Is the Glycoprotein Responsible for the Differences in Dispersal Rates between Lettuce Necrotic Yellows Virus Subgroups?

Lettuce necrotic yellows virus is a type of species in the Cytorhabdovirus genus and appears to be endemic to Australia and Aotearoa New Zealand (NZ). The population of lettuce necrotic yellows virus (LNYV) is made up of two subgroups, SI and SII. Previous studies demonstrated that SII appears to be outcompeting SI and suggested that SII may have greater vector transmission efficiency and/or higher replication rate in its host plant or insect vector. Rhabdovirus glycoproteins are important for virus-insect interactions. Here, we present an analysis of LNYV glycoprotein sequences to identify key features and variations that may cause SII to interact with its aphid vector with greater efficiency than SI. Phylogenetic analysis of glycoprotein sequences from NZ isolates confirmed the existence of two subgroups within the NZ LNYV population, while predicted 3D structures revealed the LNYV glycoproteins have domain architectures similar to Vesicular Stomatitis Virus (VSV). Importantly, changing amino acids at positions 244 and 247 of the post-fusion form of the LNYV glycoprotein altered the predicted structure of Domain III, glycosylation at N248 and the overall stability of the protein. These data support the glycoprotein as having a role in the population differences of LNYV observed between Australia and New Zealand.

Leaf Stable Isotope and Nutrient Status of Temperate Mangroves As Ecological Indicators to Assess Anthropogenic Activity and Recovery from Eutrophication.

We measured nitrogen stable isotope values (δ15N), and total phosphorus (%P) and total nitrogen (%N) contents in leaves of the temperate mangrove (Avicennia marina sp. australasica) from three coastal ecosystems exposed to various levels of human impact (Manukau, high; Mangawhai, low; and Waitemata, intermediate) in northern New Zealand. We measured δ15N values around 10‰ in environments where the major terrestrial water inputs are sewage. The highest average total nitrogen contents and δ15N values were found in the Auckland city region (Manukau Harbour) at 2.2%N and 9.9‰, respectively. The lowest values were found in Mangawhai Harbour, situated about 80 km north of Auckland city, at 2.0%N and 5.2‰, respectively. In the Waitemata Harbour, also located in Auckland city but with less exposure to human derived sewage inputs, both parameters were intermediate, at 2.1%N and 6.4‰. Total phosphorus contents did not vary significantly. Additionally, analysis of historical mangrove leaf herbarium samples obtained from the Auckland War Memorial Museum indicated that a reduction in both leaf total nitrogen and δ15N content has occurred over the past 100 years in Auckland's harbors. Collectively, these results suggest that anthropogenically derived nitrogen has had a significant impact on mangrove nutrient status in Auckland harbors over the last 100 years. The observed decrease in nitrogenous nutrients probably occurred due to sewage system improvements. We suggest that mangrove plant physiological response to nutrient excess could be used as an indicator of long-term eutrophication trends. Monitoring leaf nutrient status in mangroves can be used to assess environmental stress (sewage, eutrophication) on coastal ecosystems heavily impacted by human activities. Moreover, nitrogen and phosphorus leaf contents can be used to assess levels of available nutrients in the surrounding environments.

Surviving in a semi-marine habitat: Dietary salt exposure and salt secretion of a New Zealand intertidal skink.

Species that inhabit marine and intertidal ecosystems face osmoregulatory challenges, risking dehydration and increased ion concentrations in the body. Lizards need to either tolerate or regulate these increased ion concentrations. In this study, we aim to understand how Suter's skink (Oligosoma suteri), an intertidal skink restricted to shoreline habitats, is able to cope with the physiological stress of living in an extreme salt environment. We determined the diet, prey species' salt content, and nasal and cloacal salt excretion on Rangitoto and Motutapu Islands in northern New Zealand, where the skinks have contrasting access to terrestrial invertebrates. Analysis of stable isotopes suggests inter- and intra-population variability in Suter's skink diets. Intertidal invertebrates under washed up seaweed appear to compose a major part of the diet of the Rangitoto population, while the Motutapu population showed evidence for a mixed diet of terrestrial and intertidal invertebrates. Sodium content of prey species decreased with an increasing distance from the seawater. Field secretion of cations through nasal glands consisted primarily of Na(+), which is consistent with other marine and intertidal species. Sodium was also the primary cation in urine. In contrast, fecal cations consisted primarily of K(+). This first study into the salt secretion of an intertidal skink species provides evidence of Suter's skink's plasticity in secreting excess ions through nasal salt glands. This likely enables it to deal with the challenges of living in a semi-marine habitat.

