Bioinformatics

Background: As one of human pathogens, the genome of Uropathogenic Escherichia coli strain CFT073 was sequenced and published in 2002, which was significant in pathogenetic bacterial genomics research. However, the current RefSeq annotation of this pathogen is now outdated to some degree, due to missing or misannotation of some essential genes associated with its virulence. We carried out a systematic reannotation by combining automated annotation tools with manual efforts to provide a comprehensive understanding of virulence for the CFT073 genome.

Defining bacterial species remains a challenging problem even for the model bacterium Escherichia coli and has major practical consequences for reliable diagnosis of infectious disease agents and regulations for transport and possession of organisms of economic importance. E. coli traditionally is thought to live within the gastrointestinal tract of humans and other warm-blooded animals and not to survive for extended periods outside its host; this understanding is the basis for its widespread use as a fecal contamination indicator. Here, we report the genome sequences of nine environmentally adapted strains that are phenotypically and taxonomically indistinguishable from typical E. coli (commensal or pathogenic). We find, however, that the commensal genomes encode for more functions that are important for fitness in the human gut, do not exchange genetic material with their environmental counterparts, and hence do not evolve according to the recently proposed fragmented speciation model. These findings are consistent with a more stringent and ecologic definition for bacterial species than the current definition and provide means to start replacing traditional approaches of defining distinctive phenotypes for new species with omics-based procedures. They also have important implications for reliable diagnosis and regulation of pathogenic E. coli and for the coliform cell-counting test. evolution | genomics | species concept

Prevalence of a calcium-based alkaline phosphatase associated with the marine cyanobacterium Prochlorococcus and other ocean bacteria. Environ Microbiol 13:74-83. 3. Martinez A, Tyson GW, Delong EF (2010) Widespread known and novel phosphonate utilization pathways in marine bacteria revealed by functional screening and metagenomic analyses. Environ Microbiol 12:222-238. 4. Konstantinidis KT, DeLong EF (2008) Genomic patterns of recombination, clonal divergence and environment in marine microbial populations. ISME J 2:1052-1065.

1. There was an error in the funding statement. The correct funding statement is: This research was supported, in part, by the US Department of Energy (award DE-SC0004601). The Emory Genome Center acknowledges the Georgia Research Alliance and the...(read formal correction)

In eukaryotes, the recognition of the DNA postreplication errors and initiation of the mismatch repair is carried out by two MutS homologs: MutSa and MutSb. MutSa recognizes base mismatches and 1 to 2 unpaired nucleotides whereas MutSb recognizes longer insertion-deletion loops (IDLs) with 1 to 15 unpaired nucleotides as well as certain mismatches. Results from molecular dynamics simulations of native MutSb:IDL-containing DNA and MutSa:mismatch DNA complexes as well as complexes with swapped DNA substrates provide mechanistic insight into how the differential substrate specificities are achieved by MutSa and MutSb, respectively. Our simulations results suggest more extensive interactions between MutSb and IDL-DNA and between MutSa and mismatch-containing DNA that suggest corresponding differences in stability. Furthermore , our simulations suggest more expanded mechanistic details involving a different degree of bending when DNA is bound to either MutSa or MutSb and a more likely opening of the clamp domains when noncognate substrates are bound. The simulation results also provide detailed information on key residues in MutSb and MutSa that are likely involved in recognizing IDL-DNA and mismatch-containing DNA, respectively.

