The disaster risk and resilience landscape is constantly evolving, and so too are the approaches we take in policy and practice. Despite an extended period of disruption and social distancing, many ...lessons have been learnt over the past 12 months regarding resilience, adaptability and risk reduction.
Australian Disaster Resilience Conference presents Knowledge Week was hosted online in August, exploring the theme of 'Disaster Risk Reduction in Action: Pathways to Success'.
Adenosine deaminases acting on RNA (ADARs) are editing enzymes that convert adenosine to inosine in duplex RNA, a modification reaction with wide-ranging consequences in RNA function. Understanding ...of the ADAR reaction mechanism, the origin of editing-site selectivity, and the effect of mutations is limited by the lack of high-resolution structural data for complexes of ADARs bound to substrate RNAs. Here we describe four crystal structures of the human ADAR2 deaminase domain bound to RNA duplexes bearing a mimic of the deamination reaction intermediate. These structures, together with structure-guided mutagenesis and RNA-modification experiments, explain the basis of the ADAR deaminase domain's dsRNA specificity, its base-flipping mechanism, and its nearest-neighbor preferences. In addition, we identified an ADAR2-specific RNA-binding loop near the enzyme active site, thus rationalizing differences in selectivity observed between different ADARs. Finally, our results provide a structural framework for understanding the effects of ADAR mutations associated with human disease.
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IJS, NUK, SBMB, UL, UM, UPUK
Ruminants are responsible for a large proportion of agricultural greenhouse gas emissions in the form of methane. This can be managed. It is a global initiative to increase productivity of the ...livestock sector to meet a growing population, but with emphasis on decreasing enteric methane to achieve emissions targets. We investigated the marine red macroalga (seaweed) Asparagopsis taxiformis as a feed ingredient to fundamentally eliminate enteric methane in beef cattle fed a high grain diet and provide evidence of improved livestock production performance. Asparagopsis was included in the feed of Brahman-Angus cross steers at 0.00%, 0.05%, 0.10%, and 0.20% of feed organic matter. Emissions were monitored in respiration chambers fortnightly over 90 d of treatment, steers were weighed weekly prior to feeding, feed intake monitored daily, rumen fluid samples collected in conjunction with respiration chambers for assessment of rumen function, feces were collected for bromoform residue analysis, and meat, organ, and fat were collected post slaughter for residue analysis and sensory evaluation. Steers receiving 0.10% and 0.20% Asparagopsis demonstrated decreased methane up to 40% and 98%, and demonstrated weight gain improvements of 53% and 42%, respectively. There was no negative effect on daily feed intake, feed conversion efficiencies, or rumen function, and no residues or changes in meat eating quality were detected. Commercial production of Asparagopsis could create new economies, and with low inclusion rates of this seaweed in ruminant diets the industry has the potential to revolutionize management of greenhouse gas emissions across the ruminant livestock sector with complementary benefits to the environment, and economy of the wider agriculture sector.
