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Viperin is an important host restriction factor in control of Zika virus infection
Get PDFOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Zika virus (ZIKV) infection has emerged as a global health threat and infection of pregnant women causes intrauterine growth restriction, spontaneous abortion and microcephaly in newborns. Here we show using biologically relevant cells of neural and placental origin that following ZIKV infection, there is attenuation of the cellular innate response characterised by reduced expression of IFN-β and associated interferon stimulated genes (ISGs). One such ISG is viperin that has well documented antiviral activity against a wide range of viruses. Expression of viperin in cultured cells resulted in significant impairment of ZIKV replication, while MEFs derived from CRISPR/Cas9 derived viperin−/− mice replicated ZIKV to higher titers compared to their WT counterparts. These results suggest that ZIKV can attenuate ISG expression to avoid the cellular antiviral innate response, thus allowing the virus to replicate unchecked. Moreover, we have identified that the ISG viperin has significant anti-ZIKV activity. Further understanding of how ZIKV perturbs the ISG response and the molecular mechanisms utilised by viperin to suppress ZIKV replication will aid in our understanding of ZIKV biology, pathogenesis and possible design of novel antiviral strategies
Investigation of sphingosine kinase 1 in interferon responses during dengue virus infection
Get PDFThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Dengue virus (DENV) regulates sphingosine kinase (SK)-1 activity and chemical inhibition of SK1 reduces DENV infection. In primary murine embryonic fibroblasts (pMEFs) lacking SK1 however, DENV infection is enhanced and this is associated with induction of normal levels of interferon beta (IFN-β) but reduced levels of IFN-stimulated genes (ISGs). We have further investigated this link between SK1 and type I IFN responses. DENV infection downregulates cell-surface IFN-alpha receptor (IFNAR)1 in both wild-type (WT) and SK1−/− pMEF, but, consistent with poor ISG responses, shows reduced induction of phosphorylated (p)-STAT1 and key IFN regulatory factors (IRF)1 and −7 in SK1−/− pMEF. Direct IFN stimulation induced ISGs (viperin, IFIT1), CXCL10, IRF1 and −7 and p-STAT1. Responses, however, were significantly reduced in SK1−/− pMEF, except for IFN-stimulated CXCL10 and IRF7. Poor IFN responses in SK1−/− pMEF were associated with a small reduction in basal cell-surface IFNAR1 and IRF1 mRNA in uninfected SK1−/− compared with WT pMEF. In contrast, treatment of cells with the SK1 inhibitor, SK1-I or expression of an inhibitory SK1 short hairpin RNA (shRNA), both of which reduce DENV infection, does not alter basal IRF1 mRNA or affect type I IFN stimulation of p-STAT1. Thus, cells genetically lacking SK1 can induce many responses normally following DENV infection, but have adaptive changes in IFNAR1 and IRF1 that compromise DENV-induced type I IFN responses. This suggests a biological link between SK1 and IFN-stimulated pathways. Other approaches to reduce SK1 activity, however, do not influence these important antiviral pathways but reduce infection and may be useful antiviral strategies
Selection of microbes for control of Rhizoctonia root rot on wheat using a high throughput pathosystem
Get PDF© 2017 Elsevier. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http:// creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 12 month embargo from date of publication (July 2017) in accordance with the publisher’s archiving policyThe promise of microbial biological control of soilborne fungal pathogens of crops has yet to be fully realised with only a few strains commercialised and available to growers. One bottleneck is the availability of suitable methods to screen microorganisms for disease control efficacy relevant to controlling disease in the field. A 3-phase in planta pathosystem containing field soil was developed to screen 2310 microorganisms for control of Rhizoctonia root rot on wheat. Test strains were added to seeds as a suspension at planting and plant growth assessed at two weeks. Strains increasing plant height and number of roots (185) were tested in a replicated Rhizoctonia pot bioassay with five wheat seedlings grown for four weeks and assessed for plant growth and root disease. Forty-three strains (1.9% of strains tested) performed better than our benchmark strains and were reassessed in pot bioassays at three inoculation levels. These tested strains represented a wide diversity of microbial genotypes including fungi, (Trichoderma, Aspergillus and Cylindrocarpon) and bacteria encompassing four phyla (Actinobacteria, Firmicutes, Proteobacteria, Bacteroidetes). These results show that microbes can be successfully and rapidly screened directly for disease control on plants
Spatial and temporal variability of groundwater recharge in Geba basin, Northern Ethiopia
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http://creativecommons.org/licenses/by-nc-nd/4.0/
