Trinucleotide repeat (TNR) expansions and deletions are associated with human neurodegenerative diseases and prostate cancer. Recent studies have pointed to a linkage between oxidative DNA damage, base excision repair (BER) and TNR expansion, which is demonstrated by the observation that DNA polymerase β (pol β) gap-filling synthesis acts in concert with alternate flap cleavage by flap endonucl...

Flap endonuclease 1 (FEN1) overexpression promotes breast cancer. We investigated the role of FEN1 in cisplatin resistance and the chemosensitizing effects of curcumin in breast cancer cells. We demonstrated that FEN1 overexpression promotes cisplatin resistance in breast cancer cells, and that FEN1 knockdown enhances cisplatin sensitivity. Curcumin down-regulated FEN1 expression in a dose-depe...

The homotrimeric sliding clamp proliferating cell nuclear antigen (PCNA) mediates Okazaki fragment maturation through tight coordination of the activities of DNA polymerase δ (Pol δ), flap endonuclease 1 (FEN1) and DNA ligase I (Lig1). Little is known regarding the mechanism of partner switching on PCNA and the involvement of PCNA's three binding sites in coordinating such processes. To shed ne...

These guidelines aim to assist in the diagnosis of noise-induced hearing loss (NIHL) in medicolegal settings. The task is to distinguish between possibility and probability, the legal criterion being 'more probable than not'. It is argued that the amount of NIHL needed to qualify for that diagnosis is that which is reliably measurable and identifiable on the audiogram. The three main requiremen...

The limits to sustained energy intake are important because of their implications for reproductive output, foraging behaviour and thermoregulatory capabilities. Recent attempts to elucidate the nature of the limits to sustained energy intake have focused on peak lactation, which is the most energetically demanding period for female mammals. The hypothesis that performance of lactating animals i...

The structure-specific nuclease human flap endonuclease-1 (hFEN1) plays a key role in DNA replication and repair and may be of interest as an oncology target. We present the crystal structure of inhibitor-bound hFEN1, which shows a cyclic N-hydroxyurea bound in the active site coordinated to two magnesium ions. Three such compounds had similar IC50 values but differed subtly in mode of action. ...

As a key virulence strategy to cause bacterial leaf blight, Xanthomonas oryzae pv. oryzae (Xoo) injects into the plant cell DNA-binding proteins called transcription activator-like effectors (TALEs) that bind to effector-binding elements (EBEs) in a sequence-specific manner, resulting in host gene induction. TALEs AvrXa7, PthXo3, TalC and Tal5, found in geographically distant Xoo strains, all t...

We present ASCA observations of the nearby galaxies Dwingeloo 1 (Dw1) and Maaei 1 (Mf1). X-ray sources are clearly detected within 3 arcminutes of the optical nuclei of both galaxies. Despite the low Galactic latitude of these elds (jbj < 1) we conclude, on probability and spectral grounds, that the detected sources are intrinsic to these galaxies rather than foreground or background interloper...

Laboratory mice (strain MF1) were used to determine whether sustainable rates of energy intake are limited during lactation. Mice raising natural-sized litters (N=71) reached an asymptote in their daily food intake between days 13 and 16 of lactation at 23.1 g x day(-1) and also between litter sizes of 9 and 15 pups (22.8 g x day(-1)). A second group of 37 females had their litter sizes manipul...