Remote Effects Modulating the Spin Equilibrium of the Resting State of Cytochrome P450cam –An Investigation Using Active Site Analogues

The crystal structure of the resting state of cytochrome P450cam (CYP101), a heme thiolate protein, shows a cluster of six water molecules in the substrate binding pocket, one of which is coordinating to iron(III) as sixth ligand. The resting state is low-spin and changes to high-spin when substrate camphor binds and H2O is removed. In contrast to the protein, previously synthesised enzyme models such as H2O[BOND]FeIII(porph)(ArS−) were shown to be purely high-spin. Iron(S−)porphyrins with different distal sites mimicking proposed remote effects have been prepared and studied by cw-EPR. The results indicate that the low-spin of the resting state of P450cam is due to the fact that the water molecule coordinating to iron has an OH−-like character because of hydrogen bonding and polarisation of the water cluster, respectively.

Das mosaisch-talmudische Eherecht : auf Verlangen Kaiser Josefs des Zweiten ... erstattetes Gutachten

von Ezekiel Landau. Zum ersten Male veröffentl. u. mit Einl. u. Anm. vers. von Alexander Kisch

De cauta Judaeorum tolerantia

Halle, Univ., Diss., 1708

Endogenous α-calcitonin-gene-related peptide promotes exercise-induced, physiological heart hypertrophy in mice.

AIM It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha-calcitonin-gene-related peptide (αCGRP), known to be released from contracting skeletal muscles, is key at this remodelling. METHODS The hypertrophic effect of αCGRP was measured in vitro (cultured cardiac myocytes) and in vivo (magnetic resonance imaging) in mice. Exercise performance was assessed by determination of maximum oxygen consumption and time to exhaustion. Cardiac phenotype was defined by transcriptional analysis, cardiac histology and morphometry. Finally, we measured spontaneous activity, body fat content, blood volume, haemoglobin mass and skeletal muscle capillarization and fibre composition. RESULTS While αCGRP exposure yielded larger cultured cardiac myocytes, exercise-induced heart hypertrophy was completely abrogated by treatment with the peptide antagonist CGRP(8-37). Exercise performance was attenuated in αCGRP(-/-) mice or CGRP(8-37) treated wild-type mice but improved in animals with higher density of cardiac CGRP receptors (CLR-tg). Spontaneous activity, body fat content, blood volume, haemoglobin mass, muscle capillarization and fibre composition were unaffected, whereas heart index and ventricular myocyte volume were reduced in αCGRP(-/-) mice and elevated in CLR-tg. Transcriptional changes seen in αCGRP(-/-) (but not CLR-tg) hearts resembled maladaptive cardiac phenotype. CONCLUSIONS Alpha-calcitonin-gene-related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, αCGRP agonists might be beneficial in heart failure patients.

Die katholische Kirche und Moralpolitik in Österreich: Reformdynamiken in der Regulierung von Schwangerschaftsabbrüchen und der Anerkennung gleichgeschlechtlicher Partnerschaften

Eine vergleichende Analyse der Regulierung von Schwangerschaftsabbrüchen und gleichgeschlechtlichen Partnerschaften in Westeuropa im Zeitraum von 1960 bis 2010 zeigt, dass katholisch geprägte Staaten diese Bereiche grundsätzlich nicht weniger stark liberalisiert haben als andere Länder. Allerdings drosselt der Katholizismus offensichtlich die Geschwindigkeit von Reformprozessen. Auf Basis einer detaillierten explorativen Analyse der Politikentwicklungen in Österreich, das sehr früh die Gesetzgebung zum Schwangerschaftsabbruch lockerte, jedoch bei der Einführung registrierter homosexueller Partnerschaften lange zögerte, leiten wir induktiv theoretische Implikationen ab: Die katholische Kirche kann permissive Reformen so lange verhindern, wie institutionelle und kulturelle Gelegenheitsstrukturen nicht der säkular-liberalen Opposition behilflich sind, erfolgreiches Agenda-Setting zu betreiben und Mehrheiten für einen Politikwechsel zu gewinnen.

