Summary
Fasciola hepatica is a trematode parasite with a global distribution, which is responsible for considerable disease and production losses in a range of food producing species. It is also ...identified by WHO as a re‐emerging neglected tropical disease associated with endemic and epidemic outbreaks of disease in human populations. In Europe, F. hepatica is mostly associated with disease in sheep, cattle and goats. This study reviews the most recent advances in our understanding of the transmission, diagnosis, epidemiology and the economic impact of fasciolosis. We also focus on the impact of the spread of resistance to anthelmintics used to control F. hepatica and consider how vaccines might be developed and applied in the context of the immune‐modulation driven by the parasite. Several major research gaps are identified which, when addressed, will contribute to providing focussed and where possible, bespoke, advice for farmers on how to integrate stock management and diagnosis with vaccination and/or targeted treatment to more effectively control the parasite in the face of increasing the prevalence of infection and spread of anthelmintic resistance that are likely to be exacerbated by climate change.
Fifty surface sediment samples were collected from 12 transects through a mangrove woodland near the mouth of the Brisbane River, Australia. Samples were analyzed for 10 trace metals; measured ...concentrations (μg g
−1) were: Cu 3·1–34·1; Pb 7·7–84·7; Zn 40·8–144·0; Ag nd-2·8; Cr 7·6–116·8; V 16·4–57·9; Mo 7·6–82·6; Ni 2·4–57·6; As nd-13·0; and Cd nd-2·0. Coefficients of variation ranged from 22–153%. Sediments were moderately contaminated, with Mo being enriched by up to thirty times background levels. Spatial variation was considerable, and canonical trend analysis showed concentrations of all metals but Ag and Cr tended to increase downshore, suggesting tidal deposition was important in determining metal concentrations. Silver and Cr concentrations appeared to be a consequence of contamination from landward point sources. An investigation of different random sampling intensities showed the spatial variation required that many samples be taken for a satisfactory assessment of metal burdens. Even so, mean values were not a good indication of the possible environmental effects of the metal contamination. Since metal concentrations increase downshore in inter-tidal environments, a more appropriate sampling strategy would be to take a downshore series of samples normal to the shoreline.
Alcohol use disorder (AUD) is a common and chronic disorder with substantial effects on personal and public health. The underlying pathophysiology is poorly understood but strong evidence suggests ...significant roles of both genetic and epigenetic components. Given that alcohol affects many organ systems, we performed a cross-tissue and cross-phenotypic analysis of genome-wide methylomic variation in AUD using samples from 3 discovery, 4 replication, and 2 translational cohorts. We identified a differentially methylated region in the promoter of the proprotein convertase subtilisin/kexin 9 (PCSK9) gene that was associated with disease phenotypes. Biological validation showed that PCSK9 promoter methylation is conserved across tissues and positively correlated with expression. Replication in AUD datasets confirmed PCSK9 hypomethylation and a translational mouse model of AUD showed that alcohol exposure leads to PCSK9 downregulation. PCSK9 is primarily expressed in the liver and regulates low-density lipoprotein cholesterol (LDL-C). Our finding of alcohol-induced epigenetic regulation of PCSK9 represents one of the underlying mechanisms between the well-known effects of alcohol on lipid metabolism and cardiovascular risk, with light alcohol use generally being protective while chronic heavy use has detrimental health outcomes.
Deep roots and soil structure Gao, W.; Hodgkinson, L.; Jin, K. ...
Plant, cell and environment,
August 2016, Letnik:
39, Številka:
8
Journal Article
Recenzirano
Odprti dostop
In this opinion article we examine the relationship between penetrometer resistance and soil depth in the field. Assuming that root growth is inhibited at penetrometer resistances > 2.5 MPa, we ...conclude that in most circumstances the increases in penetrometer resistance with depth are sufficiently great to confine most deep roots to elongating in existing structural pores. We suggest that deep rooting is more likely related to the interaction between root architecture and soil structure than it is to the ability of a root to deform strong soil. Although the ability of roots to deform strong soil is an important trait, we propose it is more closely related to root exploration of surface layers than deep rooting.
