Coevolution with bacteriophages drives genome-wide host evolution and constrains the acquisition of abiotic-beneficial mutations

This is the author accepted manuscript. The final version is available from OUP via the DOI in this record.Studies of antagonistic coevolution between hosts and parasites typically focus on resistance and infectivity traits. However, coevolution could also have genome-wide effects on the hosts due to pleiotropy, epistasis, or selection for evolvability. Here, we investigate these effects in the bacterium Pseudomonas fluorescens SBW25 during approximately 400 generations of evolution in the presence or absence of bacteriophage (coevolution or evolution treatments, respectively). Coevolution resulted in variable phage resistance, lower competitive fitness in the absence of phages, and greater genome-wide divergence both from the ancestor and between replicates, in part due to the evolution of increased mutation rates. Hosts from coevolution and evolution treatments had different suites of mutations. A high proportion of mutations observed in coevolved hosts were associated with a known phage target binding site, the lipopolysaccharide (LPS), and correlated with altered LPS length and phage resistance. Mutations in evolved bacteria were correlated with higher fitness in the absence of phages. However, the benefits of these growth-promoting mutations were completely lost when these bacteria were subsequently coevolved with phages, indicating that they were not beneficial in the presence of resistance mutations (consistent with negative epistasis). Our results show that in addition to affecting genome-wide evolution in loci not obviously linked to parasite resistance, coevolution can also constrain the acquisition of mutations beneficial for growth in the abiotic environment.This work was funded by European Research Council and NERC (UK)

Optimizing fire station locations for the Istanbul metropolitan municipality

Copyright @ 2013 INFORMSThe Istanbul Metropolitan Municipality (IMM) seeks to determine locations for additional fire stations to build in Istanbul; its objective is to make residences and historic sites reachable by emergency vehicles within five minutes of a fire station’s receipt of a service request. In this paper, we discuss our development of a mathematical model to aid IMM in determining these locations by using data retrieved from its fire incident records. We use a geographic information system to implement the model on Istanbul’s road network, and solve two location models—set-covering and maximal-covering—as what-if scenarios. We discuss 10 scenarios, including the situation that existed when we initiated the project and the scenario that IMM implemented. The scenario implemented increases the city’s fire station coverage from 58.6 percent to 85.9 percent, based on a five-minute response time, with an implementation plan that spans three years

Translation and Community in the work of Elizabeth Cary

Explores the role of female community within Elizabeth Cary\u27s translations and her play, The Tragedy of Mariam

Non-Redundant Spectral Dimensionality Reduction

Spectral dimensionality reduction algorithms are widely used in numerous domains, including for recognition, segmentation, tracking and visualization. However, despite their popularity, these algorithms suffer from a major limitation known as the "repeated Eigen-directions" phenomenon. That is, many of the embedding coordinates they produce typically capture the same direction along the data manifold. This leads to redundant and inefficient representations that do not reveal the true intrinsic dimensionality of the data. In this paper, we propose a general method for avoiding redundancy in spectral algorithms. Our approach relies on replacing the orthogonality constraints underlying those methods by unpredictability constraints. Specifically, we require that each embedding coordinate be unpredictable (in the statistical sense) from all previous ones. We prove that these constraints necessarily prevent redundancy, and provide a simple technique to incorporate them into existing methods. As we illustrate on challenging high-dimensional scenarios, our approach produces significantly more informative and compact representations, which improve visualization and classification tasks

Put on a Smiley Face: Textspeak and Personality Perceptions

With the emergence of web 2.0 there has been a dramatic surge in user-generated content. Although the Internet provides greater freedom in self-presentation, computer-mediated communication is characterised by a more relaxed attitude to grammar, spelling and punctuation. The language of the Internet, or textspeak, may be suitable for casual interactions but inappropriate in professional contexts. We tested participant perceptions of an author’s personality in two distinct contexts (formal vs. informal) and manipulated the written information under three levels of textspeak: none, low and high. Participants judged the author as less conscientious and less open, but more emotionally stable when textspeak was used, however context had no impact. Personality perceptions of textspeak users differ to those who write in standard English and this is likely to extend to informal impression management contexts (e.g. online dating). These findings also have a number of implications, for example in terms of screening applicants via social media

Epidemiology and Molecular Relationships of Cryptosporidium spp. in People, Primates, and Livestock from Western Uganda

