Seed dispersal by pulp consumers, not ‘‘legitimate’’ seed dispersers, increases Guettarda viburnoides population growth

We examined the effect of seed dispersal by Purplish Jays (Cyanocorax cyanomelas; pulp consumers) and the Chestnut-eared Araçari (Pteroglossus castanotis; legitimate seed dispersers) on population growth of the small tree Guettarda viburnoides (Rubiaceae) in northeastern Bolivian savannas. Because each bird species differs with respect to feeding and post-feeding behavior, we hypothesized that seed dispersal by each species will contribute differently to the rate of increase of G. viburnoides, but that seed dispersal by either species will increase population growth when compared to a scenario with no seed dispersal. To examine the effects of individual dispersers on the future population size of G. viburnoides, we projected population growth rate using demographic models for G. viburnoides that explicitly incorporate data on quantitative and qualitative aspects of seed dispersal by each frugivore species. Our model suggests that seed dispersal by C. cyanomelas leads to positive population growth of G. viburnoides, whereas seed dispersal by P. castanotis has a detrimental effect on the population growth of this species. To our knowledge, this is the first study to report negative effects of a legitimate seed disperser on the population dynamics of the plant it consumes. Our results stress the importance of incorporating frugivore effects into population projection matrices, to allow a comprehensive analysis of the effectiveness of different dispersers for plant population dynamics

Intracanopy adjustment of leaf-level thermal tolerance is associated with microclimatic variation across the canopy of a desert tree (\u3ci\u3eAcacia papyrocarpa\u3c/i\u3e)

Tree crowns are spatially heterogeneous, sometimes resulting in significant variation in microclimate across the canopy, particularly with respect to temperature. Yet it is not known whether such localised temperature variation equates to intracanopy variation in leaf-level physiological thermal tolerance. Here, we studied whether microclimate variation across the canopy of a dominant desert tree equated to localised variation in leaf thermal thresholds (T50) among four canopy positions: upper south, upper north, lower south, lower north. Principal component analysis was used to generate a composite climatic stress variable (CSTRESS) from canopy temperature, vapour pressure deficit, and relative humidity. We also determined the average number of days that maximum temperatures exceeded the air temperature equating to this species’ critical threshold of 49 °C (AT49). To estimate how closely leaf temperatures track ambient temperature, we predicted the thermal time constant (τ) for leaves at each canopy position. We found that CSTRESS and AT49 were significantly greater in lower and north-facing positions in the canopy. Differences in wind speed with height resulted in significantly longer predicted τ for leaves positioned at lower, north-facing positions. Variation in these drivers was correlated with significantly higher T50 for leaves in these more environmentally stressful canopy positions. Our findings suggest that this species may optimise resources to protect against thermal damage at a whole-plant level. They also indicate that, particularly in desert environments with steep intracanopy microclimatic gradients, whole-plant carbon models could substantially under- or overestimate productivity under heat stress, depending on where in the canopy T50 is measured

Depression And Anxiety In Patients With Juvenile Idiopathic Arthritis: Current Insights And Impact On Quality Of Life, A Systematic Review

Depression and anxiety are prevalent in children with rheumatologic diseases, including juvenile idiopathic arthritis (JIA). However, prevalence rates and the relationship with disease outcomes, including quality of life are conflicting in the early literature. To review the current literature, determine gaps in our knowledge, and identify areas in need of further investigation, we conducted a systematic review of studies examining depression and anxiety symptoms among children with JIA and the impact these symptoms may have on disease outcomes and quality of life. Six electronic databases were searched up until January 2019. Of 799 potential articles, 60 articles were included with the main focus on 28 articles from 2009 to 2019, to concentrate on the most current evidence. We found that JIA patients experience symptoms of depression and anxiety similar to other childhood chronic diseases and at higher rates than in healthy children. Patients who experience these symptoms have worse quality of life, with some evidence pointing to depression and anxiety symptoms having a greater impact on quality of life than other disease features, such as active joint count. Family members of JIA patients experience high rates of anxiety and depression symptoms which may impact their child’s mental health and pain symptoms related to JIA. Conflicting reports of associations between depression/anxiety symptoms and disease features/disease outcomes and a paucity of longitudinal studies investigating the impact of treatment on mental health symptoms indicate areas in need of further research to effectively identify patients at greatest risk of depression and anxiety and to better understand how to treat and prevent these symptoms in youth with JIA. Family mental health should also be considered in investigations concerning mental health and disease outcomes of children with JIA

Metabolome-Informed Microbiome Analysis Refines Metadata Classifications and Reveals Unexpected Medication Transfer in Captive Cheetahs.

