Robust identification of mosaic variants in congenital heart disease.

Mosaicism due to somatic mutations can cause multiple diseases including cancer, developmental and overgrowth syndromes, neurodevelopmental disorders, autoinflammatory diseases, and atrial fibrillation. With the increased use of next generation sequencing technology, multiple tools have been developed to identify low-frequency variants, specifically from matched tumor-normal tissues in cancer studies. To investigate whether mosaic variants are implicated in congenital heart disease (CHD), we developed a pipeline using the cancer somatic variant caller MuTect to identify mosaic variants in whole-exome sequencing (WES) data from a cohort of parent/affected child trios (n = 715) and a cohort of healthy individuals (n = 416).

DNA double-strand breaks in blood lymphocytes induced by two-day Tc-MIBI myocardial perfusion scintigraphy.

Objectives: To investigate DNA double-strand breaks (DSBs) in blood lymphocytes induced by two-day Tc-MIBI myocardial perfusion scintigraphy (MPS) using y-H2AX immunofluorescence microscopy and to correlate the results with Tc activity in blood samples.

Methods: Eleven patients who underwent two-day MPS were included. DSB blood sampling was performed before and 5min, 1h and 24h after the first and second radiotracer injections.

Behavioral phenotyping of calcium channel (CACN) subunit α2δ3 knockout mice: Consequences of sensory cross-modal activation.

Sensory cross-activation is still ill-defined and research concerning the consequences of sensory mergence on normal brain function is very limited. Human studies describe behavioral benefits of people with synesthesia- a peculiar form of perception possibly due to cross-modal activation- regarding sensory and memory abilities. Here, we studied behavioral alterations in calcium channel (CACN) subunit α2δ3 knockout (KO) mice exhibiting pain-induced cortical cross-modal activation.

How To Tune the Gene Delivery and Biocompatibility of Poly(2-(4-aminobutyl)-2-oxazoline) by Self- and Coassembly.

Despite their promising potential in gene transfection, the toxicity and limited efficiency of cationic polymers as nonviral vectors are major obstacles for their broader application. The large amount of cationic charges, for example, in poly(ethylene imine) (PEI) is known to be advantageous in terms of their transfection efficiency but goes hand-in-hand with a high toxicity. Consequently, an efficient shielding of the charges is required to minimize toxic effects.

Polyethylenimine Nanoparticle-Mediated siRNA Delivery to Reduce α-Synuclein Expression in a Model of Parkinson's Disease.

RNA interference (RNAi)-based strategies that mediate the specific knockdown of target genes by administration of small interfering RNAs (siRNAs) could be applied for treatment of presently incurable neurodegenerative diseases such as Parkinson's disease. However, inefficient delivery of siRNA into neurons hampers in vivo application of RNAi. We have previously established the 4-12 kDa branched polyethylenimine (PEI) F25-LMW with superior transfection efficacy for delivery of siRNA in vivo.

A gene expression study of ornamental fin shape in Neolamprologus brichardi, an African cichlid species.

The diversity of fin morphology within and across fish taxa offers great, but still largely unexplored, opportunities to investigate the proximate mechanisms underlying fin shape variation. Relying on available genetic knowledge brought forth mainly by the comprehensive study of the zebrafish caudal fin, we explored candidate molecular mechanisms for the maintenance and formation of the conspicuously elongated filaments adorning the unpaired fins of the East African "princess cichlid" Neolamprologus brichardi. Via qPCR assays, we detected expression differences of candidate genes between elongated and short regions of intact and regenerating fins.

Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy.

Paraformaldehyde (PFA) is the most commonly used fixative for immunostaining of cells, but has been associated with various problems, ranging from loss of antigenicity to changes in morphology during fixation. We show here that the small dialdehyde glyoxal can successfully replace PFA Despite being less toxic than PFA, and, as most aldehydes, likely usable as a fixative, glyoxal has not yet been systematically tried in modern fluorescence microscopy. Here, we tested and optimized glyoxal fixation and surprisingly found it to be more efficient than PFA-based protocols.

Histone propionylation is a mark of active chromatin.

