Location and appearance of dysplastic Barrett's esophagus recurrence after endoscopic eradication therapy: no additional yield from random biopsy sampling neosquamous mucosa.

BACKGROUND AND AIMS: Surveillance after complete remission of intestinal metaplasia (CRIM) is essential. Current recommendations are to sample visible lesions first, followed by random 4-quadrant biopsy sampling of the original Barrett's esophagus (BE) length. To inform post-CRIM surveillance protocols, we aimed to identify the anatomic location, appearance, and histology of BE recurrences. METHODS: We performed an analysis of 216 patients who achieved CRIM after endoscopic eradication therapy for dysplastic BE at a Barrett's Referral Unit between 2008 and 2021. The anatomic location, recurrence histology, and endoscopic appearance of dysplastic recurrences were evaluated. RESULTS: After a median of 5.5 years (interquartile range, 2.9-7.2) of follow-up after CRIM, 57 patients (26.4%) developed nondysplastic BE (NDBE) recurrence and 18 patients (8.3%) developed dysplastic recurrence. From 8158 routine surveillance biopsy samplings of normal-appearing tubular esophageal neosquamous epithelium, the yield for recurrent NDBE or dysplasia was 0%. One hundred percent of dysplastic tubular esophageal recurrences were visible and in BE islands, whereas 77.8% of gastroesophageal junction dysplastic recurrences were nonvisible. Four distinct endoscopic features suspicious for recurrent advanced dysplasia or neoplasia were identified: buried or subsquamous BE, irregular mucosal pattern, loss of vascular pattern, and nodularity or depression. CONCLUSIONS: The yield of routine surveillance biopsy sampling of normal-appearing tubular esophageal neosquamous epithelium was zero. BE islands with indistinct mucosal or loss of vascular pattern, nodularity or depression, and/or signs of buried BE should raise clinician suspicion for advanced dysplasia or neoplasia recurrence. We suggest a new surveillance biopsy sampling protocol with a focus on meticulous inspection, followed by targeted biopsy sampling of visible lesions and random 4-quadrant biopsy sampling of the gastroesophageal junction.

Near-term forecasting of companion animal tick paralysis incidence: An iterative ensemble model.

Tick paralysis resulting from bites from Ixodes holocyclus and I. cornuatus is one of the leading causes of emergency veterinary admissions for companion animals in Australia, often resulting in death if left untreated. Availability of timely information on periods of increased risk can help modulate behaviors that reduce exposures to ticks and improve awareness of owners for the need of lifesaving preventative ectoparasite treatment. Improved awareness of clinicians and pet owners about temporal changes in tick paralysis risk can be assisted by ecological forecasting frameworks that integrate environmental information into statistical time series models. Using an 11-year time series of tick paralysis cases from veterinary clinics in one of Australia's hotspots for the paralysis tick Ixodes holocyclus, we asked whether an ensemble model could accurately forecast clinical caseloads over near-term horizons. We fit a series of statistical time series (ARIMA, GARCH) and generative models (Prophet, Generalised Additive Model) using environmental variables as predictors, and then combined forecasts into a weighted ensemble to minimise prediction interval error. Our results indicate that variables related to temperature anomalies, levels of vegetation moisture and the Southern Oscillation Index can be useful for predicting tick paralysis admissions. Our model forecasted tick paralysis cases with exceptional accuracy while preserving epidemiological interpretability, outperforming a field-leading benchmark Exponential Smoothing model by reducing both point and prediction interval errors. Using online particle filtering to assimilate new observations and adjust forecast distributions when new data became available, our model adapted to changing temporal conditions and provided further reduced forecast errors. We expect our model pipeline to act as a platform for developing early warning systems that can notify clinicians and pet owners about heightened risks of environmentally driven veterinary conditions.

