Übernahmerechtliche Angaben im Lagebericht nach HGB : eine empirische Analyse

Für nach dem 31.12.2005 beginnende Geschäftsjahre sind Aktiengesellschaften und Kommanditgesellschaften auf Aktien, die mit stimmberechtigten Aktien an einem organisierten Markt im Sinne des § 2 Abs. 7 WpÜG notiert sind, gemäß den §§ 289 Abs. 4 bzw. 315 Abs. 4 HGB verpflichtet, für eine etwaige Übernahme relevante Angaben im Lagebericht zu veröffentlichen. Der folgende Beitrag analysiert die Umsetzung der Bestimmungen in der Unternehmenspraxis anhand einer Auswahl von 30 in DAX, MDAX und SDAX gelisteten Gesellschaften für die Geschäftsjahre 2006, 2008 und 2010

Neuromuscular function and fatigue resistance of the plantar flexors following short-term cycling endurance training

Previously published studies on the effect of short-term endurance training on the neuromuscular function of the plantar flexors have shown that the H-reflex elicited at rest and during weak voluntary contractions was increased following the training regime. However, these studies did not test H-reflex modulation during isometric maximum voluntary contraction (iMVC) and did not incorporate a control group in their study design to compare the results of the endurance training group to individuals without the endurance training stimulus. Therefore, this randomized controlled study was directed to investigate the neuromuscular function of the plantar flexors at rest and during iMVC before and after eight weeks of cycling endurance training. Twenty-two young adults were randomly assigned to an intervention group and a control group. During neuromuscular testing, rate of torque development, isometric maximum voluntary torque and muscle activation were measured. Triceps surae muscle activation and tibialis anterior muscle co-activation were assessed by normalized root mean square of the EMG signal during the initial phase of contraction (0-100, 100-200 ms) and isometric maximum voluntary contraction of the plantar flexors. Furthermore, evoked spinal reflex responses of the soleus muscle (H-reflex evoked at rest and during iMVC, V-wave), peak twitch torques induced by electrical stimulation of the posterior tibial nerve at rest and fatigue resistance were evaluated. The results indicate that the endurance training did not lead to a significant change in any variable of interest. Data of the present study conflict with the outcome of previously published studies that have found an increase in H-reflex excitability after endurance training. However, these studies had not included a control group in their study design as was the case here. It is concluded that short-term cycling endurance training does not necessarily enhance H-reflex responses and fatigue resistance

Search for the Active Ingredients from a 2-Aminothiazole DMSO Stock Solution with Antimalarial Activity

Chemical decomposition of DMSO stock solutions is a common incident that can mislead biological screening campaigns. Here, we share our case study of 2-aminothiazole 1, originating from an antimalarial class that undergoes chemical decomposition in DMSO at room temperature. As previously measured biological activities observed against Plasmodium falciparum NF54 and for the target enzyme PfIspE were not reproducible for a fresh batch, we tackled the challenge to understand where the activity originated from. Solvent- and temperature-dependent studies using HRMS and NMR spectroscopy to monitor the decomposition led to the isolation and in vitro evaluation of several fractions against PfIspE. After four days of decomposition, we successfully isolated the oxygenated and dimerised compounds using SFC purification and correlated the observed activities to them. Due to the unstable nature of the two isolates, it is likely that they undergo further decomposition contributing to the overall instability of the compound

Sequential anti-cytomegalovirus response monitoring may allow prediction of cytomegalovirus reactivation after allogeneic stem cell transplantation

