Zusammenfassung. Aufgrund der hohen weltweiten Prävalenz psychischer Erkrankungen und deren Assoziation mit inaktiven Verhaltensweisen und körperlichen Komorbiditäten kommt der Förderung körperlicher ...Aktivität bei psychisch erkrankten Menschen eine wichtige Bedeutung zu. Regelmässiges Training ist mit verbessertem psychischem Wohlbefinden assoziiert und hat eine präventive Wirkung bezüglich der Entwicklung verschiedener psychischer Erkrankungen wie Depressionen, Angststörungen und wahrscheinlich auch Schlafstörungen. Zudem fanden sich positive Effekte auf chronische körperliche Komorbiditäten. Regelmässiges Training über mehrere Wochen hat bei depressiven Erkrankungen einen nachweislichen antidepressiven Effekt. Ähnliche positive Effekte auf die Symptomatik konnten für Angsterkrankungen und Schizophrenie gezeigt werden. In der Praxis empfiehlt sich das strukturierte Erheben und Fördern körperlicher Aktivität psychiatrischer Patientinnen und Patienten mit dem Ziel, wöchentlich mindestens 150 Minuten moderate und/oder 75 Minuten intensive körperliche Aktivität zu erreichen. Der Aufbau und die Weiterentwicklung ambulanter Sport- und Bewegungsangebote für Menschen mit psychischer Erkrankung spielt für die Zukunft eine wichtige Rolle.
Atherosclerotic plaque development depends on chronic inflammation of the arterial wall. A dysbiotic gut microbiota can cause low-grade inflammation, and microbiota composition was linked to ...cardiovascular disease risk. However, the role of this environmental factor in atherothrombosis remains undefined. To analyze the impact of gut microbiota on atherothrombosis, we rederived low-density lipoprotein receptor-deficient (
) mice as germfree (GF) and kept these mice for 16 weeks on an atherogenic high-fat Western diet (HFD) under GF isolator conditions and under conventionally raised specific-pathogen-free conditions (CONV-R). In spite of reduced diversity of the cecal gut microbiome, caused by atherogenic HFD, GF
mice and CONV-R
mice exhibited atherosclerotic lesions of comparable sizes in the common carotid artery. In contrast to HFD-fed mice, showing no difference in total cholesterol levels, CONV-R
mice fed control diet (CD) had significantly reduced total plasma cholesterol, very-low-density lipoprotein (VLDL), and LDL levels compared with GF
mice. Myeloid cell counts in blood as well as leukocyte adhesion to the vessel wall at the common carotid artery of GF
mice on HFD were diminished compared to CONV-R
controls. Plasma cytokine profiling revealed reduced levels of the proinflammatory chemokines CCL7 and CXCL1 in GF
mice, whereas the T-cell-related interleukin 9 (IL-9) and IL-27 were elevated. In the atherothrombosis model of ultrasound-induced rupture of the common carotid artery plaque, thrombus area was significantly reduced in GF
mice relative to CONV-R
mice.
, this atherothrombotic phenotype was explained by decreased adhesion-dependent platelet activation and thrombus growth of HFD-fed GF
mice on type III collagen.
Our results demonstrate a functional role for the commensal microbiota in atherothrombosis. In a ferric chloride injury model of the carotid artery, GF C57BL/6J mice had increased occlusion times compared to colonized controls. Interestingly, in late atherosclerosis, HFD-fed GF
mice had reduced plaque rupture-induced thrombus growth in the carotid artery and diminished
thrombus formation under arterial flow conditions.
The initial glycan transfer in asparagine-linked protein glycosylation is catalysed by the integral membrane enzyme oligosaccharyltransferase (OST). Here we study the mechanism of the bacterial PglB ...protein, a single-subunit OST, using chemically synthesized acceptor peptide analogues. We find that PglB can glycosylate not only asparagine but also glutamine, homoserine and the hydroxamate Asp(NHOH), although at much lower rates. In contrast, N-methylated asparagine or 2,4-diaminobutanoic acid (Dab) are not glycosylated. We find that of the various peptide analogues, only asparagine- or Dab-containing peptides bind tightly to PglB. Glycopeptide products are unable to bind, providing the driving force of product release. We find no suitably positioned residues near the active site of PglB that can activate the acceptor asparagine by deprotonation, making a general base mechanism unlikely and leaving carboxamide twisting as the most likely mechanistic proposal for asparagine activation.
Abstract
We study the ground state energy and the critical screening parameter of the Yukawa potential in nonrelativistic quantum mechanics. After a short review of the existing literature on these ...quantities, we apply fifth-order perturbation theory to the calculation of the ground state energy, using the exact solutions of the Coulomb potential together with a cutoff on the principal number summations. We also perform a variational calculation of the ground state energy using a Coulomb-like radial wave function and the exact solution of the corresponding minimization condition. For not too large values of the screening parameter, close agreement is found between the perturbative and variational results. For the critical screening parameter, we devise a novel method that permits us to determine it to 10 digits. This is the most precise calculation of this quantity to date, and allows us to resolve some discrepancies between previous results.
