Quantitative trait loci and genes associated with salmonid alphavirus load in Atlantic salmon: implications for pancreas disease resistance and tolerance.

Salmonid alphavirus infection results in pancreas disease causing severe economic losses for Atlantic salmon aquaculture. Knowledge about genes and pathways contributing to resistance is limited. A 54 K SNP panel was used to genotype 10 full-sibling families each consisting of ~ 110 offspring challenged with salmonid alphavirus subtype 3. Relative heart viral load was assessed at 4- and 10-weeks post-infection using quantitative PCR. A moderate genomic heritability of viral load at 4 weeks (0.15-0.21) and a high positive correlation with survival (0.91-0.98) were detected. Positions of QTL detected on chromosome 3 matched those for survival detected by other studies. The SNP of highest significance occurred in the 3' untranslated region of gig1, a fish-specific antiviral effector. Locus B of immunoglobulin heavy chain mapped to an area containing multiple SNPs with genome-wide association. Heart mRNA-seq comparing parr from families with high- versus low-genomic breeding value, and matching sample genotypes for SNPs, identified two eQTL for salmonid alphavirus load. Immune genes associated with trans-eQTL were numerous and spread throughout the genome. QTL regions contained several genes with known or predicted immune functions, some differentially expressed. The putative functional genes and variants identified could help improve marker-based selection for pancreas disease resistance.

Response of the Salmon Heart Transcriptome to Pancreas Disease: Differences Between High- and Low-Ranking Families for Resistance.

Pancreas disease caused by salmonid alphaviruses leads to severe losses in Atlantic salmon aquaculture. The aim of our study was to gain a better understanding of the biological differences between salmon with high and low genomic breeding values (H-gEBV and L-gEBV respectively) for pancreas disease resistance. Fish from H- and L-gEBV families were challenged by intraperitoneal injection of salmonid alphavirus or co-habitation with infected fish. Mortality was higher with co-habitation than injection, and for L- than H-gEBV. Heart for RNA-seq and histopathology was collected before challenge and at four- and ten-weeks post-challenge. Heart damage was less severe in injection-challenged H- than L-gEBV fish at week 4. Viral load was lower in H- than L-gEBV salmon after co-habitant challenge. Gene expression differences between H- and L-gEBV manifested before challenge, peaked at week 4, and moderated by week 10. At week 4, H-gEBV salmon showed lower expression of innate antiviral defence genes, stimulation of B- and T-cell immune function, and weaker stress responses. Retarded resolution of the disease explains the higher expression of immune genes in L-gEBV at week 10. Results suggest earlier mobilization of acquired immunity better protects H-gEBV salmon by accelerating clearance of the virus and resolution of the disease.

Resistance of Wheat Genotypes to Root-Lesion Nematode (Pratylenchus thornei) Can be Used to Predict Final Nematode Population Densities, Crop Greenness, and Grain Yield in the Field.

The root-lesion nematode Pratylenchus thornei is a major pathogen of wheat (Triticum aestivum) in many regions globally. Resistance of wheat genotypes to P. thornei can be determined from final nematode population densities in glasshouse experiments but combining results across multiple experiments presents challenges. Here, we use a factor analytic method for multiexperiment analysis of final population densities of P. thornei for 1,096 unique wheat genotypes in 22 glasshouse experiments. The resistance to P. thornei of the genotypes was effectively represented by a two-factor model with rotation of the axes to a principal components solution. Principal axes 1 and 2 (PA1 and PA2) accounted for 79 and 11% of the genetic variance, respectively, over all experiments. Final population densities of P. thornei as empirical best linear unbiased predictors (PA[1+2]-eBLUPs) from the combined glasshouse experiments were highly predictive (P < 0.001) of final nematode population densities in the soil profile, crop canopy greenness (normalized difference vegetation index), and grain yield of wheat genotypes in P. thornei-infested fields in the Australian subtropical grain region. Nine categories of resistance ratings for wheat genotypes from resistant to very susceptible were based on subdivision of the range of PA(1+2)-eBLUPs for use in growers' sowing guides. Nine genotypes were nominated as references for future resistance experiments. Most (62%) Australian wheat genotypes were in the most susceptible three categories (susceptible, susceptible to very susceptible, and very susceptible). However, resistant germplasm characterized in this study could be used in plant breeding to considerably improve the overall resistance of Australian wheat crops.

