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"David, Lawrence A."
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Measuring and mitigating PCR bias in microbiota datasets
PCR amplification plays an integral role in the measurement of mixed microbial communities via high-throughput DNA sequencing of the 16S ribosomal RNA (rRNA) gene. Yet PCR is also known to introduce multiple forms of bias in 16S rRNA studies. Here we present a paired modeling and experimental approach to characterize and mitigate PCR NPM-bias (PCR bias from non-primer-mismatch sources) in microbiota surveys. We use experimental data from mock bacterial communities to validate our approach and human gut microbiota samples to characterize PCR NPM-bias under real-world conditions. Our results suggest that PCR NPM-bias can skew estimates of microbial relative abundances by a factor of 4 or more, but that this bias can be mitigated using log-ratio linear models.
Journal Article
Rapid evolutionary innovation during an Archaean genetic expansion
Prehistory is in the genes
Hidden in the modern-day genomes of today's living organisms are the imprints of ancient biogeochemical events. Lawrence David and Eric Alm have developed a new algorithm designed to reconstruct ancient genomes, taking into account the confounding effects of horizontal gene transfer and phylogenetic uncertainty. Applying this to around 100,000 gene sequences from present-day organisms, they find the genetic imprints of major events in Earth's history, including the gradual rise of oxygen starting more than 2.5 billion years ago, and a previously unreported brief but massive expansion in genetic diversity in the Archaean, more than 2 billion years before the Cambrian explosion.
To shed light on the natural history of Precambrian life, the evolutionary history of almost 4,000 gene families across the three domains of life are mapped onto a geological timeline. Over one-quarter of modern gene families arose during a period of rapid diversification of bacterial lineages. Functionally, these genes are likely to be involved in electron transport and respiratory pathways, whereas those that arose later are implicated in functions consistent with an increasingly oxygenating biosphere.
The natural history of Precambrian life is still unknown because of the rarity of microbial fossils and biomarkers
1
,
2
. However, the composition of modern-day genomes may bear imprints of ancient biogeochemical events
3
,
4
,
5
,
6
. Here we use an explicit model of macroevolution including gene birth, transfer, duplication and loss events to map the evolutionary history of 3,983 gene families across the three domains of life onto a geological timeline. Surprisingly, we find that a brief period of genetic innovation during the Archaean eon, which coincides with a rapid diversification of bacterial lineages, gave rise to 27% of major modern gene families. A functional analysis of genes born during this Archaean expansion reveals that they are likely to be involved in electron-transport and respiratory pathways. Genes arising after this expansion show increasing use of molecular oxygen (
P
= 3.4 × 10
−8
) and redox-sensitive transition metals and compounds, which is consistent with an increasingly oxygenating biosphere.
Journal Article
Market based instruments : national experiences in environmental sustainability
\"In the field of environmental policy, there is a widespread tendency to move from command-and-control towards market based instruments that are more efficient and less costly. This book provides a fresh contribution to the literature enlightening the most relevant characteristics of economic tools, with a comprehensive review of experiences in the EU, the Asia-Pacific region and North America. Even if this is a technical book, the language is plain and the comprehension easy. There is much to learn in reading it.\"--Alberto Majocchi, University of Pavia, Italy. 'This book contains an impressive collection of papers discussing various aspects of the application of different market based instruments for environmental and climate policy. It covers questions related to the conceptualisation of environmental taxation and national experiences as well as results of modelling exercises from different countries. I highly recommend this book as it discusses the current developments in the application and assessments of market based instruments written by scholars from diverse backgrounds.' - Stefan Speck, European Environment Agency, Denmark. This detailed book explores how market based environmental strategies are used in various countries around the world. It investigates how successful sustainability strategies used by one country can be transferred and used successfully in other countries, with a minimum of new research and experimentation. Leading environmental taxation scholars discuss this question and analyse a set of key case studies. This enriching and detailed book will appeal to policy makers in government, as well as to professors in environmental law, environmental economics and environmental sustainability programmes. Students in these fields will also find much to benefit them in this book.
Book
Diet rapidly and reproducibly alters the human gut microbiome
Consuming diets rich in plant versus animal products changes the microbes found in the human gut within days, with important implications for our health and evolution.
