Disruption of EXOC6B in a patient with developmental delay,epilepsy, and a de novo balanced t(2;8) translocation

Most balanced chromosomal aberrations are not associated with a clinical phenotype, however, in some patients they may disrupt gene structure. With the development of various next-generation sequencing techniques, fast and specific analyses of the breakpoint regions of chromosomal rearrangements are possible. Here, we report on a 19-year-old woman with a de novo balanced translocation t(2;8)(p13.2;q22.1) and a severe clinical phenotype including intellectual disability, epilepsy, behavioral features resembling autism, and minor dysmorphic features. By next-generation sequencing, we defined the breakpoints and found disruption of the exocyst complex component 6B (EXOC6B) gene in intron 1 on chromosome 2p13.2 involving two Alu elements with a homology of 81%. No gene was found at the respective breakpoint on chromosome 8. Expression analysis of the EXOC6B in blood lymphocytes and buccal smear revealed reduced expression in the patient in comparison with the control. Our findings in combination with one recently published case and one other patient listed in DECIPHER v5.1 indicate EXOC6B as a gene relevant for intellectual development and electrophysiological stability.     

Graphene oxide quantum dots immobilized on mesoporous silica: preparation,characterization and electroanalytical application

Because of its high surface area and combination of various functional groups, graphene oxide (GO) is currently one of the most actively studied materials for electroanalytical applications. It is not practical to utilize self-supported GO on its own and thus it is commonly integrated with different supporting carriers. Having a large lateral size, GO can only wrap the particles of the support and thus can significantly reduce the surface area of porous materials. To achieve synergy from the high surface area and polyfunctional nature of GO, and the rigid structure of a porous support, the lateral size of GO must essentially be decreased. Recently reported graphene oxide quantum dots (GOQDs) can fulfil this task. Here we report the successful preparation of an SiO₂-GOQDs hybrid, where GOQDs have been incorporated into the mesoporous network of silica. The SiO₂-GOQDs emit a strong luminescence with a band maximum at 404 nm. The Raman spectrum of SiO₂-GOQDs shows two distinct peaks at 1585 cm⁻¹ (G-peak) and 1372 cm⁻¹ (D-peak), indicating the presence of a graphene ordered basal plane with aromatic sp²-domains and a disordered oxygen-containing structure. Covalent immobilization of GOQDs onto aminosilica via such randomly structured oxygen fragments was proven with the help of Fourier transform infrared spectroscopy, solid-state cross-polarization magic angle spinning ¹³C nuclear magnetic resonance, and X-ray photoelectron spectroscopy. SiO₂-GOQDs were used as a modifier of a carbon paste electrode for differential pulse voltammetry determination of two antibiotics (sulfamethoxazole and trimethoprim) and two endocrine disruptors (diethylstilbestrol (DES) and estriol (EST)). The modified electrodes demonstrated a significant signal enhancement for EST (370%) and DES (760%), which was explained by a π–π stacking interaction between GOQDs and the aromatic system of the analytes.

Graphene oxide quantum dots incorporated into a mesoporous silica network have been used as a modifier of a carbon paste electrode for the determination of antibiotics and hormones.     

QT Interval in Patients with Unstable Angina and Non‐Q Wave Myocardial Infarction

Background: Non‐Q wave mvocardial infarction (NQMI) and unstable angina (UAP) have similar clinical presentations and similar ST‐T changes on the electrocardiogram. The purpose of this study was to assess whether changes in QT interval might help differentiating between these entities. Methods: The QT intervals of 52 patients hospitalized with NQMI were compared to those of 52 patients hospitalized for UAP. All patients had repeated ECG for at least 4 days. Results: Maximal QTc in patients with NQMI was significantly longer than in patients with UAP (475 vs 439 ms, P < 0.0001). QTc on the admission ECG was 450 ms in patients with NQMI compared to 417 ms in UAP P < 0.005). QTc > 460 ms was present in 48% patients with NQMI and in 19% of UAP patients. Maximal QT prolongation was observed within 36 hours of admission with return to normal within 96 hours. QT dispersion was within normal range, being longer in patients with NQMI than patients with UAP (55 vs 43 ms, P < 0.003). QT prolongation was not associated with increased frequency of arrhythmia. The cause of QT prolongation in NQMI may be related to the damage of subendocardial layer exposing the M cells layer which markedly prolong action potential duration. Conclusion: Transient QT prolongation is observed in about half of patients with NQMI. These ECG changes may help differentiating between patients with NQMI and UAP already on admission. A.N.E. 2002;7(4):343–348     

Phosphorylation of human cardiac troponin I G203S and K206Q linked to familial hypertrophic cardiomyopathy affects actomyosin interaction in different ways

cAMP-dependent protein kinase (PKA)-dependent phosphorylation of the two serine residues in the amino terminal region unique to cardiac troponin I (cTnI) is known to cause two effects: (i) decrease of the maximum Ca2+-controlled thin filament-activated myosin S1-ATPase (actoS1-ATPase) activity and mean sliding velocity of reconstituted thin filaments; (ii) rightward shift of the Ca2+ activation curves of actoS1-ATPase activity, filament sliding velocity, and force generation. We have studied the influence of phosphorylation of human wild-type cTnI and of two mutant cTnI (G203S and K206Q) causing familial hypertrophic cardiomyopathy (fHCM) on the secondary structure by circular dichroism spectroscopy and on the Ca2+ regulation of actin-myosin interaction using actoS1-ATPase activity and in vitro motility assays. Both mutations slightly influence the backbone structure of cTnI but only the secondary structure of cTnI-G203S is also affected by bis-phosphorylation of cTnI. In functional studies, cTnI-G203S behaves similarly to wild-type cTnI, i.e. the mutation itself has no measurable effect and bis-phosphorylation alters the actoS1-ATPase activity and the in vitro thin filament motility in the same way as does bis-phosphorylation of wild-type cTnI. In contrast, the mutation K206Q leads to a considerable increase in the maximum actoS1-ATPase activity as well as filament motility compared to wild-type cTnI. Bis-phosphorylation of this mutant cTnI still suppresses the maximum actoS1-ATPase activity and filament sliding velocity but does no longer affect the Ca2+ sensitivity of these processes. Thus, these two fHCM-linked cTnI mutations, although reflecting similar pathological situations, exert different effects on the actomyosin system per se and in response to bis-phosphorylation of cTnI.