Ghrelin promotes intestinal epithelial cell proliferation through PI3K/Akt pathway and EGFR trans-activation both converging to ERK 1/2 phosphorylation.

Little is known about ghrelin's effects on intestinal epithelial cells even though it is known to be a mitogen for a variety of other cell types. Because ghrelin is released in close proximity to the proliferative compartment of the intestinal tract, we hypothesized that ghrelin may have potent pro-proliferative effect on intestinal epithelial cells as well. To test this hypothesis, we characterized the effects of ghrelin on FHs74Int and Caco-2 intestinal epithelial cell lines in vitro. We found that ghrelin has potent dose dependent proliferative effects in both cell lines through a yet to be characterized G protein coupled growth hormone secretagogue receptor (GHS-R) subtype. Consistent with above findings, cell cycle flowcytometric analyses demonstrated that ghrelin shifts cells from the G1 to S phase and thereby promotes cell cycle progression. Further characterization of subcellular events, suggested that ghrelin mediates its pro-proliferative effect through Adenylate cyclase (AC)-independent epidermal growth factor receptor (EGFR) trans-activation and PI3K-Akt phosphorylation. Both these pathways converge to stimulate MAPK, ERK 1/2 downstream. The role of ghrelin in states where intestinal mucosal injury and rapid mucosal repair occur warrants further investigation.

Implementation of an enhanced recovery programme following pancreaticoduodenectomy.

OBJECTIVES: The aim of this prospective study was to investigate the implementation of an enhanced recovery after surgery (ERAS) programme following pancreaticoduodenectomy (PD). METHODS: Patients undergoing PD were managed according to an ERAS protocol. Outcome measures included postoperative mortality, morbidity, hospitalization and 30-day readmission rate. Key protocol targets were: nasogastric tube (NGT) removal [postoperative day (PoD) 1]; resumption of oral fluids (PoD 1); urinary catheter removal (PoD 3); high-dependency unit (HDU) discharge (PoD 3); tolerating diet (PoD 4); drain removal (PoD 5), and hospital discharge (PoD 6). RESULTS: Data were collected for 50 patients (24 male; median age 67 years). Rates of mortality, morbidity and readmission were 4%, 46% and 4%, respectively. The median length of postoperative hospitalization was 10 days. The proportions of patients achieving key targets were: 78% for NGT removal; 82% for resumption of oral fluids; 48% for urinary catheter removal; 82% for HDU discharge; 86% for tolerating diet; 84% for meeting mobility targets, and 72% for drain removal. One patient was discharged by PoD 6, eight patients by PoD 7, 15 patients by PoD 8 and 26 patients (52%) by PoD 10. Discharge was delayed in 16 patients for social or transport-related reasons. CONCLUSIONS: The ERAS protocol was implemented safely. Achieving certain targets was challenging. Non-medical causes remain a significant factor in delayed discharge following PD.

Hospital volume and patient outcomes after cholecystectomy in Scotland: retrospective, national population based study.

