Autism-related dietary preferences mediate autism-gut microbiome associations.

There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.

Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Probiotic Bifidobacterium longum subsp. longum Protects against Cigarette Smoke-Induced Inflammation in Mice.

Bifidobacterium are prominent gut commensals that produce the short-chain fatty acid (SCFA) acetate, and they are often used as probiotics. Connections between the gut and the lung, termed the gut-lung axis, are regulated by the microbiome. The gut-lung axis is increasingly implicated in cigarette smoke-induced diseases, and cigarette smoke exposure has been associated with depletion of Bifidobacterium species. In this study, we assessed the impact of acetate-producing Bifidobacterium longum subsp. longum (WT) and a mutant strain with an impaired acetate production capacity (MUT) on cigarette smoke-induced inflammation. The mice were treated with WT or MUT B. longum subsp. longum and exposed to cigarette smoke for 8 weeks before assessments of lung inflammation, lung tissue gene expression and cecal SCFAs were performed. Both strains of B. longum subsp. longum reduced lung inflammation, inflammatory cytokine expression and adhesion factor expression and alleviated cigarette smoke-induced depletion in caecum butyrate. Thus, the probiotic administration of B. longum subsp. longum, irrespective of its acetate-producing capacity, alleviated cigarette smoke-induced inflammation and the depletion of cecal butyrate levels.

Genome-wide characterization of the routes to pluripotency.

Somatic cell reprogramming to a pluripotent state continues to challenge many of our assumptions about cellular specification, and despite major efforts, we lack a complete molecular characterization of the reprograming process. To address this gap in knowledge, we generated extensive transcriptomic, epigenomic and proteomic data sets describing the reprogramming routes leading from mouse embryonic fibroblasts to induced pluripotency. Through integrative analysis, we reveal that cells transition through distinct gene expression and epigenetic signatures and bifurcate towards reprogramming transgene-dependent and -independent stable pluripotent states. Early transcriptional events, driven by high levels of reprogramming transcription factor expression, are associated with widespread loss of histone H3 lysine 27 (H3K27me3) trimethylation, representing a general opening of the chromatin state. Maintenance of high transgene levels leads to re-acquisition of H3K27me3 and a stable pluripotent state that is alternative to the embryonic stem cell (ESC)-like fate. Lowering transgene levels at an intermediate phase, however, guides the process to the acquisition of ESC-like chromatin and DNA methylation signature. Our data provide a comprehensive molecular description of the reprogramming routes and is accessible through the Project Grandiose portal at http://www.stemformatics.org.

Quantum Chemical Methods for the Prediction of Energetic, Physical, and Spectroscopic Properties of Ionic Liquids.

The accurate prediction of physicochemical properties of condensed systems is a longstanding goal of theoretical (quantum) chemistry. Ionic liquids comprising entirely of ions provide a unique challenge in this respect due to the diverse chemical nature of available ions and the complex interplay of intermolecular interactions among them, thus resulting in the wide variability of physicochemical properties, such as thermodynamic, transport, and spectroscopic properties. It is well understood that intermolecular forces are directly linked to physicochemical properties of condensed systems, and therefore, an understanding of this relationship would greatly aid in the design and synthesis of functionalized materials with tailored properties for an application at hand. This review aims to give an overview of how electronic structure properties obtained from quantum chemical methods such as interaction/binding energy and its fundamental components, dipole moment, polarizability, and orbital energies, can help shed light on the energetic, physical, and spectroscopic properties of semi-Coulomb systems such as ionic liquids. Particular emphasis is given to the prediction of their thermodynamic, transport, spectroscopic, and solubilizing properties.

Microbiomes in respiratory health and disease: An Asia-Pacific perspective.

There is currently enormous interest in studying the role of the microbiome in health and disease. Microbiome's role is increasingly being applied to respiratory diseases, in particular COPD, asthma, cystic fibrosis and bronchiectasis. The changes in respiratory microbiomes that occur in these diseases and how they are modified by environmental challenges such as cigarette smoke, air pollution and infection are being elucidated. There is also emerging evidence that gut microbiomes play a role in lung diseases through the modulation of systemic immune responses and can be modified by diet and antibiotic treatment. There are issues that are particular to the Asia-Pacific region involving diet and prevalence of specific respiratory diseases. Each of these issues is further complicated by the effects of ageing. The challenges now are to elucidate the cause and effect relationships between changes in microbiomes and respiratory diseases and how to translate these into new treatments and clinical care. Here we review the current understanding and progression in these areas.

