Glycosidase activity in the excretory-secretory products of the liver fluke, Fasciola hepatica

Fasciola hepatica secretes proteolytic enzymes and other molecules that are essential for host penetration and migration. This mixture may include enzymes required for the degradation of supramucosal gels, which defend epithelial surfaces against pathogen entry. These contain hydrated mucins that are heavily glycosylated. Excretory-secretory products (ES) from F. hepatica were examined for a range of glycosidase activities, using synthetic 4-methylumbelliferyl glycosides as substrates. The ES product contained at least 8 different glycosidase activities, the most abundant of which were β-N- acetylhexosaminidase, β-galactosidase and β-glucosidase. Alpha-fucosidase, β-glucuronidase, α-galactosidase, α-mannosidase and neuraminidase were also present. β-N- acetylhexosaminidase and β-galactosidase were present in multiple isoforms (at least 4), whereas β-glucosidase appeared to exist as one isoenzyme with a pI <3.8. All three enzymes had acidic pH optima (4.5-5.0). Ovine small intestinal mucin was degraded by ES at pH 4.5 or 7.0, with or without active cathepsin L, the major protease found in F. hepatica ES. The ability of F. hepatica ES to degrade mucin in the presence or absence of active cathepsin L suggests that cathepsin L is not essential for mucin degradation. The abundance of β-galactosidase and β-hexosaminidase in ES supports a role for these enzymes in mucin degradation

Anomalous Dimensions of Non-Chiral Operators from AdS/CFT

Non-chiral operators with positive anomalous dimensions can have interesting applications to supersymmetric model building. Motivated by this, we develop a new method for obtaining the anomalous dimensions of non-chiral double-trace operators in N=1 superconformal field theories (SCFTs) with weakly-coupled AdS duals. Via the Hamiltonian formulation of AdS/CFT, we show how to directly compute the anomalous dimension as a bound state energy in the gravity dual. This simplifies previous approaches based on the four-point function and the OPE. We apply our method to a class of effective AdS5 supergravity models, and we find that the binding energy can have either sign. If such models can be UV completed, they will provide the first calculable examples of SCFTs with positive anomalous dimensions.Comment: 38 pages, 2 figures, refs adde

Evolutionary relationships between Rhynchosporium lolii sp. nov. and other Rhynchosporium species on grass.

Copyright: 2013 King et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThe fungal genus Rhynchosporium (causative agent of leaf blotch) contains several host-specialised species, including R. commune (colonising barley and brome-grass), R. agropyri (couch-grass), R. secalis (rye and triticale) and the more distantly related R. orthosporum (cocksfoot). This study used molecular fingerprinting, multilocus DNA sequence data, conidial morphology, host range tests and scanning electron microscopy to investigate the relationship between Rhynchosporium species on ryegrasses, both economically important forage grasses and common wild grasses in many cereal growing areas, and other plant species. Two different types of Rhynchosporium were found on ryegrasses in the UK. Firstly, there were isolates of R. commune that were pathogenic to both barley and Italian ryegrass. Secondly, there were isolates of a new species, here named R. lolii, that were pathogenic only to ryegrass species. R. lolii was most closely related to R. orthosporum, but exhibited clear molecular, morphological and host range differences. The species was estimated to have diverged from R. orthosporum ca. 5735 years before the present. The colonisation strategy of all of the different Rhynchosporium species involved extensive hyphal growth in the sub-cuticular regions of the leaves. Finally, new species-specific PCR diagnostic tests were developed that could distinguish between these five closely related Rhynchosporium species.Peer reviewedFinal Published versio

A preliminary study of the effect of closed incision management with negative pressure wound therapy over high-risk incisions

Background Certain postoperative wounds are recognised to be associated with more complications than others and may be termed high-risk. Wound healing can be particularly challenging following high-energy trauma where wound necrosis and infection rates are high. Surgical incision for joint arthrodesis can also be considered high-risk as it requires extensive and invasive surgery and postoperative distal limb swelling and wound dehiscence are common. Recent human literature has investigated the use of negative pressure wound therapy (NPWT) over high-risk closed surgical incisions and beneficial effects have been noted including decreased drainage, decreased dehiscence and decreased infection rates. In a randomised, controlled study twenty cases undergoing distal limb high-energy fracture stabilisation or arthrodesis were randomised to NPWT or control groups. All cases had a modified Robert-Jones dressing applied for 72 h postoperatively and NPWT was applied for 24 h in the NPWT group. Morphometric assessment of limb circumference was performed at six sites preoperatively, 24 and 72 h postoperatively. Wound discharge was assessed at 24 and 72 h. Postoperative analgesia protocol was standardised and a Glasgow Composite Measure Pain Score (GCPS) carried out at 24, 48 and 72 h. Complications were noted and differences between groups were assessed. Results Percentage change in limb circumference between preoperative and 24 and 72 h postoperative measurements was significantly less at all sites for the NPWT group with exception of the joint proximal to the surgical site and the centre of the operated bone at 72 h. Median discharge score was lower in the NPWT group than the control group at 24 h. No significant differences in GCPS or complication rates were noted. Conclusions Digital swelling and wound discharge were reduced when NPWT was employed for closed incision management. Larger studies are required to evaluate whether this will result in reduced discomfort and complication rates postoperatively

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

Angiogenin protects motoneurons against hypoxic injury.

