Human Rickettsial Pathogen Modulates Arthropod Organic Anion Transporting Polypeptide and Tryptophan Pathway for Its Survival in Ticks

The black-legged tick Ixodes scapularis transmits the human anaplasmosis agent, Anaplasma phagocytophilum. In this study, we show that A. phagocytophilum specifically up-regulates I. scapularis organic anion transporting polypeptide, isoatp4056 and kynurenine amino transferase (kat), a gene involved in the production of tryptophan metabolite xanthurenic acid (XA), for its survival in ticks. RNAi analysis revealed that knockdown of isoatp4056 expression had no effect on A. phagocytophilum acquisition from the murine host but affected the bacterial survival in tick cells. Knockdown of the expression of kat mRNA alone or in combination with isoatp4056 mRNA significantly affected A. phagocytophilum survival and isoatp4056 expression in tick cells. Exogenous addition of XA induces isoatp4056 expression and A. phagocytophilum burden in both tick salivary glands and tick cells. Electrophoretic mobility shift assays provide further evidence that A. phagocytophilum and XA influences isoatp4056 expression. Collectively, this study provides important novel information in understanding the interplay between molecular pathways manipulated by a rickettsial pathogen to survive in its arthropod vector

Somatic hypermutation as a generator of antinuclear antibodies in a murine model of systemic autoimmunity

Systemic lupus erythematosus (SLE) is characterized by high-avidity IgG antinuclear antibodies (ANAs) that are almost certainly products of T cell–dependent immune responses. Whether critical amino acids in the third complementarity-determining region (CDR3) of the ANA originate from V(D)J recombination or somatic hypermutation (SHM) is not known. We studied a mouse model of SLE in which all somatic mutations within ANA V regions, including those in CDR3, could be unequivocally identified. Mutation reversion analyses revealed that ANA arose predominantly from nonautoreactive B cells that diversified immunoglobulin genes via SHM. The resolution afforded by this model allowed us to demonstrate that one ANA clone was generated by SHM after a VH gene replacement event. Mutations producing arginine substitutions were frequent and arose largely (66%) from base changes in just two codons: AGC and AGT. These codons are abundant in the repertoires of mouse and human V genes. Our findings reveal the predominant role of SHM in the development of ANA and underscore the importance of self-tolerance checkpoints at the postmutational stage of B cell differentiation

Cross-seasonal effects in the American Woodcock: Conditions prior to fall migration relate to migration strategy and implications for conservation

How postbreeding habitat quality and body composition of migratory birds carry over to influence fall migration strategies and residency merits consideration when creating cross-seasonal conservation plans, especially in breeding populations that are partial migrants. We assessed the influence of postbreeding habitat quality on departure body composition and fall migration patterns in a southern New England breeding population of American Woodcock (Scolopax minor). Woodcock that overwintered near breeding areas (n = 5) had less fat upon capture in fall and used lower quality habitat during the fall than birds that eventually departed on migration (n = 17). Woodcock that departed earlier were long-distance migrants that had inhabited higher quality landscapes prior to migration, departed with less or similar fat stores, stopped over for shorter periods on migration, and arrived earlier on their more southerly wintering areas. In contrast, woodcock that departed later were short-distance migrants that had inhabited lower quality landscapes prior to migration yet stored similar or more fat upon departure, stopped over for longer periods on migration, and arrived relatively late to their more northerly wintering areas. These differences in migration strategies were evident under the same fall environmental conditions and did not appear related to individuals responding to their own condition as would be expected if they were classic condition-based carry-over effects. As such, the southern New England breeding population of woodcock is best categorized as nonfacultative partial migrants (i.e., includes residents, short-distance migrants, and long-distance migrants) that demonstrate weak connectivity between life stages; such populations are excellent for the study of the costs and benefits of migration. The stopover and wintering areas used by woodcock in the coastal mid-Atlantic states deserve conservation and management attention in order to preserve critical habitat throughout their wintering range

Mortality of Eastern Box Turtles (Terrapene c. carolina) After a Growing Season Prescribed Fire

Fire is a key natural process that has shaped ecosystem distribution and composition for hundreds of millions of years. Prescribed fire has become a common and important technique in habitat management. With its ability to alter physical and vegetative conditions, prescribed fire has the potential to change wildlife habitat characteristics in ways that benefit or harm populations of wildlife, but implications for reptiles are considered only infrequently. In May and June 2018, a prescribed burn was conducted in Rhode Island, USA. After reports of dead Eastern Box Turtles (Terrapene c. carolina), we initiated surveys in the burned area to gauge the extent of mortality and develop guidance to protect Eastern Box Turtle populations where prescribed fire is used. We found 49 dead Eastern Box Turtles across a 31.2 ha area, and based on the available evidence, we suspect that 47 of those were killed as a direct result of the prescribed fire. The post-burn mortality observed during this study is the latest among a growing list of observations of significant mortality of box turtles associated with fire, both wild and prescribed. We urge land managers to carefully consider the location, timing, and frequency of prescribed burns within the range of the Eastern Box Turtle and consider mechanical treatments as an alternative to meet habitat management goals, or prior to burning to reduce fire intensity in sensitive areas. Burning during the growing season is particularly problematic due to the high risk to box turtles active on the surface

Integrated Assessment of Behavioral and Environmental Risk Factors for Lyme Disease Infection on Block Island, Rhode Island

<div><p>Peridomestic exposure to <i>Borrelia burgdorferi</i>-infected <i>Ixodes scapularis</i> nymphs is considered the dominant means of infection with black-legged tick-borne pathogens in the eastern United States. Population level studies have detected a positive association between the density of infected nymphs and Lyme disease incidence. At a finer spatial scale within endemic communities, studies have focused on individual level risk behaviors, without accounting for differences in peridomestic nymphal density. This study simultaneously assessed the influence of peridomestic tick exposure risk and human behavior risk factors for Lyme disease infection on Block Island, Rhode Island. Tick exposure risk on Block Island properties was estimated using remotely sensed landscape metrics that strongly correlated with tick density at the individual property level. Behavioral risk factors and Lyme disease serology were assessed using a longitudinal serosurvey study. Significant factors associated with Lyme disease positive serology included one or more self-reported previous Lyme disease episodes, wearing protective clothing during outdoor activities, the average number of hours spent daily in tick habitat, the subject’s age and the density of shrub edges on the subject’s property. The best fit multivariate model included previous Lyme diagnoses and age. The strength of this association with previous Lyme disease suggests that the same sector of the population tends to be repeatedly infected. The second best multivariate model included a combination of environmental and behavioral factors, namely hours spent in vegetation, subject’s age, shrub edge density (increase risk) and wearing protective clothing (decrease risk). Our findings highlight the importance of concurrent evaluation of both environmental and behavioral factors to design interventions to reduce the risk of tick-borne infections.</p></div

Proportion of seropositive subjects living in properties with increasing shrub edge density.

<p>Residences are classified into quartiles based on increasing shrub edge density.</p

Behavioral and demographic characteristics of survey responders in relation to their serological status.

<p>Percent positive (or average) responses over the total responses for each question for behaviors and age reported by <i>B. burgdorferi</i> seropositive and seronegative participants in serological surveys between 2005 and 2011.</p><p>Use of any protective measure = use of either protective clothing, tick checking, repellent or avoiding brush.</p

Univariate models.

<p>Univariate logistic regression models of the association between human behaviors and landscape metrics and positive Lyme disease serology. Statistically significant results at p<0.05 are indicated in bold.</p