Genome mapping and characterization of the Anopheles gambiae heterochromatin

<p>Abstract</p> <p>Background</p> <p>Heterochromatin plays an important role in chromosome function and gene regulation. Despite the availability of polytene chromosomes and genome sequence, the heterochromatin of the major malaria vector <it>Anopheles gambiae </it>has not been mapped and characterized.</p> <p>Results</p> <p>To determine the extent of heterochromatin within the <it>An. gambiae </it>genome, genes were physically mapped to the euchromatin-heterochromatin transition zone of polytene chromosomes. The study found that a minimum of 232 genes reside in 16.6 Mb of mapped heterochromatin. Gene ontology analysis revealed that heterochromatin is enriched in genes with DNA-binding and regulatory activities. Immunostaining of the <it>An. gambiae </it>chromosomes with antibodies against <it>Drosophila melanogaster </it>heterochromatin protein 1 (HP1) and the nuclear envelope protein lamin Dm₀identified the major invariable sites of the proteins' localization in all regions of pericentric heterochromatin, diffuse intercalary heterochromatin, and euchromatic region 9C of the 2R arm, but not in the compact intercalary heterochromatin. To better understand the molecular differences among chromatin types, novel Bayesian statistical models were developed to analyze genome features. The study found that heterochromatin and euchromatin differ in gene density and the coverage of retroelements and segmental duplications. The pericentric heterochromatin had the highest coverage of retroelements and tandem repeats, while intercalary heterochromatin was enriched with segmental duplications. We also provide evidence that the diffuse intercalary heterochromatin has a higher coverage of DNA transposable elements, minisatellites, and satellites than does the compact intercalary heterochromatin. The investigation of 42-Mb assembly of unmapped genomic scaffolds showed that it has molecular characteristics similar to cytologically mapped heterochromatin.</p> <p>Conclusions</p> <p>Our results demonstrate that <it>Anopheles </it>polytene chromosomes and whole-genome shotgun assembly render the mapping and characterization of a significant part of heterochromatic scaffolds a possibility. These results reveal the strong association between characteristics of the genome features and morphological types of chromatin. Initial analysis of the <it>An. gambiae </it>heterochromatin provides a framework for its functional characterization and comparative genomic analyses with other organisms.</p

Project #91: Optimizing Vascular Access to Reduce CLABSI

Henry Ford Macomb Hospital experienced an increase in Central Line Associated Bloodstream Infections (CLABSI) in 2021. A significant portion were occurring in the MICU and were associated with Candida sp. Bloodstream infections negatively impact patient outcomes, provider workload, and are costly, with a median cost of $48,108 based on a meta-analysis conducted by AHRQ in 2017. By end of 2022, HFM aimed to reduce CLABSI incidence by 50%.https://scholarlycommons.henryford.com/qualityexpo2023/1004/thumbnail.jp

The Plant Pathogen Pseudomonas syringae pv. tomato Is Genetically Monomorphic and under Strong Selection to Evade Tomato Immunity

Recently, genome sequencing of many isolates of genetically monomorphic bacterial human pathogens has given new insights into pathogen microevolution and phylogeography. Here, we report a genome-based micro-evolutionary study of a bacterial plant pathogen, Pseudomonas syringae pv. tomato. Only 267 mutations were identified between five sequenced isolates in 3,543,009 nt of analyzed genome sequence, which suggests a recent evolutionary origin of this pathogen. Further analysis with genome-derived markers of 89 world-wide isolates showed that several genotypes exist in North America and in Europe indicating frequent pathogen movement between these world regions. Genome-derived markers and molecular analyses of key pathogen loci important for virulence and motility both suggest ongoing adaptation to the tomato host. A mutational hotspot was found in the type III-secreted effector gene hopM1. These mutations abolish the cell death triggering activity of the full-length protein indicating strong selection for loss of function of this effector, which was previously considered a virulence factor. Two non-synonymous mutations in the flagellin-encoding gene fliC allowed identifying a new microbe associated molecular pattern (MAMP) in a region distinct from the known MAMP flg22. Interestingly, the ancestral allele of this MAMP induces a stronger tomato immune response than the derived alleles. The ancestral allele has largely disappeared from today's Pto populations suggesting that flagellin-triggered immunity limits pathogen fitness even in highly virulent pathogens. An additional non-synonymous mutation was identified in flg22 in South American isolates. Therefore, MAMPs are more variable than expected differing even between otherwise almost identical isolates of the same pathogen strain

Intention Seekers: Conspiracist Ideation and Biased Attributions of Intentionality

