582 research outputs found

    Paraoxonase 2 protein is spatially expressed in the human placenta and selectively reduced in labour

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    Humans parturition involves interaction of hormonal, neurological, mechanical stretch and inflammatory pathways and the placenta plays a crucial role. The paraoxonases (PONs 1–3) protect against oxidative damage and lipid peroxidation, modulation of endoplasmic reticulum stress and regulation of apoptosis. Nothing is known about the role of PON2 in the placenta and labour. Since PON2 plays a role in oxidative stress and inflammation, both features of labour, we hypothesised that placental PON2 expression would alter during labour. PON2 was examined in placentas obtained from women who delivered by cesarean section and were not in labour and compared to the equivalent zone of placentas obtained from women who delivered vaginally following an uncomplicated labour. Samples were obtained from 12 sites within each placenta: 4 equally spaced apart pieces were sampled from the inner, middle and outer placental regions. PON2 expression was investigated by Western blotting and real time PCR. Two PON2 forms, one at 62 kDa and one at 43 kDa were found in all samples. No difference in protein expression of either isoform was found between the three sites in either the labour or non-labour group. At the middle site there was a highly significant decrease in PON2 expression in the labour group when compared to the non-labour group for both the 62 kDa form (p = 0.02) and the 43 kDa form (p = 0.006). No spatial differences were found within placentas at the mRNA level in either labour or non-labour. There was, paradoxically, an increase in PON2 mRNA in the labour group at the middle site only. This is the first report to describe changes in PON2 in the placenta in labour. The physiological and pathological significance of these remains to be elucidated but since PON2 is anti-inflammatory further studies are warranted to understand its role