Diet can rapidly alter gut microbiome
Diet influences the structure and function of the gut microbiota in the long term, but it is not clear how rapidly the microbiota is affected by short-term dietary change. Peter Turnbaugh and colleagues studied the effect of transition to a diet consisting entirely of either animal products or plant products on the composition and function of the human gut microbiota. They find that the community changes rapidly, within a single day, overwhelming the pre-existing inter-individual differences in microbiota composition to recapitulate expected patterns of composition and metabolic function for carnivorous and herbivorous mammals. The animal-based diet was associated with higher levels of bile-tolerant microorganisms, including the bacterium
Bilophila wadsworthia
, which has previously been linked to inflammatory bowel disease. The authors also detected intact foodborne fungi, bacteria and viruses in the distal gut.
Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut
1
,
2
,
3
,
4
,
5
, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (
Alistipes
,
Bilophila
and
Bacteroides
) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (
Roseburia
,
Eubacterium rectale
and
Ruminococcus bromii
). Microbial activity mirrored differences between herbivorous and carnivorous mammals
2
, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of
Bilophila wadsworthia
on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease
6
. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
Journal Article
Leveraging the past to prepare for the future of Air Force intelligence analysis
\"This report describes steps the U.S. Air Force can take to help ensure that it has the capability needed to provide intelligence analysis support to a broad range of service and combatant commander needs, including support to ongoing irregular warfare operations, and to conventional warfare with a near-peer competitor. It describes lessons from past operations that have direct implications for Air Force intelligence analysis or that Air Force intelligence analysis could help to address. It also describes future challenges for Air Force intelligence analysis. It makes recommendations related to doctrine, training and career field development, analysis tools, and processes that can help to address the lessons from the past and prepare Air Force intelligence analysts for the challenges of the future\"--Publisher's description.
Book
A phylogenetic transform enhances analysis of compositional microbiota data
Surveys of microbial communities (microbiota), typically measured as relative abundance of species, have illustrated the importance of these communities in human health and disease. Yet, statistical artifacts commonly plague the analysis of relative abundance data. Here, we introduce the PhILR transform, which incorporates microbial evolutionary models with the isometric log-ratio transform to allow off-the-shelf statistical tools to be safely applied to microbiota surveys. We demonstrate that analyses of community-level structure can be applied to PhILR transformed data with performance on benchmarks rivaling or surpassing standard tools. Additionally, by decomposing distance in the PhILR transformed space, we identified neighboring clades that may have adapted to distinct human body sites. Decomposing variance revealed that covariation of bacterial clades within human body sites increases with phylogenetic relatedness. Together, these findings illustrate how the PhILR transform combines statistical and phylogenetic models to overcome compositional data challenges and enable evolutionary insights relevant to microbial communities.
Journal Article
Opposing unfolded-protein-response signals converge on death receptor 5 to control apoptosis
Protein folding by the endoplasmic reticulum (ER) is physiologically
critical; its disruption causes ER stress and augments disease. ER
stress activates the unfolded protein response (UPR) to restore
homeostasis. If stress persists, the UPR induces apoptotic cell death,
but the mechanisms remain elusive. Here, we report that unmitigated ER
stress promoted apoptosis through cell-autonomous, UPR-controlled
activation of death receptor 5 (DR5). ER stressors induced DR5
transcription via the UPR mediator CHOP; however, the UPR sensor IRE1α
transiently catalyzed DR5 mRNA decay, which allowed time for adaptation.
Persistent ER stress built up intracellular DR5 protein, driving
ligand-independent DR5 activation and apoptosis engagement via
caspase-8. Thus, DR5 integrates opposing UPR signals to couple ER stress
and apoptotic cell fate.
Journal Article
A pilot study of fecal pH and redox as functional markers in the premature infant gut microbiome
The infant gut microbiome is a crucial factor in health and development. In preterm infants, altered gut microbiome composition and function have been linked to serious neonatal complications such as necrotizing enterocolitis and sepsis, which can lead to long-term disability. Although many studies have described links between microbiome composition and disease risk, there is a need for biomarkers to identify infants at risk of these complications in practice. In this pilot study, we obtained stool samples from preterm infant participants longitudinally during the first postnatal months, and measured pH and redox, as well as SCFA content and microbiome composition by 16S rRNA gene amplicon sequencing. These outcomes were compared to clinical data to better understand the role of pH and redox in infant gut microbiome development and overall health, and to assess the potential utility of pH and redox as biomarkers. We found that infants born earlier or exposed to antibiotics exhibited increased fecal pH, and that redox potential increased with postnatal age. These differences may be linked to changes in SCFA content, which was correlated with pH and increased with age. Microbiome composition was also related to birth weight, age, pH, and redox. Our findings suggest that pH and redox may serve as biomarkers of metabolic state in the preterm infant gut.
Journal Article