Primary Total Hip Arthroplasty in Patients With Ankylosing Spondylitis.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory spondyloarthropathy with hip involvement in 40% of patients. With the renewed interest in the hip-spine interplay, this study aimed to define long-term outcomes of primary total hip arthroplasty (THA) in the setting of AS. METHODS: We identified 309 hips (219 patients) with AS treated with primary THA from 1969 to 2018. Mean age was 49 years, 80% were males, and mean body mass index was 28 kg/m2. Cumulative incidences of any revision, reoperation, and dislocation were calculated utilizing a competing risk analysis. Harris Hip Scores and complications were also reported. Mean follow-up was 16 years. RESULTS: The cumulative incidence of any revision after primary THA was 2.3% at 5 years and 17.5% at 20 years. The most common reasons for revision (n = 73) were aseptic loosening (41%), osteolysis/polyethylene (PE) wear (30%, all with conventional PE), and femoral component fracture (8%). The cumulative incidence of dislocation was 1.9% at 5 years and 2.9% at 20 years. Younger age was associated with increased risk of revision (hazard ratio (HR) = 1.3, P < .01) and reoperation (HR = 1.2, P < .01), but not dislocation (HR = 0.7, P = .1). Twenty-eight hips (9%) experienced a postoperative complication not requiring reoperation. The mean Harris Hip Score improved from 51 to 76 after THA (P < .001). CONCLUSION: In this series of 309 primary THAs in patients with AS, the 20-year cumulative incidence of any revision after primary THA was 17.5%. Aseptic loosening, osteolysis/PE wear, and femoral component fracture were the most common reasons for revision. Notably, the cumulative incidence of dislocation at 20 years was only 2.9%. LEVEL OF EVIDENCE: Level IV.

Robust geographical determinants of infection prevalence and a contrasting latitudinal diversity gradient for haemosporidian parasites in Western Palearctic birds.

Identifying robust environmental predictors of infection probability is central to forecasting and mitigating the ongoing impacts of climate change on vector-borne disease threats. We applied phylogenetic hierarchical models to a data set of 2,171 Western Palearctic individual birds from 47 species to determine how climate and landscape variation influence infection probability for three genera of haemosporidian blood parasites (Haemoproteus, Leucocytozoon, and Plasmodium). Our comparative models found compelling evidence that birds in areas with higher vegetation density (captured by the normalized difference vegetation index [NDVI]) had higher likelihoods of carrying parasite infection. Magnitudes of this relationship were remarkably similar across parasite genera considering that these parasites use different arthropod vectors and are widely presumed to be epidemiologically distinct. However, we also uncovered key differences among genera that highlighted complexities in their climate responses. In particular, prevalences of Haemoproteus and Plasmodium showed strong but contrasting relationships with winter temperatures, supporting mounting evidence that winter warming is a key environmental filter impacting the dynamics of host-parasite interactions. Parasite phylogenetic community diversities demonstrated a clear but contrasting latitudinal gradient, with Haemoproteus diversity increasing towards the equator and Leucocytozoon diversity increasing towards the poles. Haemoproteus diversity also increased in regions with higher vegetation density, supporting our evidence that summer vegetation density is important for structuring the distributions of these parasites. Ongoing variation in winter temperatures and vegetation characteristics will probably have far-reaching consequences for the transmission and spread of vector-borne diseases.

Microbial associations and spatial proximity predict North American moose (Alces alces) gastrointestinal community composition.

Microbial communities are increasingly recognized as crucial for animal health. However, our understanding of how microbial communities are structured across wildlife populations is poor. Mechanisms such as interspecific associations are important in structuring free-living communities, but we still lack an understanding of how important interspecific associations are in structuring gut microbial communities in comparison with other factors such as host characteristics or spatial proximity of hosts. Here, we ask how gut microbial communities are structured in a population of North American moose Alces alces. We identify key microbial interspecific associations within the moose gut and quantify how important they are relative to key host characteristics, such as body condition, for predicting microbial community composition. We sampled gut microbial communities from 55 moose in a population experiencing decline due to a myriad of factors, including pathogens and malnutrition. We examined microbial community dynamics in this population utilizing novel graphical network models that can explicitly incorporate spatial information. We found that interspecific associations were the most important mechanism structuring gut microbial communities in moose and detected both positive and negative associations. Models only accounting for associations between microbes had higher predictive value compared to models including moose sex, evidence of previous pathogen exposure or body condition. Adding spatial information on moose location further strengthened our model and allowed us to predict microbe occurrences with ~90% accuracy. Collectively, our results suggest that microbial interspecific associations coupled with host spatial proximity are vital in shaping gut microbial communities in a large herbivore. In this case, previous pathogen exposure and moose body condition were not as important in predicting gut microbial community composition. The approach applied here can be used to quantify interspecific associations and gain a more nuanced understanding of the spatial and host factors shaping microbial communities in non-model hosts.