•The red seaweed Asparagopsis induces unprecedented enteric methane mitigation.•Productivity of beef cattle can be improved by a seaweed feed ingredient.•Asparagopsis provides an option to achieving carbon neutral red meat production.•No negative impacts induced by substantial methane abatement in beef cattle.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
During August 2020, we carried out a serological survey among students and employees at the Okinawa Institute of Science and Technology Graduate University (OIST), Japan, testing for the presence of ...antibodies against SARS-CoV-2, the causative agent of COVID-19. We used a FDA-authorized 2-step ELISA protocol in combination with at-home self-collection of blood samples using a custom low-cost finger prick-based capillary blood collection kit. Although our survey did not find any COVID-19 seropositive individuals among the OIST cohort, it reliably detected all positive control samples obtained from a local hospital and excluded all negatives controls. We found that high serum antibody titers can persist for more than 9 months post infection. Among our controls, we found strong cross-reactivity of antibodies in samples from a serum pool from two MERS patients in the anti-SARS-CoV-2-S ELISA. Here we show that a centralized ELISA in combination with patient-based capillary blood collection using as little as one drop of blood can reliably assess the seroprevalence among communities. Anonymous sample tracking and an integrated website created a stream-lined procedure. Major parts of the workflow were automated on a liquid handler, demonstrating scalability. We anticipate this concept to serve as a prototype for reliable serological testing among larger populations.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Sensing of midgut internal contents is important for ensuring appropriate hormonal response and digestion following the ingestion of dietary components. Studies in mammals have demonstrated that ...taste receptors (TRs), a subgroup of G protein-coupled receptors (GPCRs), are expressed in gut enteroendocrine cells (EECs) to sense dietary compounds and regulate the production and/or secretion of peptide hormones. Although progress has been made in identifying expression patterns of gustatory receptors (GRs) in gut EECs, it is currently unknown whether these receptors, which act as ligand-gated ion channels, serve similar functions as mammalian GPCR TRs to elicit hormone production and/or secretion. A Bombyx mori Gr, BmGr6, has been demonstrated to express in cells by oral sensory organs, midgut and nervous system; and to sense isoquercitrin and chlorogenic acid, which are non-nutritional secondary metabolites of host mulberry. Here, we show that BmGr6 co-expresses with Bommo-myosuppressin (BMS) in midgut EECs, responds to dietary compounds and is involved in regulation of BMS secretion. The presence of dietary compounds in midgut lumen after food intake resulted in an increase of BMS secretions in hemolymph of both wild-type and BmGr9 knockout larvae, but BMS secretions in BmGr6 knockout larvae decreased relative to wild-type. In addition, loss of BmGr6 led to a significant decrease in weight gain, excrement, hemolymph carbohydrates levels and hemolymph lipid levels. Interestingly, although BMS is produced in both midgut EECs and brain neurosecretory cells (NSCs), BMS levels in tissue extracts suggested that the increase in hemolymph BMS during feeding conditions is primarily due to secretion from midgut EECs. Our studies indicate that BmGr6 expressed in midgut EECs responds to the presence of dietary compounds in the lumen by eliciting BMS secretion in B. mori larvae.
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•BmGr6 is co-expressed with BMS in the enteroendocrine cells of the midgut.•Increase of dietary compounds in the gut induces a significant increase of BMS in the hemolymph.•Loss of BmGr6 results in a weakened BMS secretion response.•Loss of BmGr6 leads to reduced weight gain, reduced excretion, and reduced hemolymph carbohydrate and lipid levels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•Almost 20 different methods exist to evaluate vending machine products.•Vending machine assessment methodology complexity varies widely.•Vending product healthfulness criteria and complexity vary ...widely.•Few studies evaluate the quality of scientific practice of vending machine audits.•A universal, valid, and reliable vending machine assessment tool is recommended.
The nutritional quality of food and beverage products sold in vending machines has been implicated as a contributing factor to the development of an obesogenic food environment. How comprehensive, reliable, and valid are the current assessment tools for vending machines to support or refute these claims? A systematic review was conducted to summarize, compare, and evaluate the current methodologies and available tools for vending machine assessment. A total of 24 relevant research studies published between 1981 and 2013 met inclusion criteria for this review. The methodological variables reviewed in this study include assessment tool type, study location, machine accessibility, product availability, healthfulness criteria, portion size, price, product promotion, and quality of scientific practice. There were wide variations in the depth of the assessment methodologies and product healthfulness criteria utilized among the reviewed studies. Of the reviewed studies, 39% evaluated machine accessibility, 91% evaluated product availability, 96% established healthfulness criteria, 70% evaluated portion size, 48% evaluated price, 52% evaluated product promotion, and 22% evaluated the quality of scientific practice. Of all reviewed articles, 87% reached conclusions that provided insight into the healthfulness of vended products and/or vending environment. Product healthfulness criteria and complexity for snack and beverage products was also found to be variable between the reviewed studies. These findings make it difficult to compare results between studies. A universal, valid, and reliable vending machine assessment tool that is comprehensive yet user-friendly is recommended.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Cytidine 5′-monophosphate (CMP)-sialic acid synthetase (CSS) is an essential enzyme involved in the biosynthesis of carbohydrates and glycoconjugates containing sialic acids, a class of α-keto acids ...that are generally terminal key recognition residues by many proteins that play important biological and pathological roles. The CSS from Neisseria meningitidis (NmCSS) has been commonly used with other enzymes such as sialic acid aldolase and/or sialyltransferase in synthesizing a diverse array of compounds containing sialic acid or its naturally occurring and non-natural derivatives. To better understand its catalytic mechanism and substrate promiscuity, four NmCSS crystal structures trapped at various stages of the catalytic cycle with bound substrates, substrate analogues, and products have been obtained and are presented here. These structures suggest a mechanism for an “open” and “closed” conformational transition that occurs as sialic acid binds to the NmCSS/cytidine-5′-triphosphate (CTP) complex. The closed conformation positions critical residues to help facilitate the nucleophilic attack of sialic acid C2-OH to the α-phosphate of CTP, which is also aided by two observed divalent cations. Product formation drives the active site opening, promoting the release of products.
