Disruption of Higher Order DNA Structures in Friedreich's Ataxia (GAA)n Repeats by PNA or LNA Targeting

Expansion of (GAA)n repeats in the first intron of the Frataxin gene is associated with reduced mRNA and protein levels and the development of Friedreich’s ataxia. (GAA)n expansions form non-canonical structures, including intramolecular triplex (H-DNA), and R-loops and are associated with epigenetic modifications. With the aim of interfering with higher order H-DNA (like) DNA structures within pathological (GAA)n expansions, we examined sequence-specific interaction of peptide nucleic acid (PNA) with (GAA)n repeats of different lengths (short: n=9, medium: n=75 or long: n=115) by chemical probing of triple helical and single stranded regions. We found that a triplex structure (H-DNA) forms at GAA repeats of different lengths; however, single stranded regions were not detected within the medium size pathological repeat, suggesting the presence of a more complex structure. Furthermore, (GAA)4-PNA binding of the repeat abolished all detectable triplex DNA structures, whereas (CTT)5-PNA did not. We present evidence that (GAA)4-PNA can invade the DNA at the repeat region by binding the DNA CTT strand, thereby preventing non-canonical-DNA formation, and that triplex invasion complexes by (CTT)5-PNA form at the GAA repeats. Locked nucleic acid (LNA) oligonucleotides also inhibited triplex formation at GAA repeat expansions, and atomic force microscopy analysis showed significant relaxation of plasmid morphology in the presence of GAA-LNA. Thus, by inhibiting disease related higher order DNA structures in the Frataxin gene, such PNA and LNA oligomers may have potential for discovery of drugs aiming at recovering Frataxin expression

R. L. Hanvey collection, MSS.0624

Abstract: A collection of Ku Klux Klan material, including a copy of the handbook "Kloran," 5th ed., a leather wallet with the Klan seal, and a group photo of unidentified Ku Klux Klan women.Scope and Content Note: The collection contains a copy of the 5th edition of the "Kloran," the Ku Klux Klan handbook, and a leather wallet with the Klan seal both belonging to R. L. Hanvey. The collection also has a group photograph of unidentified Ku Klux Klan women. The photograph has been flattened and foldered and is filed in the photoroom, labeled "KKK Women."Biographical/Historical Note: R. L. Hanvey lived in Birmingham, Alabama, and was a member of the Ku Klux Klan

The quest for laser induced isomer production

Research into nuclear isomers can lead to the development of a gamma-ray laser (GRASER), thus opening up the perspective of quantum optical studies on high energetic gamma-radiation. The unique capabilities of novel, ultra-high intensity multi-tera- and petawatt laser facilities enable investigations into a possible direct population of nuclear isomers via hot electron plasmas. We present the theoretical rationale and review performed measurements. A new experimental strategy to find unambiguous evidence for the direct laser induced population of the short lived Ta-181m, will be discussed