OBJECTIVES: To define associations between hospital volume and outcomes following cholecystectomy, after adjustment for case mix using a national database. DESIGN: Retrospective, national population based study using multilevel modelling and simulation. SETTING: Locally validated administrative dataset covering all NHS hospitals in Scotland. PARTICIPANTS: All patients undergoing cholecystectomy between 1 January 1998 and 31 December 2007. MAIN OUTCOME MEASURES: Mortality, 30 day reoperation rate, 30 day readmission rate, and length of stay. RESULTS: We identified 59,918 patients who had a cholecystectomy in one of 37 hospitals: five hospitals had high volumes (>244 cholecystectomies/year), 10 had medium volumes (173-244), and 22 had low volumes (<173). Compared with low and medium volume hospitals, high volume hospitals performed more procedures non-electively (17.1% and 19.5% v 32.8%), completed more procedures laparoscopically (64.7% and 73.8% v 80.9%), and used more operative cholangiography (11.2% and 6.3% v 21.2%; χ(2) test, all P<0.001). In a well performing multivariable analysis with bias correction for a low event rate, the odds ratio for death was greater in both the low volume (odds ratio 1.45, 95% confidence interval 1.06 to 2.00, P=0.022) and medium volume (1.52, 1.11 to 2.08, P=0.010) groups than in the high volume group. However, in simulation studies, absolute risk differences between volume groups were clinically negligible for patients with average risk (number needed to treat to harm, low v high volume, 3871, 1963 to 17,118), but were significant in patients with higher risk. In models accounting for the hierarchical structure of patients in hospitals, those in medium volume hospitals were more likely to undergo reoperation (odds ratio 1.74, 1.31 to 2.30, P<0.001) or be readmitted (1.17, 1.04 to 1.31, P=0.008) after cholecystectomy than those in high volume hospitals. Length of stay was shorter in high volume hospitals than in low (hazard ratio for discharge 0.78, 0.76 to 0.79, P<0.001) or medium volume hospitals (0.75, 0.74 to 0.77, P<0.001). These differences were also only of clinical significance in patients at higher risk. CONCLUSIONS: There is wide variation among hospitals in the management of gallstone disease and an association between higher hospital volume and better outcome after a cholecystectomy. The relative risk of death is lower in high volume centres, and although absolute risk differences between volume groups are significant for elderly patients and patients with comorbidity, they are clinically negligible for those at average risk.

Homo sapiens systemic RNA interference-defective-1 transmembrane family member 1 (SIDT1) protein mediates contact-dependent small RNA transfer and microRNA-21-driven chemoresistance.

Locally initiated RNA interference (RNAi) has the potential for spatial propagation, inducing posttranscriptional gene silencing in distant cells. In Caenorhabditis elegans, systemic RNAi requires a phylogenetically conserved transmembrane channel, SID-1. Here, we show that a human SID-1 orthologue, SIDT1, facilitates rapid, contact-dependent, bidirectional small RNA transfer between human cells, resulting in target-specific non-cell-autonomous RNAi. Intercellular small RNA transfer can be both homotypic and heterotypic. We show SIDT1-mediated intercellular transfer of microRNA-21 to be a driver of resistance to the nucleoside analog gemcitabine in human adenocarcinoma cells. Documentation of a SIDT1-dependent small RNA transfer mechanism and the associated phenotypic effects on chemoresistance in human cancer cells raises the possibility that conserved systemic RNAi pathways contribute to the acquisition of drug resistance. Mediators of non-cell-autonomous RNAi may be tractable targets for novel therapies aimed at improving the efficacy of current cytotoxic agents.

Giant haemangioma of the liver: observation or resection?

BACKGROUND: Haemangiomata are the most frequent benign solid liver lesion. The management of giant (> or =5 cm) haemangiomata of the liver remains controversial. METHODS: A search of relevant peer-reviewed literature was conducted using PubMed and original articles were reviewed. RESULTS AND CONCLUSIONS: The vast majority of giant haemangiomata remain asymptomatic and have a benign and uncomplicated natural history. Decisions regarding the optimal management of giant haemangiomata depend on a high level of confidence in diagnostic imaging. Diagnostic biopsy to differentiate giant haemangiomata from malignant lesions should be discouraged. Despite limitations and alternative modalities, surgery remains the only consistently effective curative treatment for giant haemangiomata. Surgery is not generally justified to prevent complications in asymptomatic patients. Principal indications for the surgical management of giant haemangiomata include established complications, incapacitating symptoms and uncertainty of diagnosis. Patients should only be selected for surgery based on a careful assessment of risks and benefits of intervention.

Systematic review of postdischarge oral nutritional supplementation in patients undergoing GI surgery.