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IJS, KILJ, NUK, PNG, UL, UM
Molecules capable of directing changes to nucleic acid sequences are powerful tools for molecular biology and promising candidates for the therapeutic correction of disease-causing mutations. ...However, unwanted reactions at off-target sites complicate their use. Here we report selective combinations of mutant editing enzyme and directing oligonucleotide. Mutations in human ADAR2 (adenosine deaminase acting on RNA 2) that introduce aromatic amino acids at position 488 reduce background RNA editing. This residue is juxtaposed to the nucleobase that pairs with the editing site adenine, suggesting a steric clash for the bulky mutants. Replacing this nucleobase with a hydrogen atom removes the clash and restores editing activity. A crystal structure of the E488Y mutant bound to abasic site-containing RNA shows the accommodation of the tyrosine side chain. Finally, we demonstrate directed RNA editing in vitro and in human cells using mutant ADAR2 proteins and modified guide RNAs with reduced off-target activity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Animal heterotrimeric G proteins are activated by guanine nucleotide exchange factors (GEF), typically seven transmembrane receptors that trigger GDP release and subsequent GTP binding. In contrast, ...the Arabidopsis thaliana G protein (AtGPA1) rapidly activates itself without a GEF and is instead regulated by a seven transmembrane Regulator of G protein Signaling (7TM-RGS) protein that promotes GTP hydrolysis to reset the inactive (GDP-bound) state. It is not known if this unusual activation is a major and constraining part of the evolutionary history of G signaling in eukaryotes. In particular, it is not known if this is an ancestral form or if this mechanism is maintained, and therefore constrained, within the plant kingdom. To determine if this mode of signal regulation is conserved throughout the plant kingdom, we analyzed available plant genomes for G protein signaling components, and we purified individually the plant components encoded in an informative set of plant genomes in order to determine their activation properties in vitro. While the subunits of the heterotrimeric G protein complex are encoded in vascular plant genomes, the 7TM-RGS genes were lost in all investigated grasses. Despite the absence of a Gα-inactivating protein in grasses, all vascular plant Gα proteins examined rapidly released GDP without a receptor and slowly hydrolyzed GTP, indicating that these Gα are self-activating. We showed further that a single amino acid substitution found naturally in grass Gα proteins reduced the Gα-RGS interaction, and this amino acid substitution occurred before the loss of the RGS gene in the grass lineage. Like grasses, non-vascular plants also appear to lack RGS proteins. However, unlike grasses, one representative non-vascular plant Gα showed rapid GTP hydrolysis, likely compensating for the loss of the RGS gene. Our findings, the loss of a regulatory gene and the retention of the "self-activating" trait, indicate the existence of divergent Gα regulatory mechanisms in the plant kingdom. In the grasses, purifying selection on the regulatory gene was lost after the physical decoupling of the RGS protein and its cognate Gα partner. More broadly these findings show extreme divergence in Gα activation and regulation that played a critical role in the evolution of G protein signaling pathways.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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