Structural basis for the coiled-coil architecture of human CtIP.

The DNA repair factor CtIP has a critical function in double-strand break (DSB) repair by homologous recombination, promoting the assembly of the repair apparatus at DNA ends and participating in DNA-end resection. However, the molecular mechanisms of CtIP function in DSB repair remain unclear. Here, we present an atomic model for the three-dimensional architecture of human CtIP, derived from a multi-disciplinary approach that includes X-ray crystallography, small-angle X-ray scattering (SAXS) and diffracted X-ray tracking (DXT).

The effects of nostalgia cues in sexual health advertising.

An experimental design was conducted to investigate message effectiveness between reminiscence-bump format (RBF)/nostalgia message formats with traditional message formats in the context of health communication ads about sexual health. Reminiscence bumps, defined as a point in one's life where people can recall their life events, are proposed as a means for improving nostalgic advertising message effectiveness measure in the research. The dependent variables were emotional response, response efficacy (i.

Use of the PHM Framework to Create Safe-Sex Ads Targeted to Mature Women 50 and Older.

This research applies the Witte's persuasive health message (PHM) framework to the development of creative concepts that promote sexual health strategies to senior-aged women. The PHM framework proposes an integrated approach to improving message effectiveness and maximizing persuasion in health communication campaigns. A focus group method was used to explore two research questions focused on message effectiveness and persuasion.

CtIP tetramer assembly is required for DNA-end resection and repair.

Mammalian CtIP protein has major roles in DNA double-strand break (DSB) repair. Although it is well established that CtIP promotes DNA-end resection in preparation for homology-dependent DSB repair, the molecular basis for this function has remained unknown. Here we show by biophysical and X-ray crystallographic analyses that the N-terminal domain of human CtIP exists as a stable homotetramer.

Substance P release in the cat spinal cord upon afferent C-fibre stimulation is not attenuated by clonidine at analgesic doses.

In anaesthetized cats, antibody microprobes were used to measure the release of immunoreactive substance P (irSP) in the lumbar dorsal horn during electrical stimulation of primary afferent fibres at intensities suprathreshold for unmyelinated fibres. Release of irSP was detected in the region of the superficial dorsal horn. This evoked release was not reduced by clonidine hydrochloride, administered intravenously or by superfusion of the dorsal cord surface.

Fusion suppression and sub-barrier breakup of weakly bound nuclei.

The mechanism for the large suppression of complete fusion in the 9Be+208Pb reaction has been investigated through measurement of sub-barrier breakup of 9Be. Excluding breakup through the 8Be ground state, whose lifetime is too long, a prompt breakup component remains, having sufficient probability to explain the observed suppression of complete fusion. This appears to be associated with interactions at the nuclear surface.

Unexpected inhibition of fusion in nucleus-nucleus collisions.

Unstable heavy atomic nuclei not found in nature can be created by fusing two stable nuclei, in a process analogous to colliding charged droplets of liquid. Recently, the formation of a handful of super-heavy nuclei with atomic numbers 114 (ref. 1) and 116 (ref.

Long-term depression of C-fibre-evoked spinal field potentials by stimulation of primary afferent A delta-fibres in the adult rat.

Long-term potentiation (LTP) of spinal C-fibre-evoked field potentials can be induced by brief electrical stimulation of afferent C-fibres, by natural noxious stimulation of skin or by acute nerve injury. Here, we report that in urethane anaesthetized, adult rats prolonged high frequency burst stimulation of the sciatic nerve at Adelta-fibre strength produced long-term depression (LTD) of C-fibre-evoked field potentials, and also depressed the increased amplitudes of C-fibre-evoked field potentials recorded after LTP had been established (depotentiation). Electrical stimulation of Abeta-fibres failed to induce LTD or depotentiation.

Modulation of cutaneous nociceptor activity by electrical stimulation in the brain stem does not inhibit the nociceptive excitation of dorsal horn neurons.

In anesthetized cats, recordings were obtained from single lumbar dorsal horn neurons and from primary afferent fibers of the posterior tibial nerve excited by controlled noxious radiant heating of glabrous hindpaw skin. Electrical stimulation in four brain stem regions (periaqueductal gray and lateral reticular formation in the midbrain, raphe and reticular formation in the medulla) during noxious skin heating markedly reduced the nociceptive excitation of the dorsal horn neurons. In contrast, such brain stem stimulation had small and variable effects upon the noxious heat-evoked activity in the primary afferent fibers; both increases and decreases were observed.