An inverse latitudinal gradient in infection probability and phylogenetic diversity for Leucocytozoon blood parasites in New World birds.

Geographic variation in environmental conditions as well as host traits that promote parasite transmission may impact infection rates and community assembly of vector-transmitted parasites. Identifying the ecological, environmental and historical determinants of parasite distributions and diversity is therefore necessary to understand disease outbreaks under changing environments. Here, we identified the predictors and contributions of infection probability and phylogenetic diversity of Leucocytozoon (an avian blood parasite) at site and species levels across the New World. To explore spatial patterns in infection probability and lineage diversity for Leucocytozoon parasites, we surveyed 69 bird communities from Alaska to Patagonia. Using phylogenetic Bayesian hierarchical models and high-resolution satellite remote-sensing data, we determined the relative influence of climate, landscape, geography and host phylogeny on regional parasite community assembly. Infection rates and parasite diversity exhibited considerable variation across regions in the Americas. In opposition to the latitudinal gradient hypothesis, both the diversity and prevalence of Leucocytozoon parasites decreased towards the equator. Host relatedness and traits known to promote vector exposure neither predicted infection probability nor parasite diversity. Instead, the probability of a bird being infected with Leucocytozoon increased with increasing vegetation cover (NDVI) and moisture levels (NDWI), whereas the diversity of parasite lineages decreased with increasing NDVI. Infection rates and parasite diversity also tended to be higher in cooler regions and higher latitudes. Whereas temperature partially constrains Leucocytozoon diversity and infection rates, landscape features, such as vegetation cover and water body availability, play a significant role in modulating the probability of a bird being infected. This suggests that, for Leucocytozoon, the barriers to host shifting and parasite host range expansion are jointly determined by environmental filtering and landscape, but not by host phylogeny. Our results show that integrating host traits, host ancestry, bioclimatic data and microhabitat characteristics that are important for vector reproduction are imperative to understand and predict infection prevalence and diversity of vector-transmitted parasites. Unlike other vector-transmitted diseases, our results show that Leucocytozoon diversity and prevalence will likely decrease with warming temperatures.

Definitive Resection Arthroplasty of the Knee: A Surprisingly Viable Treatment to Manage Intractable Infection in Selected Patients.

BACKGROUND: Resection arthroplasty of the hip is considered a viable option after multiple failed attempts to eradicate a prosthetic joint infection (PJI). However, much less information about resection arthroplasty of the knee is available. The goals of this study were to determine the success of infection eradication with a resection arthroplasty of the knee and subsequent functional outcomes in this group. METHODS: We retrospectively identified 25 knees (23 patients) treated with resection arthroplasty of the knee for PJI performed at a single institution between 1974 and 2016. The mean age at resection arthroplasty was 65 years. The mean body mass index was 37 kg/m2, and the mean Charleston Comorbidity Index was 5. Patients had a mean of 5 operations on the knee (mean of 3 operations for infection) before the resection arthroplasty. Failure to eradicate the infection was defined as any reoperation for infection. Clinical outcomes were assessed via ambulatory status, use of gait aids, and ongoing pain. The mean follow-up was 4 years. RESULTS: At most recent follow-up, 84% (21 of 25) of knees were free of infection. Three patients had recurrent infection within the first year, and 1 patient had a late infection at 4 years postoperatively. However, only 1 patient required a subsequent amputation. Forty-five percent were community ambulators, 35% were household ambulators, and 20% were only able to transfer. All patients required knee bracing and assistive devices. Fifteen percent of patients were using long-term narcotics. CONCLUSION: This large series demonstrates the results of selected use of resection arthroplasty as a treatment for recalcitrant periprosthetic knee infections that have failed multiple attempts to eradicate an ongoing PJI. The resection definitively solved the infection in 84% of patients. Functional results were variable but surprisingly good in some. All patients required bracing and assistive devices.