    Ecosystem service provision by marine habitats in Southeast Asia

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    Southeast Asia is an area of rich marine biodiversity providing a host of ecosystem services that contribute to the well-being of coastal communities and beyond. Sustainable management of ecosystems and the services they provide requires a good understanding of their underlying ecological functions and processes. This understanding can be gained through the rigorous assessment of studies identifying and quantifying ecological functions and ecosystem services. The aims of this study were to review the ecosystem services provided by marine and coastal habitats in Southeast Asia. The ecosystem service potential was scored for each habitat. The review was focused on nine key marine and coastal habitats, identified across four case study sites in Southeast Asia, contributing 18 marine relevant ecosystem services. The approach comprised a literature review supplemented with observations from experts from the case study areas. The four case study sites consist of three Man and Biosphere Reserves in Southeast Asia: Palawan in the Philippines, Cu Lao Cham- Hoi An in Viet Nam, Take-Bonerate Kepulauan Selayar in Indonesia, and a recently gazetted marine protected area, the Tun Mustapha Marine Park in Malaysia (Figure 1). The nine key habitats (eight benthic and one pelagic) covered in this review, identified as highly relevant for most case study sites, were mangrove forests, coral reefs, seagrass meadows, sand, mud, rock, coarse substratum, pelagic and modified habitats. Further division of these habitats into sub-habitats on the basis of biological type and substrate type was used to capture data on differential provision of ecosystem services within the broad habitat types. To ensure relevance in the four case study sites, firstly an ecosystem services typology was created tailored to these sites. After exploring several ecosystem service typologies, our final classification was adapted from the Common International Classification of Ecosystem services (CICES) V4.3 because it was considered to be most relevant to the objectives of this task. Provisioning, regulation and maintenance, and cultural services were assessed. Provisioning services focused on food for consumption by humans from plants, pelagic animals, demersal fish and invertebrates; energy from harvested plants; other materials from plants and animals, such as fibres, building and housing materials, medicines, decoration, handicrafts and souvenirs; and genetic material from plants and animals (including seeds, spat, spores, whole plants or animals, individual genes), for example seed or brood-stock collection for aquaculture and mangrove replanting and new plantations. Regulation and maintenance services assessed were treatment and assimilation of wastes or toxic substances; coastal erosion control; water flow regulation contributing to dampening the intensity of storm, floods, tsunamis, and hurricanes and the maintenance of localized water flows such as coastal current structures; maintenance of nursery,reproduction and feeding habitats; maintenance of critical habitats for charismatic species such as turtles, dugongs, cetaceans, sharks, seahorses, bats, fireflies, birds, monkeys, orchids and other epiphytes; and climate regulation through impacts on the hydrological cycle, temperature regulation, and the contribution to regulation of climate-influencing gases in the atmosphere, for example through carbon sequestration and long-term, decadal storage. Cultural services examined included uses of habitats as places for active and passive recreation; ceremonial activities; creative activities; and knowledge-based activities, such as educational activities, and citizen science or community environmental activities. The comprehensive literature review included peer-reviewed scientific research literature as well as grey literature such as government and other reports. To ensure a wide breadth of coverage, the research focused on studies from Southeast Asia. When no evidence was found in the literature, evidence was sought from experts, and where useful, was accompanied by observations from the authors in their respective case study sites. The evidence gathered was used to assess the potential of each habitat to provide an ecosystem service, rather than to assess the actual provision of ecosystem services from each case study site. This important distinction allows the differentiation between services provided by the ecosystem (i.e. the potential supply of ecosystem services that a habitat could deliver) and (achieved or used) benefits (i.e. the demand for ecosystem services). The knowledge gained from the literature, local and regional reports, together with observations from the study team and experts, was critically assessed using a robust methodology that captured different types of information together with a confidence score for the supporting evidence. The contribution of each habitat to each ecosystem service was then scored relative to other habitats. Our objective was to provide baseline information to enable better understanding of the ecosystem services arising from marine and coastal habitats in SE Asia. This provides a foundation for future assessments of natural capital and ecosystem services which may be used to inform sustainable management. The report will serve as a useful reference to many different readers. Regulators, managers of marine sites and policy makers might use this report to inform their management choices. This should enable more sustainable use of the marine environment and maximise the ecosystem service provision of all types of services addressed in this study. Stakeholders of the marine environment such as fisherfolk or residents might use this report to help them engage in management processes, to gain deeper understanding of the marine environment or confirm their observations of the marine environment. Academics can use it as a reference source or a base for further studies, in particular for valuation studies or when considering the trade-offs between ecosystem services in marine and coastal habitats. Finally, it is hoped that this report may bring a new appreciation and understanding of the marine environment and the life support it provides to society and inspire readers to improve management of the marine environment. This report is one of the outputs of the UK Research and Innovation’s Global Challenges Research Fund (UKRI GCRF) Blue Communities Programme (GCRF Blue Communities Global Challenges Research Fund via the United Kingdom Research and Innovation (UKRI) under grant agreement reference NE/P021107/1, www.blue-communities.org), which aims to “build capacity for sustainable interactions with marine ecosystems for the benefit of the health, well-being, food security and livelihoods of coastal communities in SE Asia”. GCRF Blue Communities is developing interdisciplinary research capability and lasting collaborations that can facilitate innovative application of integrated planning in the marine environment and respond to the UN Sustainable Development Goals of ‘no poverty’, ‘zero hunger’, ‘good health and well-being’ for coastal communities as well as ‘conserve and sustainably use the oceans, seas and marine resources for sustainable development’ through the sustainable use of marine resources

    Canine respiratory coronavirus employs caveolin-1-mediated pathway for internalization to HRT-18G cells

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    Canine respiratory coronavirus (CRCoV), identified in 2003, is a member of the Coronaviridae family. The virus is a betacoronavirus and a close relative of human coronavirus OC43 and bovine coronavirus. Here, we examined entry of CRCoV into human rectal tumor cells (HRT-18G cell line) by analyzing co-localization of single virus particles with cellular markers in the presence or absence of chemical inhibitors of pathways potentially involved in virus entry. We also targeted these pathways using siRNA. The results show that the virus hijacks caveolin-dependent endocytosis to enter cells via endocytic internalization

