The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age >/= 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN.     

Spectral correspondence between visual spectral sensitivity and bioluminescence emission spectra in the click beetle Pyrophorus punctatissimus (Coleoptera: Elateridae)

The presence of two spectral mechanisms, near-ultraviolet and green (lambda(max)=545nm), is strongly suggested by electroretinographic visual spectral sensitivity curves obtained under dark and red chromatic adaptation conditions in the compound eyes of the click beetle Pyrophorus punctatissimus. The bioluminescence emission of the dorsal prothoracic lanterns is deep green (lambda(max)=543nm) and that of the ventral abdominal lantern is lime green (lambda(max)=556nm) in colour in P. punctatissimus. A broad green visual receptor would detect both deep green and lime green bioluminescent optical signals.     

Differential Role of Hippocampal cAMP-Dependent Protein Kinase in Short- and Long-Term Memory

One-trial step-down inhibitory (passive) avoidance training is followed by two peaks of cAMP-dependent protein kinase (PKA) activity in rat CA1: one immediately after training and the other 3 h later. The second peak relies on the first: Immediate posttraining infusion into CA1 of the inhibitor of the regulatory subunit of PKA, Rp-cAMPS, at a dose that reduces PKA activity during less than 90 min, cancelled both peaks. Long-term memory (LTM) of this task measured at 24 h depends on the two peaks: Rp-cAMPS given into CA1 0 or 175 min posttraining, but not between those times, blocked LTM. However, the effect of immediate posttraining Rp-cAMPS on LTM could not be reversed by the activator of the regulatory subunit of PKA, Sp-cAMPS, given at 180 min, which suggests that, for LTM, the first peak may be more important than the second. When given at 0, 22, 45, or 90, but not at 175 min from training, Rp-cAMPS blocked short-term memory (STM) measured at 90 or 180 min. This effect of immediate posttraining Rp-cAMPS infusion on STM but not that on LTM was readily reversed by Sp-cAMPS infused 22 min later. On its own, Sp-cAMPS had effects exactly opposite to those of the inhibitor. It enhanced LTM when given at 0 or 175 min from training, and it enhanced STM when given at 0, 22, 45, or 90 min from training. These findings show that STM and LTM formation require separate PKA-dependent processes in CA1. STM relies on the continued activity of the enzyme during the first 90 min. LTM relies on the two peaks of PKA activity that occur immediately and 180 min posttraining.     

Arabidopsis nonresponding to oxylipins locus NOXY7 encodes a yeast GCN1 homolog that mediates noncanonical translation regulation and stress adaptation

Stress adaptation and translational regulation was studied using noxy7 (nonresponding to oxylipins7) from a series of Arabidopsis thaliana mutants. We identified the noxy7 mutation in At1g64790, which encodes a homolog of the yeast translational regulator General Control Nonderepressible1 (GCN1) that activates the GCN2 kinase; GCN2 in turn phosphorylates the α subunit of the translation initiation factor eIF2. This regulatory circuit is conserved in yeast and mammals, in which phosphorylated eIF2α (P‐eIF2α) facilitates stress adaptation by inhibiting protein synthesis. In phenotypic and de novo protein synthesis studies with Arabidopsis mutants, we found that NOXY7/GCN1 and GCN2 mediate P‐eIF2α formation and adaptation to amino acid deprivation; however, P‐eIF2α formation is not linked to general protein synthesis arrest. Additional evidence suggested that NOXY7/GCN1 but not GCN2 regulates adaptation to mitochondrial dysfunction, high boron concentration, and activation of plant immunity to infection by Pseudomonas syringae pv tomato (Pst). In these responses, NOXY7/GCN1 acts with GCN20 to regulate translation in a noncanonical pathway independently of GCN2 and P‐eIF2α. These results show the lesser functional relevance of GCN2 and P‐eIF2α in plants relative to other eukaryotes and highlight the prominent role of NOXY7/GCN1 and GCN20 in regulation of translation and stress adaptation in plants.     

