Succession of fungi on dead and live wood in brackish water in Brunei

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Lentiviral and AAV-mediated expression of palivizumab offer protection against Respiratory Syncytial Virus infection

Respiratory syncytial virus (RSV) infection is a common cause of hospitalisation in infants and the elderly. Palivizumab prophylaxis is the only approved treatment modality but is costly and only offered to select vulnerable populations. Here, we investigated gene delivery approaches via recombinant adeno-associated virus (rAAV2/8) and simian immunodeficiency virus (rSIV.F/HN) vectors to achieve sustained in vivo production of palivizumab in a murine model. Delivery of palivizumab-expressing vectors 28 days prior to RSV challenge resulted in complete protection from RSV-induced weight loss. This approach offers prophylaxis against RSV infection, allowing for wider use and reduction in treatment costs in vulnerable populations

Type I interferon signaling deficiency results in dysregulated innate immune responses to SARS-CoV-2 in mice

SARS-CoV-2 is a newly emerged coronavirus, causing the global pandemic of respiratory coronavirus disease (COVID-19). The type I interferon (IFN) pathway is of particular importance for anti-viral defence and recent studies identified that type I IFNs drive early inflammatory responses to SARS-CoV-2. Here, we use a mouse model of SARS-CoV-2 infection, facilitating viral entry by intranasal recombinant Adeno-Associated Virus (rAAV) transduction of hACE2 in wildtype (WT) and type I IFN-signalling-deficient (Ifnar1-/- ) mice, to study type I IFN signalling deficiency and innate immune responses during SARS-CoV-2 infection. Our data show that type I IFN signaling is essential for inducing anti-viral effector responses to SARS-CoV-2, control of virus replication and to prevent enhanced disease. Furthermore, hACE2-Ifnar1-/- mice had increased gene expression of the chemokine Cxcl1 and airway infiltration of neutrophils as well as a reduced and delayed production of monocyte-recruiting chemokine CCL2. hACE2-Ifnar1-/- mice showed altered recruitment of inflammatory myeloid cells to the lung upon SARS-CoV-2 infection, with a shift from Ly6C+ to Ly6C- expressing cells. Together, our findings suggest that type I IFN deficiency results in a dysregulated innate immune response to SARS-CoV-2 infection. This article is protected by copyright. All rights reserved

Gut thinking: the gut microbiome and mental health beyond the head

Background: In recent decades, dominant models of mental illness have become increasingly focused on the head, with mental disorders being figured as brain disorders. However, research into the active role that the microbiome-gut-brain axis plays in affecting mood and behaviour may lead to the conclusion that mental health is more than an internalised problem of individual brains. Objective: This article explores the implications of shifting understandings about mental health that have come about through research into links between the gut microbiome and mental health problems such as depression and anxiety. It aims to analyse the different ways that the lines between mind and body and mental and physical health are re-shaped by this research, which is starting to inform clinical and public understanding. Design: As mental health has become a pressing issue of political and public concern it has become increasingly constructed in socio-cultural and personal terms beyond clinical spaces, requiring a conceptual response that exceeds biomedical inquiry. This article argues that an interdisciplinary critical medical humanities approach is well positioned to analyse the impact of microbiome-gut-brain research on conceptions of mind. Results: The entanglement of mind and matter evinced by microbiome-gut-brain axis research potentially provides a different way to conceptualise the physical and social concomitants of mental distress. Conclusion: Mental health is not narrowly located in the head but is assimilated by the physical body and intermingled with the natural world, requiring different methods of research to unfold the meanings and implications of gut thinking for conceptions of human selfhood

Taking stock of gene therapy for cystic fibrosis

The identification of the cystic fibrosis (CF) gene opened the way for gene therapy. In the ten years since then, proof of principle in vitro and then in animal models in vivo has been followed by numerous clinical studies using both viral and non-viral vectors to transfer normal copies of the gene to the lungs and noses of CF patients. A wealth of data have emerged from these studies, reflecting enormous progress and also helping to focus and define key difficulties that remain unresolved. Gene therapy for CF remains the most promising possibility for curative rather than symptomatic therapy

The use of carboxymethylcellulose gel to increase non-viral gene transfer in mouse airways

We have assessed whether viscoelastic gels known to inhibit mucociliary clearance can increase lipid-mediated gene transfer. Methylcellulose or carboxymethylcellulose (0.25 to 1.5%) were mixed with complexes of the cationic lipid GL67A and plasmids encoding luciferase and perfused onto the nasal epithelium of mice. Survival after perfusion with 1% CMC or1% MC was 90 and 100%, respectively. In contrast 1.5% CMC was uniformly lethal likely due to the viscous solution blocking the airways. Perfusion with 0.5% CMC containing lipid/DNA complexes reproducibly increased gene expression by approximately 3-fold (n= 16, p<0.05). Given this benefit, likely related to increased duration of contact, we also assessed the effect of prolonging contact time of the liposome/DNA complexes by delivering our standard 80 μg DNA dose over either approximately 22 or 60 min of perfusion. This independently increased gene transfer by 6-fold (n=8, p<0.05) and could be further enhanced by the addition of 0.5% CMC, leading to an overall 25-fold enhancement (n=8, p<0.001) in gene expression. As a result of these interventions CFTR transgene mRNA transgene levels were increased several logs above background. Interestingly, this did not lead to correction of the ion transport defects in the nasal epithelium of cystic fibrosis mice nor for immunohistochemical quantification of CFTR expression. To assess if 0.5% CMC also increased gene transfer in the mouse lung, we used whole body nebulisation chambers. CMC was nebulised for 1 hr immediately before, or simultaneously with GL67A/pCIKLux. The former did not increase gene transfer, whereas co-administration significantly increased gene transfer by 4-fold (p<0.0001, n=18). This study suggests that contact time of non-viral gene transfer agents is a key factor for gene delivery, and suggests two methods which may be translatable for use in man

