Orientia and Rickettsia: different flowers from the same garden

Recent discoveries of basal extracellular Rickettsiales have illuminated divergent evolutionary paths to host dependency in later-evolving lineages. Family Rickettsiaceae, primarily comprised of numerous protist- and invertebrate-associated species, also includes human pathogens from two genera, Orientia and Rickettsia. Once considered sister taxa, these bacteria form distinct lineages with newly appreciated lifestyles and morphological traits. Contrasting other rickettsial human pathogens in Family Anaplasmataceae, Orientia and Rickettsia species do not reside in host-derived vacuoles and lack glycolytic potential. With only a few described mechanisms, strategies for commandeering host glycolysis to support cytosolic growth remain to be discovered. While regulatory systems for this unique mode of intracellular parasitism are unclear, conjugative transposons unique to Orientia and Rickettsia species provide insights that are critical for determining how these obligate intracellular pathogens overtake eukaryotic cytosol

Migration for family and labour market outcomes in Sweden

Using information on stated motives for migrating among working-age individuals in the 2007 Swedish Motives for Migration survey(N = 1,852),we use multinomial logistic regression to examine whether and how moves for family reasons are linked to labour market outcomes in ways that differ from migration initiated for other motives, including more overtly labour-related factors. The results indicate that family-based migration is associated with worse labour market outcomes than migration for employment or other reasons. Additionally, family-motivated migrants with co-resident children are more likely to experience labour market deterioration than those without children. Among those who were unemployed before moving, those who reported family as a motive for moving were significantly more likely to be employed after the move. These results help us better assess how families and social networks impact economic outcomes-negatively in some circumstances and positively in others

Conjugative Transposons and Their Cargo Genes Vary across Natural Populations of Rickettsia buchneri Infecting the Tick Ixodes scapularis

Rickettsia buchneri (formerly Rickettsia endosymbiont of Ixodes scapularis, or REIS) is an obligate intracellular endoparasite of the black-legged tick, the primary vector of Lyme disease in North America. It is noteworthy among the rickettsiae for its relatively large genome (1.8 Mb) and extraordinary proliferation of mobile genetic elements (MGEs), which comprise nearly 35% of its genome. Previous analysis of the R. buchneri genome identified several integrative conjugative elements named Rickettsiales amplified genomic elements (RAGEs); the composition of these RAGEs suggests that continued genomic invasions by MGEs facilitated the proliferation of rickettsial genes related to an intracellular lifestyle. In this study, we compare the genomic diversity at RAGE loci among sequenced rickettsiae that infect three related Ixodes spp., including two strains of R. buchneri and Rickettsia endosymbiont of Ixodes pacificus strain Humboldt, as well as a closely related species R. tamurae infecting Amblyomma testudinarium ticks. We further develop a novel multiplex droplet digital PCR assay and use it to quantify copy number ratios of chromosomal R. buchneri RAGE-A and RAGE-B to the single-copy gene gltA within natural populations of I. scapularis. Our results reveal substantial diversity among R. buchneri at these loci, both within individual ticks as well as in the I. scapularis population at large, demonstrating that genomic rearrangement of MGEs is an active process in these intracellular bacteria

Louse- and flea-borne rickettsioses: biological and genomic analyses

In contrast to 15 or more validated and/or proposed tick-borne spotted fever group species, only three named medically important rickettsial species are associated with insects. These insect-borne rickettsiae are comprised of two highly pathogenic species, Rickettsia prowazekii (the agent of epidemic typhus) and R. typhi (the agent of murine typhus), as well as R. felis, a species with unconfirmed pathogenicity. Rickettsial association with obligate hematophagous insects such as the human body louse (R. prowazekii transmitted by Pediculus h. humanus) and several flea species (R. typhi and R. felis, as well as R. prowazekii in sylvatic form) provides rickettsiae the potential for further multiplications, longer transmission cycles and rapid spread among susceptible human populations. Both human body lice and fleas are intermittent feeders capable of multiple blood meals per generation, facilitating the efficient transmission of rickettsiae to several disparate hosts within urban/rural ecosystems. While taking into consideration the existing knowledge of rickettsial biology and genomic attributes, we have analyzed and summarized the interacting features that are unique to both the rickettsiae and their vector fleas and lice. Furthermore, factors that underlie rickettsial changing ecology, where native mammalian populations are involved in the maintenance of rickettsial cycle and transmission, are discussed