Revision Total Hip Arthroplasty in Patients With Ankylosing Spondylitis: Long-Term Results.

BACKGROUND: Ankylosing spondylitis (AS) is a common inflammatory spondyloarthropathy with hip involvement in 40% of patients. With the recent interest in the hip-spine interplay, the purpose of this study was to define the long-term outcomes of revision total hip arthroplasty (THA) in the setting of AS. METHODS: 174 hips in patients with AS treated with revision THA from 1969 to 2016 were identified. Mean age at revision THA was 53 years and 76% were male. Cumulative incidences of any re-revision, reoperation, and dislocation were calculated using a competing risk analysis. Mean follow-up was 13 years. RESULTS: The cumulative incidence of any re-revision after index revision THA was 7% at 5 years and 36% at 20 years. Cumulative incidence of any reoperation was 9% at 5 years and 38% at 20 years. Cumulative incidence of dislocation was 6% at 5 years and 8% at 20 years. Revision THAs performed with contemporary implants (2000-2016) had a lower but statistically nonsignificant cumulative incidence of any re-revision when compared with historical implants (before 2000) at 5 years (5% vs 8%), 10 years (11% vs 18%), and 15 years (11% vs 38%) (hazard ratio, 0.47; 95% confidence interval, 0.17-1.33; P = .016). CONCLUSION: In this large series of 174 revision THAs in patients with AS, the cumulative incidence of dislocation was 8% at 20 years. The 20-year cumulative incidence of any re-revision was 36%, which is similar to reported rates in patients with comparable demographic features without AS. LEVEL OF EVIDENCE: Level IV.

Climate variation influences host specificity in avian malaria parasites.

Parasites with low host specificity (e.g. infecting a large diversity of host species) are of special interest in disease ecology, as they are likely more capable of circumventing ecological or evolutionary barriers to infect new hosts than are specialist parasites. Yet for many parasites, host specificity is not fixed and can vary in response to environmental conditions. Using data on host associations for avian malaria parasites (Apicomplexa: Haemosporida), we develop a hierarchical model that quantifies this environmental dependency by partitioning host specificity variation into region- and parasite-level effects. Parasites were generally phylogenetic host specialists, infecting phylogenetically clustered subsets of available avian hosts. However, the magnitude of this specialisation varied biogeographically, with parasites exhibiting higher host specificity in regions with more pronounced rainfall seasonality and wetter dry seasons. Recognising the environmental dependency of parasite specialisation can provide useful leverage for improving predictions of infection risk in response to global climate change.

Unravelling changing interspecific interactions across environmental gradients using Markov random fields.

Inferring interactions between co-occurring species is key to identify processes governing community assembly. Incorporating interspecific interactions in predictive models is common in ecology, yet most methods do not adequately account for indirect interactions (where an interaction between two species is masked by their shared interactions with a third) and assume interactions do not vary along environmental gradients. Markov random fields (MRF) overcome these limitations by estimating interspecific interactions, while controlling for indirect interactions, from multispecies occurrence data. We illustrate the utility of MRFs for ecologists interested in interspecific interactions, and demonstrate how covariates can be included (a set of models known as Conditional Random Fields, CRF) to infer how interactions vary along environmental gradients. We apply CRFs to two data sets of presence-absence data. The first illustrates how blood parasite (Haemoproteus, Plasmodium, and nematode microfilaria spp.) co-infection probabilities covary with relative abundance of their avian hosts. The second shows that co-occurrences between mosquito larvae and predatory insects vary along water temperature gradients. Other applications are discussed, including the potential to identify replacement or shifting impacts of highly connected species along climate or land-use gradients. We provide tools for building CRFs and plotting/interpreting results as an R package.

Global spread of helminth parasites at the human-domestic animal-wildlife interface.