We present a molecular-level model for the origin and evolution of the translation system, using a 3D comparative method. In this model, the ribosome evolved by accretion, recursively adding expansion segments, iteratively growing, subsuming, and freezing the rRNA. Functions of expansion segments in the ancestral ribosome are assigned by correspondence with their functions in the extant ribosome. The model explains the evolution of the large ribosomal subunit, the small ribosomal subunit, tRNA, and mRNA. Prokaryotic ribosomes evolved in six phases, sequentially acquiring capabilities for RNA folding, catalysis, subunit association, correlated evolution, decoding, energy-driven translocation, and surface proteinization. Two additional phases exclusive to eukaryotes led to tentacle-like rRNA expansions. In this model, ribosomal proteinization was a driving force for the broad adoption of proteins in other biological processes. The exit tunnel was clearly a central theme of all phases of ribosomal evolution and was continuously extended and rigidified. In the primitive noncoding ribosome, proto-mRNA and the small ribosomal subunit acted as cofactors, positioning the activated ends of tRNAs within the peptidyl transferase center. This association linked the evolution of the large and small ribosomal subunits, proto-mRNA, and tRNA. RNA evolution | translation | origin of life | A-minor interactions T he ribosome retains interpretable molecular records of a world of primordial molecules (1) from around 4 billion years ago (2–9). The records are maintained in rRNA secondary and 3D structures, which are fully conserved throughout the tree of life, and in rRNA sequences, which are more variable (SI Appendix, Fig. S1). Here we use information within ribosomes from each major branch of the tree of life to reconstruct much of the emergence of the universal translational machinery. Large Ribosomal Subunit Evolution Previously, we reported a 3D comparative method that revealed a molecular level chronology of the evolution of the large ribosomal subunit (LSU) rRNA (10). Insertion fingerprints are evident when comparing 3D structures of LSU rRNAs of various sizes from various species. These insertion fingerprints mark sites where rRNA expands, recording growth steps on a molecular level. Within the common core of the LSU rRNA, insertion fingerprints were used to identify ancient growth sites. We showed that insertion fingerprints provide a roadmap from the first steps in the formation of the peptidyl transferase center (PTC) (10) located in the ancient heart of the LSU (2–6), culminating in the common core. Small Ribosomal Subunit, LSU, tRNA, and mRNA Evolution Here, using the 3D comparative method, we establish a comprehensive and coherent model for the evolution of the entire ribosome. This model covers the LSU rRNA, small ribosomal subunit (SSU) rRNA, tRNA, and mRNA. The evolution of each of these components is reconciled at the molecular level to a common chronology. This evolutionary model, which we call the " accretion model, " is fully grounded in structural data in the form of insertion fingerprints and molecular interactions. The model describes iterative accretion of rRNA fragments in the form of expansion segments. The timeline of the accretion model initiates in ancient proto-biology in the initial building up of the functional centers, proceeds to the establishment of the common core, and continues to the development of large metazoan rRNAs. Incremental evolution of function is mapped out by stepwise accretion of rRNA. In the extant ribosome, specific segments of rRNA perform specific functions including peptidyl transfer, subunit association, decoding, and energy-driven translocation (11). The model assumes that the correlations of rRNA segments with their functions have been reasonably maintained over the broad course of ribosomal evolution. Therefore the model maps out the time course of acquisition of function. Breadth of function increased as the ribosome grew in size. rRNA Variation Expansion segments (" ES " indicates LSU expansion segments, and " es " indicates SSU expansion segments) (7, 8, 12, 13) are small, folding-competent RNA fragments that are inserted into common core rRNA over evolution, increasing rRNA length without substantially perturbing the structure of the common core. Recursive insertion of expansion segments leads to variation in the length of rRNAs. In extant species, rRNA lengths vary according to well-defined rules. (i) rRNA length tends to increase from bacteria/archaea, which approximate the common core, to protists, to metazoa (9, 10). (ii) Size variation is significantly greater in eukaryotes than in prokaryotes and in LSU rRNAs than in SSU rRNAs (8). (iii) Variation is focused at a few specific sites of the common core (7–10, 14, 15). (iv) Variation is excluded from the interior and from functional regions of the rRNA such as the PTC, the decoding center, the core of the subunit interface, and tRNA-binding sites (16). (v) rRNA size generally increases with organismal complexity (10). Here, we consider ancestral expansion segments, which are found within Significance The ribosome, in analogy with a tree, contains a record of its history, spanning 4 billion years of life on earth. The information contained within ribosomes connects us to the prehistory of biology. Details of ribosomal RNA variation, observed by comparing three-dimensional structures of ribo-somes across the tree of life, form the basis of our molecular-level model of the origins and evolution of the translational system. We infer many steps in the evolution of translation, mapping out acquisition of structure and function, revealing much about how modern biology originated from ancestral chemical systems.