Baclofen and the Release of Neuropeptides in the Cat Spinal Cord.

The antibody microprobe technique was used to study the effect of baclofen on the release of immunoreactive substance P and immunoreactive calcitonin gene-related peptide within the lower lumbar spinal cord of pentobarbitone-anaesthetized spinalized cats. Both peptides were released in the region of the substantia gelatinosa during ipsilateral noxious cutaneous stimulation or high-intensity electrical stimulation of a hind limb nerve. Intravenous administration of baclofen suppressed the excitation of lumbar dorsal horn neurons, but did not produce detectable alterations of the evoked release of immunoreactive substance P or immunoreactive calcitonin gene-related peptide in the superficial grey matter dorsal to these neurons.

Intraspinal release of substance P and calcitonin gene-related peptide during opiate dependence and withdrawal.

The antibody microprobe technique was used to study the release of immunoreactive substance P and immunoreactive calcitonin gene-related peptide within the lower lumbar spinal cord of anaesthetized spinalized cats pretreated twice daily for 3.5 days with increasing doses of morphine hydrochloride (2-20 mg/kg, i.p.

Dynorphin A: in vivo release in the spinal cord of the cat.

The antibody microprobe technique was used to study the release of immunoreactive dynorphin A within the lower lumbar spinal cord of anaesthetised cats. A basal release was observed in the dorsal horn, centered in the region of lamina I, but was abolished by spinal cord transection at the thoracolumbar junction. Release of dynorphin A in the lamina I region was evoked by high-frequency electrical stimulation of unmyelinated primary afferent fibres, whereas stimulation of myelinated (including A delta) afferents was ineffective.

Morphine does not reduce the intraspinal release of calcitonin gene-related peptide in the cat.

In anaesthetised cats, antibody microprobes were used to measure the release of immunoreactive calcitonin gene-related peptide (irCGRP) in the lumbar dorsal horn during stimulation of non-nociceptive or nociceptive primary afferent fibres. Release of irCGRP was detected in the substantia gelatinosa, where immunostaining for CGRP was subsequently observed. Intravenous administration of morphine did not affect release of irCGRP detected during either non-nociceptive or nociceptive afferent stimulation.

Morphine and substance P release in the spinal cord.

In anaesthetised cats, antibody microprobes were used to measure the release of immunoreactive substance P (irSP) in the lumbar dorsal horn during noxious cutaneous stimulation or high-intensity electrical stimulation of a hind limb nerve. The major region of irSP release detected was centered on the substantia gelatinosa, with lesser release at the dorsal cord surface. Release at these sites was unchanged by systemic administration of morphine, or of morphine followed by naloxone.

Electrical stimulation of primary afferent A fibres does not reduce substance P release in the dorsal horn of the cat.

Antibody microprobes were used to measure the release of immunoreactive substance P in the dorsal horn of anaesthetised cats during noxious mechanical or thermal stimulation of the hind limb. Concomitant electrical stimulation of the ipsilateral tibial or sural nerve at intensities sufficient to excite only A alpha beta or additionally A delta primary afferent fibres did not reduce the release of substance P evoked by noxious stimuli. The results suggest that segmental inhibition produced in the dorsal horn by electrical stimulation of peripheral nerves is not mediated by presynaptic inhibition of substance P release from nociceptive primary afferent fibres.

Somatostatin: evidence for a role in thermal nociception.

In barbiturate-anaesthetized spinalized cats, antibody microprobes were used to investigate the release of immunoreactive somatostatin (irSS) in the lumbar dorsal horn in response to cutaneous stimuli. In the absence of applied stimulation, a significant basal release of irSS was present in the region of the substantia gelatinosa. Such release was not increased by innocuous or noxious cutaneous mechanical stimuli nor by innocuous thermal stimuli, but was increased by noxious thermal stimulation.

Release of sensory neuropeptides in the spinal cord: studies with calcitonin gene-related peptide and galanin.

In anaesthetized cats, antibody microprobes were used to investigate the release of immunoreactive calcitonin gene-related peptide and galanin in the lower lumbar spinal cord. In the absence of applied stimulation, a basal release of both peptides was detected at the level of the substantia gelatinosa. This release of calcitonin gene-related peptide was not altered by innocuous thermal cutaneous stimulation nor by electrical stimulation of low-threshold myelinated primary afferent fibres, but was increased by noxious thermal or noxious mechanical cutaneous stimuli and by electrical stimulation of unmyelinated primary afferents.