Changes in species distributions open novel parasite transmission routes at the human-wildlife interface, yet the strength of biotic and biogeographical factors that prevent or facilitate parasite host shifting are not well understood. We investigated global patterns of helminth parasite (Nematoda, Cestoda, Trematoda) sharing between mammalian wildlife species and domestic mammal hosts (including humans) using >24,000 unique country-level records of host-parasite associations. We used hierarchical modelling and species trait data to determine possible drivers of the level of parasite sharing between wildlife species and either humans or domestic animal hosts. We found the diet of wildlife species to be a strong predictor of levels of helminth parasite sharing with humans and domestic animals, followed by a moderate effect of zoogeographical region and minor effects of species' habitat and climatic niches. Combining model predictions with the distribution and ecological profile data of wildlife species, we projected global risk maps that uncovered strikingly similar patterns of wildlife parasite sharing across geographical areas for the different domestic host species (including humans). These similarities are largely explained by the fact that widespread parasites are commonly recorded infecting several domestic species. If the dietary profile and position in the trophic chain of a wildlife species largely drives its level of helminth parasite sharing with humans/domestic animals, future range shifts of host species that result in novel trophic interactions may likely increase parasite host shifting and have important ramifications for human and animal health.

Airborne geographical dispersal of Q fever from livestock holdings to human communities: a systematic review and critical appraisal of evidence.

BACKGROUND: Q fever is a zoonotic disease caused by Coxiella burnetii. This bacterium survives harsh conditions and attaches to dust, suggesting environmental dispersal is a risk factor for outbreaks. Spatial epidemiology studies collating evidence on Q fever geographical contamination gradients are needed, as human cases without occupational exposure are increasing worldwide. METHODS: We used a systematic literature search to assess the role of distance from ruminant holdings as a risk factor for human Q fever outbreaks. We also collated evidence for other putative drivers of C. burnetii geographical dispersal. RESULTS: In all documented outbreaks, infective sheep or goats, not cattle, was the likely source. Evidence suggests a prominent role of airborne dispersal; Coxiella burnetii travels up to 18 km on gale force winds. In rural areas, highest infection risk occurs within 5 km of sources. Urban outbreaks generally occur over smaller distances, though evidence on attack rate gradients is limited. Wind speed / direction, spreading of animal products, and stocking density may all contribute to C. burnetii environmental gradients. CONCLUSIONS: Q fever environmental gradients depend on urbanization level, ruminant species, stocking density and wind speed. While more research is needed, evidence suggests that residential exclusion zones around holdings may be inadequate to contain this zoonotic disease, and should be species-specific.

Assessing glenosphere position: superior approach versus deltopectoral for reverse shoulder arthroplasty.

BACKGROUND: The anterosuperior (AS) approach for reverse total shoulder arthroplasty (RTSA) has been reported as a risk factor for baseplate malposition because of potential difficulty in glenoid exposure. The objective of this study was to compare glenoid baseplate position between the AS and deltopectoral (DP) approaches in relation to the surgeon's experience and to evaluate the effect of placement on clinical outcomes. METHODS: There were 109 shoulders that underwent RTSA for cuff tear arthropathy or osteoarthritis with cuff tearing by a single surgeon. The AS approach was used in 87 shoulders. Clinical, radiographic, and functional outcomes were assessed for all patients with a minimum of 2 years of follow-up. Initial postoperative radiographs of all 109 shoulders were assessed for baseplate positioning. RESULTS: The mean change in glenoid inclination was 3.0° inferior with the AS approach and 2.5° inferior with the DP approach (P = .68). Pain scores (P = .14), range of motion, and American Shoulder and Elbow Surgeons scores (P = .16) improved in both groups, without a difference between approach. Scapular notching was noted in 68.5% of AS shoulders and 72.4% of DP shoulders (P = .78). Over time, there was a trend to place the glenoid baseplate more caudal with less inferior tilt. DISCUSSION AND CONCLUSION: Both approaches produce similar baseplate position, clinical outcomes, and rates of scapular notching when they are used for RTSA. Attempts to inferiorize the glenoid baseplate through the AS approach may increase the risk of superior inclination.

Integrating phylogenetic and ecological distances reveals new insights into parasite host specificity.

