Yersinia pestis Evolution on a Small Timescale: Comparison of Whole Genome Sequences from North America

Yersinia pestis, the etiologic agent of plague, was responsible for several devastating epidemics throughout history and is currently of global importance to current public heath and biodefense efforts. Y. pestis is widespread in the Western United States. Because Y. pestis was first introduced to this region just over 100 years ago, there has been little time for genetic diversity to accumulate. Recent studies based upon single nucleotide polymorphisms have begun to quantify the genetic diversity of Y. pestis in North America.To examine the evolution of Y. pestis in North America, a gapped genome sequence of CA88-4125 was generated. Sequence comparison with another North American Y. pestis strain, CO92, identified seven regions of difference (six inversions, one rearrangement), differing IS element copy numbers, and several SNPs.The relatively large number of inverted/rearranged segments suggests that North American Y. pestis strains may be undergoing inversion fixation at high rates over a short time span, contributing to higher-than-expected diversity in this region. These findings will hopefully encourage the scientific community to sequence additional Y. pestis strains from North America and abroad, leading to a greater understanding of the evolutionary history of this pathogen

MRI texture analysis of subchondral bone at the tibial plateau

OBJECTIVES: To determine the feasibility of MRI texture analysis as a method of quantifying subchondral bone architecture in knee osteoarthritis (OA).   METHODS: Asymptomatic subjects aged 20-30 (group 1, n = 10), symptomatic patients aged 40-50 (group 2, n = 10) and patients scheduled for knee replacement aged 55-85 (group 3, n = 10) underwent high spatial resolution T1-weighted coronal 3T knee MRI. Regions of interest were created in the medial (MT) and lateral (LT) tibial subchondral bone from which 20 texture parameters were calculated. T2 mapping of the tibial cartilage was performed in groups 1 and 2. Mean parameter values were compared between groups using ANOVA. Linear discriminant analysis (LDA) was used to evaluate the ability of texture analysis to classify subjects correctly.   RESULTS: Significant differences in 18/20 and 12/20 subchondral bone texture parameters were demonstrated between groups at the MT and LT respectively. There was no significant difference in mean MT or LT cartilage T2 values between group 1 and group 2. LDA demonstrated subject classification accuracy of 97 % (95 % CI 91-100 %).   CONCLUSION: MRI texture analysis of tibial subchondral bone may allow detection of alteration in subchondral bone architecture in OA. This has potential applications in understanding OA pathogenesis and assessing response to treatment.   KEY POINTS: • Improved techniques to monitor OA disease progression and treatment response are desirable • Subchondral bone (SB) may play significant role in the development of OA • MRI texture analysis is a method of quantifying changes in SB architecture • Pilot study showed that this technique is feasible and reliable • Significant differences in SB texture were demonstrated between individuals with/without OA

Comparative Genomics of 2009 Seasonal Plague (Yersinia pestis) in New Mexico

Plague disease caused by the Gram-negative bacterium Yersinia pestis routinely affects animals and occasionally humans, in the western United States. The strains native to the North American continent are thought to be derived from a single introduction in the late 19th century. The degree to which these isolates have diverged genetically since their introduction is not clear, and new genomic markers to assay the diversity of North American plague are highly desired. To assay genetic diversity of plague isolates within confined geographic areas, draft genome sequences were generated by 454 pyrosequencing from nine environmental and clinical plague isolates. In silico assemblies of Variable Number Tandem Repeat (VNTR) loci were compared to laboratory-generated profiles for seven markers. High-confidence SNPs and small Insertion/Deletions (Indels) were compared to previously sequenced Y. pestis isolates. The resulting panel of mutations allowed clustering of the strains and tracing of the most likely evolutionary trajectory of the plague strains. The sequences also allowed the identification of new putative SNPs that differentiate the 2009 isolates from previously sequenced plague strains and from each other. In addition, new insertion points for the abundant insertion sequences (IS) of Y. pestis are present that allow additional discrimination of strains; several of these new insertions potentially inactivate genes implicated in virulence. These sequences enable whole-genome phylogenetic analysis and allow the unbiased comparison of closely related isolates of a genetically monomorphic pathogen

Post-imperialism, postcolonialism and beyond: towards a periodisation of cultural discourse about colonial legacies

Taking German history and culture as a starting point, this essay suggests a historical approach to reconceptualising different forms of literary engagement with colonial discourse, colonial legacies and (post-) colonial memory in the context of Comparative Postcolonial Studies. The deliberate blending of a historical, a conceptual and a political understanding of the ‘postcolonial’ in postcolonial scholarship raises problems of periodisation and historical terminology when, for example, anti-colonial discourse from the colonial period or colonialist discourse in Weimar Germany are labelled ‘postcolonial’. The colonial revisionism of Germany’s interwar period is more usefully classed as post-imperial, as are particular strands of retrospective engagement with colonial history and legacy in British, French and other European literatures and cultures after 1945. At the same time, some recent developments in Francophone, Anglophone and German literature, e.g. Afropolitan writing, move beyond defining features of postcolonial discourse and raise the question of the post-postcolonial

In vivo measures of cartilage deformation: patterns in healthy and osteoarthritic female knees using 3T MR imaging

