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"Allen, Jonathan"
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Social behaviour : genes, ecology and evolution
\"Humans live in large and extensive societies and spend much of their time interacting socially. Likewise, most other animals also interact socially. Social behaviour is of constant fascination to biologists and psychologists of many disciplines, from behavioural ecology to comparative biology and sociobiology. The two major approaches used to study social behaviour involve either the mechanism of behaviour - where it has come from and how it has evolved, or the function of the behaviour studied. With guest articles from leaders in the field, theoretical foundations along with recent advances are presented to give a truly multidisciplinary overview of social behaviour, for advanced undergraduate and graduate students. Topics include aggression, communication, group living, sexual behaviour and co-operative breeding. With examples ranging from bacteria to social mammals and humans, a variety of research tools are used, including candidate gene approaches, quantitative genetics, neuro-endocrine studies, cost-benefit and phylogenetic analyses and evolutionary game theory\"--Provided by publisher.
Book
Characterization of the core and accessory genomes of Pseudomonas aeruginosa using bioinformatic tools Spine and AGEnt
Background
Pseudomonas aeruginosa
is an important opportunistic pathogen responsible for many infections in hospitalized and immunocompromised patients. Previous reports estimated that approximately 10% of its 6.6 Mbp genome varies from strain to strain and is therefore referred to as “accessory genome”. Elements within the accessory genome of
P. aeruginosa
have been associated with differences in virulence and antibiotic resistance. As whole genome sequencing of bacterial strains becomes more widespread and cost-effective, methods to quickly and reliably identify accessory genomic elements in newly sequenced
P. aeruginosa
genomes will be needed.
Results
We developed a bioinformatic method for identifying the accessory genome of
P. aeruginosa
. First, the core genome was determined based on sequence conserved among the completed genomes of twelve reference strains using Spine, a software program developed for this purpose. The core genome was 5.84 Mbp in size and contained 5,316 coding sequences. We then developed an
in silico
genome subtraction program named AGEnt to filter out core genomic sequences from
P. aeruginosa
whole genomes to identify accessory genomic sequences of these reference strains. This analysis determined that the accessory genome of
P. aeruginosa
ranged from 6.9-18.0% of the total genome, was enriched for genes associated with mobile elements, and was comprised of a majority of genes with unknown or unclear function. Using these genomes, we showed that AGEnt performed well compared to other publically available programs designed to detect accessory genomic elements. We then demonstrated the utility of the AGEnt program by applying it to the draft genomes of two previously unsequenced
P. aeruginosa
strains, PA99 and PA103.
Conclusions
The
P. aeruginosa
genome is rich in accessory genetic material. The AGEnt program accurately identified the accessory genomes of newly sequenced
P. aeruginosa
strains, even when draft genomes were used. As
P. aeruginosa
genomes become available at an increasingly rapid pace, this program will be useful in cataloging the expanding accessory genome of this bacterium and in discerning correlations between phenotype and accessory genome makeup. The combination of Spine and AGEnt should be useful in defining the accessory genomes of other bacterial species as well.
Journal Article
March 4 : scientists, students, and society
Based on talks and events from March 4, 1969, at Massachusetts Institute of Technology, when students and scientists gathered, concerned about the misuse of science; included the Union of Concerned Scientists.
Book
Predicting tumor cell line response to drug pairs with deep learning
Background
The National Cancer Institute drug pair screening effort against 60 well-characterized human tumor cell lines (NCI-60) presents an unprecedented resource for modeling combinational drug activity.
Results
We present a computational model for predicting cell line response to a subset of drug pairs in the NCI-ALMANAC database. Based on residual neural networks for encoding features as well as predicting tumor growth, our model explains 94% of the response variance. While our best result is achieved with a combination of molecular feature types (gene expression, microRNA and proteome), we show that most of the predictive power comes from drug descriptors. To further demonstrate value in detecting anticancer therapy, we rank the drug pairs for each cell line based on model predicted combination effect and recover 80% of the top pairs with enhanced activity.
Conclusions
We present promising results in applying deep learning to predicting combinational drug response. Our feature analysis indicates screening data involving more cell lines are needed for the models to make better use of molecular features.
Journal Article
Fiat flux : the writings of Wilson R. Bachelor, nineteenth-century country doctor and philosopher
Wilson R. Bachelor was a Tennessee native who moved with his family to Franklin County, Arkansas, in 1870. A country doctor and natural philosopher, Bachelor was impelled to chronicle his life from 1870 to 1902, documenting the family's move to Arkansas, their settling a farm in Franklin County, and Bachelor's medical practice. Bachelor was an avid reader with wide-ranging interests in literature, science, nature, politics, and religion, and he became a self-professed freethinker in the 1870s. He was driven by a concept he called \"fiat flux,\" an awareness of the \"rapid flight of time\" that motivated him to treat the people around him and the world itself as precious and fleeting.