A Tangled Web: Origins of Reproductive Parasitism

While typically a flea parasite and opportunistic human pathogen, the presence of Rickettsia felis (strain LSU-Lb) in the non-blood- feeding, parthenogenetically reproducing booklouse, Liposcelis bostrychophila, provides a system to ascertain factors governing not only host transitions but also obligate reproductive parasitism (RP). Analysis of plasmid pLbAR, unique to R. felis str. LSU-Lb, revealed a toxin–antitoxin module with similar features to prophage-encoded toxin–antitoxin modules utilized by parasitic Wolbachia strains to induce another form of RP, cytoplasmic incompatibility, in their arthropod hosts. Curiously, multiple deubiquitinase and nuclease domains of the large (3,841 aa) pLbAR toxin, as well the entire antitoxin, facilitated the detection of an assortment of related proteins from diverse intracellular bacteria, including other reproductive parasites. Our description of these remarkable components of the intracellular mobilome, including their presence in certain arthropod genomes, lends insight on the evolution of RP, while invigo- rating research on parasite-mediated biocontrol of arthropod-borne viral and bacterial pathogens

Major depressive disorder in a family study of obsessive–compulsive disorder with pediatric probands

Objective: This study examined the comorbidity of obsessive–compulsive disorder (OCD) with major depressive disorder (MDD) in a family study of OCD with pediatric probands. Method: This study assessed the lifetime prevalence of MDD in 141 first‐degree relatives (FDR) and 452 second‐degree relatives (SDR) of pediatric probands with OCD and healthy controls, and identified variables associated with MDD in case FDR. All available FDR were directly interviewed blind to proband status; parents were also interviewed to assess the family psychiatric history of FDR and SDR. Best‐estimate diagnoses were made using all sources of information. Data were analyzed with logistic regression and robust Cox regression models. Results: Lifetime MDD prevalence was significantly higher in case than in control FDR (30.4 versus 15.4%). Lifetime MDD prevalence was significantly higher in FDR of case probands with MDD than in FDR of case probands without MDD or control FDR (46.3 versus 19.7 versus 15.4%, respectively). MDD in case FDR was significantly associated with MDD in case probands and with age and OCD in those relatives. Lifetime MDD prevalence was similar in case and control SDR. However, lifetime MDD prevalence was significantly higher in SDR of case probands with MDD than in SDR of case probands without MDD or control SDR (31.9 versus 16.8 versus 15.4%, respectively). Conclusions: MDD prevalence was significantly higher in both FDR and SDR of case probands with MDD than in relatives of case probands without MDD or control relatives, suggesting that pediatric OCD comorbid with MDD is a complex familial syndrome. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/87090/1/20824_ftp.pd

Percutaneous Transvenous Melody Valve-in-Ring Procedure for Mitral Valve Replacement

ObjectivesThe purpose of this study was to demonstrate the feasibility of percutaneous transvenous mitral valve-in-ring (VIR) implantation using the Melody valve in an ovine model.BackgroundThe recurrence of mitral regurgitation following surgical mitral valve (MV) repair in both adult and pediatric patients remains a significant clinical problem. Mitral annuloplasty rings are commonly used in MV repair procedures and may serve as secure landing zones for percutaneous valves.MethodsFive sheep underwent surgical MV annuloplasty (24 mm, n = 2; 26 mm, n = 2; 28 mm, n = 1). Animals underwent cardiac catheterization with VIR implantation via a transfemoral venous, transatrial septal approach 1 week following surgery. Hemodynamic, angiographic, and echocardiographic data were recorded before and after VIR.ResultsVIR was technically successful and required <1 h of procedure time in all animals. Fluoroscopy demonstrated securely positioned Melody valves within the annuloplasty ring in all animals. Angiography revealed no significant MV regurgitation in 4 and moderate central MV regurgitation in the animal with the 28-mm annuloplasty. All animals demonstrated vigorous left ventricular function, no outflow tract obstruction, and no aortic valve insufficiency.ConclusionsThis study demonstrated the feasibility of a purely percutaneous approach to MV replacement in patients with preexisting annuloplasty rings. This novel approach may be of particular benefit to patients with failed repair of ischemic mitral regurgitation and in pediatric patients with complex structural heart disease