Does Dynamic Tape change the walking biomechanics of women with greater trochanteric pain syndrome? A blinded randomised controlled crossover trial.

OBJECTIVES: There is considerable debate among clinicians as to whether sports tape can provide mechanical support and pain relief. People with greater trochanteric pain syndrome (GTPS) have increased adduction moment, adduction angle and pelvic obliquity, likely contributing to the continuation of the pathology. We aimed to see if Dynamic Tape® could control these movements and reduce pain. METHODS: Fifty women with GTPS participated in a three-dimensional gait analysis. Each participant performed three walking trials: baseline, and two subsequent trials, with active and sham applications of Dynamic Tape. The order of active and sham taping was randomised. Differences in kinetic and kinematic data were analysed using mixed model linear regressions for each condition. Pain scores were obtained before and immediately after walking trials. RESULTS: Hip adduction moment was reduced at first peak by both active (p < 0.001) and sham tape (p = 0.028), with no between group difference; at second peak by the active taping (p < 0.001), with a between-group difference (p < 0.001). Adduction angle was reduced at first peak by both active (p < 0.001) and sham taping (p = 0.026), with the active taping producing a larger effect (p = 0.004); at mid-stance by active taping (p = 0.003), with a between-group difference (p = 0.002); there was no reduction at second peak. Internal rotation was reduced at the first (p < 0.001) and second peaks (p < 0.001), and mid-stance by the active taping alone (p < 0.001). Pelvic obliquity was reduced at the first peak (p = 0.019), mid-stance (p < 0.001) and second peak (p < 0.001) by the active tape, with a between-group difference at mid-stance (p = 0.03). Both the active and sham taping resulted in a clinically meaningful pain reduction. CONCLUSION: Dynamic Tape produced a mechanical effect and a meaningful reduction in pain in women with GTPS. The extent that placebo or somatosensory input may have had on these results is not clear. CLINICAL TRIAL REGISTRATION NUMBER: ACTRN12617001611314.

Time-resolved stimulated emission depletion and energy transfer dynamics in two-photon excited EGFP.

Time and polarization-resolved stimulated emission depletion (STED) measurements are used to investigate excited state evolution following the two-photon excitation of enhanced green fluorescent protein (EGFP). We employ a new approach for the accurate STED measurement of the hitherto unmeasured degree of hexadecapolar transition dipole moment alignment α40 present at a given excitation-depletion (pump-dump) pulse separation. Time-resolved polarized fluorescence measurements as a function of pump-dump delay reveal the time evolution of α40 to be considerably more rapid than predicted for isotropic rotational diffusion in EGFP. Additional depolarization by homo-Förster resonance energy transfer is investigated for both α20 (quadrupolar) and α40 transition dipole alignments. These results point to the utility of higher order dipole correlation measurements in the investigation of resonance energy transfer processes.

Zika virus: oral healthcare implications.

Zika virus (ZIKV) infection has been recognised since 1947, but just recently it became a worldwide major public health problem. The most common features of ZIKV infection are fever, cutaneous rash, arthralgia and conjunctivitis but most affected patients with the clinical disease present with only mild symptoms. However, severe neurological complications have been described: there is an occasional association with Guillain-Barre syndrome, and emerging data indicate an association between vertical transmission of ZIKV infection and microcephaly, but no specific orofacial manifestations have yet been reported. ZIKV is present in body fluids and has also been demonstrated in the saliva, but there is as yet no reliable evidence to support ZIKV transmission via this pathway. Transmission in oral health care should be effectively prevented using standard infection control measures. There are currently no specific treatments for Zika virus disease and no vaccines available, so prevention of ZIKV is based on vector control.

Dual oxidase 2 and glutathione peroxidase gene expression are elevated in hyperimmunized sheep challenged with Haemonchus contortus.