The range of hosts a pathogen infects (host specificity) is a key element of disease risk that may be influenced by both shared phylogenetic history and shared ecological attributes of prospective hosts. Phylospecificity indices quantify host specificity in terms of host relatedness, but can fail to capture ecological attributes that increase susceptibility. For instance, similarity in habitat niche may expose phylogenetically unrelated host species to similar pathogen assemblages. Using a recently proposed method that integrates multiple distances, we assess the relative contributions of host phylogenetic and functional distances to pathogen host specificity (functional-phylogenetic host specificity). We apply this index to a data set of avian malaria parasite (Plasmodium and Haemoproteus spp.) infections from Melanesian birds to show that multihost parasites generally use hosts that are closely related, not hosts with similar habitat niches. We also show that host community phylogenetic ß-diversity (Pßd) predicts parasite Pßd and that individual host species carry phylogenetically clustered Haemoproteus parasite assemblages. Our findings were robust to phylogenetic uncertainty, and suggest that phylogenetic ancestry of both hosts and parasites plays important roles in driving avian malaria host specificity and community assembly. However, restricting host specificity analyses to either recent or historical timescales identified notable exceptions, including a 'habitat specialist' parasite that infects a diversity of unrelated host species with similar habitat niches. This work highlights that integrating ecological and phylogenetic distances provides a powerful approach to better understand drivers of pathogen host specificity and community assembly.

What Are the Complications, Survival, and Outcomes After Revision to Reverse Shoulder Arthroplasty in Patients Older Than 80 Years?

BACKGROUND: By the time patients with a failed shoulder arthroplasty require revision surgery, a substantial number are older than 80 years. The risk of complications of revision arthroplasty in this elderly population is largely unknown and needs to be considered when contemplating whether these patients are too frail for revision surgery. QUESTIONS/PURPOSES: (1) What are the 90-day medical and surgical complications after revision to reverse shoulder arthroplasty (RSA) in patients older than 80 years? (2) What are the 2- and 5-year survival rates after revision? (3) Was there an improvement in pain at rest or with activity, range of motion (ROM), and strength after revision surgery? METHODS: Between 2004 and 2013, 38 patients who were older than 80 years (84 ± 3 years) underwent revision surgery to a RSA. Of those, five were lost to followup before 2 years, and two had died within 2 years of revision surgery, leaving 31 for analysis of our survivorship, pain, ROM, and strength endpoints at a minimum of 2 years or until revision surgery had occurred (mean, 28 months; range, 1-77 months); all 38 patients were included for purposes of evaluating medical and surgical complications at 90 days. During the period in question, our general indication for using RSA included failure of previous shoulder arthroplasty because of instability, glenoid loosening with bone loss, or rotator cuff insufficiency. The indication for revision to RSA did not change during the study period. The index procedure (revision to RSA at the age of 80 years or older) was the first revision arthroplasty in 33 (87%) patients and the second in five (13%) patients. We tallied 90-day medical and surgical complications by performing a retrospective chart and institutional joint registry review. The cumulative incidence of implant loosening (implant migration or tilting, or complete radiolucent lines present) and revision surgery was calculated at 2 and 5 years using competing risk of death method. Pain levels at rest or with activity (rated in a 1 to 5 Likert-type scale) were collected through a retrospective chart review and values before and after surgery were compared. RESULTS: Medical complications occurred in three of 38 (8%) patients and surgical complications occurred in five of 38 (13%) patients. The 90-day mortality was 3% (one of 38 patients), and the total mortality was 26% (10 of 38 patients). The cumulative incidence of revision was 11% (95% CI, 0%-20%) at 2 years and 16% (95% CI, 1%-30%) at 5 years; the cumulative incidence of loosening was 8% (95% CI, 0%-20%) at 2 years and 16% (95% CI, 1%-30%) at 5 years. Pain at rest or with activity improved from pre- to postoperation (preoperative: median, 4 [range, 2-5]; postoperative: median, 1 [range, 1-4]; median difference: -2, 95% CI -3 to 0; p < 0.000). The active ROM improved during the preoperative compared with postoperative periods: mean ± SD forward flexion of 52° ± 40° to 109° ± 44°, respectively (mean difference: 56; 95% CI, 40-72; p < 0.000), and mean ± SD external rotation of 15° ± 22° to 31° ± 21°, respectively (mean difference: 16; 95% CI, 8-25; p < 0.000). CONCLUSIONS: Age should not be used as a reason to not consider revision surgery to RSA in patients older than 80 years. Further studies with a prospective design, larger sample size, investigating risk factors for complications or poor outcome, and incorporation of functional scores are required. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Automodification switches PARP-1 function from chromatin architectural protein to histone chaperone.