Background: Reconstitution of cytomegalovirus-specific CD3+CD8+ T cells (CMV-CTLs) after allogeneic hematopoietic stem cell transplantation (HSCT) is necessary to bring cytomegalovirus (CMV) reactivation under control. However, the parameters determining protective CMV-CTL reconstitution remain unclear to date. Design and Methods: In a prospective tri-center study, CMV-CTL reconstitution was analyzed in the peripheral blood from 278 patients during the year following HSCT using 7 commercially available tetrameric HLA-CMV epitope complexes. All patients included could be monitored with at least CMV-specific tetramer. Results: CMV-CTL reconstitution was detected in 198 patients (71%) after allogeneic HSCT. Most importantly, reconstitution with 1 CMV-CTL per µl blood between day +50 and day +75 post-HSCT discriminated between patients with and without CMV reactivation in the R+/D+ patient group, independent of the CMV-epitope recognized. In addition, CMV-CTLs expanded more daramtaically in patients experiencing only one CMV-reactivation than those without or those with multiple CMV reactivations. Monitoring using at least 2 tetramers was possible in 63% (n = 176) of the patients. The combinations of particular HLA molecules influenced the numbers of CMV-CTLs detected. The highest CMV-CTL count obtained for an individual tetramer also changed over time in 11% of these patients (n = 19) resulting in higher levels of HLA-B*0801 (IE-1) recognizing CMV-CTLs in 14 patients. Conclusions: Our results indicate that 1 CMV-CTL per µl blood between day +50 to +75 marks the beginning of an immune response against CMV in the R+/D+ group. Detection of CMV-CTL expansion thereafter indicates successful resolution of the CMV reactivation. Thus, sequential monitoring of CMV-CTL reconstitution can be used to predict patients at risk for recurrent CMV reactivation

Long-term benefit-risk balance of drug-eluting vs. bare-metal stents in daily practice: does stent diameter matter? Three-year follow-up of BASKET

Aims To assess the long-term benefit-risk ratio of drug-eluting (DES) vs. bare-metal stents (BMS) relative to stent size. Methods and results All 826 consecutive BASKET (BAsel Stent Kosten-Effektivitäts Trial) patients randomized 2:1 to DES vs. BMS were followed after 3 years. Data were analysed separately for patients with small stents (<3.0 mm vessel/<4.0 mm bypass grafts, n = 268) vs. only large stents (≥3.0 mm native vessels, n = 558). Clinical events were related to stent thrombosis. Three-year clinical target-vessel revascularization rates remained borderline reduced after DES [9.9 vs. 13.9% (BMS), P = 0.07], particularly in patients with small stents (10.7 vs. 19.8%, P = 0.03; large stents: 9.5 vs. 11.5%, P = 0.44). Cardiac death/myocardial infarction (MI) rates (12.7 vs. 10.0%, P = 0.30) were similar, however, death/MI beyond 6 months was higher after DES [9.1 vs. 3.8% (BMS), P = 0.009], mainly due to increased late death/MI in patients with large stents (9.7 vs. 3.1%, P = 0.006). The results paralleled findings for stent thrombosis. Conclusion The clinical benefit of DES was maintained at no overall increased risk of death or death/MI up to 3 years. However, death/MI rates were increased in DES vs. BMS patients beyond 6 months, particularly in patients with large stents, paralleling findings for stent thrombosis. Thus, stent size seems to influence the 3-year benefit-risk ratio after DES implantatio

Human Coronavirus NL63 Open Reading Frame 3 encodes a virion-incorporated N-glycosylated membrane protein

Background: Human pathogenic coronavirus NL63 (hCoV-NL63) is a group 1 (alpha) coronavirus commonly associated with respiratory tract infections. In addition to known non-structural and structural proteins all coronaviruses have one or more accessory proteins whose functions are mostly unknown. Our study focuses on hCoV-NL63 open reading frame 3 (ORF 3) which is a highly conserved accessory protein among coronaviruses. Results: In-silico analysis of the 225 amino acid sequence of hCoV-NL63 ORF 3 predicted a triple membranespanning protein. Expression in infected CaCo-2 and LLC-MK2 cells was confirmed by immunofluorescence and Western blot analysis. The protein was detected within the endoplasmatic reticulum/Golgi intermediate compartment (ERGIC) where coronavirus assembly and budding takes place. Subcellular localization studies using recombinant ORF 3 protein transfected in Huh-7 cells revealed occurrence in ERGIC, Golgi- and lysosomal compartments. By fluorescence microscopy of differently tagged envelope (E), membrane (M) and nucleocapsid (N) proteins it was shown that ORF 3 protein colocalizes extensively with E and M within the ERGIC. Using N-terminally FLAG-tagged ORF 3 protein and an antiserum specific to the C-terminus we verified the proposed topology of an extracellular N-terminus and a cytosolic C-terminus. By in-vitro translation analysis and subsequent endoglycosidase H digestion we showed that ORF 3 protein is N-glycosylated at the N-terminus. Analysis of purified viral particles revealed that ORF 3 protein is incorporated into virions and is therefore an additional structural protein. Conclusions: This study is the first extensive expression analysis of a group 1 hCoV-ORF 3 protein. We give evidence that ORF 3 protein is a structural N-glycosylated and virion-incorporated protein.Web of Scienc