RNASeqBrowser: a genome browser for simultaneous visualization of raw strand specific RNAseq reads and UCSC genome browser custom tracks.

BACKGROUND: Strand specific RNAseq data is now more common in RNAseq projects. Visualizing RNAseq data has become an important matter in Analysis of sequencing data. The most widely used visualization tool is the UCSC genome browser that introduced the custom track concept that enabled researchers to simultaneously visualize gene expression at a particular locus from multiple experiments. Our objective of the software tool is to provide friendly interface for visualization of RNAseq datasets. RESULTS: This paper introduces a visualization tool (RNASeqBrowser) that incorporates and extends the functionality of the UCSC genome browser. For example, RNASeqBrowser simultaneously displays read coverage, SNPs, InDels and raw read tracks with other BED and wiggle tracks -- all being dynamically built from the BAM file. Paired reads are also connected in the browser to enable easier identification of novel exon/intron borders and chimaeric transcripts. Strand specific RNAseq data is also supported by RNASeqBrowser that displays reads above (positive strand transcript) or below (negative strand transcripts) a central line. Finally, RNASeqBrowser was designed for ease of use for users with few bioinformatic skills, and incorporates the features of many genome browsers into one platform. CONCLUSIONS: The features of RNASeqBrowser: (1) RNASeqBrowser integrates UCSC genome browser and NGS visualization tools such as IGV. It extends the functionality of the UCSC genome browser by adding several new types of tracks to show NGS data such as individual raw reads, SNPs and InDels. (2) RNASeqBrowser can dynamically generate RNA secondary structure. It is useful for identifying non-coding RNA such as miRNA. (3) Overlaying NGS wiggle data is helpful in displaying differential expression and is simple to implement in RNASeqBrowser. (4) NGS data accumulates a lot of raw reads. Thus, RNASeqBrowser collapses exact duplicate reads to reduce visualization space. Normal PC's can show many windows of NGS individual raw reads without much delay. (5) Multiple popup windows of individual raw reads provide users with more viewing space. This avoids existing approaches (such as IGV) which squeeze all raw reads into one window. This will be helpful for visualizing multiple datasets simultaneously. RNASeqBrowser and its manual are freely available at http://www.australianprostatecentre.org/research/software/rnaseqbrowser or http://sourceforge.net/projects/rnaseqbrowser/.

Anticipated climate and land-cover changes reveal refuge areas for Borneo's orang-utans.

Habitat loss and climate change pose a double jeopardy for many threatened taxa, making the identification of optimal habitat for the future a conservation priority. Using a case study of the endangered Bornean orang-utan, we identify environmental refuges by integrating bioclimatic models with projected deforestation and oil-palm agriculture suitability from the 1950s to 2080s. We coupled a maximum entropy algorithm with information on habitat needs to predict suitable habitat for the present day and 1950s. We then projected to the 2020s, 2050s and 2080s in models incorporating only land-cover change, climate change or both processes combined. For future climate, we incorporated projections from four model and emission scenario combinations. For future land cover, we developed spatial deforestation predictions from 10 years of satellite data. Refuges were delineated as suitable forested habitats identified by all models that were also unsuitable for oil palm - a major threat to tropical biodiversity. Our analyses indicate that in 2010 up to 260,000 km(2) of Borneo was suitable habitat within the core orang-utan range; an 18-24% reduction since the 1950s. Land-cover models predicted further decline of 15-30% by the 2080s. Although habitat extent under future climate conditions varied among projections, there was majority consensus, particularly in north-eastern and western regions. Across projections habitat loss due to climate change alone averaged 63% by 2080, but 74% when also considering land-cover change. Refuge areas amounted to 2000-42,000 km(2) depending on thresholds used, with 900-17,000 km(2) outside the current species range. We demonstrate that efforts to halt deforestation could mediate some orang-utan habitat loss, but further decline of the most suitable areas is to be expected given projected changes to climate. Protected refuge areas could therefore become increasingly important for ongoing translocation efforts. We present an approach to help identify such areas for highly threatened species given environmental changes expected this century.

Deep-transcriptome and ribonome sequencing redefines the molecular networks of pluripotency and the extracellular space in human embryonic stem cells.