Even high-quality collection and reporting of study metadata in microbiome studies can lead to various forms of inadvertently missing or mischaracterized information that can alter the interpretation or outcome of the studies, especially with nonmodel organisms. Metabolomic profiling of fecal microbiome samples can provide empirical insight into unanticipated confounding factors that are not possible to obtain even from detailed care records. We illustrate this point using data from cheetahs from the San Diego Zoo Safari Park. The metabolomic characterization indicated that one cheetah had to be moved from the non-antibiotic-exposed group to the antibiotic-exposed group. The detection of the antibiotic in this second cheetah was likely due to grooming interactions with the cheetah that was administered antibiotics. Similarly, because transit time for stool is variable, fecal samples within the first few days of antibiotic prescription do not all contain detected antibiotics, and the microbiome is not yet affected. These insights significantly altered the way the samples were grouped for analysis (antibiotic versus no antibiotic) and the subsequent understanding of the effect of the antibiotics on the cheetah microbiome. Metabolomics also revealed information about numerous other medications and provided unexpected dietary insights that in turn improved our understanding of the molecular patterns on the impact on the community microbial structure. These results suggest that untargeted metabolomic data provide empirical evidence to correct records and aid in the monitoring of the health of nonmodel organisms in captivity, although we also expect that these methods may be appropriate for other social animals, such as cats.IMPORTANCE Metabolome-informed analyses can enhance omics studies by enabling the correct partitioning of samples by identifying hidden confounders inadvertently misrepresented or omitted from carefully curated metadata. We demonstrate here the utility of metabolomics in a study characterizing the microbiome associated with liver disease in cheetahs. Metabolome-informed reinterpretation of metagenome and metabolome profiles factored in an unexpected transfer of antibiotics, preventing misinterpretation of the data. Our work suggests that untargeted metabolomics can be used to verify, augment, and correct sample metadata to support improved grouping of sample data for microbiome analyses, here for nonmodel organisms in captivity. However, the techniques also suggest a path forward for correcting clinical information in microbiome studies more broadly to enable higher-precision analyses

Transitions between Mild Cognitive Impairment, Dementia, and Mortality:The Importance of Olfaction

BackgroundThe existing literature suggests that impaired olfaction may be an early marker for cognitive decline. Tracking the earliest stages of the progression to dementia is paramount, and yet the importance of olfactory ability throughout cognitive states and death remains unclear.MethodsDrawing data from the Rush Memory and Aging Project (N = 1 501; 74% female), olfactory ability was assessed using the Brief Smell Identification Test (range = 0-16), while cognitive states (unimpaired, mild cognitive impairment [MCI], and dementia) were determined using a 3-step neuropsychological diagnostic protocol at up to 15 annual occasions. Multistate survival models simultaneously estimated the association of olfactory ability on transitions through cognitive states and death, while multinomial regression models estimated cognitively unimpaired and total life expectancies.ResultsHigher olfactory scores were associated with a reduced risk of transitioning from unimpaired cognition to MCI (hazard ratio [HR] = 0.86, 95% confidence interval [CI] = 0.82-0.88) and from MCI to dementia (HR = 0.89, 95% CI = 0.86-0.93), indicating that 1-unit increase in olfactory scores was associated with an approximate 14% and 11% reduction in risk, respectively. Additionally, higher olfactory scores were associated with a greater likelihood of transitioning backward from MCI to unimpaired cognition (HR = 1.07, 95% CI = 1.02-1.12). Furthermore, higher baseline olfactory scores were associated with more years of longevity without cognitive impairment. However, olfaction was not associated with the transition to death when accounting for transitions through cognitive states.ConclusionsFindings suggest that higher olfactory identification scores are associated with a decreased risk of transitioning to impaired cognitive states and that associations between olfaction and mortality may occur primarily through the pathway of neurodegeneration