Background
Although the United Kingdom (UK) cleft surgeons follow a similar training pathway, and cleft centers adhere to similar protocols regarding the timing of palate surgery and surgical ...technique, speech outcomes still vary between centers.
Objective
To explore the training experiences of consultant cleft lip and palate (CL/P) surgeons, performing a Sommerlad radical intravelar veloplasty (IVVP) and their approach to teaching others.
Design
An exploratory, qualitative approach was adopted to understand the views of UK cleft surgeons performing a Sommerlad radical IVVP and discuss what was important during training and upon qualifying as a consultant.
Method
A semi-structured interview schedule was designed, interviews were conducted in-person or via videoconferencing, depending on preference and availability, with interested surgeons. The interviews were recorded, transcribed, and checked for accuracy. Analysis involved inductive thematic analysis.
Results
Fourteen cleft consultants from the UK participated (3F:11M). Seven of the consultants were trained in plastic surgery and four in maxillofacial surgery. Seven themes were identified from the thematic analysis. Three themes, namely Learning to perform palate repair, Teaching others to perform palate repair, and Ongoing learning as a consultant are discussed.
Conclusions
Cleft palate repair is clearly a technically challenging procedure to learn and teach with the potential to cause harm if performed incorrectly. Positive changes have been made to improve exposure to palate surgery, encourage practice away from the patient, and increase supervised practical experience. The role of colleagues in providing mentorship and support appears invaluable. We provide some simple recommendations that may improve the training experience and ensure parity for all trainees.
This study investigated the structural and physicochemical changes that occur in milk, a naturally designed complex structured emulsion, during gastric digestion using the bottle-fed piglet as an ...animal model. The gastric digestions of cow, goat, and sheep milk were compared in male piglets euthanized at different postfeeding times to collect the stomach chyme. The cow and noncow milks separated into curd (aggregated caseins) and liquid (mostly soluble whey) phases in the piglet's stomach. For milk from all the species, the curd remained longer in the stomach because of its slow disintegration, whereas the liquid phase emptied readily. The majority of the fat globules were found to be entrapped within the protein network of the curd. The rate of release of fat globules was strongly dependent on the breakdown of the surrounding protein network of the curd. The consistency of the gastric curds changed as digestion progressed, with goat and sheep milk curds having relatively softer curd consistency and less fused protein networks, especially toward the end of digestion. This might have led to the lower protein and fat retention in the goat and sheep milk curds and relatively faster gastric emptying of these nutrients from goat and sheep milk in comparison to cow milk. This in vivo study provided new and enhanced understanding of the mechanisms of the gastric digestion of milk from different species. It may have implications for developing bioinspired structures for the controlled digestion and delivery of nutrients.
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Over the past decade, numerous reports describe the generation and increasing utility of non-small-cell lung cancer (NSCLC) patient-derived xenografts (PDX) from tissue biopsies. While PDX have ...proven useful for genetic profiling and preclinical drug testing, the requirement of a tissue biopsy limits the available patient population, particularly those with advanced oligometastatic disease. Conversely, ‘liquid biopsies’ such as circulating tumour cells (CTCs) are minimally invasive and easier to obtain. Here, we present a clinical case study of a NSCLC patient with advanced metastatic disease, a never smoker whose primary tumour was EGFR and ALK wild-type. We demonstrate for the first time, tumorigenicity of their CTCs to generate a patient CTC-derived eXplant (CDX).
CTCs were enriched at diagnosis and again 2 months later during disease progression from 10 ml blood from a 48-year-old NSCLC patient and implanted into immunocompromised mice. Resultant tumours were morphologically, immunohistochemically, and genetically compared with the donor patient's diagnostic specimen. Mice were treated with cisplatin and pemetrexed to assess preclinical efficacy of the chemotherapy regimen given to the donor patient.