Poly [ADP-ribose] polymerase 1 (PARP-1) is a highly abundant chromatin-associated enzyme. It catalyzes the NAD(+)-dependent polymerization of long chains of poly-ADP ribose (PAR) onto itself in response to DNA damage and other cues. More recently, the enzymatic activity of PARP-1 has also been implicated in the regulation of gene expression. The molecular basis for the functional switch from chromatin architectural protein to transcription factor and DNA damage responder, triggered by PARP-1 automodification, is unknown. Here, we show that unmodified PARP-1 engages in at least two high-affinity binding modes with chromatin, one of which does not involve free DNA ends, consistent with its role as a chromatin architectural protein. Automodification reduces PARP-1 affinity for intact chromatin but not for nucleosomes with exposed DNA ends. Automodified (AM) PARP-1 has the ability to sequester histones (both in vitro and in cells) and to assemble nucleosomes efficiently in vitro. This unanticipated nucleosome assembly activity of AM-PARP-1, coupled with the fast turnover of the modification, suggests a model in which DNA damage or transcription events trigger transient histone chaperone activity.

Co-infections and environmental conditions drive the distributions of blood parasites in wild birds.

Experimental work increasingly suggests that non-random pathogen associations can affect the spread or severity of disease. Yet due to difficulties distinguishing and interpreting co-infections, evidence for the presence and directionality of pathogen co-occurrences in wildlife is rudimentary. We provide empirical evidence for pathogen co-occurrences by analysing infection matrices for avian malaria (Haemoproteus and Plasmodium spp.) and parasitic filarial nematodes (microfilariae) in wild birds (New Caledonian Zosterops spp.). Using visual and genus-specific molecular parasite screening, we identified high levels of co-infections that would have been missed using PCR alone. Avian malaria lineages were assigned to species level using morphological descriptions. We estimated parasite co-occurrence probabilities, while accounting for environmental predictors, in a hierarchical multivariate logistic regression. Co-infections occurred in 36% of infected birds. We identified both positively and negatively correlated parasite co-occurrence probabilities when accounting for host, habitat and island effects. Two of three pairwise avian malaria co-occurrences were strongly negative, despite each malaria parasite occurring across all islands and habitats. Birds with microfilariae had elevated heterophil to lymphocyte ratios and were all co-infected with avian malaria, consistent with evidence that host immune modulation by parasitic nematodes facilitates malaria co-infections. Importantly, co-occurrence patterns with microfilariae varied in direction among avian malaria species; two malaria parasites correlated positively but a third correlated negatively with microfilariae. We show that wildlife co-infections are frequent, possibly affecting infection rates through competition or facilitation. We argue that combining multiple diagnostic screening methods with multivariate logistic regression offers a platform to disentangle impacts of environmental factors and parasite co-occurrences on wildlife disease.

Why fly the extra mile? Using stress biomarkers to assess wintering habitat quality in migratory shorebirds.