A sequential biopsy sampling method was used to investigate oxidant and antioxidant gene responses in resistant sheep challenged with Haemonchus contortus larvae or a sham saline challenge. The expression of key sheep oxidant and antioxidant producing genes were measured in sequential samples removed from the abomasums at days 0, 1, 2, 3, 5, 7 and 28 post challenge. Gene expression levels at each time point were compared to expression at day 0, and levels of the various genes were also correlated to other markers of infection including immune cell counts and cytokine gene expression. The early response to larval challenge infection in resistant animals was marked by a divergence of two groups of host oxidant producing genes: the dual oxidase group (DUOX2/DUOXA2) showing increases in expression to day 7, while members of the phagocytic NADPH oxidase (PHOX) group showed significant decreases in expression. The change in DUOX2 expression between days zero and seven, when host resistance to infection is mediated, was negatively correlated to final worm burden suggesting NADPH oxidase expression may play a role in parasite expulsion. Expression of the DUOX group oxidants was positively correlated to expression of the Th2 cytokine IL4. Changes in host antioxidant pathways between different members of the glutathione peroxidase family (intestinal and plasma GPX) and genes involved in glutathione metabolism were also observed. This first study of the putative roles of oxidant production by the dual oxidase group, antioxidant glutathione pathways, immune cell populations, and cytokine profiles, in the development of resistance to infection by hyperimmune sheep are discussed.

Low frequency of anti-endomysial antibodies in recurrent aphthous stomatitis.

INTRODUCTION: The aetiology of recurrent aphthous stomatitis (RAS) remains unknown. An association between RAS and coeliac diseases (CD) has previously been suggested, but the supporting evidence remains equivocal. The aim of the present study was to determine the likely frequency of CD in a large cohort of patients with well-defined RAS, by detailed haematological and serological analysis, including the detection of anti-endomysium and anti-reticulin antibodies. MATERIALS AND METHODS: The study comprised 87 patients with minor RAS. Full blood counts and the presence of IgA anti-endomysial and IgA anti-reticulin antibodies were estimated in all patients. RESULTS: The frequency of anti-endomysium and anti-reticulin antibodies was not elevated in patients with RAS and no patients with RAS had other serological features of CD. CONCLUSIONS: It is concluded that there is little significant aetiological link between RAS and CD, and that screening RAS patients for key serological markers of CD is of little clinical value.

Bisphosphonates--a word of caution.

There have been recent reports from various centres of a possible association between avascular necrosis of the jaws and the use of bisphosphonates. This commentary reviews the available data and alerts clinicians to a possible adverse reaction in the oral cavity to a group of drugs that are commonly prescribed.

Oral pemphigus vulgaris: a case report and literature update.

INTRODUCTION: Pemphigus vulgaris is a rare cause of oral mucosal ulceration. CLINICAL PICTURE: A 47-year-old Chinese man presented with a 3-month history of oral ulceration. There were no lesions on the skin or other mucosal sites. Histology and immunostaining were consistent with pemphigus vulgaris. TREATMENT: Systemic and topical corticosteroids were instituted, together with topical antifungals. Conventional periodontal therapy was carried out to improve gingival/oral health. OUTCOME: Control of oral ulceration was achieved with re-establishment of normal oral function. No other sites to date have been involved. CONCLUSIONS: Chronic oral ulceration can be the sole manifestation of pemphigus vulgaris, at least initially. Early recognition of this lesion may prevent delayed diagnosis and inappropriate treatment of a potentially chronic dermatological condition.

Desquamative gingivitis: a sign of mucocutaneous disorders--a review.

Desquamative gingivitis is a clinical term to describe red, painful, glazed and friable gingivae which may be a manifestation of some mucocutaneous conditions such as lichen planus or the vesiculobullous disorders. It is important to be aware of this rare clinical entity so as to distinguish desquamative gingivitis from plaque induced gingivitis which is an extremely common condition, easily recognized and treated daily by the dental practitioner. This article gives an overview of desquamative gingivitis, its presentation, the possible causes, diagnosis and treatment. Early recognition of these lesions may prevent delayed diagnosis and inappropriate treatment of potentially serious dermatological diseases.

Gene flow on the ice: genetic differentiation among Adélie penguin colonies around Antarctica.