    HOXB5 Cooperates with NKX2-1 in the Transcription of Human RET

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    The enteric nervous system (ENS) regulates peristaltic movement of the gut, and abnormal ENS causes Hirschsprung's disease (HSCR) in newborns. HSCR is a congenital complex genetic disorder characterised by a lack of enteric ganglia along a variable length of the intestine. The receptor tyrosine kinase gene (RET) is the major HSCR gene and its expression is crucial for ENS development. We have previously reported that (i) HOXB5 transcription factor mediates RET expression, and (ii) mouse with defective HOXB5 activity develop HSCR phenotype. In this study, we (i) elucidate the underlying mechanisms that HOXB5 mediate RET expression, and (ii) examine the interactions between HOXB5 and other transcription factors implicated in RET expression. We show that human HOXB5 binds to the promoter region 5′ upstream of the binding site of NKX2-1 and regulates RET expression. HOXB5 and NKX2-1 form a protein complex and mediate RET expression in a synergistic manner. HSCR associated SNPs at the NKX2-1 binding site (-5G>A rs10900296; -1A>C rs10900297), which reduce NKX2-1 binding, abolish the synergistic trans-activation of RET by HOXB5 and NKX2-1. In contrast to the synergistic activation of RET with NKX2-1, HOXB5 cooperates in an additive manner with SOX10, PAX3 and PHOX2B in trans-activation of RET promoter. Taken together, our data suggests that HOXB5 in coordination with other transcription factors mediates RET expression. Therefore, defects in cis- or trans-regulation of RET by HOXB5 could lead to reduction of RET expression and contribute to the manifestation of the HSCR phenotype

    Efficacy of insect larval meal to replace fish meal in juvenile barramundi, Lates calcarifer reared in freshwater

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    The present experiment was conducted to evaluate the efficacy of dietary protein from black soldier fly, Hermetia illucens, larval meal (BSFL) to replace fish meal (FM) protein in juvenile barramundi, Lates calcarifer. Larvae of black soldier fly were fed with the underutilised crop, sesbania, Sesbania grandiflora. Five isonitrogenous (44% crude protein) and isocaloric (16.0 kJ available energy/g) experimental diets were formulated to replace FM using processed BSFL meal at 0 (control), 25% (BSFL25), 50% (BSFL50), 75% (BSFL75) and 100% (BSFL100). Data for proximate and amino acid analysis suggested BSFL meal as an inferior protein ingredient than FM, but parallel to soybean meal. At the end of 8 weeks of fish feeding trial, there were no significant differences in the average weight gain (WG) and specific growth rate among the group of fish-fed control, BSFL25 and BSFL50 diets (P < 0.05). Although numerical differences were recorded in the fish whole-body proximate composition, crude protein and moisture content were not much affected by the different dietary treatments. Essential amino acids including arginine, histidine, lysine and methionine were found to be higher in the whole body of fish-fed BSFL100 diet. Broken line regression analysis of average WG showed an optimum FM replacement level of 28.4% with BSFL meal. Therefore, the present experiment clearly demonstrates that the maximal dietary inclusion level of BSFL meal as FM protein replacer for the optimum growth of juvenile barramundi reared in freshwater could be greater than 28.4% but less than 50%, without any adverse effects on the fish whole-body proximate and amino acid composition

    Performance of aquatic plant species for phytoremediation of arsenic-contaminated water

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    This study investigates the effectiveness of aquatic macrophyte and microphyte for phytoremediation of water bodies contaminated with high arsenic concentration. Water hyacinth (Eichhornia crassipes) and two algae (Chlorodesmis sp. and Cladophora sp.) found near arsenic-enriched water bodies were used to determine their tolerance toward arsenic and their effectiveness to uptake arsenic thereby reducing organic pollution in arsenic-enriched wastewater of different concentrations. Parameters like pH, chemical oxygen demand (COD), and arsenic concentration were monitored. The pH of wastewater during the course of phytoremediation remained constant in the range of 7.3–8.4, whereas COD reduced by 50–65 % in a period of 15 days. Cladophora sp. was found to survive up to an arsenic concentration of 6 mg/L, whereas water hyacinth and Chlorodesmis sp. could survive up to arsenic concentrations of 2 and 4 mg/L, respectively. It was also found that during a retention period of 10 days under ambient temperature conditions, Cladophora sp. could bring down arsenic concentration from 6 to <0.1 mg/L, Chlorodesmis sp. was able to reduce arsenic by 40−50 %; whereas, water hyacinth could reduce arsenic by only 20 %. Cladophora sp. is thus suitable for co-treatment of sewage and arsenic-enriched brine in an algal pond having a retention time of 10 days. The identified plant species provides a simple and cost-effective method for application in rural areas affected with arsenic problem. The treated water can be used for irrigation