Conspiracist beliefs are widespread and potentially hazardous. A growing body of research suggests that cognitive biases may play a role in endorsement of conspiracy theories. The current research examines the novel hypothesis that individuals who are biased towards inferring intentional explanations for ambiguous actions are more likely to endorse conspiracy theories, which portray events as the exclusive product of intentional agency. Study 1 replicated a previously observed relationship between conspiracist ideation and individual differences in anthropomorphisation. Studies 2 and 3 report a relationship between conspiracism and inferences of intentionality for imagined ambiguous events. Additionally, Study 3 again found conspiracist ideation to be predicted by individual differences in anthropomorphism. Contrary to expectations, however, the relationship was not mediated by the intentionality bias. The findings are discussed in terms of a domain-general intentionality bias making conspiracy theories appear particularly plausible. Alternative explanations are suggested for the association between conspiracism and anthropomorphism

Les dix commandements de l'économiste-analyste de politique

The incorporation of economic approaches into policymaking requires special skills on the part of the economist. This article examines the use of economics in government as illustrated by the experience of the natural resources agencies. It presents ten guiding rules for the practicing policy economist : (1 ) be economical about the use of economics ; (2) discount for political demand ; (3) dare to be «quick-and-dirty» ; (4) think like a manager ; (5) analyze equity as well as efficiency ; (6) know your market ; (7) pay your organizational dues ; (8) profit from action-forcing events ; (9) do not oversell economic analysis ; and (10) learn policy economics by doing it.The incorporation of economic approaches into policymaking requires special skills on the part of the economist. This article examines the use of economics in government as illustrated by the experience of the natural resources agencies. It presents ten guiding rules for the practicing policy economist : (1 ) be economical about the use of economics ; (2) discount for political demand ; (3) dare to be «quick-and-dirty» ; (4) think like a manager ; (5) analyze equity as well as efficiency ; (6) know your market ; (7) pay your organizational dues ; (8) profit from action-forcing events ; (9) do not oversell economic analysis ; and (10) learn policy economics by doing it.Leman Christopher K., Nelson Robert H. Les dix commandements de l'économiste-analyste de politique. In: Politiques et management public, vol. 1, n° 1, 1983. pp. 129-160

Ten commandments for policy economists

The incorporation of economic approaches into policymaking requires special skills on the part of the economist. This article examines the use of economics in government as illustrated by the experience of the natural resources agencies. It presents ten guiding rules for the practicing policy economist: (1) be economical about the use of economics; (2) discount for political demand; (3) dare to be “quick-and-dirty”; (4) think like a manager; (5) analyze equity as well as efficiency; (6) know your market; (7) pay your organizational dues; (8) profit from action-forcing events; (9) do not oversell economic analysis; and (10) learn policy economics by doing it.

Genome landscape and evolutionary plasticity of chromosomes in malaria mosquitoes.

Nonrandom distribution of rearrangements is a common feature of eukaryotic chromosomes that is not well understood in terms of genome organization and evolution. In the major African malaria vector Anopheles gambiae, polymorphic inversions are highly nonuniformly distributed among five chromosomal arms and are associated with epidemiologically important adaptations. However, it is not clear whether the genomic content of the chromosomal arms is associated with inversion polymorphism and fixation rates.To better understand the evolutionary dynamics of chromosomal inversions, we created a physical map for an Asian malaria mosquito, Anopheles stephensi, and compared it with the genome of An. gambiae. We also developed and deployed novel Bayesian statistical models to analyze genome landscapes in individual chromosomal arms An. gambiae. Here, we demonstrate that, despite the paucity of inversion polymorphisms on the X chromosome, this chromosome has the fastest rate of inversion fixation and the highest density of transposable elements, simple DNA repeats, and GC content. The highly polymorphic and rapidly evolving autosomal 2R arm had overrepresentation of genes involved in cellular response to stress supporting the role of natural selection in maintaining adaptive polymorphic inversions. In addition, the 2R arm had the highest density of regions involved in segmental duplications that clustered in the breakpoint-rich zone of the arm. In contrast, the slower evolving 2L, 3R, and 3L, arms were enriched with matrix-attachment regions that potentially contribute to chromosome stability in the cell nucleus.These results highlight fundamental differences in evolutionary dynamics of the sex chromosome and autosomes and revealed the strong association between characteristics of the genome landscape and rates of chromosomal evolution. We conclude that a unique combination of various classes of genes and repetitive DNA in each arm, rather than a single type of repetitive element, is likely responsible for arm-specific rates of rearrangements