Histones are highly covalently modified, but the functions of many of these modifications remain unknown. In particular, it is unclear how histone marks are coupled to cellular metabolism and how this coupling affects chromatin architecture. We identified histone H3 Lys14 (H3K14) as a site of propionylation and butyrylation in vivo and carried out the first systematic characterization of histone propionylation.

[Psychiatric and Somatic Comorbidities of Eating Disorders and Obesity in Female Adolescent and Adult Inpatients].

The main aim of this study was to determine the prevalence of somatic and psychiatric comorbidities in female inpatients diagnosed with an eating disorder or obesity. Statutory health insurance data (11 - 25 years, N = 1269) was analysed. The most frequent comorbidities for both groups were affective, neurotic, stress-related and somatoform as well as personality disorders and diseases of the digestive system.

[Implementation of Evidence-Based Prevention Programs for Eating Disorders: PriMa and Torera in Daily School Life].

Background: Prevalence rates for eating disorders remained stable over the years despite the implementation of numerous prevention strategies. This may be due to discrepancies between research and practice and scientific findings are not fully applied to the care of risk groups. The school-based programs PriMa and Torera for primary prevention of eating disorders have been delivered in Thuringian schools since 2004.

Autophagy-Dependent Generation of Free Fatty Acids Is Critical for Normal Neutrophil Differentiation.

Neutrophils are critical and short-lived mediators of innate immunity that require constant replenishment. Their differentiation in the bone marrow requires extensive cytoplasmic and nuclear remodeling, but the processes governing these energy-consuming changes are unknown. While previous studies show that autophagy is required for differentiation of other blood cell lineages, its function during granulopoiesis has remained elusive.

Cation selectivity of the presequence translocase channel Tim23 is crucial for efficient protein import.

Virtually all mitochondrial matrix proteins and a considerable number of inner membrane proteins carry a positively charged, N-terminal presequence and are imported by the TIM23 complex (presequence translocase) located in the inner mitochondrial membrane. The voltage-regulated Tim23 channel constitutes the actual protein-import pore wide enough to allow the passage of polypeptides with a secondary structure. In this study, we identify amino acids important for the cation selectivity of Tim23.

Autophagy dictates metabolism and differentiation of inflammatory immune cells.

The role of macroautophagy/autophagy, a conserved lysosomal degradation pathway, during cellular differentiation has been well studied over the last decade. In particular, evidence for its role during immune cell differentiation is growing. Despite the description of a variety of dramatic immune phenotypes in tissue-specific autophagy knockout models, the underlying mechanisms are still under debate.

Neuroanatomy of pain-deficiency and cross-modal activation in calcium channel subunit (CACN) α2δ3 knockout mice.

The phenotype of calcium channel subunit (CACN) α2δ3 knockout (KO) mice includes sensory cross-activation and deficient pain perception. Sensory cross-activation defines the activation of a sensory cortical region by input from another modality due to reorganization in the brain such as after sensory loss. To obtain mechanistic insight into both phenomena, we employed a comprehensive battery of neuroanatomical techniques.

[Brief Instruments in German for the Assessment of Disordered Eating].

The development of brief instruments is an important area in the clinical and psychological assessment in the past years. Brief instruments reveal many advantages due to their efficiency and shortness for the users. However, the psychometric standards of development and validation were often neglected during the construction of short forms.

SIFamide Translates Hunger Signals into Appetitive and Feeding Behavior in Drosophila.

Animal behavior is, on the one hand, controlled by neuronal circuits that integrate external sensory stimuli and induce appropriate motor responses. On the other hand, stimulus-evoked or internally generated behavior can be influenced by motivational conditions, e.g.

Photoactivatable Mussel-Based Underwater Adhesive Proteins by an Expanded Genetic Code.

Marine mussels exhibit potent underwater adhesion abilities under hostile conditions by employing 3,4-dihydroxyphenylalanine (DOPA)-rich mussel adhesive proteins (MAPs). However, their recombinant production is a major biotechnological challenge. Herein, a novel strategy based on genetic code expansion has been developed by engineering efficient aminoacyl-transfer RNA synthetases (aaRSs) for the photocaged noncanonical amino acid ortho-nitrobenzyl DOPA (ONB-DOPA).

