The structure and organization of repetitive elements in fish genomes are still relatively poorly understood, although most of these elements are believed to be located in heterochromatic regions. ...Repetitive elements are considered essential in evolutionary processes as hotspots for mutations and chromosomal rearrangements, among other functions - thus providing new genomic alternatives and regulatory sites for gene expression. The present study sought to characterize repetitive DNA sequences in the genomes of Semaprochilodus insignis (Jardine & Schomburgk, 1841) and Semaprochilodus taeniurus (Valenciennes, 1817) and identify regions of conserved syntenic blocks in this genome fraction of three species of Prochilodontidae (Semaprochilodus insignis, Semaprochilodus taeniurus, and Prochilodus lineatus (Valenciennes, 1836) by cross-FISH using Cot-1 DNA (renaturation kinetics) probes. We found that the repetitive fractions of the genomes of Semaprochilodus insignis and Semaprochilodus taeniurus have significant amounts of conserved syntenic blocks in hybridization sites, but with low degrees of similarity between them and the genome of Prochilodus lineatus, especially in relation to B chromosomes. The cloning and sequencing of the repetitive genomic elements of Semaprochilodus insignis and Semaprochilodus taeniurus using Cot-1 DNA identified 48 fragments that displayed high similarity with repetitive sequences deposited in public DNA databases and classified as microsatellites, transposons, and retrotransposons. The repetitive fractions of the Semaprochilodus insignis and Semaprochilodus taeniurus genomes exhibited high degrees of conserved syntenic blocks in terms of both the structures and locations of hybridization sites, but a low degree of similarity with the syntenic blocks of the Prochilodus lineatus genome. Future comparative analyses of other prochilodontidae species will be needed to advance our understanding of the organization and evolution of the genomes in this group of fish.
Die Autorin untersucht die Professionalisierungsbemühungen in der Beraterbranche am Beispiel der Ziele und Aktivitäten des "Bundes Deutscher Unternehmensberater" (BDU). Der Berufsverband setzt sich ...z. B. für den gesetzlichen Schutz der Bezeichnung "Unternehmensberater" ein, er fordert Mindeststandards bei der Ausbildung und propagiert berufsethische Verhaltensgrundsätze. Die Autorin zeigt auf dem Hintergrund von Theorien der sozialen Schließung, dass die gesellschaftliche Stellung eines Berufes kein Zufallsprodukt gesellschaftlicher Differenzierung darstellt, sondern dass sie ein durch die Berufsangehörigen beeinflusster Prozess ist. Sie betrachtet die Beraterbranche unter dem Blickwinkel erfolgreicher Professionalisierung und untersucht dabei folgende Fragen: Wer ist für eine Professionalisierung und wer ist dagegen? Welche Aspekte weisen auf eine Ungewissheitsreduktion durch die Professionalisierung der Branche hin? Welche Bemühungen und Erfolge sind bei der Ausbildung, dem gesetzlichen Schutz der Berufsbezeichnung und der Festigung einer Berufsethik zu erkennen? (ICI2).
The synthesis of cytochrome c oxidase 2 (SCO2) gene encodes for a mitochondrial located metallochaperone essential for the synthesis of the cytochrome c oxidase (COX) subunit 2. Recessive mutations ...in SCO2 have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency and in only four cases with axonal neuropathy. Here, we identified a homozygous pathogenic variant (c.361G > C; p.Gly121Arg) in SCO2 in two brothers with isolated axonal motor neuropathy. To address pathogenicity of the amino acid substitution, biochemical studies were performed and revealed increased level of the mutant SCO2‐protein and dysregulation of COX subunits in leukocytes and moreover unraveled decrease of proteins involved in the manifestation of neuropathies. Hence, our combined data strengthen the concept of SCO2 being causative for a very rare form of axonal neuropathy, expand its molecular genetic spectrum and provide first biochemical insights into the underlying pathophysiology.
Mac1 is a transcriptional activator whose activity is inhibited by copper ions. Mutagenesis studies were carried out to map residues important in the copper inhibition of Mac1 activity. Seven new ...missense mutations were identified that resulted in copper-independent Mac1 transcriptional activation. All seven mutations were clustered in one of two C-terminal cysteine-rich motifs, designated the C1 motif. All but one of the constitutive Mac1 mutations occurred in one of the conserved six residues in the264CXC(X)4CXC(X)2C(X)2H279C1 motif. The lone exception was a L260S substitution. Two additionalMAC1 mutations exhibiting constitutive activity were in-frame deletions encompassing portions C1. Engineered mutations in the second cysteine-rich motif did not yield a constitutively active Mac1. These results are consistent with the C1 motif being the copper-regulatory switch. Both cysteine-rich motifs exhibited transactivation activity, although the C1 activator was weak relative to the C2 activator. Limited copper metalloregulation of Mac1 was observed with only the C1 activator fused to the N-terminal DNA binding domain. Thus, the two Cys-rich motifs appear to function independently. The C1 motif appears to be a functional copper-regulatory domain.
