Activation of the galanin receptor 2 in the periphery reverses nerve injury-induced allodynia

<p>Abstract</p> <p>Background</p> <p>Galanin is expressed at low levels in the intact sensory neurons of the dorsal root ganglia with a dramatic increase after peripheral nerve injury. The neuropeptide is also expressed in primary afferent terminals in the dorsal horn, spinal inter-neurons and in a number of brain regions known to modulate nociception. Intrathecal administration of galanin modulates sensory responses in a dose-dependent manner with inhibition at high doses. To date it is unclear which of the galanin receptors mediates the anti-nociceptive effects of the neuropeptide and whether their actions are peripherally and/or centrally mediated. In the present study we investigated the effects of direct administration into the receptive field of galanin and the galanin receptor-2/3-agonist Gal2-11 on nociceptive primary afferent mechanical responses in intact rats and mice and in the partial saphenous nerve injury (PSNI) model of neuropathic pain.</p> <p>Results</p> <p>Exogenous galanin altered the responses of mechano-nociceptive C-fibre afferents in a dose-dependent manner in both naive and nerve injured animals, with low concentrations facilitating and high concentrations markedly inhibiting mechano-nociceptor activity. Further, use of the galanin fragment Gal2-11 confirmed that the effects of galanin were mediated by activation of galanin receptor-2 (GalR2). The inhibitory effects of peripheral GalR2 activation were further supported by our demonstration that after PSNI, mechano-sensitive nociceptors in galanin over-expressing transgenic mice had significantly higher thresholds than in wild type animals, associated with a marked reduction in spontaneous neuronal firing and C-fibre barrage into the spinal cord.</p> <p>Conclusions</p> <p>These findings are consistent with the hypothesis that the high level of endogenous galanin in injured primary afferents activates peripheral GalR2, which leads to an increase in C-fibre mechanical activation thresholds and a marked reduction in evoked and ongoing nociceptive responses.</p

Recognition memory, self-other source memory, and theory-of-mind in children with autism spectrum disorder.

This study investigated semantic and episodic memory in autism spectrum disorder (ASD), using a task which assessed recognition and self-other source memory. Children with ASD showed undiminished recognition memory but significantly diminished source memory, relative to age- and verbal ability-matched comparison children. Both children with and without ASD showed an “enactment effect”, demonstrating significantly better recognition and source memory for self-performed actions than other-person-performed actions. Within the comparison group, theory-of-mind (ToM) task performance was significantly correlated with source memory, specifically for other-person-performed actions (after statistically controlling for verbal ability). Within the ASD group, ToM task performance was not significantly correlated with source memory (after controlling for verbal ability). Possible explanations for these relations between source memory and ToM are considered

Fatal Cases of Influenza A in Childhood

In the northern hemisphere winter of 2003–04 antigenic variant strains (A/Fujian/411/02 –like) of influenza A H3N2 emerged. Circulation of these strains in the UK was accompanied by an unusually high number of laboratory confirmed influenza associated fatalities in children. This study was carried out to better understand risk factors associated with fatal cases of influenza in children.Case histories, autopsy reports and death registration certificates for seventeen fatal cases of laboratory confirmed influenza in children were analyzed. None had a recognized pre-existing risk factor for severe influenza and none had been vaccinated. Three cases had evidence of significant bacterial co-infection. Influenza strains recovered from fatal cases were antigenically similar to those circulating in the community. A comparison of protective antibody titres in age stratified cohort sera taken before and after winter 2003–04 showed that young children had the highest attack rate during this season (21% difference, 95% confidence interval from 0.09 to 0.33, p = 0.0009). Clinical incidences of influenza-like illness (ILI) in young age groups were shown to be highest only in the years when novel antigenic drift variants emerged.This work presents a rare insight into fatal influenza H3N2 in healthy children. It confirms that circulating seasonal influenza A H3N2 strains can cause severe disease and death in children in the apparent absence of associated bacterial infection or predisposing risk factors. This adds to the body of evidence demonstrating the burden of severe illness due to seasonal influenza A in childhood

The Ctf18 RFC-like complex positions yeast telomeres but does not specify their replication time

Peer reviewedPreprin

The biogeography of South African terrestrial plant invasions

Thousands of plant species have been introduced, intentionally and accidentally, to South Africa from many parts of the world. Alien plants are now conspicuous features of many South African landscapes and hundreds of species have naturalised (i.e. reproduce regularly without human intervention), many of which are also invasive (i.e. have spread over long distances). There is no comprehensive inventory of alien, naturalised, and invasive plants for South Africa, but 327 plant taxa, most of which are invasive, are listed in national legislation. We collated records of 759 plant taxa in 126 families and 418 genera that have naturalised in natural and semi-natural ecosystems. Over half of these naturalised taxa are trees or shrubs, just under a tenth are in the families Fabaceae (73 taxa) and Asteraceae (64); genera with the most species are Eucalyptus,Acacia, and Opuntia. The southern African Plant Invaders Atlas (SAPIA) provides the best data for assessing the extent of invasions at the national scale. SAPIA data show that naturalised plants occur in 83% of quarter-degree grid cells in the country. While SAPIA data highlight general distribution patterns (high alien plant species richness in areas with high native plant species richness and around the main human settlements), an accurate, repeatable method for estimating the area invaded by plants is lacking. Introductions and dissemination of alien plants over more than three centuries, and invasions over at least 120 years (and especially in the last 50 years) have shaped the distribution of alien plants in South Africa. Distribution patterns of naturalised and invasive plants define four ecologically-meaningful clusters or “alien plant species assemblage zones”, each with signature alien plant taxa for which trait-environment interactions can be postulated as strong determinants of success. Some widespread invasive taxa occur in high frequencies across multiple zones; these taxa occur mainly in riparian zones and other azonal habitats,or depend on human-mediated disturbance, which weakens or overcomes the factors that determine specificity to any biogeographical region

