Search for: All records

Abstract During recent decades, pathogens that originated in bats have become an increasing public health concern. A major challenge is to identify how those pathogens spill over into human populations to generate a pandemic threat 1 . Many correlational studies associate spillover with changes in land use or other anthropogenic stressors 2,3 , although the mechanisms underlying the observed correlations have not been identified 4 . One limitation is the lack of spatially and temporally explicit data on multiple spillovers, and on the connections among spillovers, reservoir host ecology and behaviour and viral dynamics. We present 25 years of data on land-use change, bat behaviour and spillover of Hendra virus from Pteropodid bats to horses in subtropical Australia. These data show that bats are responding to environmental change by persistently adopting behaviours that were previously transient responses to nutritional stress. Interactions between land-use change and climate now lead to persistent bat residency in agricultural areas, where periodic food shortages drive clusters of spillovers. Pulses of winter flowering of trees in remnant forests appeared to prevent spillover. We developed integrative Bayesian network models based on these phenomena that accurately predicted the presence or absence of clusters of spillovers in each ofmore »the 25 years. Our long-term study identifies the mechanistic connections between habitat loss, climate and increased spillover risk. It provides a framework for examining causes of bat virus spillover and for developing ecological countermeasures to prevent pandemics.« less

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that affects the viability of upper and lower motor neurons. Current options for treatment are limited, necessitating deeper understanding of the mechanisms underlying ALS pathogenesis. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a six-transmembrane protein that acts on the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers some proteins to the membrane. GDE2 is required for the survival of spinal motor neurons but whether GDE2 neuroprotective activity is disrupted in ALS is not known. We utilized a combination of mouse models and patient post-mortem samples to evaluate GDE2 functionality in ALS. Haplogenetic reduction of GDE2 exacerbated motor neuron degeneration and loss in SOD1 G93A mice but not in control SOD1 WT transgenic animals, indicating that GDE2 neuroprotective function is diminished in the context of SOD1 G93A . In tissue samples from patients with ALS, total levels of GDE2 protein were equivalent to healthy controls; however, membrane levels of GDE2 were substantially reduced. Indeed, GDE2 was found to aberrantly accumulate in intracellular compartments of ALS motor cortex, consistent with a disruption of GDE2 function at the cell surface. Supporting the impairment of GDE2 activity in ALS, tandem-mass-tag mass spectrometry revealedmore »a pronounced reduction of GPI-anchored proteins released into the CSF of patients with ALS compared with control patients. Taken together, this study provides cellular and biochemical evidence that GDE2 distribution and activity is disrupted in ALS, supporting the notion that the failure of GDE2-dependent neuroprotective pathways contributes to neurodegeneration and motor neuron loss in disease. These observations highlight the dysregulation of GPI-anchored protein pathways as candidate mediators of disease onset and progression and accordingly, provide new insight into the mechanisms underlying ALS pathogenesis.« less

Mucin proteins provide mechanistic insights into how genes can evolve to gain novel functions.

Abstract Perinatal infection with Streptococcus agalactiae , or Group B Streptococcus (GBS), is associated with preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS with macrophages, essential sentinel immune cells that defend the gravid reproductive tract. Transcriptional analyses of GBS-macrophage co-cultures reveal enhanced expression of a gene encoding a putative metal resistance determinant, cadD . Deletion of cadD reduces GBS survival in macrophages, metal efflux, and resistance to metal toxicity. In a mouse model of ascending infection during pregnancy, the ΔcadD strain displays attenuated bacterial burden, inflammation, and cytokine production in gestational tissues. Furthermore, depletion of host macrophages alters cytokine expression and decreases GBS invasion in a cadD -dependent fashion. Our results indicate that GBS cadD plays an important role in metal detoxification, which promotes immune evasion and bacterial proliferation in the pregnant host.

One critical step in the challenging process of curricular reform is determining how closely a curriculum aligns with national recommendations. Here, we examine the alignment of teaching, assessment, and student experience in undergraduate biology courses with the Vision and Change core competency recommendations. We applied the intended–enacted–experienced curriculum model to obtain a more complete, multiperspective view of the curriculum. First, we developed and piloted the BioSkills Curriculum Survey with more than 100 biology instructors across five institutions. Using multilevel logistic regression modeling of the survey data, we found that instructors were equally likely to report teaching all competencies; however, they reported assessing some competencies more than others. After adding course characteristics to our model, we found that the likelihood of teaching certain competencies depended on course type. Next, we analyzed class materials and student perceptions of instruction in 10 biology courses in one department. Within this smaller sample, we found that instructors messaged a narrower range of competency learning outcomes on their syllabi than they reported teaching on the survey. Finally, modeling revealed that inclusion of an outcome on assessments, but not syllabi, increased the likelihood that students and their instructor agreed whether it was taught.

The black flying fox ( Pteropus alecto ) is a natural reservoir for Hendra virus, a paramyxovirus that causes fatal infections in humans and horses in Australia. Increased excretion of Hendra virus by flying foxes has been hypothesized to be associated with physiological or energetic stress in the reservoir hosts. The objective of this study was to explore the leukocyte profiles of wild-caught P . alecto , with a focus on describing the morphology of each cell type to facilitate identification for clinical purposes and future virus spillover research. To this end, we have created an atlas of images displaying the commonly observed morphological variations across each cell type. We provide quantitative and morphological information regarding the leukocyte profiles in bats captured at two roost sites located in Redcliffe and Toowoomba, Queensland, Australia, over the course of two years. We examined the morphology of leukocytes, platelets, and erythrocytes of P . alecto using cytochemical staining and characterization of blood films through light microscopy. Leukocyte profiles were broadly consistent with previous studies of P . alecto and other Pteropus species. A small proportion of individual samples presented evidence of hemoparasitic infection or leukocyte morphological traits that are relevant for future researchmore »on bat health, including unique large granular lymphocytes. Considering hematology is done by visual inspection of blood smears, examples of the varied cell morphologies are included as a visual guide. To the best of our knowledge, this study provides the first qualitative assessment of P . alecto leukocytes, as well as the first set of published hematology reference images for this species.« less