Transport And Golgi Organization protein 2 (TANGO2) deficiency has recently been identified as a rare metabolic disorder with a distinct clinical and biochemical phenotype of recurrent metabolic ...crises, hypoglycemia, lactic acidosis, rhabdomyolysis, arrhythmias, and encephalopathy with cognitive decline. We report nine subjects from seven independent families, and we studied muscle histology, respiratory chain enzyme activities in skeletal muscle and proteomic signature of fibroblasts. All nine subjects carried autosomal recessive TANGO2 mutations. Two carried the reported deletion of exons 3 to 9, one homozygous, one heterozygous with a 22q11.21 microdeletion inherited in trans. The other subjects carried three novel homozygous (c.262C>T/p.Arg88*; c.220A>C/p.Thr74Pro; c.380+1G>A), and two further novel heterozygous (c.6_9del/p.Phe6del); c.11‐13delTCT/p.Phe5del mutations. Immunoblot analysis detected a significant decrease of TANGO2 protein. Muscle histology showed mild variation of fiber diameter, no ragged‐red/cytochrome c oxidase‐negative fibers and a defect of multiple respiratory chain enzymes and coenzyme Q10 (CoQ10) in two cases, suggesting a possible secondary defect of oxidative phosphorylation. Proteomic analysis in fibroblasts revealed significant changes in components of the mitochondrial fatty acid oxidation, plasma membrane, endoplasmic reticulum‐Golgi network and secretory pathways. Clinical presentation of TANGO2 mutations is homogeneous and clinically recognizable. The hemizygous mutations in two patients suggest that some mutations leading to allele loss are difficult to detect. A combined defect of the respiratory chain enzymes and CoQ10 with altered levels of several membrane proteins provides molecular insights into the underlying pathophysiology and may guide rational new therapeutic interventions.
Background and purpose
Myotonic dystrophy type 1 (DM1) is the most common form of adult-onset muscular dystrophy and is caused by an repeat expansion r(CUG)
exp
located in the 3' untranslated region ...of the
DMPK
gene. Symptoms include skeletal and cardiac muscle dysfunction and fibrosis. In DM1, there is a lack of established biomarkers in routine clinical practice. Thus, we aimed to identify a blood biomarker with relevance for DM1-pathophysiology and clinical presentation.
Methods
We collected fibroblasts from 11, skeletal muscles from 27, and blood samples from 158 DM1 patients. Moreover, serum, cardiac, and skeletal muscle samples from DMSXL mice were included. We employed proteomics, immunostaining, qPCR and ELISA. Periostin level were correlated with CMRI-data available for some patients.
Results
Our studies identified Periostin, a modulator of fibrosis, as a novel biomarker candidate for DM1: proteomic profiling of human fibroblasts and murine skeletal muscles showed significant dysregulation of Periostin. Immunostaining on skeletal and cardiac muscles from DM1 patients and DMSXL mice showed an extracellular increase of Periostin, indicating fibrosis. qPCR studies indicated increased
POSTN
expression in fibroblasts and muscle. Quantification of Periostin in blood samples from DMSXL mice and two large validation cohorts of DM1 patients showed decreased levels in animals and diseased individuals correlating with repeat expansion and disease severity and presence of cardiac symptoms identified by MRI. Analyses of longitudinal blood samples revealed no correlation with disease progression.
Conclusions
Periostin might serve as a novel stratification biomarker for DM1 correlating with disease severity, presence of cardiac malfunction and fibrosis.
Freiheit und Selbstbestimmung sind zentrale Werte unserer heutigen Arbeitswelt: Die Beziehungen zwischen Organisationen und Arbeitskräften werden marktorientierter, Beschäftigungsrisiken müssen ...zunehmend von Individuen getragen werden und Unternehmertum wird zum Ideal arbeitnehmerischen Handelns. Am Beispiel einer qualitativen Fallstudie zur Amway GmbH untersuchen wir, wie die mit einer individuellen Leistungsverantwortung verbundenen Gerechtigkeits- und Gemeinschaftsprobleme durch ein Unternehmen „gelöst” bzw. abgeschwächt werden können. Wir kennzeichnen das diesbezügliche Arrangement als einen „sozialen Kontrakt”, der entlang von vier Dimensionen eine Balance zwischen den Werten Freiheit, Gemeinschaft und Gerechtigkeit herzustellen versucht, und diskutieren Besonderheiten und mögliche Verallgemeinerungen unserer Fallstudie.