Ṭaʻam ṭaʻame ha-miḳra

auctore Daniele Weimaro

Comparison of morphological and rheological conditions between conventional and eversion carotid endarterectomy using computational fluid dynamics - a pilot study

PURPOSE To compare postoperative morphological and rheological conditions after eversion carotid endarterectomy versus conventional carotid endarterectomy using computational fluid dynamics. BASIC METHODS Hemodynamic metrics (velocity, wall shear stress, time-averaged wall shear stress and temporal gradient wall shear stress) in the carotid arteries were simulated in one patient after conventional carotid endarterectomy and one patient after eversion carotid endarterectomy by computational fluid dynamics analysis based on patient specific data. PRINCIPAL FINDINGS Systolic peak of the eversion carotid endarterectomy model showed a gradually decreased pressure along the stream path, the conventional carotid endarterectomy model revealed high pressure (about 180 Pa) at the carotid bulb. Regions of low wall shear stress in the conventional carotid endarterectomy model were much larger than that in the eversion carotid endarterectomy model and with lower time-averaged wall shear stress values (conventional carotid endarterectomy: 0.03-5.46 Pa vs. eversion carotid endarterectomy: 0.12-5.22 Pa). CONCLUSIONS Computational fluid dynamics after conventional carotid endarterectomy and eversion carotid endarterectomy disclosed differences in hemodynamic patterns. Larger studies are necessary to assess whether these differences are consistent and might explain different rates of restenosis in both techniques.

Ein šin maiśebuch : komṭ her libn mann un froien un ṭuṭ doś šin maiśe buch an šoien ; mit 300 un eṭlichi maiśes bai agndr gbrachṭ ... ir libi laiṭ di do zain lib hober fun ṭaiṭš leienn ...

Digitalisat der Ausg. Frankfurt an der Oder, 1708/09

Impact of common risk factors of fibrosis progression in chronic hepatitis C.

OBJECTIVE The natural course of chronic hepatitis C varies widely. To improve the profiling of patients at risk of developing advanced liver disease, we assessed the relative contribution of factors for liver fibrosis progression in hepatitis C. DESIGN We analysed 1461 patients with chronic hepatitis C with an estimated date of infection and at least one liver biopsy. Risk factors for accelerated fibrosis progression rate (FPR), defined as ≥0.13 Metavir fibrosis units per year, were identified by logistic regression. Examined factors included age at infection, sex, route of infection, HCV genotype, body mass index (BMI), significant alcohol drinking (≥20 g/day for ≥5 years), HIV coinfection and diabetes. In a subgroup of 575 patients, we assessed the impact of single nucleotide polymorphisms previously associated with fibrosis progression in genome-wide association studies. Results were expressed as attributable fraction (AF) of risk for accelerated FPR. RESULTS Age at infection (AF 28.7%), sex (AF 8.2%), route of infection (AF 16.5%) and HCV genotype (AF 7.9%) contributed to accelerated FPR in the Swiss Hepatitis C Cohort Study, whereas significant alcohol drinking, anti-HIV, diabetes and BMI did not. In genotyped patients, variants at rs9380516 (TULP1), rs738409 (PNPLA3), rs4374383 (MERTK) (AF 19.2%) and rs910049 (major histocompatibility complex region) significantly added to the risk of accelerated FPR. Results were replicated in three additional independent cohorts, and a meta-analysis confirmed the role of age at infection, sex, route of infection, HCV genotype, rs738409, rs4374383 and rs910049 in accelerating FPR. CONCLUSIONS Most factors accelerating liver fibrosis progression in chronic hepatitis C are unmodifiable.

Sēfer Qav hay-yāšār : ... le-tôʿelet han-nefeš we-gûf û-nešāmā ...

ḥibberô ... Ṣevî Hîrš Ben-... Aharôn Šemû'ēl Qaydanover

Maḥzôr : bi-lšôn aškenaz mik-kôl haš-šānā ; qôl rinnā w-îšûaʿ be-ōhôlê ṣaddîqîm ; doś iz ṭaiṭš šṭim gizang un hilf in gitzelṭ fun tzadikim ...

Digitalisat der Ausg. Franqfurṭ, [1708/09]

Sēfer Yōsîppôn

ḥibbērô ... Yôsēf Ben-Gōryôn hak-kōhēn ...