Screw pyrolysis technology for sewage sludge treatment.

Sewage sludge quantities have grown continuously since the introduction of the European Directive (UWWTD 91/271/EEC) relating to the treatment of urban wastewater. In the present, most of the sewage sludge is combusted in single fuels incineration plants or is co-fired in waste incineration or coal power plants. The combustion of sewage sludge is a proven technology.

Alterations of M1 and M4 acetylcholine receptors in the genetically dystonic (dt) hamster and moderate antidystonic efficacy of M1 and M4 anticholinergics.

Striatal cholinergic dysfunction has been suggested to play a critical role in the pathophysiology of dystonia. In the dt hamster, a phenotypic model of paroxysmal dystonia, M1 antagonists exerted moderate antidystonic efficacy after acute systemic administration. In the present study, we examined the effects of the M4 preferring antagonist tropicamid and whether long-term systemic or acute intrastriatal injections of the M1 preferring antagonist trihexyphenidyl are more effective in mutant hamsters.

Cellular differentiation state modulates the mRNA export activity of SR proteins.

SR proteins function in nuclear pre-mRNA processing, mRNA export, and translation. To investigate their cellular dynamics, we developed a quantitative assay, which detects differences in nucleocytoplasmic shuttling among seven canonical SR protein family members. As expected, SRSF2 and SRSF5 shuttle poorly in HeLa cells but surprisingly display considerable shuttling in pluripotent murine P19 cells.

A Molecular Tweezer Ameliorates Motor Deficits in Mice Overexpressing α-Synuclein.

Aberrant accumulation and self-assembly of α-synuclein are tightly linked to several neurodegenerative diseases called synucleinopathies, including idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Deposition of fibrillar α-synuclein as insoluble inclusions in affected brain cells is a pathological hallmark of synucleinopathies. However, water-soluble α-synuclein oligomers may be the actual culprits causing neuronal dysfunction and degeneration in synucleinopathies.

Monitoring the surface quality of silver plasmon waveguides with nonlinear photoemission electron microscopy and in-situ ion sputtering.

We use photoemission electron microscopy (PEEM) with single- and two-photon excitation to study the properties of surface plasmon polaritons (SPPs) in tapered silver stripe waveguides. Arrays of waveguides with different widths, grating coupler geometries, and taper angles are fabricated using electron beam lithography (EBL) on Si and indium-tin-oxide (ITO)-covered glass substrates. The presence of propagating SPP modes is indicated by modulations of the non-linear photoemission intensity which run along the length of the waveguide - the result of interfering SPPs reflected from the edges.

Switchable Cas9.

Ever since its discovery, Cas9 from Streptococcus pyogenes has revolutionized biology by enabling analysis and engineering of genomes with unprecedented precision and ease. To fine-tune on-target effects and to mitigate adverse effects caused by untimely and off-target action of Cas9, strategies have been developed to control its activity at the post-translational stage via external trigger signals. Control is either achieved by modifying the Cas9 protein itself or its programmable RNA molecules.

Long Noncoding RNA MANTIS Facilitates Endothelial Angiogenic Function.

Background: The angiogenic function of endothelial cells is regulated by numerous mechanisms, but the impact of long noncoding RNAs (lncRNAs) has hardly been studied. We set out to identify novel and functionally important endothelial lncRNAs.

Methods: Epigenetically controlled lncRNAs in human umbilical vein endothelial cells were searched by exon-array analysis after knockdown of the histone demethylase JARID1B.

The Temporal Tuning of the Drosophila Motion Detectors Is Determined by the Dynamics of Their Input Elements.

Detecting the direction of motion contained in the visual scene is crucial for many behaviors. However, because single photoreceptors only signal local luminance changes, motion detection requires a comparison of signals from neighboring photoreceptors across time in downstream neuronal circuits. For signals to coincide on readout neurons that thus become motion and direction selective, different input lines need to be delayed with respect to each other.