Meta-QTL analysis of seed iron and zinc concentration and content in common bean (<Emphasis Type="Italic">Phaseolus vulgaris</Emphasis> L.)

Key message

Twelve meta-QTL for seed Fe and Zn concentration and/or content were identified from 87 QTL originating from seven population grown in sixteen field trials. These meta-QTL include 2 specific to iron, 2 specific to zinc and 8 that co-localize for iron and zinc concentrations and/or content.

Abstract

Common bean (Phaseolus vulgaris L.) is the most important legume for human consumption worldwide and it is an important source of microelements, especially iron and zinc. Bean biofortification breeding programs develop new varieties with high levels of Fe and Zn targeted for countries with human micronutrient deficiencies. Biofortification efforts thus far have relied on phenotypic selection of raw seed mineral concentrations in advanced generations. While numerous quantitative trait loci (QTL) studies have been conducted to identify genomic regions associated with increased Fe and Zn concentration in seeds, these results have yet to be employed for marker-assisted breeding. The objective of this study was to conduct a meta-analysis from seven QTL studies in Andean and Middle American intra- and inter-gene pool populations to identify the regions in the genome that control the Fe and Zn levels in seeds. Two meta-QTL specific to Fe and two meta-QTL specific to Zn were identified. Additionally, eight Meta QTL that co-localized for Fe and Zn concentration and/or content were identified across seven chromosomes. The Fe and Zn shared meta-QTL could be useful candidates for marker-assisted breeding to simultaneously increase seed Fe and Zn. The physical positions for 12 individual meta-QTL were identified and within five of the meta-QTL, candidate genes were identified from six gene families that have been associated with transport of iron and zinc in plants.

     

Chickens with humanized immunoglobulin genes generate antibodies with high affinity and broad epitope coverage to conserved targets

Transgenic animal platforms for the discovery of human monoclonal antibodies have been developed in mice, rats, rabbits and cows. The immune response to human proteins is limited in these animals by their tolerance to mammalian-conserved epitopes. To expand the range of epitopes that are accessible, we have chosen an animal host that is less phylogenetically related to humans. Specifically, we generated transgenic chickens expressing antibodies from immunoglobulin heavy and light chain loci containing human variable regions and chicken constant regions. From these birds, paired human light and heavy chain variable regions are recovered and cloned as fully human recombinant antibodies. The human antibody-expressing chickens exhibit normal B cell development and raise immune responses to conserved human proteins that are not immunogenic in mice. Fully human monoclonal antibodies can be recovered with sub-nanomolar affinities. Binning data of antibodies to a human protein show epitope coverage similar to wild type chickens, which we previously showed is broader than that produced from rodent immunizations.     

Ebselen impairs cellular oxidative state and induces endoplasmic reticulum stress and activation of crucial mitogen‐activated protein kinases in pancreatic tumour AR42J cells

Ebselen (2‐phenyl‐1,2‐benzisoselenazol‐3(2H)‐one) is an organoselenium radical scavenger compound, which has strong antioxidant and anti‐inflammatory effects. However, evidence suggests that this compound could exert deleterious actions on cell physiology. In this study, we have analyzed the effect of ebselen on rat pancreatic AR42J cells. Cytosolic free‐Ca²⁺ concentration ([Ca²⁺]_c), cellular oxidative status, setting of endoplasmic reticulum stress, and phosphorylation of major mitogen‐activated protein kinases were analyzed. Our results show that ebselen evoked a concentration‐dependent increase in [Ca²⁺]_c. The compound induced an increase in the generation of reactive oxygen species in the mitochondria. We also observed an increase in global cysteine oxidation in the presence of ebselen. In the presence of ebselen an impairment of cholecystokinin‐evoked amylase release was noted. Moreover, involvement of the unfolded protein response markers, ER chaperone and signaling regulator GRP78/BiP, eukaryotic translation initiation factor 2α and X‐box binding protein 1 was detected. Finally, increases in the phosphorylation of SAPK/JNK, p38 MAPK, and p44/42 MAPK in the presence of ebselen were also observed. Our results provide evidences for an impairment of cellular oxidative state and enzyme secretion, the induction of endoplasmic reticulum stress and the activation of crucial mitogen‐activated protein kinases in the presence of ebselen. As a consequence ebselen exerts a potential toxic effect on AR42J cells.     