Pediatric SLE hospitalization Personal non-commercial use only

ABSTRACT. Objective. In the setting of recent healthcare advances and emphasis on reduced spending, we aimed to characterize US trends in inpatient healthcare use and mortality for pediatric systemic lupus erythematosus (SLE). Methods. We performed a retrospective, serial, cross-sectional analysis of the national Kids' Inpatient Database (for 2000, 2003, 2006, and 2009). We identified patients with SLE aged 2 to 21 years using an International Classification of Diseases, 9th revision (ICD-9) code of 710.0 listed as a discharge diagnosis. Using sampling weights, we estimated trends in hospitalization, inpatient mortality, procedure rates, and length of stay (LOS). We analyzed patient and hospital-specific risk factors for mortality and LOS, and compared those outcomes to those without SLE. Results. We identified 26,903 estimated pediatric SLE hospitalizations. The hospitalization rate of 8.6 (95% CI 7.6-9.6) per 100,000 population and mean LOS of 5.9 days (95% CI 5.6-6.2) were stable over time. We found a significant downward trend in mortality, decreasing from 1% to 0.6% (p = 0.04), which paralleled a less pronounced trend for those without SLE. The rate of dialysis, blood transfusions, and vascular catheterization procedures increased. Patients with SLE nephritis and non-white race were at risk for increased healthcare use and death. Conclusion. Pediatric SLE hospitalization rate and LOS remained stable, but inpatient mortality decreased as the rate of common therapeutic procedures increased. More research is needed to understand the drivers of these relationships

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Observational and Dynamical Characterization of Main-Belt Comet P/2010 R2 (La Sagra)

We present observations of comet-like main-belt object P/2010 R2 (La Sagra) obtained by Pan-STARRS 1 and the Faulkes Telescope-North on Haleakala in Hawaii, the University of Hawaii 2.2 m, Gemini-North, and Keck I telescopes on Mauna Kea, the Danish 1.54 m telescope at La Silla, and the Isaac Newton Telescope on La Palma. An antisolar dust tail is observed from August 2010 through February 2011, while a dust trail aligned with the object's orbit plane is also observed from December 2010 through August 2011. Assuming typical phase darkening behavior, P/La Sagra is seen to increase in brightness by >1 mag between August 2010 and December 2010, suggesting that dust production is ongoing over this period. These results strongly suggest that the observed activity is cometary in nature (i.e., driven by the sublimation of volatile material), and that P/La Sagra is therefore the most recent main-belt comet to be discovered. We find an approximate absolute magnitude for the nucleus of H_R=17.9+/-0.2 mag, corresponding to a nucleus radius of ~0.7 km, assuming an albedo of p=0.05. Using optical spectroscopy, we find no evidence of sublimation products (i.e., gas emission), finding an upper limit CN production rate of Q_CN<6x10^23 mol/s, from which we infer an H2O production rate of Q_H2O<10^26 mol/s. Numerical simulations indicate that P/La Sagra is dynamically stable for >100 Myr, suggesting that it is likely native to its current location and that its composition is likely representative of other objects in the same region of the main belt, though the relatively close proximity of the 13:6 mean-motion resonance with Jupiter and the (3,-2,-1) three-body mean-motion resonance with Jupiter and Saturn mean that dynamical instability on larger timescales cannot be ruled out.Comment: 23 pages, 13 figures, accepted for publication in A

Fungal iron availability during deep seated candidiasis is defined by a complex interplay involving systemic and local events

Peer reviewedPublisher PD

A Model for Rigorously Applying the Exploration, Preparation, Implementation, Sustainment (EPIS) Framework in the Design and Measurement of a Large Scale Collaborative Multi-Site Study

Background This paper describes the means by which a United States National Institute on Drug Abuse (NIDA)-funded cooperative, Juvenile Justice-Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), utilized an established implementation science framework in conducting a multi-site, multi-research center implementation intervention initiative. The initiative aimed to bolster the ability of juvenile justice agencies to address unmet client needs related to substance use while enhancing inter-organizational relationships between juvenile justice and local behavioral health partners. Methods The EPIS (Exploration, Preparation, Implementation, Sustainment) framework was selected and utilized as the guiding model from inception through project completion; including the mapping of implementation strategies to EPIS stages, articulation of research questions, and selection, content, and timing of measurement protocols. Among other key developments, the project led to a reconceptualization of its governing implementation science framework into cyclical form as the EPIS Wheel. The EPIS Wheel is more consistent with rapid-cycle testing principles and permits researchers to track both progressive and recursive movement through EPIS. Moreover, because this randomized controlled trial was predicated on a bundled strategy method, JJ-TRIALS was designed to rigorously test progress through the EPIS stages as promoted by facilitation of data-driven decision making principles. The project extended EPIS by (1) elucidating the role and nature of recursive activity in promoting change (yielding the circular EPIS Wheel), (2) by expanding the applicability of the EPIS framework beyond a single evidence-based practice (EBP) to address varying process improvement efforts (representing varying EBPs), and (3) by disentangling outcome measures of progression through EPIS stages from the a priori established study timeline. Discussion The utilization of EPIS in JJ-TRIALS provides a model for practical and applied use of implementation frameworks in real-world settings that span outer service system and inner organizational contexts in improving care for vulnerable populations. Trial registration NCT02672150. Retrospectively registered on 22 January 2016