Gel-like inclusions of C-terminal fragments of TDP-43 sequester stalled proteasomes in neurons

International audienceAggregation of the multifunctional RNA-binding protein TDP-43 defines large subgroups of amyotrophic lateral sclerosis and frontotemporal dementia and correlates with neurodegeneration in both diseases. In disease, characteristic C-terminal fragments of ~25 kDa ("TDP-25") accumulate in cytoplasmic inclusions. Here, we analyze gain-of-function mechanisms of TDP-25 combining cryo-electron tomography, proteomics, and functional assays. In neurons, cytoplasmic TDP-25 inclusions are amorphous, and photobleaching experiments reveal gel-like biophysical properties that are less dynamic than nuclear TDP-43. Compared with full-length TDP-43, the TDP-25 interactome is depleted of low-complexity domain proteins. TDP-25 inclusions are enriched in 26S proteasomes adopting exclusively substrate-processing conformations, suggesting that inclusions sequester proteasomes, which are largely stalled and no longer undergo the cyclic conformational changes required for proteolytic activity. Reporter assays confirm that TDP-25 impairs proteostasis, and this inhibitory function is enhanced by ALScausing TDP-43 mutations. These findings support a pathophysiological relevance of proteasome dysfunction in ALS/FTD

Pre-emptive Allogeneic Hematopoietic Stem Cell Transplantation in Ataxia Telangiectasia

Ataxia telangiectasia (A-T) is a primary immunodeficiency with mutations in the gene encoding the A-T mutated (ATM) protein that interacts with immune, hematopoietic, and endocrine targets resulting in broad multi-systemic clinical manifestations with a devastating outcome. Apart from a progressive neurodegenerative disorder, A-T leads to significantly increased susceptibility to malignancies. It is a matter of discussion whether pre-emptive allogeneic hematopoietic stem cell transplantation (alloHSCT) using a reduced intensity conditioning regimen would be an option to restore immune-competence and prevent malignancy, as shown in animal models, because conventional treatment protocols of malignant diseases using radio- and/or chemotherapy have a high rate of therapy-related morbidity and mortality in these patients. We present the course of the disease, including immune reconstitution and neurological outcome following pre-emptive alloHSCT in a 4-year-old boy with A-T on a 6 year follow-up. Our manuscript provides a proof-of-concept of alloHSCT as an individual pre-emptive treatment strategy from which some A-T patients might benefit

UniHI 4: new tools for query, analysis and visualization of the human protein–protein interactome

Human protein interaction maps have become important tools of biomedical research for the elucidation of molecular mechanisms and the identification of new modulators of disease processes. The Unified Human Interactome database (UniHI, http://www.unihi.org) provides researchers with a comprehensive platform to query and access human protein–protein interaction (PPI) data. Since its first release, UniHI has considerably increased in size. The latest update of UniHI includes over 250 000 interactions between ∼22 300 unique proteins collected from 14 major PPI sources. However, this wealth of data also poses new challenges for researchers due to the complexity of interaction networks retrieved from the database. We therefore developed several new tools to query, analyze and visualize human PPI networks. Most importantly, UniHI allows now the construction of tissue-specific interaction networks and focused querying of canonical pathways. This will enable researchers to target their analysis and to prioritize candidate proteins for follow-up studies