The NSCLC CDX expressed lung lineage markers TTF1 and CK7 and was unresponsive to cisplatin and pemetrexed. Examination of blood samples matched to that used for CDX generation revealed absence of CTCs using the CellSearch EpCAM-dependent platform, whereas size-based CTC enrichment revealed abundant heterogeneous CTCs of which ∼80% were mesenchymal marker vimentin positive. Molecular analysis of the CDX, mesenchymal and epithelial CTCs revealed a common somatic mutation confirming tumour origin and showed CDX RNA and protein profiles consistent with the predominantly mesenchymal phenotype.
This study shows that the absence of NSCLC CTCs detected by CellSearch (EpCAM+) does not preclude CDX generation, highlighting epithelial to mesenchymal transition and the functional importance of mesenchymal CTCs in dissemination of this disease.
Schizophrenia is a complex disorder, and there is substantial evidence supporting a genetic etiology. Despite this, prior attempts to localize susceptibility loci have produced predominantly ...suggestive findings. A genome-wide scan for schizophrenia susceptibility loci in 22 extended families with high rates of schizophrenia provided highly significant evidence of linkage to chromosome 1 (1q21-q22), with a maximum heterogeneity logarithm of the likelihood of linkage (lod) score of 6.50. This linkage result should provide sufficient power to allow the positional cloning of the underlying susceptibility gene.
Genetic and functional studies have revealed that both common and rare variants of several nicotinic acetylcholine receptor subunits are associated with nicotine dependence (ND). In this study, we ...identified variants in 30 candidate genes including nicotinic receptors in 200 sib pairs selected from the Mid-South Tobacco Family population with equal numbers of African Americans (AAs) and European Americans (EAs). We selected 135 of the rare and common variants and genotyped them in the Mid-South Tobacco Case-Control (MSTCC) population, which consists of 3088 AAs and 1430 EAs. None of the genotyped common variants showed significant association with smoking status (smokers vs non-smokers), Fagerström Test for ND scores or indexed cigarettes per day after Bonferroni correction. Rare variants in NRXN1, CHRNA9, CHRNA2, NTRK2, GABBR2, GRIN3A, DNM1, NRXN2, NRXN3 and ARRB2 were significantly associated with smoking status in the MSTCC AA sample, with weighted sum statistic (WSS) P-values ranging from 2.42 × 10(-3) to 1.31 × 10(-4) after 10(6) phenotype rearrangements. We also observed a significant excess of rare nonsynonymous variants exclusive to EA smokers in NRXN1, CHRNA9, TAS2R38, GRIN3A, DBH, ANKK1/DRD2, NRXN3 and CDH13 with WSS P-values between 3.5 × 10(-5) and 1 × 10(-6). Variants rs142807401 (A432T) and rs139982841 (A452V) in CHRNA9 and variants V132L, V389L, rs34755188 (R480H) and rs75981117 (N549S) in GRIN3A are of particular interest because they are found in both the AA and EA samples. A significant aggregate contribution of rare and common coding variants in CHRNA9 to the risk for ND (SKAT-C: P=0.0012) was detected by applying the combined sum test in MSTCC EAs. Together, our results indicate that rare variants alone or combined with common variants in a subset of 30 biological candidate genes contribute substantially to the risk of ND.
This policy-capturing study, conducted in China, investigated the cognitive basis of managerial decisions to make a corporate charitable donation, a global issue in the context of corporate social ...responsibility (CSR) research and practice. Participants (N = 376) responded to a series of scenarios manipulating pressure from the five stakeholders (government, customers, competitors, employees, and shareholders) most commonly addressed by CSR research. The independent variables examined included organizational factors (industry, ownership, previous company donation, firm size, firm age, and perceived CEO attitudes toward charity) and the participants' personal values. Results indicate a large positive effect of shareholder and governmental pressure on the decision with lesser positive effects from customers and competitors. Surprisingly, employee pressure had a negative effect on the decision to make a charitable donation. Further, personal values and perceived CEO attitudes toward charity were significantly related to the decisions participants made. In line with our theorizing, the findings indicate that a combination of personal, organizational, and institutional factors was salient in the minds of decision makers.
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