    Subthalamic nucleus deep brain stimulation in elderly patients – analysis of outcome and complications

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    BACKGROUND: There is an ongoing discussion about age limits for deep brain stimulation (DBS). Current indications for DBS are tremor-dominant disorders, Parkinson's disease, and dystonia. Electrode implantation for DBS with analgesia and sedation makes surgery more comfortable, especially for elderly patients. However, the value of DBS in terms of benefit-risk ratio in this patient population is still uncertain. METHODS: Bilateral electrode implantation into the subthalamic nucleus (STN) was performed in a total of 73 patients suffering from Parkinson's disease. Patients were analyzed retrospectively. For this study they were divided into two age groups: group I (age <65 years, n = 37) and group II (age ≥ 65 years, n = 36). Examinations were performed preoperatively and at 6-month follow-up intervals for 24 months postoperatively. Age, UPDRS motor score (part III) on/off, Hoehn & Yahr score, Activity of Daily Living (ADL), L-dopa medication, and complications were determined. RESULTS: Significant differences were found in overall performance determined as ADL scores (group I: 48/71 points, group II: 41/62 points [preoperatively/6-month postoperatively]) and in the rate of complications (group I: 4 transient psychosis, 4 infections in a total of 8 patients, group II: 2 deaths [unrelated to surgery], 1 intracerebral hemorrhage, 7 transient psychosis, 3 infections, 2 pneumonia in a total of 13 patients), (p < 0.05). Interestingly, changes in UPDRS scores, Hoehn & Yahr scores, and L-dopa medication were not statistically different between the two groups. CONCLUSION: DBS of the STN is clinically as effective in elderly patients as it is in younger ones. However, a more careful selection and follow-up of the elderly patients are required because elderly patients have a higher risk of surgery-related complications and a higher morbidity rate

    Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer

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    INTRODUCTION: Tamoxifen therapy reduces the risk of recurrence and prolongs the survival of oestrogen-receptor-positive patients with breast cancer. Even if most patients benefit from tamoxifen, many breast tumours either fail to respond or become resistant. Because tamoxifen is extensively metabolised by polymorphic enzymes, one proposed mechanism underlying the resistance is altered metabolism. In the present study we investigated the prognostic and/or predictive value of functional polymorphisms in cytochrome P450 3A5 CYP3A5 (*3), CYP2D6 (*4), sulphotransferase 1A1 (SULT1A1; *2) and UDP-glucuronosyltransferase 2B15 (UGT2B15; *2) in tamoxifen-treated patients with breast cancer. METHODS: In all, 677 tamoxifen-treated postmenopausal patients with breast cancer, of whom 238 were randomised to either 2 or 5 years of tamoxifen, were genotyped by using PCR with restriction fragment length polymorphism or PCR with denaturing high-performance liquid chromatography. RESULTS: The prognostic evaluation performed in the total population revealed a significantly better disease-free survival in patients homozygous for CYP2D6*4. For CYP3A5, SULT1A1 and UGT2B15 no prognostic significance was observed. In the randomised group we found that for CYP3A5, homozygous carriers of the *3 allele tended to have an increased risk of recurrence when treated for 2 years with tamoxifen, although this was not statistically significant (hazard ratio (HR) = 2.84, 95% confidence interval (CI) = 0.68 to 11.99, P = 0.15). In the group randomised to 5 years' tamoxifen the survival pattern shifted towards a significantly improved recurrence-free survival (RFS) among CYP3A5*3-homozygous patients (HR = 0.20, 95% CI = 0.07 to 0.55, P = 0.002). No reliable differences could be seen between treatment duration and the genotypes of CYP2D6, SULT1A1 or UGT2B15. The significantly improved RFS with prolonged tamoxifen treatment in CYP3A5*3 homozygotes was also seen in a multivariate Cox model (HR = 0.13, CI = 0.02 to 0.86, P = 0.03), whereas no differences could be seen for CYP2D6, SULT1A1 and UGT2B15. CONCLUSION: The metabolism of tamoxifen is complex and the mechanisms responsible for the resistance are unlikely to be explained by a single polymorphism; instead it is a combination of several mechanisms. However, the present data suggest that genetic variation in CYP3A5 may predict response to tamoxifen therapy
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