Migratory birds make decisions about how far to travel based on cost-benefit trade-offs. However, in many cases the net effect of these trade-offs is unclear. We sought to address this question by measuring feather corticosterone (CORTf), leucocyte profile, avian malaria parasite prevalence and estimating fueling rates in three spatially segregated wintering populations of the migratory shorebird ruddy turnstone Arenaria interpres during their stay in the winter habitat. These birds fly from the high-Arctic breeding ground to Australia, but differ in that some decide to end their migration early (Broome, Western Australia), whereas others travel further to either South Australia or Tasmania. We hypothesized that the extra costs in birds migrating greater distances and overwintering in colder climates would be offset by benefits when reaching their destination. This would be evidenced by lower stress biomarkers in populations that travel further, owing to the expected benefits of greater resources and improved vitality. We show that avian malaria prevalence and physiological stress levels were lower in birds flying to South Australia and Tasmania than those overwintering in Broome. Furthermore, our modeling predicts that birds in the southernmost locations enjoy higher fueling rates. Our data are consistent with the interpretation that birds occupying more costly wintering locations in terms of higher migratory flight and thermoregulatory costs are compensated by better feeding conditions and lower blood parasite infections, which facilitates timely and speedy migration back to the breeding ground. These data contribute to our understanding of cost-benefit trade-offs in the decision making underlying migratory behaviour.

Differences in host species relationships and biogeographic influences produce contrasting patterns of prevalence, community composition and genetic structure in two genera of avian malaria parasites in southern Melanesia.

Host-parasite interactions have the potential to influence broadscale ecological and evolutionary processes, levels of endemism, divergence patterns and distributions in host populations. Understanding the mechanisms involved requires identification of the factors that shape parasite distribution and prevalence. A lack of comparative information on community-level host-parasite associations limits our understanding of the role of parasites in host population divergence processes. Avian malaria (haemosporidian) parasites in bird communities offer a tractable model system to examine the potential for pathogens to influence evolutionary processes in natural host populations. Using cytochrome b variation, we characterized phylogenetic diversity and prevalence of two genera of avian haemosporidian parasites, Plasmodium and Haemoproteus, and analysed biogeographic patterns of lineages across islands and avian hosts, in southern Melanesian bird communities to identify factors that explain patterns of infection. Plasmodium spp. displayed isolation-by-distance effects, a significant amount of genetic variation distributed among islands but insignificant amounts among host species and families, and strong local island effects with respect to prevalence. Haemoproteus spp. did not display isolation-by-distance patterns, showed marked structuring of genetic variation among avian host species and families, and significant host species prevalence patterns. These differences suggest that Plasmodium spp. infection patterns were shaped by geography and the abiotic environment, whereas Haemoproteus spp. infection patterns were shaped predominantly by host associations. Heterogeneity in the complement and prevalence of parasite lineages infecting local bird communities likely exposes host species to a mosaic of spatially divergent disease selection pressures across their naturally fragmented distributions in southern Melanesia. Host associations for Haemoproteus spp. indicate a capacity for the formation of locally co-adapted host-parasite relationships, a feature that may limit intraspecific gene flow or range expansions of closely related host species.

Molecular and morphological characterization of Haemoproteus (Parahaemoproteus) ptilotis, a parasite infecting Australian honeyeaters (Meliphagidae), with remarks on prevalence and potential cryptic speciation.

Avian Haemoproteus (Haemosporida) parasites occur in birds on all continents apart from Antarctica. Molecular screening techniques have uncovered previously unforeseen levels of Haemoproteus lineage diversity; however, fewer than 20% of genetic parasite lineages have been linked to morphological descriptions. The process of linking morphological descriptions to DNA barcodes for Haemoproteus spp. is important for the study of host-parasite interactions and the potential for cryptic speciation. Here, we describe cytochrome-b barcodes and morphological diagnostics for the identification of Haemoproteus (Parahaemoproteus) ptilotis, a systematically confusing parasite found in Australian honeyeaters (family Meliphagidae). We characterised infections from the original type host (Lichenostomus chrysops; Family Meliphagidae) as well as from four co-occurring meliphagid species in southeast Queensland, Australia, to investigate intraspecific variation in morphology and lineage identity. We recorded eight lineages that grouped into a well-supported monophyletic group, supporting the linkage of the described lineages to H. ptilotis. However, comparisons of diagnostics between the type host and co-occurring meliphagid hosts revealed high genetic diversity and variable morphology that could be indicative of cryptic speciation. This study highlights that morphological descriptions alongside molecular characterisation remain crucial if we are to gain an understanding of the true diversity and host specificity of protozoan parasites in Australia and elsewhere.