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Variants of HCMV UL18 sequenced directly from clinical specimens associate with antibody and T-cell responses to HCMV
Get PDFAround 80% of adults worldwide carry human cytomegaloviris (HCMV). The HCMV gene UL18 is a homolog of HLA class I genes and encodes a protein with high affinity for the NK and T-cell cytotoxicity inhibitor LIR-1. UL18 was deep sequenced from blood, saliva or urine from Indonesian people with HIV (PWH) (n = 28), Australian renal transplant recipients (RTR) (n = 21), healthy adults (n = 7) and neonates (n = 4). 95% of samples contained more than one variant of HCMV UL18, as defined by carriage of nonsynonymous variations. When aligned with immunological markers of the host’s burden of HCMV, the S318N variation associated with high levels of antibody reactive with HCMV lysate in PWH over 12 months on antiretroviral therapy. The A107T variation associated with HCMV antibody levels and inflammatory biomarkers in PWH at early timepoints. Variants D32G, D248N, V250A and E252D aligned with elevated HCMV antibody levels in RTR, while M191K, E196Q and F165L were associated with HCMV-reactive T-cells and proportions of Vδ2− γδ T-cells—populations linked with high burdens of HCMV. We conclude that UL18 is a highly variable gene, where variation may alter the persistent burden of HCMV and/or the host response to that burden
O.11 Identification of a novel heterozygous DYSF variant in a large family with a dominantly-inherited dysferlinopathy
No full textDysferlinopathy is an autosomal recessive muscular dystrophy, caused by bi-allelic variants in the gene encoding dysferlin (DYSF). Onset typically occurs in the second to third decade and is characterised by slowly progressive skeletal muscle weakness and atrophy of proximal and/or distal muscles of the limb girdles. There are rare cases of symptomatic DYSF variant carriers. Here, we report a large family with a dominantly inherited hyperCKemia and late-onset muscular dystrophy. Genetic analysis identified a co-segregating novel DYSF variant [NM_003494.4: c.6207del, p.(Tyr2070Metfs*4)]. No secondary variants in DYSF or other dystrophy-related genes were identified on whole genome sequencing and analysis of the proband's DNA. Skeletal muscle involvement was milder and later onset than typical dysferlinopathy presentations; these clinical signs manifested in only three individuals, all between the fourth and sixth decades of life. All individuals heterozygous for the c.6207del variant had hyperCKemia. Histological analysis of skeletal muscle biopsies across three generations showed clear dystrophic signs, including inflammatory infiltrate, regenerating myofibres, increased variability in myofibre size, and internal nuclei. Muscle magnetic resonance imaging revealed fatty replacement of muscle in two individuals. Western blot and immunohistochemical analysis of muscle biopsy demonstrated consistent reduction of dysferlin staining. Allele-specific quantitative PCR analysis of DYSF mRNA from patient muscle found that the variant, localised to the extreme C-terminus of dysferlin, does not activate post-transcriptional mRNA decay. We propose that this inheritance pattern may be underappreciated and that other late-onset muscular dystrophy cases with mono-allelic DYSF variants, particularly C-terminal premature truncation variants, may represent dominant forms of disease
Network analysis of 18 attention-deficit/hyperactivity disorder symptoms suggests the importance of “Distracted” and “Fidget” as central symptoms: Invariance across age, gender, and subtype presentations
Get PDFThe network theory of mental disorders conceptualizes psychiatric symptoms as networks of symptoms that causally interact with each other. Our present study aimed to explore the symptomatic structure in children with attention-deficit/hyperactivity disorder (ADHD) using network analyses. Symptom network based on 18 items of ADHD Rating Scale-IV was evaluated in 4,033 children and adolescents with ADHD. The importance of nodes was evaluated quantitatively by examining centrality indices, including Strength, Betweenness and Closeness, as well as Predictability and Expected Influence (EI). In addition, we compared the network structure across different subgroups, as characterized by ADHD subtypes, gender and age groups to evaluate its invariance. A three-factor-community structure was identified including inattentive, hyperactive and impulsive clusters. For the centrality indices, the nodes of “Distracted” and “Fidget” showed high closeness and betweenness, and represented a bridge linking the inattentive and hyperactive/impulsive domains. “Details” and “Fidget” were the most common endorsed symptoms in inattentive and hyperactive/impulsive domains respectively. On the contrary, the “Listen” item formed a peripheral node showing weak links with all other items within the inattentive cluster, and the “Loss” item as the least central node by all measures of centrality and with low predictability value. The network structure was relatively invariant across gender, age and ADHD subtypes/presentations. The 18 items of ADHD core symptoms appear not equivalent and interchangeable. “Distracted” and “Fidget” should be considered as central, or core, symptoms for further evaluation and intervention. The network-informed differentiation of these symptoms has the potentials to refine the phenotype and reduce heterogeneity