Cells can adapt to hypoxia through the activation of hypoxia-inducible factor-1 (HIF-1), which in turn regulates the expression of hypoxia-responsive genes. Defects in hypoxic signaling have been suggested to underlie the degeneration of motoneurons in amyotrophic lateral sclerosis (ALS). We have recently identified mutations in the hypoxia-responsive gene, angiogenin (ANG), in ALS patients, and have shown that ANG is constitutively expressed in motoneurons. Here, we show that HIF-1alpha is sufficient and required to activate ANG in cultured motoneurons exposed to hypoxia, although ANG expression does not change in a transgenic ALS mouse model or in sporadic ALS patients. Administration of recombinant ANG or expression of wild-type ANG protected motoneurons against hypoxic injury, whereas gene silencing of ang1 significantly increased hypoxia-induced cell death. The previously reported ALS-associated ANG mutations (Q12L, K17I, R31K, C39W, K40I, I46V) all showed a reduced neuroprotective activity against hypoxic injury. Our data show that ANG plays an important role in endogenous protective pathways of motoneurons exposed to hypoxia, and suggest that loss of function rather than loss of expression of ANG is associated with ALS

Species identification by experts and non-experts: comparing images from field guides

Accurate species identification is fundamental when recording ecological data. However, the ability to correctly identify organisms visually is rarely questioned. We investigated how experts and non-experts compared in the identification of bumblebees, a group of insects of considerable conservation concern. Experts and non-experts were asked whether two concurrent bumblebee images depicted the same or two different species. Overall accuracy was below 60% and comparable for experts and non-experts. However, experts were more consistent in their answers when the same images were repeated, and more cautious in committing to a definitive answer. Our findings demonstrate the difficulty of correctly identifying bumblebees using images from field guides. Such error rates need to be accounted for when interpreting species data, whether or not they have been collected by experts. We suggest that investigation of how experts and non-experts make observations should be incorporated into study design, and could be used to improve training in species identification

How useful are volunteers for visual biodiversity surveys? An evaluation of skill level and group size during a conservation expedition

The ability of volunteers to undertake different tasks and accurately collect data is critical for the success of many conservation projects. In this study, a simulated herpetofauna visual encounter survey was used to compare the detection and distance estimation accuracy of volunteers and more experienced observers. Experience had a positive effect on individual detection accuracy. However, lower detection performance of less experienced volunteers was not found in the group data, with larger groups being more successful overall, suggesting that working in groups facilitates detection accuracy of those with less experience. This study supports the idea that by optimizing survey protocols according to the available resources (time and volunteer numbers), the sampling efficiency of monitoring programs can be improved and that non-expert volunteers can provide valuable contributions to visual encounter-based biodiversity surveys. Recommendations are made for the improvement of survey methodology involving non-expert volunteers

Recent breast cancer trends among Asian/Pacific Islander, Hispanic, and African-American women in the US: changes by tumor subtype

Abstract available at publisher's website

A narrative review on the similarities and dissimilarities between myalgic encephalomyelitis/chronic fatigue syndrome (me/cfs) and sickness behavior

It is of importance whether myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a variant of sickness behavior. The latter is induced by acute infections/injury being principally mediated through proinflammatory cytokines. Sickness is a beneficial behavioral response that serves to enhance recovery, conserves energy and plays a role in the resolution of inflammation. There are behavioral/symptomatic similarities (for example, fatigue, malaise, hyperalgesia) and dissimilarities (gastrointestinal symptoms, anorexia and weight loss) between sickness and ME/CFS. While sickness is an adaptive response induced by proinflammatory cytokines, ME/CFS is a chronic, disabling disorder, where the pathophysiology is related to activation of immunoinflammatory and oxidative pathways and autoimmune responses. While sickness behavior is a state of energy conservation, which plays a role in combating pathogens, ME/CFS is a chronic disease underpinned by a state of energy depletion. While sickness is an acute response to infection/injury, the trigger factors in ME/CFS are less well defined and encompass acute and chronic infections, as well as inflammatory or autoimmune diseases. It is concluded that sickness behavior and ME/CFS are two different conditions