Akademische Gedenkfeier zu Ehren von Herrn Professor Dr. med. Wolfgang Trautwein : 16. Juni 2011

Um seine wissenschaftlichen Leistungen und seinen Rang in der deutschen und internationalen Physiologie zu würdigen, veranstaltete die Fachrichtung Physiologie der Medizinischen Fakultät der Universität des Saarlandes zu Ehren ihres am 7. April 2011 verstorbenen Kollegen Prof. Dr. med. Wolfgang Trautwein am 16. Juni 2011 im Robert-Stämpfli-Hörsaal des Physiologischen Instituts eine akademische Gedenkfeier. Nach seinen beiden auf umfassenden Recherchen basierenden chronikalischen Darstellungen zur Institutsgeschichte „Vom Physiologischen Institut zum CIPMM Homburg/Saar“ 2016 und „70 Jahre Physiologisches Institut Homburg/Saar“ 2019 sicherte der Unterzeichner auch die Videoaufzeichnung dieser akademischen Gedenkfeier und erstellte die vorliegende Textfassung, wobei die gehaltenen Ansprachen und die verwendeten Fotos von allen Vortragenden mit Ausnahme des 2017 verstorbenen Kollegen Prof. Dr. Robert F. Schmidt autorisiert wurden. In die Gedenkfeier war auch das sehr informative autobiographische Interview integriert, das Prof. Dr. Jürgen Hescheler und Dr. Martin Feld am 26. August 2001 mit Prof. Dr. Wolfgang Trautwein, der von 1971 bis 1990 als Direktor des II. Physiologischen Instituts der Medizinischen Fakultät der Universität des Saarlandes agierte, über seine Stationen in der Physiologie aufzeichnen konnten. Die enge Kooperation mit dem Universitätsarchiv (Dr. Wolfgang Müller) ermöglicht nun die Dokumentation der wissenschaftsgeschichtlich interessanten akademischen Gedenkfeier in der Reihe der „Universitätsreden“. Das Video der Gedenkfeier wird im Physiologischen Institut des Centrums für Integrative Physiologie und Molekulare Medizin CIPMM in Homburg sowie im Archiv der Universität des Saarlandes in Saarbrücken verwahrt

Cardiac calcium signalling pathologies associated with defective calmodulin regulation of type 2 ryanodine receptor: Ca2+signalling consequences of defective CaM binding to RyR2

Cardiac ryanodine receptor (RyR2) is a homotetramer of 560 kDa polypeptides regulated by calmodulin (CaM), which decreases its open probability at diastolic and systolic Ca2+ concentrations. Point mutations in the CaM-binding domain of RyR2 (W3587A/L3591D/F3603A, RyR2ADA) in mice result in severe cardiac hypertrophy, poor left ventricle contraction and death by postnatal day 16, suggesting that CaM inhibition of RyR2 is required for normal cardiac function. Here, we report on Ca2+ signalling properties of enzymatically isolated, Fluo-4 dialysed whole cell clamped cardiac myocytes from 10–15-day-old wild-type (WT) and homozygous Ryr2ADA/ADA mice. Spontaneously occurring Ca2+ spark frequency, measured at −80 mV, was 14-fold lower in mutant compared to WT myocytes. ICa, though significantly smaller in mutant myocytes, triggered Ca2+ transients that were of comparable size to those of WT myocytes, but with slower activation and decay kinetics. Caffeine-triggered Ca2+ transients were about three times larger in mutant myocytes, generating three- to four-fold bigger Na+-Ca2+ exchanger NCX currents (INCX). Mutant myocytes often exhibited Ca2+ transients of variable size and duration that were accompanied by similarly alternating and slowly activating INCX. The data suggest that RyR2ADA mutation produces significant reduction in ICa density and ICa-triggered Ca2+ release gain, longer but infrequently occurring Ca2+ sparks, larger sarcoplasmic reticulum Ca2+ loads, and spontaneous Ca2+ releases accompanied by activation of large and potentially arrhythmogenic inward INCX

Variant detection sensitivity and biases in whole genome and exome sequencing

BACKGROUND: Less than two percent of the human genome is protein coding, yet that small fraction harbours the majority of known disease causing mutations. Despite rapidly falling whole genome sequencing (WGS) costs, much research and increasingly the clinical use of sequence data is likely to remain focused on the protein coding exome. We set out to quantify and understand how WGS compares with the targeted capture and sequencing of the exome (exome-seq), for the specific purpose of identifying single nucleotide polymorphisms (SNPs) in exome targeted regions. RESULTS: We have compared polymorphism detection sensitivity and systematic biases using a set of tissue samples that have been subject to both deep exome and whole genome sequencing. The scoring of detection sensitivity was based on sequence down sampling and reference to a set of gold-standard SNP calls for each sample. Despite evidence of incremental improvements in exome capture technology over time, whole genome sequencing has greater uniformity of sequence read coverage and reduced biases in the detection of non-reference alleles than exome-seq. Exome-seq achieves 95% SNP detection sensitivity at a mean on-target depth of 40 reads, whereas WGS only requires a mean of 14 reads. Known disease causing mutations are not biased towards easy or hard to sequence areas of the genome for either exome-seq or WGS. CONCLUSIONS: From an economic perspective, WGS is at parity with exome-seq for variant detection in the targeted coding regions. WGS offers benefits in uniformity of read coverage and more balanced allele ratio calls, both of which can in most cases be offset by deeper exome-seq, with the caveat that some exome-seq targets will never achieve sufficient mapped read depth for variant detection due to technical difficulties or probe failures. As WGS is intrinsically richer data that can provide insight into polymorphisms outside coding regions and reveal genomic rearrangements, it is likely to progressively replace exome-seq for many applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2105-15-247) contains supplementary material, which is available to authorized users

Identification of Radiopure Titanium for the LZ Dark Matter Experiment and Future Rare Event Searches

The LUX-ZEPLIN (LZ) experiment will search for dark matter particle interactions with a detector containing a total of 10 tonnes of liquid xenon within a double-vessel cryostat. The large mass and proximity of the cryostat to the active detector volume demand the use of material with extremely low intrinsic radioactivity. We report on the radioassay campaign conducted to identify suitable metals, the determination of factors limiting radiopure production, and the selection of titanium for construction of the LZ cryostat and other detector components. This titanium has been measured with activities of $^{238}$U$_{e}$~$<$1.6~mBq/kg, $^{238}$U$_{l}$~$<$0.09~mBq/kg, $^{232}$Th$_{e}$~$=0.28\pm 0.03$~mBq/kg, $^{232}$Th$_{l}$~$=0.25\pm 0.02$~mBq/kg, $^{40}$K~$<$0.54~mBq/kg, and $^{60}$Co~$<$0.02~mBq/kg (68\% CL). Such low intrinsic activities, which are some of the lowest ever reported for titanium, enable its use for future dark matter and other rare event searches. Monte Carlo simulations have been performed to assess the expected background contribution from the LZ cryostat with this radioactivity. In 1,000 days of WIMP search exposure of a 5.6-tonne fiducial mass, the cryostat will contribute only a mean background of $0.160\pm0.001$(stat)$\pm0.030$(sys) counts.Comment: 13 pages, 3 figures, accepted for publication in Astroparticle Physic