Recent RNA-sequencing studies have shown remarkable complexity in the mammalian transcriptome. The ultimate impact of this complexity on the predicted proteomic output is less well defined. We have undertaken strand-specific RNA sequencing of multiple cellular RNA fractions (>20 Gb) to uncover the transcriptional complexity of human embryonic stem cells (hESCs). We have shown that human embryonic stem (ES) cells display a high degree of transcriptional diversity, with more than half of active genes generating RNAs that differ from conventional gene models. We found evidence that more than 1000 genes express long 5' and/or extended 3'UTRs, which was confirmed by "virtual Northern" analysis. Exhaustive sequencing of the membrane-polysome and cytosolic/untranslated fractions of hESCs was used to identify RNAs encoding peptides destined for secretion and the extracellular space and to demonstrate preferential selection of transcription complexity for translation in vitro. The impact of this newly defined complexity on known gene-centric network models such as the Plurinet and the cell surface signaling machinery in human ES cells revealed a significant expansion of known transcript isoforms at play, many predicting possible alternative functions based on sequence alterations within key functional domains.

The Post-war Revival of Canadian Planning: Assessing the Impact of the Community Planning Association of Canada.

The Community Planning Association of Canada (CPAC) advocated for the re-establishment of planning in post-war Canada. During this period, the federal government set reconstruction objectives, and both Central (now Canada) Mortgage and Housing Corporation (CMHC) and the CPAC were formed. We believe that 1944-1947 was a critical juncture establishing planned suburban development in Canada as a path-dependent process with tremendous momentum into the 21st-century. Using a historical-institutional approach, the role of CMHC and the influence of the CPAC is examined. Analysis relying on extensive archival material demonstrates that the CPAC gave a tremendous push along the path-dependent process of suburbanization.

ArachnoServer 2.0, an updated online resource for spider toxin sequences and structures.

ArachnoServer (www.arachnoserver.org) is a manually curated database providing information on the sequence, structure and biological activity of protein toxins from spider venoms. These proteins are of interest to a wide range of biologists due to their diverse applications in medicine, neuroscience, pharmacology, drug discovery and agriculture. ArachnoServer currently manages 1078 protein sequences, 759 nucleic acid sequences and 56 protein structures. Key features of ArachnoServer include a molecular target ontology designed specifically for venom toxins, current and historic taxonomic information and a powerful advanced search interface. The following significant improvements have been implemented in version 2.0: (i) the average and monoisotopic molecular masses of both the reduced and oxidized form of each mature toxin are provided; (ii) the advanced search feature now enables searches on the basis of toxin mass, external database accession numbers and publication date in ArachnoServer; (iii) toxins can now be browsed on the basis of their phyletic specificity; (iv) rapid BLAST searches based on the mature toxin sequence can be performed directly from the toxin card; (v) private silos can be requested from research groups engaged in venoms-based research, enabling them to easily manage and securely store data during the process of toxin discovery; and (vi) a detailed user manual is now available.

[Abnormal glucose tolerance and long-term prognosis in patients with acute myocardial infarction].

STUDY AIM: to assess clinical outcomes and cardiovascular events during long-term follow-up after acute myocardial infarction (AMI) in patients (pts) with newly detected abnormal glucose tolerance (AGT). MATERIAL AND METHODS: Consecutive AMI pts (n=391, 24.3% with diabetes mellitus [DM]) were enrolled in the study. Pts with no DM underwent an oral glucose tolerance test (OGTT) at discharge (around 12-th day). All pts were divided into 3 groups: group I - pts with normal glucose tolerance (NGT), group II - pts with AGT, including impaired glucose tolerance (IGT) and newly diagnosed DM (NDM), group III - pts with previously known DM. General and cardiovascular mortality, adverse cardiovascular events during long-term follow-up (26.8+/-6 months) were studied. RESULTS: According to the OGTT 67.9% pts had NGT and 32.1% had AGT (28.7% IGT and 3.4% NDM). Pts with disturbances of glucose metabolism were older, had abdominal obesity, more frequently had Killip class >2 on admission, as well as reduced ejection fraction, left ventricular aneurism and progression of chronic heart failure at discharge. Cardiovascular and general mortality during follow-up were significantly higher in pts with AGT and DM compared to NGT (27.4 vs. 22.1 vs 11.1%, p=0.002, and 23.2 vs. 20.2 vs 10.1%, p<0.05, respectively). The incidence of recurrent nonfatal MI and stroke were similar in the three groups, however the proportion of subjects with heart failure NYHA class >2, revascularization procedures, hospitalization due to cardiovascular events was higher in pts with abnormalities of carbohydrate metabolism. CONCLUSIONS: Abnormal glucose tolerance (IGT and NDM) has high prevalence in AMI patients without known DM, is a major risk factor for future cardiovascular events and is associated with unfavorable long term prognosis after MI.