A contingent valuation study to estimate the parental willingness-to-pay for childhood diarrhoea and gender bias among rural households in India

We used contingent valuation technique to estimate the parental willingness to pay for an episode of diarrhoea among 324 children of both sexes aged between five and seven years in two rural villages of Chennai in India. The aim was to examine if there was any gender bias in the parental willingness to treat children for a diarrhoeal episode, and if so to what extent. The willingness to pay was specified as a hedonic function of the duration and severity of an episode, and of parents' socioeconomic characteristics. The findings suggest that parents were willing to pay more to protect their male child compared to the female child suffering from a diarrhoeal episode. The median willingness to pay to avoid an episode for male and female children were calculated at Rs. 33.7 (approx. US$0.72) and Rs. 25.2 (approx. US$ 0.54) respectively – a difference of around 34%. After adjusting for the greater duration and severity of the illness, it was found that the difference between the two medians increased to 51%

The Expression and Localization of N-Myc Downstream-Regulated Gene 1 in Human Trophoblasts

The protein N-Myc downstream-regulated gene 1 (NDRG1) is implicated in the regulation of cell proliferation, differentiation, and cellular stress response. NDRG1 is expressed in primary human trophoblasts, where it promotes cell viability and resistance to hypoxic injury. The mechanism of action of NDRG1 remains unknown. To gain further insight into the intracellular action of NDRG1, we analyzed the expression pattern and cellular localization of endogenous NDRG1 and transfected Myc-tagged NDRG1 in human trophoblasts exposed to diverse injuries. In standard conditions, NDRG1 was diffusely expressed in the cytoplasm at a low level. Hypoxia or the hypoxia mimetic cobalt chloride, but not serum deprivation, ultraviolet (UV) light, or ionizing radiation, induced the expression of NDRG1 in human trophoblasts and the redistribution of NDRG1 into the nucleus and cytoplasmic membranes associated with the endoplasmic reticulum (ER) and microtubules. Mutation of the phosphopantetheine attachment site (PPAS) within NDRG1 abrogated this pattern of redistribution. Our results shed new light on the impact of cell injury on NDRG1 expression patterns, and suggest that the PPAS domain plays a key role in NDRG1's subcellular distribution. © 2013 Shi et al

Memory for Self-Performed Actions in Individuals with Asperger Syndrome

Memory for action is enhanced if individuals are allowed to perform the corresponding movements, compared to when they simply listen to them (enactment effect). Previous studies have shown that individuals with Autism Spectrum Disorders (ASD) have difficulties with processes involving the self, such as autobiographical memories and self performed actions. The present study aimed at assessing memory for action in Asperger Syndrome (AS). We investigated whether adults with AS would benefit from the enactment effect when recalling a list of previously performed items vs. items that were only visually and verbally experienced through three experimental tasks (Free Recall, Old/New Recognition and Source Memory). The results showed that while performance on Recognition and Source Memory tasks was preserved in individuals with AS, the enactment effect for self-performed actions was not consistently present, as revealed by the lower number of performed actions being recalled on the Free Recall test, as compared to adults with typical development. Subtle difficulties in encoding specific motor and proprioceptive signals during action execution in individuals with AS might affect retrieval of relevant personal episodic information. These disturbances might be associated to an impaired action monitoring system

Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands

Haemonchus contortus appears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resistance, we compared the abomasal mucosal transcriptome of the two breeds in response to Haemonchus infection using RNAseq technology. The transcript abundance of 711 and 50 genes were significantly impacted by infection in CHB and CS, respectively (false discovery rate <0.05) while 27 of these genes were significantly affected in both breeds. Likewise, 477 and 16 Gene Ontology (GO) terms were significantly enriched in CHB and CS, respectively (P < 1.0 × 10(−4)). A broad range of mechanisms have evolved in resistant CHB to provide protection against the parasite. Our findings suggest that readily inducible acute inflammatory responses, complement activation, accelerated cell proliferation and subsequent tissue repair, and immunity directed against parasite fecundity all contributed to the development of host resistance to parasitic infection in the resistant breed

Quantification of the pathological response and fate in the lung and pleura of chrysotile in combination with fine particles compared to amosite-asbestos following short-term inhalation exposure

The marked difference in biopersistence and pathological response between chrysotile and amphibole asbestos has been well documented. This study is unique in that it has examined a commercial chrysotile product that was used as a joint compound. The pathological response was quantified in the lung and translocation of fibers to and pathological response in the pleural cavity determined. This paper presents the final results from the study. Rats were exposed by inhalation 6 h/day for 5 days to a well-defined fiber aerosol. Subgroups were examined through 1 year. The translocation to and pathological response in the pleura was examined by scanning electron microscopy and confocal microscopy (CM) using noninvasive methods.The number and size of fibers was quantified using transmission electron microscopy and CM. This is the first study to use such techniques to characterize fiber translocation to and the response of the pleural cavity. Amosite fibers were found to remain partly or fully imbedded in the interstitial space through 1 year and quickly produced granulomas (0 days) and interstitial fibrosis (28 days). Amosite fibers were observed penetrating the visceral pleural wall and were found on the parietal pleural within 7 days postexposure with a concomitant inflammatory response seen by 14 days. Pleural fibrin deposition, fibrosis, and adhesions were observed, similar to that reported in humans in response to amphibole asbestos. No cellular or inflammatory response was observed in the lung or the pleural cavity in response to the chrysotile and sanded particles (CSP) exposure. These results provide confirmation of the important differences between CSP and amphibole asbestos