ObjectiveTo explore and to compare the magnitude and spatial pattern of in vivo femorotibial cartilage deformation in healthy and in osteoarthritic (OA) knees.MethodsOne knee each in 30 women (age: 55 ± 6 years; BMI: 28 ± 2.4 kg/m(2); 11 healthy and 19 with radiographic femorotibial OA) was examined at 3Tesla using a coronal fat-suppressed gradient echo SPGR sequence. Regional and subregional femorotibial cartilage thickness was determined under unloaded and loaded conditions, with 50% body weight being applied to the knee in 20° knee flexion during imaging.ResultsCartilage became significantly (p < 0.05) thinner during loading in the medial tibia (-2.7%), the weight-bearing medial femur (-4.1%) and in the lateral tibia (-1.8%), but not in the lateral femur (+0.1%). The magnitude of deformation in the medial tibia and femur tended to be greater in osteoarthritic knees than in healthy knees. The subregional pattern of cartilage deformation was similar for the different stages of radiographic OA.ConclusionOsteoarthritic cartilage tended to display greater deformation upon loading than healthy cartilage, suggesting that knee OA affects the mechanical properties of cartilage. The pattern of in vivo deformation indicated that cartilage loss in OA progression is mechanically driven

Flea Diversity as an Element for Persistence of Plague Bacteria in an East African Plague Focus

Plague is a flea-borne rodent-associated zoonotic disease that is caused by Yersinia pestis and characterized by long quiescent periods punctuated by rapidly spreading epidemics and epizootics. How plague bacteria persist during inter-epizootic periods is poorly understood, yet is important for predicting when and where epizootics are likely to occur and for designing interventions aimed at local elimination of the pathogen. Existing hypotheses of how Y. pestis is maintained within plague foci typically center on host abundance or diversity, but little attention has been paid to the importance of flea diversity in enzootic maintenance. Our study compares host and flea abundance and diversity along an elevation gradient that spans from low elevation sites outside of a plague focus in the West Nile region of Uganda (∼725–1160 m) to higher elevation sites within the focus (∼1380–1630 m). Based on a year of sampling, we showed that host abundance and diversity, as well as total flea abundance on hosts was similar between sites inside compared with outside the plague focus. By contrast, flea diversity was significantly higher inside the focus than outside. Our study highlights the importance of considering flea diversity in models of Y. pestis persistence

Novel Plasmids and Resistance Phenotypes in Yersinia pestis: Unique Plasmid Inventory of Strain Java 9 Mediates High Levels of Arsenic Resistance

Growing evidence suggests that the plasmid repertoire of Yersinia pestis is not restricted to the three classical virulence plasmids. The Java 9 strain of Y. pestis is a biovar Orientalis isolate obtained from a rat in Indonesia. Although it lacks the Y. pestis-specific plasmid pMT, which encodes the F1 capsule, it retains virulence in mouse and non-human primate animal models. While comparing diverse Y. pestis strains using subtractive hybridization, we identified sequences in Java 9 that were homologous to a Y. enterocolitica strain carrying the transposon Tn2502, which is known to encode arsenic resistance. Here we demonstrate that Java 9 exhibits high levels of arsenic and arsenite resistance mediated by a novel promiscuous class II transposon, named Tn2503. Arsenic resistance was self-transmissible from Java 9 to other Y. pestis strains via conjugation. Genomic analysis of the atypical plasmid inventory of Java 9 identified pCD and pPCP plasmids of atypical size and two previously uncharacterized cryptic plasmids. Unlike the Tn2502-mediated arsenic resistance encoded on the Y. enterocolitica virulence plasmid; the resistance loci in Java 9 are found on all four indigenous plasmids, including the two novel cryptic plasmids. This unique mobilome introduces more than 105 genes into the species gene pool. The majority of these are encoded by the two entirely novel self-transmissible plasmids, which show partial homology and synteny to other enterics. In contrast to the reductive evolution in Y. pestis, this study underlines the major impact of a dynamic mobilome and lateral acquisition in the genome evolution of the plague bacterium

A systematic review of the relationship between subchondral bone features, pain and structural pathology in peripheral joint osteoarthritis

Introduction: Bone is an integral part of the osteoarthritis (OA) process. We conducted a systematic literature review in order to understand the relationship between non-conventional radiographic imaging of subchondral bone, pain, structural pathology and joint replacement in peripheral joint OA. Methods: A search of the Medline, EMBASE and Cochrane library databases was performed for original articles reporting association between non-conventional radiographic imaging-assessed subchondral bone pathologies and joint replacement, pain or structural progression in knee, hip, hand, ankle and foot OA. Each association was qualitatively characterised by a synthesis of the data from each analysis based upon study design, adequacy of covariate adjustment and quality scoring. Results: In total 2456 abstracts were screened and 139 papers were included (70 cross-sectional, 71 longitudinal analyses; 116 knee, 15 hip, six hand, two ankle and involved 113 MRI, eight DXA, four CT, eight scintigraphic and eight 2D shape analyses). BMLs, osteophytes and bone shape were independently associated with structural progression or joint replacement. BMLs and bone shape were independently associated with longitudinal change in pain and incident frequent knee pain respectively. Conclusion: Subchondral bone features have independent associations with structural progression, pain and joint replacement in peripheral OA in the hip and hand but especially in the knee. For peripheral OA sites other than the knee, there are fewer associations and independent associations of bone pathologies with these important OA outcomes which may reflect fewer studies; for example the foot and ankle were poorly studied. Subchondral OA bone appears to be a relevant therapeutic target. Systematic review: PROSPERO registration number: CRD 4201300500

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta