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ABSTRACT Lyme disease, caused by spirochetes in the Borrelia burgdorferi sensu lato clade within the Borrelia genus, is transmitted by Ixodes ticks and is currently the most prevalent and rapidly expanding tick-borne disease in Europe and North America. We report complete genome sequences of 47 isolates that encompass all established species in this clade while highlighting the diversity of the widespread human pathogenic species B. burgdorferi. A similar set of plasmids has been maintained throughout Borrelia divergence, indicating that they are a key adaptive feature of this genus. Phylogenetic reconstruction of all sequenced Borrelia genomes revealed the original divergence of Eurasian and North American lineages and subsequent dispersals that introduced B. garinii, B. bavariensis, B. lusitaniae, B. valaisiana, and B. afzelii from East Asia to Europe and B. burgdorferi and B. finlandensis from North America to Europe. Molecular phylogenies of the universally present core replicons (chromosome and cp26 and lp54 plasmids) are highly consistent, revealing a strong clonal structure. Nonetheless, numerous inconsistencies between the genome and gene phylogenies indicate species dispersal, genetic exchanges, and rapid sequence evolution at plasmid-borne loci, including key host-interacting lipoprotein genes. While localized recombination occurs uniformly on the main chromosome at a rate comparable to mutation, lipoprotein-encoding loci are recombination hotspots on the plasmids, suggesting adaptive maintenance of recombinant alleles at loci directly interacting with the host. We conclude that within- and between-species recombination facilitates adaptive sequence evolution of host-interacting lipoprotein loci and contributes to human virulence despite a genome-wide clonal structure of its natural populations.IMPORTANCELyme disease (also called Lyme borreliosis in Europe), a condition caused by spirochete bacteria of the genus Borrelia, transmitted by hard-bodied Ixodes ticks, is currently the most prevalent and rapidly expanding tick-borne disease in the United States and Europe. Borrelia interspecies and intraspecies genome comparisons of Lyme disease-related bacteria are essential to reconstruct their evolutionary origins, track epidemiological spread, identify molecular mechanisms of human pathogenicity, and design molecular and ecological approaches to disease prevention, diagnosis, and treatment. These Lyme disease-associated bacteria harbor complex genomes that encode many genes that do not have homologs in other organisms and are distributed across multiple linear and circular plasmids. The functional significance of most of the plasmid-borne genes and the multipartite genome organization itself remains unknown. Here we sequenced, assembled, and analyzed whole genomes of 47 Borrelia isolates from around the world, including multiple isolates of the human pathogenic species. Our analysis elucidates the evolutionary origins, historical migration, and sources of genomic variability of these clinically important pathogens. We have developed web-based software tools (BorreliaBase.org) to facilitate dissemination and continued comparative analysis of Borrelia genomes to identify determinants of human pathogenicity.

To explore the confinement of high-energy ions above the space charge limit, we have developed a hybrid magnetic and electrostatic confinement device called an Orbitron. The Orbitron is a crossed-field device combining aspects of magnetic mirrors, magnetrons, and orbital ion traps. Ions are confined in orbits around a high-voltage cathode with co-rotating electrons confined by a relatively weak magnetic field. Experimental and computational investigations focus on reaching ion densities above the space charge limit through the co-confinement of electrons. The experimental apparatus and suite of diagnostics are being developed to measure the critical parameters, such as plasma density, particle energy, and fusion rate for high-energy, non-thermal plasma conditions in the Orbitron. Initial results from experimental and computational efforts have revealed the need for cathode voltages on the order of 100–300 kV, leading to the development of a custom high voltage, ultra-high vacuum bushing rated for 300 kV.

Abstract Lyme borreliosis (LB) is the most common vector‐borne disease in the Northern Hemisphere caused by spirochetes belonging to the Borrelia burgdorferi sensu lato (Bbsl) complex. Borrelia spirochetes circulate in obligatory transmission cycles between tick vectors and different vertebrate hosts. To successfully complete this complex transmission cycle, Bbsl encodes for an arsenal of proteins including the PFam54 protein family with known, or proposed, influences to reservoir host and/or vector adaptation. Even so, only fragmentary information is available regarding the naturally occurring level of variation in the PFam54 gene array especially in relation to Eurasian‐distributed species. Utilizing whole genome data from isolates (n = 141) originated from three major LB‐causing Borrelia species across Eurasia (B. afzelii, B. bavariensis, and B. garinii), we aimed to characterize the diversity of the PFam54 gene array in these isolates to facilitate understanding the evolution of PFam54 paralogs on an intra‐ and interspecies level. We found an extraordinarily high level of variation in the PFam54 gene array with 39 PFam54 paralogs belonging to 23 orthologous groups including five novel paralogs. Even so, the gene array appears to have remained fairly stable over the evolutionary history of the studied Borrelia species. Interestingly, genes outside Clade IV, which contains genes encoding for proteins associated with Borrelia pathogenesis, more frequently displayed signatures of diversifying selection between clades that differ in hypothesized vector or host species. This could suggest that non‐Clade IV paralogs play a more important role in host and/or vector adaptation than previously expected, which would require future lab‐based studies to validate.

Abstract Background Bacteria of the Borrelia burgdorferi sensu lato (s.l.) complex can cause Lyme borreliosis. Different B. burgdorferi s.l. genospecies vary in their host and vector associations and human pathogenicity but the genetic basis for these adaptations is unresolved and requires completed and reliable genomes for comparative analyses. The de novo assembly of a complete Borrelia genome is challenging due to the high levels of complexity, represented by a high number of circular and linear plasmids that are dynamic, showing mosaic structure and sequence homology. Previous work demonstrated that even advanced approaches, such as a combination of short-read and long-read data, might lead to incomplete plasmid reconstruction. Here, using recently developed high-fidelity (HiFi) PacBio sequencing, we explored strategies to obtain gap-free, complete and high quality Borrelia genome assemblies. Optimizing genome assembly, quality control and refinement steps, we critically appraised existing techniques to create a workflow that lead to improved genome reconstruction. Results Despite the latest available technologies, stand-alone sequencing and assembly methods are insufficient for the generation of complete and high quality Borrelia genome assemblies. We developed a workflow pipeline for the de novo genome assembly for Borrelia using several types of sequence data and incorporating multiple assemblers to recover the complete genome including both circular and linear plasmid sequences. Conclusion Our study demonstrates that, with HiFi data and an ensemble reconstruction pipeline with refinement steps, chromosomal and plasmid sequences can be fully resolved, even for complex genomes such as Borrelia. The presented pipeline may be of interest for the assembly of further complex microbial genomes.

The paper investigates the existence of position-independentsegments in written and typed word production. In twoexperiments, we employed the segmental interference effect tofirst replicate past findings that naming a picture is moredifficult in the context of another picture with which it sharessegments in the same position (e.g., glow-flow) compared toan unrelated word (e.g., glow-cave). We then tested a newcondition, in which the same target word is paired with ananagram of the original competitor (glow-wolf). Critically, theanagram shared the same number of segments with the targetword, but never in the same position. Both experiments foundrobust interference for targets produced in the context ofanagrams, with a magnitude comparable to the interferenceinduced by the position-overlapping word. The results suggestthat not only are position-independent segments represented inthe production system, but they also play a critical role inactivating segmentally related words and creating competitionduring word production.

Many educators view makerspaces as a means of increasing student engagement in K-12 classrooms. As faculty and staff of the College of Education at the University of Saskatchewan, we have noted low comfort levels in using and experimenting with technology. For this reason, we decided to create a place in which pre-service teachers could test and discuss technologies that they could eventually use in their teaching practice. Our endeavor eventually morphed into a space for current teachers, student teachers, technical support staff, faculty members, and interested community members. Having piloted workshops for six months, we are now evaluating our decisions and shaping new approaches for the current academic year. Our main challenges include ensuring inclusivity across age, gender, and culture; adopting suitable facilitation styles; and ensuring the workshops lead to useful discussions of technology and teaching practice.

Geminates (or double letters) are a feature of many languages,including English. Studies of the spelling errors produced byindividuals with orthographic working memory deficits haveprovided evidence that geminates are not produced as two in-dependent instances of the same letter. Instead, there must bea special mechanism in the orthographic system that producesgeminates. Several theories have attempted to model suchmechanisms. However, in most cases, the predictions of suchtheories have been tested using data from single-case neuro-psychological studies. In the current study, we re-evaluatethese theories using the largest corpus of geminate errors intyping collected to date, and show that no theory can explainall the findings. We then propose an enhanced model of gem-ination that can.

The classic Baddeley and Hitch (1974) model divides workingmemory into domain-specific subsystems and a shared, do-main-general central executive, which plays a role in allocatingresources to items stored in the subsystems. The nature of thisresource—in particular, its quantization (discrete vs. continu-ous) and the flexibility of its allocation—has been studied ex-tensively in the visual domain, with evidence from experimentsusing continuous response measures providing support formodels with flexibly and continuously divisible resources. Itremains unclear, however, whether similar mechanisms medi-ate the division of resources in phonological working memory.In this paper, we show that, despite representational differencesbetween visual and auditory processing, continuous measurescan also be employed for studying phonological workingmemory. Using such measures, we demonstrate that the prin-ciples of resource division in visual and phonological pro-cessing are indeed similar, providing evidence for a domain-general mechanism for allocating working memory resources.

A novel strain gauge force transducer was developed to minimize the number of strain gauges needed to determine the magnitudes of loads when the locations are known. This innovative methodology requires only one strain gauge for each force magnitude desired, reducing the complexity and cost associated with traditional approaches. The theory was verified with laboratory experiments. Seven uniaxial strain gauges were attached to the underside of a simply supported, slender, aluminum beam. One or more loads were applied either directly atop strain gauges or in known positions between strain gauges. Experiments were conducted on several different single and double-load configurations to evaluate the extent of the new methodology which yielded average errors under 5% for the cases where loads were direct atop strain gauges and 6.6% for the cases where the loads were between strain gauges. These findings indicate the potential of this novel strain gauge force transducer to revolutionize load measurement in scenarios where load locations are predetermined.

There is a paucity of quality measures to assess the care for the range of unhealthy alcohol use, ranging from risky drinking to alcohol use disorders. Using a two-phase expert panel review process, we sought to develop an expanded set of quality of care measures for unhealthy alcohol use, focusing on outpatient care delivered in both primary care and specialty care settings. This process generated 25 candidate measures. Eight measures address screening and assessment, 11 address aspects of treatment, and six address follow-up. These quality measures represent high priority targets for future development, including creating detailed technical specifications and pilot testing them to evaluate their utility in terms of feasibility, reliability, and validity.