TY  - JOUR
A1  - Rodríguez-Mari, Adriana
A1  - Wilson, Catherine
A1  - Titus, Tom A.
A1  - Canestro, Cristian
A1  - BreMiller, Ruth A.
A1  - Yan, Yi-Lin
A1  - Nanda, Indrajit
A1  - Johnston, Adam
A1  - Kanki, John P.
A1  - Gray, Erin M.
A1  - He, Xinjun
A1  - Spitsbergen, Jan
A1  - Schindler, Detlev
A1  - Postlethwait, John H.
T1  - Roles of brca2 (fancd1) in Oocyte Nuclear Architecture, Gametogenesis, Gonad Tumors, and Genome Stability in Zebrafish
JF  - PLoS Genetics
N2  - Functional near-infrared spectroscopy (fNIRS) is an established optical neuroimaging method for measuring functional hemodynamic responses to infer neural activation. However, the impact of individual anatomy on the sensitivity of fNIRS measuring hemodynamics within cortical gray matter is still unknown. By means of Monte Carlo simulations and structural MRI of 23 healthy subjects (mean age: (25.0 +/- 2.8) years), we characterized the individual distribution of tissue-specific NIR-light absorption underneath 24 prefrontal fNIRS channels. We, thereby, investigated the impact of scalp-cortex distance (SCD), frontal sinus volume as well as sulcal morphology on gray matter volumes (V(gray)) traversed by NIR-light, i.e. anatomy-dependent fNIRS sensitivity. The NIR-light absorption between optodes was distributed describing a rotational ellipsoid with a mean penetration depth of (23.6 +/- 0.7) mm considering the deepest 5% of light. Of the detected photon packages scalp and bone absorbed (96.4 +/- 9: 7)% and V(gray) absorbed (3.1 +/- 1.8)% of the energy. The mean V(gray) volume (1.1 +/- 0.4)cm(3) was negatively correlated (r = - .76) with the SCD and frontal sinus volume (r = - .57) and was reduced by 41.5% in subjects with relatively large compared to small frontal sinus. Head circumference was significantly positively correlated with the mean SCD (r = .46) and the traversed frontal sinus volume (r = .43). Sulcal morphology had no significant impact on V(gray). Our findings suggest to consider individual SCD and frontal sinus volume as anatomical factors impacting fNIRS sensitivity. Head circumference may represent a practical measure to partly control for these sources of error variance.
KW  - oocytes
KW  - zebrafish
KW  - genetic causes of cancer
KW  - testes
KW  - apoptosis
KW  - gonads
KW  - sperm
KW  - embryos
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142285
VL  - 7
IS  - 3
ER  - 
TY  - JOUR
A1  - Meier, Daniel
A1  - Schindler, Detlev
T1  - Fanconi Anemia Core Complex Gene Promoters Harbor Conserved Transcription Regulatory Elements
N2  - The Fanconi anemia (FA) gene family is a recent addition to the complex network of proteins that respond to and repair certain types of DNA damage in the human genome. Since little is known about the regulation of this novel group of genes at the DNA level, we characterized the promoters of the eight genes (FANCA, B, C, E, F, G, L and M) that compose the FA core complex. The promoters of these genes show the characteristic attributes of housekeeping genes, such as a high GC content and CpG islands, a lack of TATA boxes and a low conservation. The promoters functioned in a monodirectional way and were, in their most active regions, comparable in strength to the SV40 promoter in our reporter plasmids. They were also marked by a distinctive transcriptional start site (TSS). In the 59 region of each promoter, we identified a region that was able to negatively regulate the promoter activity in HeLa and HEK 293 cells in isolation. The central and 39 regions of the promoter sequences harbor binding sites for several common and rare transcription factors, including STAT, SMAD, E2F, AP1 and YY1, which indicates that there may be cross-connections to several established regulatory pathways. Electrophoretic mobility shift assays and siRNA experiments confirmed the shared regulatory responses between the prominent members of the TGF-b and JAK/STAT pathways and members of the FA core complex. Although the promoters are not well conserved, they share region and sequence specific regulatory motifs and transcription factor binding sites (TBFs), and we identified a bi-partite nature to these promoters. These results support a hypothesis based on the co-evolution of the FA core complex genes that was expanded to include their promoters.
KW  - Fanconi-Anämie
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68917
ER  -