Regina Hermann

DNA structure can regulate genome function. Four-stranded DNA G-quadruplex (G4) structures have been implicated in transcriptional regulation; however, previous studies have not directly addressed the role of an individual G4 within its endogenous cellular context. Using CRISPR to genetically abrogate endogenous G4 structure folding, we directly interrogate the G4 found within the upstream regulatory region of the critical human MYC oncogene. G4 loss leads to suppression of MYC transcription from the P1 promoter that is mediated by the deposition of a de novo nucleosome alongside alterations in RNA polymerase recruitment. We also show that replacement of the endogenous MYC G4 with a different G4 structure from the KRAS oncogene restores G4 folding and MYC transcription. Moreover, we demonstrate that the MYC G4 structure itself, rather than its sequence, recruits transcription factors and histone modifiers. Overall, our work establishes that G4 structures are important features of transcriptional regulation that coordinate recruitment of key chromatin proteins and the transcriptional machinery through interactions with DNA secondary structure, rather than primary sequence.

BACKGROUND: A normal computed tomography (CT) scan of the pulmonary arteries in the presence of parenchymal and pleural abnormalities may indicate a false-negative diagnosis of pulmonary embolism (PE). Multi-channel detector CT (MDCT) with thinner collimation may improve the detection of small peripheral PEs causing such abnormalities. PURPOSE: To investigate parenchymal and pleural findings visualized by contrast-enhanced MDCT in patients with and without PE, and to identify possible predictors of PE. MATERIAL AND METHODS: 129 patients with clinical signs of PE were included. In all patients an iopromide-enhanced 64-MDCT (64x0.625 mm collimation, pitch 1.375, overlapping reconstruction with a slice thickness of 0.625 mm, increment of overlapping slice reconstruction 0.43) was performed within 24 h after the onset of the symptoms. RESULTS: MDCT detected PE in 45 of the 129 patients (35%). PE and parenchymal/pleural findings were localized predominantly within the lower lobes. Wedge-shaped opacities were significantly associated with PE (OR =3.00; 95% confidence interval 1.13-7.91). Vascular signs were only visualized in patients with PE. Nodules, consolidations, atelectasis, or effusions were not predictive of PE. CONCLUSION: The present MDCT study verified that parenchymal and pleural findings can be found in patients with or without PE. Wedge-shaped opacities and vascular signs were significantly associated with PE and therefore can be potential predictors of PE.

We present a comprehensive transport investigation of the itinerant antiferromagnet ${\mathrm{Mn}}_{3}\mathrm{Si}$ which undergoes a spin density wave (SDW) order below ${T}_{N}\ensuremath{\sim}21.3\phantom{\rule{4pt}{0ex}}\mathrm{K}$. The electrical resistivity, the thermal conductivity, and the Hall, Seebeck, and Nernst effects exhibit pronounced anomalies at the SDW transition. At temperatures higher than ${T}_{N}$ our data provide strong evidence for a large fluctuation regime which extends up to $\ensuremath{\sim}200\phantom{\rule{4pt}{0ex}}\mathrm{K}$ in the resistivity, the Seebeck effect, and the Nernst effect. From the comparison of our results with other prototype SDW materials, viz., LaFeAsO and chromium, we conclude that many of the observed features are of generic character.

Bone diseases represent an increasing health burden worldwide, and basic research remains necessary to better understand the complexity of these pathologies and to improve and expand existing prevention and treatment approaches. In the present study, 216 bone samples from the caput femoris and collum femoris of 108 patients with degenerative or dysplastic coxarthrosis, hip fracture, or osteonecrosis were evaluated for the proportion of trabecular bone (TB) and expression of parathyroid hormone (PTH) type 1 receptor (PTH1R), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL). Serum levels of PTH, OPG, soluble RANKL (sRANKL), alkaline phosphatase (AP), osteocalcin, total procollagen type-1 intact N-terminal propeptide (TP1NP), tartrate-resistant acid phosphatase type 5b (TRAP5b), sclerostin, and C-telopeptide of type-1 collagen (ICTP) were also determined. Age was positively correlated with serum levels of PTH, OPG, and sclerostin but negatively associated with TB and sRANKL. Women exhibited less TB, lower sclerostin and ICTP, and higher TRAP5b. Impaired kidney function was associated with shorter bone decalcification time, less TB, lower sRANKL, and higher serum PTH, OPG, and sclerostin. Furthermore, correlations were observed between bone PTH1R and OPG expression and between serum PTH, OPG, and AP. There were also positive correlations between serum OPG and TP1NP; serum OPG and sclerostin; serum AP, osteocalcin, and TRAP5b; and serum sclerostin and ICTP. Serum OPG was negatively associated with sRANKL. In summary, clear relationships between specific bone metabolism markers were observed, and distinct influences of age, sex, and kidney function, thus underscoring their suitability as diagnostic or prognostic markers.