This author accepted manuscript is made available following 24 month embargo from date of publication (July 2017) in accordance with the publisher’s archiving policyWetSpa, a physically based, spatially distributed watershed model, has been used to study the spatial and temporal variation of recharge in the Geba basin, Northern Ethiopia. The model covers an area of about 4, 249 km2 and integrates elevation, soil and land-use data, hydrometeorological and river discharge data. The Geba basin has a highly variable topography ranging from 1000 to 3280 m with an average slope of 12.9%. The area is characterized by a distinct wet and long dry season with a mean annual precipitation of 681 mm and temperatures ranging between 6.5 °C and 32 °C. The model was simulated on daily basis for nearly four years (January 1, 2000 to December 18, 2003). It resulted in a good agreement between measured and simulated streamflow hydrographs with Nash-Sutcliffe efficiency of almost 70% and 85% for, respectively, the calibration and validation. The water balance terms show very strong spatial and temporal variability, about 3.8% of the total precipitation is intercepted by the plant canopy; 87.5% infiltrates into the soil (of which 13% percolates, 2.7% flows laterally off and 84.2% evapotranspired from the root zone), and 7.2% is surface runoff. The mean annual recharge varies from about 45 mm (2003) to 208 mm (2001), with average of 98.6 mm/yr. On monthly basis, August has the maximum (73 mm) and December the lowest (0.1 mm) recharge. The mean annual groundwater recharge spatially varies from 0 to 371 mm; mainly controlled by the distribution of rainfall amount, followed by soil and land-use, and to a certain extent, slope. About 21% of Geba has a recharge larger than 120 mm and 1% less than 5 mm
Το Παράδοξο της Άπειρης Ταυτότητας στον Νάνο Βαλαωρίτη
Get PDFAll rights reserved © 2017, Modern Greek Studies Association of Australia and New Zealand. Reproduced with permission of the publisher.Please note: This article is in Greek. The Paradox of Infinite Identity in Nanos Valaoritis: The subject of Nanos Valaoritis’ writing is investigated through the theses of Whitehead and Deleuze on the construction of an infinite identity with binary direction, future and historic, passive and active, causal and effective. The paradox of this identity is that language itself exceeds the limits and restores them in an endless balancing of a limitless becoming, resulting in the loss (reversal) of the name. The personal uncertainty is an objective structure of the “pure Event”, to the extent that it is moving in two directions simultaneously, thus fragmenting the subject to capture the “New”. The event, along with the extension, the intension and the appearance of eternal objects, creates the conception of the New, which includes the form, the subjective aim (transitivity), and satisfaction (production of New, playable models, “counter-effectuation”), thus explaining the process of the unconscious, the humorous and “deterritorialised” in Valaoritis’ writing
Investigation of sphingosine kinase 1 in interferon responses during dengue virus infection
Get PDFThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, userswill need to obtain permission fromthe license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/Dengue virus (DENV) regulates sphingosine kinase (SK)-1 activity and chemical inhibition of SK1 reduces DENV infection. In primary murine embryonic fibroblasts (pMEFs) lacking SK1 however, DENV infection is enhanced and this is associated with induction of normal levels of interferon beta (IFN-β) but reduced levels of IFN-stimulated genes (ISGs). We have further investigated this link between SK1 and type I IFN responses. DENV infection downregulates cell-surface IFN-alpha receptor (IFNAR)1 in both wild-type (WT) and SK1−/− pMEF, but, consistent with poor ISG responses, shows reduced induction of phosphorylated (p)-STAT1 and key IFN regulatory factors (IRF)1 and −7 in SK1−/− pMEF. Direct IFN stimulation induced ISGs (viperin, IFIT1), CXCL10, IRF1 and −7 and p-STAT1. Responses, however, were significantly reduced in SK1−/− pMEF, except for IFN-stimulated CXCL10 and IRF7. Poor IFN responses in SK1−/− pMEF were associated with a small reduction in basal cell-surface IFNAR1 and IRF1 mRNA in uninfected SK1−/− compared with WT pMEF. In contrast, treatment of cells with the SK1 inhibitor, SK1-I or expression of an inhibitory SK1 short hairpin RNA (shRNA), both of which reduce DENV infection, does not alter basal IRF1 mRNA or affect type I IFN stimulation of p-STAT1. Thus, cells genetically lacking SK1 can induce many responses normally following DENV infection, but have adaptive changes in IFNAR1 and IRF1 that compromise DENV-induced type I IFN responses. This suggests a biological link between SK1 and IFN-stimulated pathways. Other approaches to reduce SK1 activity, however, do not influence these important antiviral pathways but reduce infection and may be useful antiviral strategies
Obstructive Sleep Apnoea: Therapeutic Options and Challenges