Variable Step Random Walks and Self-Similar Distributions

We study a scenario under which variable step random walks give anomalous statistics. We begin by analyzing the Martingale Central Limit Theorem to find a sufficient condition for the limit distribution to be non-Gaussian. We note that the theorem implies that the scaling index $\zeta$ is 1/2. For corresponding continuous time processes, it is shown that the probability density function $W(x;t)$ satisfies the Fokker-Planck equation. Possible forms for the diffusion coefficient are given, and related to $W(x,t)$. Finally, we show how a time-series can be used to distinguish between these variable diffusion processes and L\'evy dynamics.Comment: 13pages, 2 figure

Named Entity Recognition for Bacterial Type IV Secretion Systems

Research on specialized biological systems is often hampered by a lack of consistent terminology, especially across species. In bacterial Type IV secretion systems genes within one set of orthologs may have over a dozen different names. Classifying research publications based on biological processes, cellular components, molecular functions, and microorganism species should improve the precision and recall of literature searches allowing researchers to keep up with the exponentially growing literature, through resources such as the Pathosystems Resource Integration Center (PATRIC, patricbrc.org). We developed named entity recognition (NER) tools for four entities related to Type IV secretion systems: 1) bacteria names, 2) biological processes, 3) molecular functions, and 4) cellular components. These four entities are important to pathogenesis and virulence research but have received less attention than other entities, e.g., genes and proteins. Based on an annotated corpus, large domain terminological resources, and machine learning techniques, we developed recognizers for these entities. High accuracy rates (>80%) are achieved for bacteria, biological processes, and molecular function. Contrastive experiments highlighted the effectiveness of alternate recognition strategies; results of term extraction on contrasting document sets demonstrated the utility of these classes for identifying T4SS-related documents

Multimodal image analysis and subvalvular dynamics in ischemic mitral regurgitation

Background: The exact geometric pathogenesis of leaflet tethering in ischemic mitral regurgitation (IMR) and the relative contribution of each component of the mitral valve complex (MVC) remain largely unknown. In this study, we sought to further elucidate mitral valve (MV) leaflet remodeling and papillary muscle dynamics in an ovine model of IMR with magnetic resonance imaging (MRI) and 3-dimensional echocardiography (3DE). Methods: Multimodal imaging combining 3DE and MRI was used to analyze the MVC at baseline, 30 minutes post–myocardial infarction (MI), and 12 weeks post-MI in ovine IMR models. Advanced 3D imaging software was used to trace the MVC from each modality, and the tracings were verified against resected specimens. Results: 3DE MV remodeling was regionally heterogenous and observed primarily in the anterior leaflet, with significant increases in surface area, especially in A2 and A3. The posterior leaflet was significantly shortened in P2 and P3. Mean posteromedial papillary muscle (PMPM) volume was decreased from 1.9 ± 0.2 cm3 at baseline to 0.9 ± 0.3 cm3 at 12 weeks post-MI (P <.05). At 12 weeks post-MI, the PMPM was predominately displaced horizontally and outward along the intercommissural axis with minor apical displacement. The subvalvular contribution to tethering is a combination of unilateral movement, outward displacement, and degeneration of the PMPM. These findings have led to a proposed new framework for characterizing PMPM dynamics in IMR. Conclusions: This study provides new insights into the complex interrelated and regionally heterogenous valvular and subvalvular mechanisms involved in the geometric pathogenesis of IMR tethering