The Importance of Physical Activity for Mental Health
Due to the worldwide high prevalence of psychiatric disorders and its association with sedentary behavior and comorbid physical diseases, ...increasing physical activity in psychiatric populations is of high importance. Regular physical activity is associated with increased mental wellbeing and has shown to have preventive effects on depression, anxiety disorders and probably sleep disorders. Additionally, positive effects on comorbid chronic physical diseases have been found. Exercise as treatment for several weeks has shown to have an antidepressant effect. Similar positive effects on symptoms have been found in anxiety disorders and schizophrenia. Therefore, assessing and promoting physical activity is advisable in clinical psychiatric practice. Patients should be coached to reach at least a weekly average of 150 minutes of moderate and/or 75 minutes of vigorous physical activity. Establishing physical activity and exercise groups is of utmost importance for psychiatric outpatients.
Optical-domain transient grating (TG) spectroscopy is a versatile background-free four-wave-mixing technique that is used to probe vibrational, magnetic and electronic degrees of freedom in the time ...domain1. The newly developed coherent X-ray free-electron laser sources allow its extension to the X-ray regime. X-rays offer multiple advantages for TG: their large penetration depth allows probing the bulk properties of materials, their element specificity can address core excited states, and their short wavelengths create excitation gratings with unprecedented momentum transfer and spatial resolution. Here, we demonstrate TG excitation in the hard X-ray range at 7.1 keV. In bismuth germanate (BGO), the non-resonant TG excitation generates coherent optical phonons detected as a function of time by diffraction of an optical probe pulse. This experiment demonstrates the ability to probe bulk properties of materials and paves the way for ultrafast coherent four-wave-mixing techniques using X-ray probes and involving nanoscale TG spatial periods.A four-wave mixing technique is developed in the hard X-ray range. A diamond phase grating in an X-ray beam path creates a periodic excitation pattern on a sample via the Talbot effect. The response of the periodic excitation is probed by an optical pulse.
Although knowledge on inflammatory signaling pathways driving cancer initiation and progression has been increasing, molecular mechanisms in hepatocarcinogenesis are still far from being completely ...understood. Hepatocyte-specific deletion of the MAPKKK Tak1 in mice recapitulates important steps of hepatocellular carcinoma (HCC) development, including the occurrence of cell death, steatohepatitis, dysplastic nodules, and HCCs. However, overactivation of Tak1 in mice upon deletion of its deubiquitinase Cyld also results in steatohepatitis and HCC development. To investigate Tak1 and Cyld in human HCCs, we created a tissue microarray to analyze their expression by immunohistochemistry in a large and well-characterized cohort of 871 HCCs of 561 patients. In the human liver and HCC, Tak1 is predominantly present as its isoform Tak1A and predominantly localizes to cell nuclei. Tak1 is upregulated in diethylnitrosamine-induced mouse HCCs as well as in human HCCs independent of etiology and is further induced in distant metastases. A high nuclear Tak1 expression is associated with short survival and vascular invasion. When we overexpressed Tak1A in Huh7 cells, we observed increased tumor cell migration, whereas overexpression of full-length Tak1 had no significant effect. A combined score of low Cyld and high Tak1 expression was an independent prognostic marker in a multivariate Cox regression model.
To analyse long-term outcome and clinical prognostic factors in medulloblastoma.
We analysed 280 patients with medulloblastoma (3-18 years) included from 1991 to 1997 in the randomised multicentre ...trial HIT'91 comparing pre-('sandwich') and postradiation ('maintenance') chemotherapy (median follow-up of survivors for 10 years).
In 187 patients with complete staging, overall survival (OS) was higher after maintenance compared to sandwich treatment for M0 (10-year OS 91% and 62%, p=0.001) and M1 patients (10-year OS 70% and 34%, p=0.020). In M2/3 disease, 10-year OS was 42% and 45%. Incomplete staging, metastases, younger age and sandwich chemotherapy were independent adverse risk factors. Twelve percent of all relapses (13 of 107) occurred after more than five years, and 12 patients had secondary neoplasms.
After maintenance therapy, long-term survival was excellent in fully assessable patients with localised medulloblastoma, and favourable for M1 patients. Patients should be followed longer for late relapses and secondary tumours.
Diazomethane is an attractive C1 building block in organic chemistry, but its hazardous nature presents scale-up challenges to this date. The use of a Teflon AF2400 membrane, most commonly in a ...tube-in-tube reactor setup, is the current state-of-the-art methodology for inherently safer laboratory-scale generation, separation, and consumption of anhydrous diazomethane. For the successful scale-up of this membrane process, the key mass transfer coefficient of the AF2400 membrane, its permeability for diazomethane, was investigated. We report in this contribution a novel methodology to determine diazomethane permeability for the rational scale-up of membrane processes for the safe handling of diazomethane. Missing physical properties of diazomethane were established, and the full mass balance of in situ-generated diazomethane within the tube-in-tube reactor was experimentally validated. A numerical model of the membrane reactor system in combination with experimental data yielded a permeability value of 414 barrer. This result enables scale-up development of the laboratory membrane reactor toward production-scale systems.
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