Cryptosporidium is a common gastrointestinal parasite known for its zoonotic potential. We found Cryptosporidium in 32.4% of people, 11.1% of non-human primates, and 2.2% of livestock in the region of Kibale National Park, Uganda. In people, infection rates were higher in one community than elsewhere, and fetching water from an open water source increased the probability of infection. Phylogenetic analyses identified clusters of Cryptosporidium with mixed host origins in people, primates, and livestock outside the park; however, parasites from primates inside the park were genetically divergent, suggesting a separate sylvatic transmission cycle. Infection was not associated with clinical disease in people, even in the case of co-infection with the gastrointestinal parasite Giardia duodenalis. Parasites such as Cryptosporidium may be maintained through frequent cross-species transmission in tropical settings where people, livestock, and wildlife interact frequently, but the parasite may undergo more host-specific transmission where such interactions do not occur. Persistent low-level shedding and immunity may limit the clinical effects of infection in such settings

Pneumomediastinum from nasal insufflation of cocaine

Chest pain is a common presenting symptom of cocaine users to the emergency department that requires a thorough work up. Pneumomediastinum is an uncommon complication of cocaine abuse that occurs more commonly when cocaine is smoked, but can also occur when cocaine is nasally insufflated. Our case report presents a patient with pneumomediastinum secondary to cocaine insufflation and reviews the necessary diagnostic tests that must be performed to rule out secondary pneumomediastinum, a severe life-threatening condition. Our case is unique, as it is one of a few reported cases of pneumomediastinum occurring after the use of intranasal cocaine

A rare variant of the superficial ulnar artery, and its clinical implications: a case report

The superficial ulnar artery is a rare variation of the upper limb arterial system that arises from the brachial or axillary artery and runs superficial to the muscles arising from the medial epicondyle [1-3]. The incidence is about 0.7 to 7% [1,4,5]. In our routine dissections we found a superficial ulnar artery, which crossed the cubital fossa superficial to the bicipital aponeurosis making it highly vulnerable to intra-arterial injection. This is a rare variation that every medical and nursing staff member should know about

An examination of cancer epidemiology studies among populations living close to toxic waste sites

<p>Abstract</p> <p>Background</p> <p>Toxic waste sites contain a broad range of suspected or confirmed human carcinogens, and remain a source of concern to many people, particularly those living in the vicinity of a site. Despite years of study, a consensus has not emerged regarding the cancer risk associated with such sites.</p> <p>Methods</p> <p>We examined the published, peer-reviewed literature addressing cancer incidence or mortality in the vicinity of toxic waste sites between 1980 and 2006, and catalogued the methods employed by such studies.</p> <p>Results</p> <p>Nineteen studies are described with respect to eight methodological criteria. Most were ecological, with minimal utilization of hydrogeological or air pathway modeling. Many did not catalogue whether a potable water supply was contaminated, and very few included contaminant measurements at waste sites or in subjects' homes. Most studies did not appear to be responses to a recognized cancer mortality cluster. Studies were highly variable with respect to handling of competing risk factors and multiple comparisons.</p> <p>Conclusion</p> <p>We conclude that studies to date have generated hypotheses, but have been of limited utility in determining whether populations living near toxic waste sites are at increased cancer risk.</p

The CAG repeat at the Huntington disease gene in the Portuguese population : insights into its dynamics and to the origin of the mutation

Huntington disease (HD) is caused by an expansion of a CAG repeat. This repeat is a dynamic mutation that tends to undergo intergenerational instability. We report the analysis of the CAG repeat in a large population sample (2,000 chromosomes) covering all regions of Portugal, and a haplotype study of (CAG)n and (CCG)n repeats in 140 HD Portuguese families. Intermediate class 2 alleles represented 3.0% of the population; and two expanded alleles (36 and 40 repeats, 0.11%) were found. There was no evidence for geographical clustering of the intermediate or expanded alleles. The Portuguese families showed three different HD founder haplotypes associated with 7-, 9- or 10-CCG repeats, suggesting the possibility of different origins for theHDmutation among this population. The haplotype carrying the 7-CCG repeat was the most frequent, both in normal and in expanded alleles. In general, we propose that three mechanisms, occurring at different times,may lead to the evolution from normal CAGs to full expansion: first, a mutation bias towards larger alleles; then, a stepwise process that could explain the CAGdistributions observed in themore recent haplotypes; and, finally, a pool of intermediate (class 2) alleles more prone to give rise to expanded HD alleles.Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BD/9759/ 2003.Instituto de Genética Médica Jacinto Magalhães