The gray matter volume of the amygdala is correlated with the perception of melodic intervals: a voxel-based morphometry study

Music is not simply a series of organized pitches, rhythms, and timbres, it is capable of evoking emotions. In the present study, voxel-based morphometry (VBM) was employed to explore the neural basis that may link music to emotion. To do this, we identified the neuroanatomical correlates of the ability to extract pitch interval size in a music segment (i.e., interval perception) in a large population of healthy young adults (N = 264). Behaviorally, we found that interval perception was correlated with daily emotional experiences, indicating the intrinsic link between music and emotion. Neurally, and as expected, we found that interval perception was positively correlated with the gray matter volume (GMV) of the bilateral temporal cortex. More important, a larger GMV of the bilateral amygdala was associated with better interval perception, suggesting that the amygdala, which is the neural substrate of emotional processing, is also involved in music processing. In sum, our study provides one of first neuroanatomical evidence on the association between the amygdala and music, which contributes to our understanding of exactly how music evokes emotional responses

Climate-fungal pathogen modeling predicts loss of up to one-third of tea growing areas

This is the final version. Available from Frontiers Media via the DOI in this record. Climate change will affect numerous crops in the future; however, perennial crops, such as tea, are particularly vulnerable. Climate change will also strongly influence fungal pathogens. Here, we predict how future climatic conditions will impact tea and its associated pathogens. We collected data on the three most important fungal pathogens of tea (Colletotrichum acutatum, Co. camelliae, and Exobasidium vexans) and then modeled distributions of tea and these fungal pathogens using current and projected climates. The models show that baseline tea-growing areas will become unsuitable for Camellia sinensis var. sinensis (15 to 32% loss) and C. sinensis var. assamica (32 to 34% loss) by 2050. Although new areas will become more suitable for tea cultivation, existing and potentially new fungal pathogens will present challenges in these areas, and they are already under other land-use regimes. In addition, future climatic scenarios suitable range of fungal species and tea suitable cultivation (respectively in CSS and CSA) growing areas are Co. acutatum (44.30%; 31.05%), Co. camelliae (13.10%; 10.70%), and E. vexans (10.20%; 11.90%). Protecting global tea cultivation requires innovative approaches that consider fungal genomics as part and parcel of plant pathology.International Postdoctoral Exchange Fellowship ProgramCAS President’s International Fellowship Initiative (PIFI)China Postdoctoral Science FoundationYunnan Human Resources and Social Security Department FoundationNational Science Foundation of China (NSFC)National Science Foundation of China (NSFC)BBSRCCAS President’s International Fellowship Initiative (PIFI)National Science Foundation of China (NSFC)Thailand Research FundsChiang Mai Universit

Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi

DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi

Increased plasma membrane cholesterol in cystic fibrosis cells correlates with CFTR genotype and depends on de novo cholesterol synthesis

<p>Abstract</p> <p>Background</p> <p>Previous observations demonstrate that <it>Cftr</it>-null cells and tissues exhibit alterations in cholesterol processing including perinuclear cholesterol accumulation, increased <it>de novo </it>synthesis, and an increase in plasma membrane cholesterol accessibility compared to wild type controls. The hypothesis of this study is that membrane cholesterol accessibility correlates with CFTR genotype and is in part influenced by <it>de novo </it>cholesterol synthesis.</p> <p>Methods</p> <p>Electrochemical detection of cholesterol at the plasma membrane is achieved with capillary microelectrodes with a modified platinum coil that accepts covalent attachment of cholesterol oxidase. Modified electrodes absent cholesterol oxidase serves as a baseline control. Cholesterol synthesis is determined by deuterium incorporation into lipids over time. Incorporation into cholesterol specifically is determined by mass spectrometry analysis. All mice used in the study are on a C57Bl/6 background and are between 6 and 8 weeks of age.</p> <p>Results</p> <p>Membrane cholesterol measurements are elevated in both R117H and ΔF508 mouse nasal epithelium compared to age-matched sibling wt controls demonstrating a genotype correlation to membrane cholesterol detection. Expression of wt CFTR in CF epithelial cells reverts membrane cholesterol to WT levels further demonstrating the impact of CFTR on these processes. In wt epithelial cell, the addition of the CFTR inhibitors, Gly H101 or CFTR_inh-172, for 24 h surprisingly results in an initial drop in membrane cholesterol measurement followed by a rebound at 72 h suggesting a feedback mechanism may be driving the increase in membrane cholesterol. <it>De novo </it>cholesterol synthesis contributes to membrane cholesterol accessibility.</p> <p>Conclusions</p> <p>The data in this study suggest that CFTR influences cholesterol trafficking to the plasma membrane, which when depleted, leads to an increase in <it>de novo </it>cholesterol synthesis to restore membrane content.</p