The chromosome‐level genome of female ginseng ( Angelica sinensis ) provides insights into molecular mechanisms and evolution of coumarin biosynthesis
No full textCoumarins are natural products with important medicinal values, and include simple coumarins, furanocoumarins and pyranocoumarins. Female ginseng (Angelica sinensis) is a renowned herb with abundant coumarins, originated in China and known for the treatment of female ailments for thousands of years. The molecular basis of simple coumarin biosynthesis in A. sinensis and the evolutionary history of the genes involved in furanocoumarin biosynthesis are largely unknown. Here, we generated the first chromosome-scale genome of A. sinensis. It has a genome size of 2.37 Gb, which was generated by combining PacBio and Hi-C sequencing technologies. The genome was predicted to contain 43 202 protein-coding genes dispersed mainly on 11 pseudochromosomes. We not only provided evidence for whole-genome duplication (WGD) specifically occurring in the Apioideae subfamily, but also demonstrated the vital role of tandem duplication for phenylpropanoid biosynthesis in A. sinensis. Combined analyses of transcriptomic and metabolomic data revealed key genes and candidate transcription factors regulating simple coumarin biosynthesis. Furthermore, phylogenomic synteny network analyses suggested prenyltransferase genes involved in furanocoumarin biosynthesis evolved independently in the Moraceae, Fabaceae, Rutaceae and Apiaceae after ζ and ε WGD. Our work sheds light on coumarin biosynthesis, and provides a benchmark for accelerating genetic research and molecular breeding in A. sinensis
Global meta‐analysis reveals incomplete recovery of soil conditions and invertebrate assemblages after ecological restoration in agricultural landscapes
No full textRestoration of old fields in agricultural landscapes has become increasingly important for conservation of species and their habitats owing to habitat destruction and rapid environmental change. Studies examining the outcomes of old field restoration predominantly focus on plant, and sometimes, vertebrate communities. Fewer studies have systematically investigated the effects of restoration efforts on soil properties or ground‐dwelling invertebrates and there is limited synthesis of these data.
We conducted a global meta‐analysis of published studies to assess the effects of old field restoration on soil properties and soil invertebrate abundance and richness. We anticipated increased vegetation cover would improve soil properties towards reference condition and in turn, this would promote invertebrate abundance and richness. Studies were included if field sites had a history of cropping or livestock grazing.
We identified 42 studies (1994–2019) from 16 countries that met our criteria. More studies assessed passive restoration methods than active planting, and native species were more commonly planted than exotic species.
Results showed that restoration improved soil conditions with respect to total nitrogen, magnesium, soil carbon, bulk density and porosity when compared to controls; however, conditions similar to those in reference ecosystems were generally not achieved, even 50+ years after restoration had been initiated. Moderator analyses showed few significant tends, however, bulk density improved with age, and in passively restored versus reference ecosystems. Outcomes for soil carbon and bulk density were most predominant in the top soil when compared to the degraded ecosystem. We detected no consistent trends for the effect of restoration on soil invertebrate richness and abundance compared to the control or reference ecosystems.
Synthesis and applications. Our global meta‐analysis found strong evidence that old field restoration in agricultural landscapes had positive effects on soil condition but did not lead to full recovery when compared to a reference ecosystem. We detected few and idiosyncratic effects for invertebrates. Further research is needed to understand effects of restoration on soil invertebrate functional groups and to develop management interventions that accelerate the restoration of soil condition
Solution-phase decomposition of ferrocene into wüstite-iron oxide core–shell nanoparticles
No full textWe report an improved method for the controlled solvent-phase decomposition of ferrocene into highly crystalline monodisperse iron oxide nanoparticles at relatively low temperatures. Solution-phase decomposition of ferrocene into nanoparticles has received little attention in the literature, due to the percieved stability of ferrocene. However, we synthesised wüstite FeO-iron oxide core–shell nanoparticles by thermally decomposing ferrocene in 1-octadecene solvent and in the presence of oleic acid and oleylamine, as surfactants. We report procedures that provide cubic and spherical core–shell iron oxide nanoparticles whose size (29.3 ± 2.3 nm for spheres, 38.6 ± 6.9 nm for distorted cubes and 23.5 ± 2.4 nm for distorted cubes with concave faces) and shape can be controlled through simple adjustments to reaction parameters. Transmission electron microscopy, scanning transmission electron microscopy, energy dispersive X-ray spectroscopy, electron energy-loss spectroscopy and powder X-ray diffraction analysis methods were used to characterise the nanoparticles
The impact of bariatric surgery on serum tryptophan–kynurenine pathway metabolites
