FcγReceptors IIa on Cardiomyocytes and Their Potential Functional Relevance in Dilated Cardiomyopathy

ObjectivesThe purpose of this study was to investigate how cardiac autoantibodies might contribute to cardiac dysfunction in patients suffering from dilated cardiomyopathy (DCM).BackgroundIn the majority of DCM patients, it is possible to detect antibodies with negative inotropic effect on cardiomyocytes. The manner in which these antibodies impair cardiac function is poorly understood.MethodsImmunoglobulin (Ig)G was prepared from plasma of 11 DCM patients containing antibodies that induced a negative inotropic effect on cardiomyocytes. We analyzed the effects of antibodies/IgG fragments on calcium transients and on systolic cell shortening of adult rat cardiomyocytes and investigated the dependency of these effects on potential cardiomyocyte Fc receptors.ResultsIn contrast to control subjects, intact IgG from DCM patients reduced calcium transients and cell shortening of cardiomyocytes. The F(ab′)2fragments of these antibodies did not induce these effects but inhibited the functional effects of DCM-IgG of the respective patients’ IgG. These effects were also inhibited by Fc fragments of normal IgG. Reconstitution of the Fc part by incubation of cardiomyocytes with DCM-F(ab′)2fragments followed by goat-anti-human-F(ab′)-IgG again induced reduction of cell shortening and of calcium transients. In rat and human ventricular cardiomyocytes, Fcγreceptors IIa (CD32) were demonstrated by immunofluorescence.ConclusionsOur findings indicate that DCM-IgG-F(ab′)2bind to their cardiac antigen(s), but the Fc part might trigger the negative inotropic effects via the newly detected Fcγreceptor on cardiomyocytes. These results point to a novel potential mechanism for antibody-induced impairment of cardiac function in DCM patients

Stimulated Raman Scattering (SRS) in α‐AlOOH (Diaspore)

In single crystals of orthorhombic α‐AlOOH, known also as mineral diaspore, χ(3)‐nonlinear lasing by stimulated Raman scattering (SRS) and Raman‐induced four‐wave mixing (RFWM) is investigated. Picosecond pumping at 1.064 µm wavelength produces a broadband Stokes and anti‐Stokes frequency comb with up to 25 SRS‐ and RFWM‐generated emission lines. All observed Stokes and anti‐Stokes lasing components in the visible and near‐IR are identified and attributed to a single SRS‐promoting vibration mode with ωSRS ≈ 445 cm−1. The first Stokes steady‐state Raman gain coefficient in the visible spectral range is estimated to a value not less than 0.36 cm GW−1

Insights into hominid evolution from the gorilla genome sequence.

Gorillas are humans' closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago. In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Flap adhesion and effect on postoperative complication rates using Tissuglu((R)) in mastectomy patients

Post-mastectomy seroma and related complications are common problems in modern oncological surgery. Occurrence rates of up to 59 % have been reported in literature. High-risk patients, that is, those who have undergone previous surgeries, present with a high body mass index, have had radiation or chemotherapy, present a particular challenge. Noninvasive measures such as fibrin-based sealants have thus far not been able to effectively reduce complications associated with fluid accumulation. A recent study using a lysine-derived urethane adhesive named TissuGlu(A (R)) however, showed promising results in patients after abdominoplasty. 32 consecutively recruited patients received a mastectomy using a gold standard mastectomy technique as well as TissuGlu(A (R)) flap fixation. A control group of 173 patients, having received a gold standard mastectomy-only, was analyzed retrospectively, totaling 205 patients. Primary endpoints were post-discharge seroma formation and revision surgery/re-hospitalization. Secondary endpoints were initial seroma volume, postoperative pain, hematoma formation and day of drain removal. No significant difference in seroma formation was demonstrated. The revision surgery/re-hospitalization rate was reduced from 6.9 to 0 %, though this did not reach significance. Significant improvement could be shown in the TissuGlu(A (R)) group regarding time to drain removal (17 % decrease), and hematoma formation (14 % decrease). No difference was shown in postoperative pain. Although patient numbers are still small, advantages in revision surgery/re-hospitalization rate, hematoma formation as well as time to drain removal was shown for the TissuGlu(A (R)) group. Therapeutic, IV