Get PDFCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Obstructive sleep apnoea (OSA) is a common sleep disorder that is associated with significant negative health outcomes including cardiovascular disease, daytime sleepiness, neurocognitive deficits, and increased motor vehicle and workplace accidents. There is wide variation in OSA symptoms and other downstream effects between patients highlighting the need to individualise therapy. Continuous positive airway pressure delivered by a face mask is the gold standard treatment, but adherence to this therapy is poor and improvements in outcomes are often incomplete. A range of alternative treatments are available and may suit different patients. These include behavioural treatments such as weight loss, mandibular advancement using an oral device, sleep posture modification, upper airway surgery, and upper airway muscle stimulation. Towards individualised OSA therapy, novel phenotyping approaches are being developed to identify the specific pathophysiological causes of OSA applying to individual patients. Furthermore, research is underway to help identify patients with OSA at higher risk of daytime sleepiness and adverse cardiovascular and neurocognitive consequences and predict how individuals might respond to treatment. In this article, we review the prevalence, risk factors, and main consequences of OSA; the main treatment modalities available at present; and some new methods for phenotyping patients with OSA that hold promise for a more personalised and effective approach to screening, diagnosis, and treatment
Breastfeeding initiation and support: A literature review of what women value and the impact of early discharge
Get PDF© 2016 Australian College of Midwives. Published by Elsevier Ltd.Problem
Early discharge following birth has become an emerging phenomenon in many countries. It is likely early discharge has an impact on the establishment of breastfeeding.
Objective
To critically appraise the evidence on what women value in relation to breastfeeding initiation and support, and investigate the impact early discharge can have on these values.
Method
A literature search was conducted for publications since 2005 using the following databases: Cumulative Index of Nursing and Allied Health Literature (CINAHL), Medline, Scopus and PsycINFO; 21 primary articles were selected and included in the review.
Findings
There is no standard definition for ‘early discharge’ worldwide. Due to inconsistent definitions worldwide and minimal literature using a 24 h definition, research defining early discharge as up to 72 h postpartum is included. Seven key factors in relation to breastfeeding initiation and support following early discharge were identified, namely trust and security, consistent advice, practical breastfeeding support, breastfeeding education, comfortable environment, positive attitudes and emotional support, and individualised care.
Conclusion
The findings suggest individualised postnatal lengths of stay may be beneficial for the initiation of breastfeeding. Five values were not impacted by early discharge, but rather individual midwives’ practice. There is consensus in the literature that early discharge promoted a comfortable environment to support breastfeeding initiation. Wide variations in the definition of early postnatal discharge made it difficult to draw influential conclusions. Therefore, further research is required
Contribution of Mutations in Known Mendelian Glaucoma Genes to Advanced Early-Onset Primary Open-Angle Glaucoma
No full textThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Purpose: Primary open-angle glaucoma (POAG) and primary congenital glaucoma (PCG) with Mendelian inheritance are caused by mutations in at least nine genes. Utilizing whole-exome sequencing, we examined the disease burden accounted for by these known Mendelian glaucoma genes in a cohort of individuals with advanced early-onset POAG.
Methods: The cases exhibited advanced POAG with young age of diagnosis. Cases and examined local controls were subjected to whole-exome sequencing. Nine hundred ninety-three previously sequenced exomes of Australian controls were called jointly with our dataset. Qualifying variants were selected based on predicted pathogenicity and rarity in public domain gene variant databases. Case–control mutational burdens were calculated for glaucoma-linked genes.
Results: Two hundred eighteen unrelated POAG participants and 103 nonglaucomatous controls were included in addition to 993 unexamined controls. Fifty-eight participants (26.6%) harbored rare potentially pathogenic variants in known glaucoma genes. Enrichment of qualifying variants toward glaucoma was present in all genes except WDR36, in which controls harbored more variants, and TBK1, in which no qualifying variants were detected in cases or controls. After multiple testing correction, only MYOC showed statistically significant enrichment of qualifying variants (odds ratio [OR] = 16.62, P = 6.31×10−16).
Conclusions: Rare, potentially disease-causing variants in Mendelian POAG genes that showed enrichment in our dataset were found in 22.9% of advanced early-onset POAG cases. MYOC variants represented the largest monogenic cause in POAG. The association between WDR36 and POAG was not supported, and the majority of POAG cases did not harbor a potentially disease-causing variant in the remaining Mendelian genes