Draft genome sequence of two "Candidatus Intestinicoccus colisanans" strains isolated from faeces of healthy humans.

OBJECTIVES: In order to provide a better insight into the functional capacity of the human gut microbiome, we isolated a novel bacterium, "Candidatus Intestinicoccus colisanans" gen. nov. sp. nov., and performed whole genome sequencing. This study will provide new insights into the functional potential of this bacterium and its role in modulating host health and well-being. We expect that this data resource will be useful in providing additional insight into the diversity and functional potential of the human microbiome. DATA DESCRIPTION: Here, we report the first draft genome sequences of "Candidatus Intestinicoccus colisanans" strains MH27-1 and MH27-2, recovered from faeces collected from healthy human donors. The genomes were sequenced using short-read Illumina technology and whole-genome-based comparisons and phylogenomics reconstruction indicate that "Candidatus Intestinicoccus colisanans" represents a novel genus and species within the family Acutalibacteraceae. Both genomes were estimated to be > 98% completed and to range in size from 2.9 to 3.3 Mb with a G + C content of approximately 51%. The gene repertoire of "Candidatus Intestinicoccus colisanans" indicate it is likely a saccharolytic gut bacterium.

Implications of large-scale infrastructure development for biodiversity in Indonesian Borneo.

Indonesia is embarking on an ambitious relocation of its capital city to Kalimantan, Borneo, bringing with it major urban and road infrastructure. Yet, despite being one of the world's most biologically diverse regions, the potential implications of this development for wildlife have yet to be fully assessed. We explored the potential impacts of the capital relocation, and road expansion and upgrades to critical habitat for medium-large mammals (>1 kg) using camera trap data from 11 forested landscapes. We applied Bayesian multi-species occupancy models to predict community and species-level responses to anthropogenic and environmental factors. We extrapolated spatial patterns of occupancy and species diversity across the forests of Kalimantan and identified "critical habitats" as the top 20th percentile of occupancy and species richness values. We subsequently overlapped these critical habitat layers with infrastructure impact zones to estimate the area that could potentially be affected by direct or secondary impacts. At both the community and species-level, distance to primary roads had the strongest negative influence on habitat-use. Occupancy was also influenced by forest quality and multidimensional poverty conditions in adjacent villages, demonstrating the sensitivity of biodiversity to socio-ecological pressures. Less than 1 % of the critical habitat for the threatened mammal community lay within the direct impact zone (30 km radius) of the capital relocation. However, approximately 16 % was located within 200 km and could potentially be affected by uncontrolled secondary impacts such as urban sprawl and associated regional development. The often-overlooked secondary implications of upgrading existing roads could also intersect a large amount of critical habitat for lowland species. Mitigating far-reaching secondary impacts of infrastructure development should be fully incorporated into environmental impact assessments. This will provide Indonesia with an opportunity to set an example of sustainable infrastructure development in the tropics.

X-MATE: a flexible system for mapping short read data.

SUMMARY: Accurate and complete mapping of short-read sequencing to a reference genome greatly enhances the discovery of biological results and improves statistical predictions. We recently presented RNA-MATE, a pipeline for the recursive mapping of RNA-Seq datasets. With the rapid increase in genome re-sequencing projects, progression of available mapping software and the evolution of file formats, we now present X-MATE, an updated version of RNA-MATE, capable of mapping both RNA-Seq and DNA datasets and with improved performance, output file formats, configuration files, and flexibility in core mapping software. AVAILABILITY: Executables, source code, junction libraries, test data and results and the user manual are available from http://grimmond.imb.uq.edu.au/X-MATE/.

Unprecedented fire activity above the Arctic Circle linked to rising temperatures.

