of the tumors. TGF-beta R1 was equally present in Antoni A and Antoni B areas of the tumors. TGF-beta R2 was found immunohistochemically in 77%. In addition, all tumors showed strong expression of TGF-beta. No correlation between TGF-beta R1 or R2 expression and clinicopathologic parameters such as age, sex, clinical symptoms, growth pattern, and proliferation acitivity as measured by Ki-67 (MIB-1) staining was found. Moreover, all schwannomas studied contained TGF-beta, TGF-beta R1, and TGF-beta R2 mRNA. Therefore, the TGF-beta/TGF-beta R1 and -R2 system is present in human schwannomas, but its biologic role for tumor development and growth remains unclear.     

Dendritic cell maturation stage determines susceptibility to the proteasome inhibitor bortezomib

The proteasome inhibitor bortezomib has been used successfully in the treatment of non-Hodgkin lymphomas in humans, and in the treatment of graft versus host disease (GVHD) and autoimmune diseases in animal models. The mechanism of growth inhibition and immunosuppression is only partly understood. Here, we have evaluated the differential effect of bortezomib on human monocyte derived immature and mature dendritic cells (DCs) as the maturation stage of DCs determines their function. We found bortezomib to induce apoptotic cell death in immature DCs and to a much lesser extent, in mature DCs. Furthermore, cytokine-induced maturation of immature DCs was inhibited by bortezomib, whereas already matured DCs remained unaffected as seen by phenotype and allo-stimulatory capacity. This corresponded to a decreased NF-kappaB activity in immature DCs, whereas NF-kappaB activity of mature DCs was not affected. In conclusion, our data expand on previous reports on the effects of proteasome inhibitors on human monocyte-derived DCs by demonstrating a differential effect of bortezomib on immature versus mature DCs. Our findings suggest a potential role of bortezomib in modulating immune responses in humans through inhibition of DC maturation.     

Arousal responses to olfactory or trigeminal stimulation during sleep

STUDY OBJECTIVES: The interaction of sensory physiology and sleep has been studied for various sensory systems. Nevertheless, the question whether chemosensory (especially olfactory) stimuli may lead to arousals during sleep remains under discussion. Specifically, the central processing of olfactory information shows fundamental differences compared to other sensory systems. DESIGN: Prospective controlled trial. SETTING: Sleep research facility, University Hospital. PARTICIPANTS: Five young healthy, normosmic volunteers. INTERVENTION: Intranasal chemosensory stimulation during sleep was based on air-dilution olfactometry. For olfactory stimulation H2S (smell of rotten eggs) was used in 4 concentrations (1, 2, 4, and 8 ppm). For trigeminal stimulation CO2 (stinging sensation) was also administered in 4 concentrations (10%, 20%, 40%, and 60% v/v) while odorless stimuli were used for control. MEASUREMENTS: Arousal reactions due to chemosensory stimulation were assessed during overnight polysomnography 30 seconds after the presentation of every stimulus during 23 nights of testing. RESULTS: For olfactory testing, an average number of 703 olfactory stimuli and 157 odorless controls were used for analysis per subject. Even the highest stimulus concentration did not produce an increase in arousal frequency. For trigeminal testing, an average number of 405 stimuli and 79 controls were used for analysis per subject, and an increase in arousal frequency was observed following the increase of stimulus concentration. CONCLUSIONS: With the present results we were able to demonstrate that, in contrast to trigeminal stimulation, the presentation of a strong but selective olfactory stimulus does not lead to arousals during nocturnal sleep in humans.     

Choosing the optimal fit function: comparison of the Akaike information criterion and the F-test

In many circumstances of data fitting one has to choose the optimal fitting function or model among several alternatives. Criteria or tests on which this decision is based are necessary and have to be well selected. In this preliminary analysis the application of the corrected Akaike information criterion is demonstrated considering the example of determining pharmacokinetic parameters for the blood serum time activity curves of 111In-labeled anti-CD66 antibody. Another model selection criterion, the F-test, is used for comparison. For the investigated data the corrected Akaike information criterion has proved to be an effective and efficient approach, applicable to nested and non-nested models.