Each summer Adélie penguins breed in large disjunct colonies on ice-free areas around the Antarctic continent. Comprising > 10 million birds, this species represents a dominant feature of the Antarctic ecosystem. The patchy distribution within a large geographical range, natal philopatry and a probable history of refugia, suggest that this species is likely to exhibit significant genetic differentiation within and among colonies. We present data from seven microsatellite DNA loci for 442 individuals from 13 locations around the Antarctic continent. With the exception of one locus, there was no significant genic or genotypic heterogeneity across populations. Pairwise FST values were low with no value > 0.02. When all colonies were compared in a single analysis, the overall FST value was 0.0007. Moreover, assignment tests were relatively ineffective at correctly placing individuals into their respective collection sites. These data reveal a lack of genetic differentiation between Adélie penguin colonies around the Antarctic continent, despite substantial levels of genetic variation. We consider this homogeneity in terms of the dispersal of individuals among colonies and the size of breeding groups and discuss our results in terms of the glacial history of Antarctica.

The carboxy-terminal hydrophobic domain of TIG3, a class II tumor suppressor protein, is required for appropriate cellular localization and optimal biological activity.

TIG3 is a recently discovered class II tumor suppressor protein, originally isolated from retinoid-treated cultured epidermal keratinocytes, that suppresses the proliferation of a variety of epithelial cell types. In the present study, we examine the ability of this protein to reduce CHO, T47D and HaCaT cell proliferation, and the role of the carboxy-terminal hydrophobic domain in this regulation. Vector-mediated expression of the full length TIG3 protein, TIG31-164, results in a 50-70% reduction colony formation efficiency. Expression of a truncated mutant, TIG31-134, that lacks the putative carboxy-terminal membrane-anchoring domain, results in a partial loss of ability to suppress colony formation. The fact that the truncated protein remains partially active suggests that both the amino- and carboxy-terminal regions of TIG3 are required for optimal growth suppression. The full-length protein is distributed in a perinuclear location, and is not present in the nucleus. TIG31-134, in contrast, is distributed in the cytoplasm. Thus, a change in location is associated with the partial loss of activity. We also monitored the distribution of green fluorescent protein (GFP)-TIG3 fusion proteins. GFP-TIG31-164 was localized in a pattern similar to that observed for TIG31-164, while GFP-TIG31-134 displayed a distribution pattern similar to GFP. This suggests that the c-terminal hydrophobic domain has an important role in determining the intracellular localization of TIG3. In addition, GFP-TIG31-164 retains the ability to inhibit cell function, while GFP-TIG31-134 is inactive.

Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3, is decreased in psoriasis and skin cancer.

Tazarotene-induced gene-3 (TIG-3), isolated from human keratinocytes treated with the retinoic acid receptor-selective retinoid Tazarotene, is homologous to H-rev, a class II tumor suppressor. TIG-3 gene localized to chromosome 11q23, a site of loss of heterozygosity in several malignancies. Retinoids influence epidermal differentiation and are used to treat and prevent skin cancer. Therefore, we studied TIG-3 mRNA expression in psoriasis and in basal and SCCs by in situ hybridization and a quantitative QT-RT-PCR assay. Psoriasis lesions had significantly lower staining (median, 3) than paired normal control skin (median, 4; P = 0.012). TIG-3 mRNA was significantly higher in normal control skin (P = 0.001), in paired adjacent skin (median, 3; P = 0.007), and in overlying epidermis (median, 3.0; P = 0.0001) than in 21 SCC specimens as a group (median, 1.5).

Lichenoid tissue reactions of the oral mucosa.

The lichenoid tissue reaction (LTR) is characterised by epidermal basal cell damage and a variable subepithelial inflammatory infiltrate. There is a range of mucosal lesions exhibiting the LTR, chief of which is Oral Lichen Planus (OLP). The other oral lichenoid lesions resemble OLP clinically and histologically and at times it can be difficult to differentiate between the lesions. The important oral lichenoid lesions are reviewed in this paper.

Should UK emergency physicians undertake diagnostic ultrasound examinations?

From the published evidence there is no doubt that emergency physicians in America can undertake focused ultrasound examinations and that, by extrapolation, this would also be the case for UK emergency physicians. If this skill is to become part of the diagnostic armamentarium of the emergency physician, however, it needs to be demonstrated to be cost effective compared with the alternatives already available to the hospital. Trials to test for this benefit should adopt a hospital and not an emergency department perspective if the results are to influence health policy and specialty training.