Mutation Carriers with Reduced C-Afferent Density Reveal Cortical Dynamics of Pain-Action Relationship during Acute Pain.

The evidence that action shapes perception has become widely accepted, for example, in the domain of vision. However, the manner in which action-relevant factors might influence the neural dynamics of acute pain processing has remained underexplored, particularly the functional roles of anterior insula (AI) and midanterior cingulate cortex (mid-ACC), which are frequently implicated in acute pain. To address this, we examined a unique group of heterozygous carriers of the rare R221W mutation on the nerve growth factor (NGF) gene. R221W carriers show a congenitally reduced density of C-nociceptor afferent nerves in the periphery, but can nonetheless distinguish between painful and nonpainful stimulations. Despite this, carriers display a tendency to underreact to acute pain behaviorally, thus exposing a potential functional gap in the pain-action relationship and allowing closer investigation of how the brain integrates pain and action information. Heterozygous R221W carriers and matched controls performed a functional magnetic resonance imaging (fMRI) task designed to dissociate stimulus type (painful or innocuous) from current behavioral relevance (relevant or irrelevant), by instructing participants to either press or refrain from pressing a button during thermal stimulation. Carriers' subjective pain thresholds did not differ from controls', but the carrier group showed decreased task accuracy. Hemodynamic activation in AI covaried with task performance, revealing a functional role in pain-action integration with increased responses for task-relevant painful stimulation ("signal," requiring button-press execution) over task-irrelevant stimulation ("noise," requiring button-press suppression). As predicted, mid-ACC activation was associated with action execution regardless of pain. Functional connectivity between AI and mid-ACC increased as a function of reported urge to withdraw from the stimulus, suggesting a joint role for these regions in motivated action during pain. The carrier group showed greater activation of primary sensorimotor cortices-but not the AI and mid-ACC regions-during pain and action, suggesting compensatory processing. These findings indicate a critical role for the AI-mid-ACC axis in supporting a flexible, adaptive action selection during pain, alongside the accompanying subjective experience of an urge to escape the pain.

Simple Wave-Optical Superpositions as Prime Number Sieves.

We encode the sequence of prime numbers into simple superpositions of identical waves, mimicking the archetypal prime number sieve of Eratosthenes. The primes are identified as zeros accompanied by phase singularities in a physically generated wave field for integer valued momenta. Similarly, primes are encoded in the diffraction pattern from a simple single aperture and in the harmonics of a single vibrating resonator. Further, diffraction physics connections to number theory reveal how to encode all Gaussian primes, twin primes, and how to construct wave fields with amplitudes equal to the divisor function at integer spatial frequencies. Remarkably, all of these basic diffraction phenomena reveal that the naturally irregular sequence of primes can arise from trivially ordered wave superpositions.

Quantitative elemental analysis of bovine ovarian follicles using X-ray fluorescence imaging.

The X-ray Fluorescence Micro-spectroscopy (XFM) beamline at the Australian Synchrotron was used to image 97 follicle histological sections from 45 different bovine ovaries focusing on healthy antral follicles ranging from small (<4 mm) up to preovulatory sizes (>16 mm) and on antral follicles undergoing atresia. This analysis identified five elements (Cu, Fe, Zn, Se and Br) consistently present within the ovarian tissue with Fe, Zn and Se localised to specific structures. GeoPIXE v6.4g was subsequently used to extract quantitative information pertaining to the elemental concentrations surrounding each of these follicles. Statistical analysis suggested that significant elemental differences were evident between follicle groups sorted according to their health status (Fe and Br), and their size (Se). Se appeared to be the element which most greatly distinguished large antral follicles from smaller counterparts. The ability to use synchrotron radiation to measure trace element distributions in bovine follicles at such high resolutions could have a significant impact on understanding the mechanisms of follicular development. This research is intended to form a baseline study of healthy cycling ovaries which could later be extended to disease states, thereby improving our current understanding of infertility and endocrine diseases involving the ovary.

Effect of environment on the long-term consequences of chronic pain.

Much evidence from pain patients and animal models shows that chronic pain does not exist in a vacuum but has varied comorbidities and far-reaching consequences. Patients with long-term pain often develop anxiety and depression and can manifest changes in cognitive functioning, particularly with working memory. Longitudinal studies in rodent models also show the development of anxiety-like behavior and cognitive changes weeks to months after an injury causing long-term pain. Brain imaging studies in pain patients and rodent models find that chronic pain is associated with anatomical and functional alterations in the brain. Nevertheless, studies in humans reveal that lifestyle choices, such as the practice of meditation or yoga, can reduce pain perception and have the opposite effect on the brain as does chronic pain. In rodent models, studies show that physical activity and a socially enriched environment reduce pain behavior and normalize brain function. Together, these studies suggest that the burden of chronic pain can be reduced by nonpharmacological interventions.

Correction: X-Ray fluorescence imaging and other analyses identify selenium and GPX1 as important in female reproductive function.

Correction for 'X-Ray fluorescence imaging and other analyses identify selenium and GPX1 as important in female reproductive function' by M. J. Ceko et al., Metallomics, 2014, DOI: .

X-Ray fluorescence imaging and other analyses identify selenium and GPX1 as important in female reproductive function.

Studies of selenium (Se) status indicate that Se is necessary for fertility but how precisely is not known. We aimed to show that Se was important in bovine female reproductive function. The elemental distribution in the bovine ovary (n = 45 sections) was identified by X-ray fluorescence (XRF) imaging. Se was consistently localized to the granulosa cell layer of large (>10 mm) healthy follicles. Inductively Coupled Plasma - Mass Spectrometry revealed tenfold higher Se in the bovine follicle wall compared to corpora lutea. Gene expression analysis of selenoprotein genes GPX1, GPX3, VIMP and SELM in bovine granulosa cells revealed that only GPX1 was significantly up-regulated in large healthy follicles compared to the small healthy or atretic follicles (P < 0.05). Western immunoblotting identified GPX1 protein in bovine granulosa cells of large healthy follicles, but not of small healthy follicles. To assess if GPX1 was important in human follicles, cumulus cells from women undergoing IVF/ICSI with single embryo transfer were collected. Oocytes and embryos were cultured and transferred independently in 30 patients undergoing elective single embryo transfer. Gene expression of GPX1 was significantly higher in human cumulus cells from cumulus-oocyte complexes yielding a pregnancy (P < 0.05). We present the first XRF imaging of mammalian ovaries showing that Se is consistently localized to the granulosa cells of large healthy follicles. We conclude that Se and selenoproteins are elevated in large healthy follicles and may play a critical role as an antioxidant during late follicular development.