The question of whether illegal immigration is positively related to crime rates in the United States has been heavily publicized since current U.S. president Donald Trump announced his candidacy for president in 2015. This study explores the relationship between changes in illegal immigration and changes in violent crime rates at the state level during the period from 2009 to 2014. Data came from the Pew Research Center and the FBI's Uniform Crime Reports. It is found that changes in the percent of a population made up of undocumented immigrants is not significantly correlated with changes in violent crime rates among U.S. states for which data on both parameters exist (n=13), consistent with previous research on this topic. Background The putative link between illegal immigration and crime in the United States has received considerable attention since Donald Trump announced his candidacy for President in 2015, decrying that Mexican people migrating illegally to the United States were ".. . bringing drugs. They're bringing crime. They're rapists. And some, I assume, are good people."(cri, 2015) While considerable research has been done on the relationship between overall immigration and crime rates (e.g. (Ousey and Kubrin, 2018), less research has been done on the relationship between illegal immigration and crime in the United States. Overall trends, however, show that while the number of immigrants in the United States has increased in the United States in recent decades, violent and overall crime rates have dropped significantly over the same time period. As Sampson noted in 2008:(Sampson, 2008) (page 29) ".. . immigration-even if illegal-is associated with lower crime rates in most disadvantaged urban neighborhoods." Some have questioned whether the negative relationship between immigration and crime can be extended to apply specifically to undocumented immigrants. To this objection, Sampson wrote that ".. . in areas and times of high legal immigration we find accompanying surges of illegal entrants. It would be odd indeed if illegal aliens descended on areas with no other immigrants or where they had no pre-existing networks.. . Because crime tends to be negatively associated with undifferentiated immigration measures.. . we can disconfirm the idea that increasing illegal immigration is associated with increasing crime."(Sampson, 2008) (page 30) Overall trends show that the number of undocumented immigrants in the United States increased steadily from 1990 to 2007, before declining slightly thereafter.(us) In contrast, the national violent crime rate declined significantly from this time (from 729.6 to 471.8 per 100,000 people).(sta) The studies that have been done include one published in 2016, entitled "The Trump Hypothesis".(Green, 2016). This study found found no relationship between undocumented Mexican immigrants and violent

While there is compelling evidence of the effectiveness of COVID-19 vaccines, increasing attention has also been paid to the fact that, like all vaccines, they are not 100% effective. Therefore, some fully vaccinated people have developed "breakthrough" cases of COVID-19, and some of these individuals have died as a result. The purpose of this study was to estimate the number of fully vaccinated or "breakthrough" deaths from COVID-19 in the United States. Data was compiled from state COVID-19 dashboards and various other sources for as many states as possible. As of March 27, 2022 based on data from 46 U.S. states and the District of Columbia, an estimated minimum of 57,617 breakthrough COVID-19 deaths had occurred in the United States. Furthermore, based on this incomplete data, a total of 12.8% of all COVID-19 deaths in the included regions and time periods were among fully vaccinated individuals (whether boosted or not). Extrapolating this data to the entire United States implies that the minimum total number of such deaths as of March 27, 2022 was 79,917. Data from a MMWR article, if similarly extrapolated to the entire country, implies a significantly larger number of breakthrough deaths throughout the United States: 99,152.

RNA-based therapies offer unique advantages for treating pediatric brain tumors. However, the systemic delivery remains a major problem due to degradation of unmodified RNA in biological fluids, poor brain accumulation, and poor cancer cell uptake or escape from the endosomal lipid bilayer barrier. While nanoparticle encapsulation can prolong circulation time and facilitate cellular uptake, their accumulation in brain tumor remains particularly poor due to their low permeability across the blood-brain barrier and limited intratumoral penetration. Focused ultrasound, when combined with circulating microbubbles (MB-FUS) provides a physical method to transiently modulate the brain tumor microenvironment (TME) and improve nanoparticle delivery. Here, we have examined the delivery of siRNA targeting the Smoothened (SMO) pathway, packaged in 50 nm cationic lipid-polymer hybrid nanoparticles (cLPH:siRNA-SMO), combined with MB-FUS in murine SmoA2 sonic hedgehog (SHH) medulloblastoma. At 30 ...