OBJECTIVE: To determine whether nutritional supplementation following hospital discharge in patients who undergo gastrointestinal (GI) surgery is beneficial in specific outcome measures. METHODS: A systematic review was conducted of randomized controlled trials comparing nutritional supplements vs a "standard care" regimen given to patients following discharge from hospital after GI surgery. Outcome measures were weight change, quality of life, clinical complications, fatigue, and hand grip strength. RESULTS: Four studies were identified. Postdischarge oral nutritional supplements were found to be safe and increased energy intake, protein intake, and weight in patients after discharge from hospital. The greatest gains in weight were seen in malnourished patients. Little evidence was found that nutritional supplements reduce morbidity or improve quality of life, fatigue, or hand-grip strength. Only one study was methodologically adequate, and none were powered to detect differences in clinical complications. CONCLUSIONS: In patients who undergo GI surgery and receive nutritional supplements after discharge from hospital, little evidence of clinical benefit was found, principally through lack of robust data. All the studies were under-powered or not specifically designed to show benefit during this period. It is recommended that nutritional supplements be offered to malnourished patients or those at high risk of poor dietary intake at discharge from hospital.

Exogenous ghrelin modulates release of pro-inflammatory and anti-inflammatory cytokines in LPS-stimulated macrophages through distinct signaling pathways.

BACKGROUND: Ghrelin, an orexigenic 28-amino-acid peptide, has been studied primarily in relation to the control of appetite and fat metabolism. In addition to these well-known functions, ghrelin, and its target receptors, growth hormone secretagogue receptors (GHS-Rs), have been localized to neutrophils, lymphocytes, and macrophages, which suggests that ghrelin may be involved in immune modulation. METHODS: To assess the therapeutic role of ghrelin in production of pro-inflammatory and anti-inflammatory cytokines, the effects of exogenous ghrelin administration on the regulation of cytokine release in lipopolysaccharide (LPS)-activated murine RAW 264.7 macrophages were analyzed. RESULTS: Ghrelin and GHS-Rs are expressed in murine macrophages. In addition, exogenous ghrelin inhibited the production of pro-inflammatory cytokines IL-1beta and TNF-alpha in LPS-stimulated murine macrophages in a dose dependent and time-dependent fashion. Exogenous ghrelin pretreatment resulted in a decrease in LPS-induced NFkappaB activation and was presumably the reason for this ghrelin-mediated effect. In contrast to these findings, exogenous ghrelin significantly augmented the release of the anti-inflammatory cytokine IL-10 in a dose-dependent and time-dependent fashion from LPS-stimulated murine macrophages. Ghrelin administration enhanced activation of p38 MAPK, which is known to control the release of IL-10 in macrophages independent of the NFkappaB pathway. These effects of ghrelin on both pro-inflammatory and anti-inflammatory cytokines were offset when a specific GHS-R receptor antagonist was added to the culture media. CONCLUSIONS: These data suggest that ghrelin has potent anti-inflammatory properties through modulation of secretion of both pro-inflammatory and anti-inflammatory cytokines from LPS-stimulated macrophages through distinct signaling cascades. Therapeutic utility of ghrelin to control, modulate, or treat pathologic inflammatory conditions like endotoxemic shock and ulcerative colitis requires additional investigation.

RRM2 induces NF-kappaB-dependent MMP-9 activation and enhances cellular invasiveness.

Ribonucleotide reductase is a dimeric enzyme that catalyzes conversion of ribonucleotide 5'-diphosphates to their 2'-deoxynucleotide forms, a rate-limiting step in the production of 2'-deoxyribonucleoside 5'-triphosphates required for DNA synthesis. The ribonucleotide reductase M2 subunit (RRM2) is a determinant of malignant cellular behavior in a range of human cancers. We examined the effect of RRM2 overexpression on pancreatic adenocarcinoma cellular invasiveness and nuclear factor-kappaB (NF-kappaB) transcription factor activity. RRM2 overexpression increases pancreatic adenocarcinoma cellular invasiveness and MMP-9 expression in a NF-kappaB-dependent manner. RNA interference (RNAi)-mediated silencing of RRM2 expression attenuates cellular invasiveness and NF-kappaB activity. NF-kappaB is a key mediator of the invasive phenotypic changes induced by RRM2 overexpression.