Book
Riverscape dynamics and habitat utilization structure evolutionary diversification in a clade of Amazonian electric fishes
Rivers have long been implicated in the processes of macroevolutionary diversification, but only recently have tools emerged to quantify habitat volume and connectivity across modern and ancient landscapes. Here we compare biodiversity patterns in a diverse clade of Amazonian electric fishes with the predictions of three alternative hypotheses of rivers as: (1) semi-permeable dispersal barriers, (2) branching drainage networks, and (3) dynamic with a reticulated history of connections; i.e., river capture. We found support for all three hypotheses, with large river corridors as partial dispersal barriers to small-river species, interfluves as barriers to large-river species, and contrasting patterns of local (alpha) diversity and species-turnover (beta diversity) in large and small rivers. River captures are faster in smaller rivers with rare but expansive mega-river capture events, facilitating dispersal of small-river clades across watersheds. These results support the role of riverine dynamics as principle agents driving continental diversification of megadiverse tropical aquatic faunas.
Journal Article
Systemic infection facilitates transmission of Pseudomonas aeruginosa in mice
Health care-associated infections such as
Pseudomonas aeruginosa
bacteremia pose a major clinical risk for hospitalized patients. However, these systemic infections are presumed to be a “dead-end” for
P. aeruginosa
and to have no impact on transmission. Here, we use a mouse infection model to show that
P. aeruginosa
can spread from the bloodstream to the gallbladder, where it replicates to extremely high numbers. Bacteria in the gallbladder can then seed the intestines and feces, leading to transmission to uninfected cage-mate mice. Our work shows that the gallbladder is crucial for spread of
P. aeruginosa
from the bloodstream to the feces during bacteremia, a process that promotes transmission in this experimental system. Further research is needed to test to what extent these findings are relevant to infections in patients.
Pseudomonas aeruginosa
bacteremia is presumed to be a ‘dead-end’ for the pathogen and to have no impact on transmission. Here the authors show, in mice, that the bacteria can spread from the bloodstream via the gallbladder to the intestines and feces, leading to transmission to uninfected animals.
Journal Article
Carryover effects in a sea star: juvenile resource availability does not compensate for a poor larval environment
Carryover effects are widespread in nature and can link early-life experiences to the regulation of populations. However, for organisms with complex life cycles, it is unclear whether offspring can overcome negative early-life experiences when provided with abundant post-metamorphic resources. We tested this by rearing larvae of the keystone sea star Asterias forbesi, under high or low food conditions, and then reared the juveniles for 2–3 weeks under one of four food treatments. Larvae reared under low food conditions took longer to reach metamorphosis and settled as smaller juveniles with fewer spines. For early settlers (mean age at settlement = 24.0 d), carryover effects of low larval food significantly reduced post-metamorphic size, mussel consumption and growth. However for late settlers (mean age at settlement = 29.3 d), there were no carryover effects of larval food availability detected post-metamorphosis. The differences between early and late settlers may indicate a trade-off between larval duration and the presence of carryover effects. Our data suggest that carryover effects mediated by body size at settlement could determine post-metamorphic survival, growth, and performance, ultimately impacting the recruitment of this keystone predator.
Journal Article
Differential laboratory passaging of SARS-CoV-2 viral stocks impacts the in vitro assessment of neutralizing antibodies
Viral populations in natural infections can have a high degree of sequence diversity, which can directly impact immune escape. However, antibody potency is often tested in vitro with a relatively clonal viral populations, such as laboratory virus or pseudotyped virus stocks, which may not accurately represent the genetic diversity of circulating viral genotypes. This can affect the validity of viral phenotype assays, such as antibody neutralization assays. To address this issue, we tested whether recombinant virus carrying SARS-CoV-2 spike (VSV-SARS-CoV-2-S) stocks could be made more genetically diverse by passage, and if a stock passaged under selective pressure was more capable of escaping monoclonal antibody (mAb) neutralization than unpassaged stock or than viral stock passaged without selective pressures. We passaged VSV-SARS-CoV-2-S four times concurrently in three cell lines and then six times with or without polyclonal antiserum selection pressure. All three of the monoclonal antibodies tested neutralized the viral population present in the unpassaged stock. The viral inoculum derived from serial passage without antiserum selection pressure was neutralized by two of the three mAbs. However, the viral inoculum derived from serial passage under antiserum selection pressure escaped neutralization by all three mAbs. Deep sequencing revealed the rapid acquisition of multiple mutations associated with antibody escape in the VSV-SARS-CoV-2-S that had been passaged in the presence of antiserum, including key mutations present in currently circulating Omicron subvariants. These data indicate that viral stock that was generated under polyclonal antiserum selection pressure better reflects the natural environment of the circulating virus and may yield more biologically relevant outcomes in phenotypic assays. Thus, mAb assessment assays that utilize a more genetically diverse, biologically relevant, virus stock may yield data that are relevant for prediction of mAb efficacy and for enhancing biosurveillance.
Journal Article