Arctic fires can release large amounts of carbon from permafrost peatlands. Satellite observations reveal that fires burned ~4.7 million hectares in 2019 and 2020, accounting for 44% of the total burned area in the Siberian Arctic for the entire 1982-2020 period. The summer of 2020 was the warmest in four decades, with fires burning an unprecedentedly large area of carbon-rich soils. We show that factors of fire associated with temperature have increased in recent decades and identified a near-exponential relationship between these factors and annual burned area. Large fires in the Arctic are likely to recur with climatic warming before mid-century, because the temperature trend is reaching a threshold in which small increases in temperature are associated with exponential increases in the area burned.

Slowing deforestation in Indonesia follows declining oil palm expansion and lower oil prices.

Much concern about tropical deforestation focuses on oil palm plantations, but their impacts remain poorly quantified. Using nation-wide interpretation of satellite imagery, and sample-based error calibration, we estimated the impact of large-scale (industrial) and smallholder oil palm plantations on natural old-growth ("primary") forests from 2001 to 2019 in Indonesia, the world's largest palm oil producer. Over nineteen years, the area mapped under oil palm doubled, reaching 16.24 Mha in 2019 (64% industrial; 36% smallholder), more than the official estimates of 14.72 Mha. The forest area declined by 11% (9.79 Mha), including 32% (3.09 Mha) ultimately converted into oil palm, and 29% (2.85 Mha) cleared and converted in the same year. Industrial plantations replaced more forest than detected smallholder plantings (2.13 Mha vs 0.72 Mha). New plantations peaked in 2009 and 2012 and declined thereafter. Expansion of industrial plantations and forest loss were correlated with palm oil prices. A price decline of 1% was associated with a 1.08% decrease in new industrial plantations and with a 0.68% decrease of forest loss. Deforestation fell below pre-2004 levels in 2017-2019 providing an opportunity to focus on sustainable management. As the price of palm oil has doubled since the start of the COVID-19 pandemic, effective regulation is key to minimising future forest conversion.

Cross-sectional study for COVID-19-related mortality predictors in a Brazilian state-wide landscape: the role of demographic factors, symptoms and comorbidities.

OBJECTIVE: The Brazilian state of Paraná has suffered from COVID-19 effects, understanding predictors of increased mortality in health system interventions prevent hospitalisation of patients. We selected the best models to evaluate the association of death with demographic characteristics, symptoms and comorbidities based on three levels of clinical severity for COVID-19: non-hospitalised, hospitalised non-ICU ward and ICU ward. DESIGN: Cross-sectional survey using binomial mixed models. SETTING: COVID-19-positive cases diagnosed by reverse transcription-PCR of municipalities located in Paraná State. PATIENTS: Cases of anonymous datasets of electronic medical records from 1 April 2020 to 31 December 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: The best prediction factors were chosen based on criteria after a stepwise analysis using multicollinearity measure, lower Akaike information criterion and goodness-of-fit χ2 tests from univariate to multivariate contexts. RESULTS: Male sex was associated with increased mortality among non-hospitalised patients (OR 1.76, 95% CI 1.47 to 2.11) and non-ICU patients (OR 1.22, 95% CI 1.05 to 1.43) for symptoms and for comorbidities (OR 1.89, 95% CI 1.59 to 2.25, and OR 1.30, 95% CI 1.11 to 1.52, respectively). Higher mortality occurred in patients older than 35 years in non-hospitalised (for symptoms: OR 4.05, 95% CI 1.55 to 10.54; and for comorbidities: OR 3.00, 95% CI 1.24 to 7.27) and in hospitalised over 40 years (for symptoms: OR 2.72, 95% CI 1.08 to 6.87; and for comorbidities: OR 2.66, 95% CI 1.22 to 5.79). Dyspnoea was associated with increased mortality in non-hospitalised (OR 4.14, 95% CI 3.45 to 4.96), non-ICU (OR 2.41, 95% CI 2.04 to 2.84) and ICU (OR 1.38, 95% CI 1.10 to 1.72) patients. Neurological disorders (OR 2.16, 95% CI 1.35 to 3.46), neoplastic (OR 3.22, 95% CI 1.75 to 5.93) and kidney diseases (OR 2.13, 95% CI 1.36 to 3.35) showed the majority of increased mortality for ICU as well in the three levels of severity jointly with heart disease, diabetes and CPOD. CONCLUSIONS: These findings highlight the importance of the predictor's assessment for the implementation of public healthcare policy in response to the COVID-19 pandemic, mainly to understand how non-pharmaceutical measures could mitigate the virus impact over the population.