Get PDFThis study aims to explore the immediate effects of bariatric surgery on serum tryptophan–kynurenine pathway metabolites in individuals with type 2 diabetes and BMI > 30. With the goal of providing insight into the link between tryptophan pathway metabolites, type 2 diabetes, and chronic obesity-induced inflammation. This longitudinal study included 20 participants. Half were diagnosed with type 2 diabetes. 11 and 9 underwent RYGB and SG respectively. Blood samples were obtained at pre-operative and 3 months post-operative timepoints. Tryptophan and downstream metabolites of the kynurenine pathway were quantified with an ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionisation method. At 3 months post-operation, RYGB led to significant reductions in tryptophan, kynurenic acid and xanthurenic acid levels when compared to baseline. Significant reductions of the same metabolites after surgery were also observed in individuals with T2D irrespective of surgical procedure. These metabolites were significantly correlated with serum HbA1c levels and BMI. Bariatric surgery, in particular RYGB reduces serum levels of tryptophan and its downstream kynurenine metabolites. These metabolites are associated with T2D and thought to be potentially mechanistic in the systemic processes of obesity induced inflammation leading to insulin resistance. Its reduction after surgery is associated with an improvement in glycaemic control (HbA1c)
Synthesis and characterization of novel silane derivatives of phenothiazinium photosensitisers
No full textPhenothiazine based dyes are widely explored dyes for their antibacterial and photosensitising applications. Despite their amazing optical and photosensitising (theranostic) properties, their usage in nanomedicine is very low compared to other organic dyes. This is due to the lack of reactive functional groups for encapsulating them into metal oxide nanoparticles. This work describes the synthesis of three different phenothiazinium alkoxysilane derivatives by oxidative amination of 10H-phenothiazine using amino alkoxysilanes. The new derivatives were characterized using NMR, FT-IR, DSC/TGA, and mass spectral studies. Optical and photosensitising properties (absorption spectrum, photostability, and singlet oxygen quantum yield) of the silane derivatives were investigated using UV–Visible spectroscopy. These compounds are suitable for conjugation with silica in the sol-gel synthesis of silica nanoparticles and silica surface coaters, which will reduce dye leakage and improve the dye efficacy in the treatment of cancer and light activated antimicrobial surfaces
Taxonomy and systematics of the new Australo-Pacific orb-weaving spider genus Socca (Araneae: Araneidae)
No full textThe new Australo-Pacific orb-weaving spider genus Socca is established to include 12 species from Australia: Socca pustulosa (Walckenaer, 1841) comb. nov. (type species; also present in New Zealand); S. arena sp. nov., S. australis sp. nov. S. caiguna sp. nov., S. elvispresleyi sp. nov., S. eugeni sp. nov., S. johnnywarreni sp. nov., S. kullmanni sp. nov., S. levyashini sp. nov., S. pleia sp. nov., S. senicaudata (Simon, 1908) comb. nov. (= Araneus senicaudatus simplex Simon, 1908 syn. nov.) and S. sydneyica (Keyserling, 1887) comb. nov. (= Epeira inquieta Keyserling, 1887 syn. nov.). Socca gen. nov. includes medium-sised, nocturnal orb-weaving spiders. It differs from other backobourkiine genera by five tubercles posteriorly on the abdomen and a tri-partite terminal apophysis of the male pedipalp. The epigyne plate in females is about as wide as long and the scape elongate and reaches posteriorly beyond the epigyne plate. Specimens of five Socca gen. nov. species were sequenced for the mitochondrial gene cytochrome c oxidase subunit 1 (COI). The preliminary phylogeny supports our morphological species but does not confirm species-groups based on morphology and suggests that New Zealand S. pustulosa comb. nov. populations originate from south-eastern Australia
Ensuring planetary survival: the centrality of organic carbon in balancing the multifunctional nature of soils
No full textNot only do soils provide 98.7% of the calories consumed by humans, they also provide numerous other functions upon which planetary survivability closely depends. However, our continuously increasing focus on soils for biomass provision (food, fiber, and energy) through intensive agriculture is rapidly degrading soils and diminishing their capacity to deliver other vital functions. These tradeoffs in soil functionality – the increased provision of one function at the expense of other critical planetary functions – are the focus of this review. We examine how land-use change for biomass provision has decreased the ability of soils to regulate the carbon pool and thereby contribute profoundly to climate change, to cycle the nutrients that sustain plant growth and ecosystem health, to protect the soil biodiversity upon which many other functions depend, and to cycle the Earth’s freshwater supplies. We also examine how this decreasing ability of soil to provide these other functions can be halted and reversed. Despite the complexity and the interconnectedness of soil functions, we show that soil organic carbon plays a central role and is a master indicator for soil functioning and that we require a better understanding of the factors controlling the behavior and persistence of C in soils. Given the threats facing humanity and their economies, it is imperative that we recognize that Soil Security is itself an existential challenge and that we need to increase our focus on the multiple functions of soils for long-term human welfare and survivability of the planet