Differential long-term impacts of a management control program of axis deer and wild boar in a protected area of north-eastern Argentina

Exotic ungulates are among the top global invasive mammals and a threat to biodiversity. Axis deer (Axis axis) and wild boar (Sus scrofa) are of increasing concern in multiple regions. A management program reduced wild boar abundance and soil damage below target levels through controlled still shooting from watchtowers and dog-hunting performed by recreational hunters at El Palmar National Park, Argentina. Here we assess program impacts on axis deer over a 10-year period in which 2380 deer were dispatched, and document two largely unexpected outcomes: increasing axis deer abundance toward a plateau, and a strong inverse correlation between deer and wild boar numbers. Unlike the initial steep decline and subsequent stabilization of wild boar, deer abundance indexed by standardized catch-per-unit-effort increased at 37.6% per year over 0–5 years post-intervention (YPI) and stabilized from 7 YPI on when still-shooting effort averaged 948 hunting party-hours per quarter. Deer catch was non-linearly related to still-shooting effort. Timing of deer and boar catches did not differ significantly regardless of sex, season and YPI. Catch-per-unit-effort indices and nightly spotlight deer counts showed similarly increasing trends. The fraction of older adult deer declined over 0–4 YPI and remained stable thereafter. Sex ratios were consistently skewed toward males only among older adults. Failure to reduce deer abundance may be explained by several major processes: protracted exponential growth of the deer population after park invasion; deer regional expansion with increasing immigration; insufficient sex- and stage-biased hunting mortality, and competitor (and perhaps predator) release from wild boar.     

Step on it: can footprints from tracking tunnels be used to identify lizard species?

There are few effective or efficient established methods for monitoring cryptic herpetofauna. Footprint tracking tunnels are routinely used to index small mammal populations, but also have potential for monitoring herpetofauna. We evaluated the utility of tracking tunnels for identification of New Zealand lizards using captive- and wild-sourced animals (four skink and eight gecko species). All skink prints that we obtained were indistinct or obscure, but we obtained relatively clear, measurable prints for all gecko species. We found that identification to species level was possible for the two gecko species for which we had a large sample—Naultinus gemmeus and Woodworthia ‘Otago large’—using linear discriminant analysis (the best model correctly assigned 96.1% of individuals). Our findings suggest that footprints from tracking tunnels may be used to distinguish between species of geckos. Additional research is needed to assess the ability to further discriminate intra- and inter-genera lizard footprints from tracking tunnels, and the utility of the technique for surveying and monitoring lizard populations.     

PCR gut analysis reveals that Tenuiphantes tenuis (Araneae: Linyphiidae) is a potentially significant predator of Argentine stem weevil,Listronotus bonariensis (Coleoptera: Curculionidae), in New Zealand pastures

Polymerase chain reaction (PCR) gut analysis was conducted on specimens of the introduced spider Tenuiphantes tenuis collected from dairy pasture in Canterbury, New Zealand. PCR primers were specifically designed to amplify a fragment of the mitochondrial gene cytochrome c oxidase subunit 1 (COI) from Listronotus bonariensis and revealed that this major pasture pest species is consumed in the field by T. tenuis. The field predation rate of L. bonariensis by T. tenuis was estimated from our PCR results together with published data on the degradation of DNA and the density of T. tenuis in Canterbury pastures. We found that T. tenuis is a potentially significant predator of L. bonariensis in New Zealand pastures.