AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major components, collagen IV and laminin. We used this model to demonstrate that antibody targeted blockade of CTLD2, the second of eight C-type lectin-like domains in Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) that can recognize glycosylated collagens, reversed actinomyosin-based contractility [myosin-light chain-2 (MLC2) phosphorylation], loss of cell polarity, loss of cell–cell junctions, luminal infiltration and basal invasion induced by AGE-modified basal lamina matrix in PEC acini. Our in vitro results were concordant with luminal occlusion of acini in the prostate glands of adult Endo180ΔEx2–6/ΔEx2–6 mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour in non-transformed PECs via a molecular mechanism linked to cancer progression. This study provides a rationale for targeting CTLD2 in Endo180 in prostate cancer and other pathologies in which increased basal lamina thickness and tissue stiffness are driving factors

Convergence of marine megafauna movement patterns in coastal and open oceans

Author Posting. © The Author(s), 2017. This is the author's version of the work. It is posted here for personal use, not for redistribution. The definitive version was published in Proceedings of the National Academy of Sciences of the United States of America 115 (2018): 3072-3077, doi:10.1073/pnas.1716137115.The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals’ movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyse a global dataset of 2.8 million locations from > 2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared to more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal micro-habitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise and declining oxygen content.Workshops funding granted by the UWA Oceans Institute, AIMS, and KAUST. AMMS was supported by an ARC Grant DE170100841 and an IOMRC (UWA, AIMS, CSIRO) fellowship; JPR by MEDC (FPU program, Spain); DWS by UK NERC and Save Our Seas Foundation; NQ by FCT (Portugal); MMCM by a CAPES fellowship (Ministry of Education)

Local, national, and regional viral haemorrhagic fever pandemic potential in Africa: a multistage analysis

Summary Background: Predicting when and where pathogens will emerge is difficult, yet, as shown by the recent Ebola and Zika epidemics, effective and timely responses are key. It is therefore crucial to transition from reactive to proactive responses for these pathogens. To better identify priorities for outbreak mitigation and prevention, we developed a cohesive framework combining disparate methods and data sources, and assessed subnational pandemic potential for four viral haemorrhagic fevers in Africa, Crimean–Congo haemorrhagic fever, Ebola virus disease, Lassa fever, and Marburg virus disease. Methods: In this multistage analysis, we quantified three stages underlying the potential of widespread viral haemorrhagic fever epidemics. Environmental suitability maps were used to define stage 1, index-case potential, which assesses populations at risk of infection due to spillover from zoonotic hosts or vectors, identifying where index cases could present. Stage 2, outbreak potential, iterates upon an existing framework, the Index for Risk Management, to measure potential for secondary spread in people within specific communities. For stage 3, epidemic potential, we combined local and international scale connectivity assessments with stage 2 to evaluate possible spread of local outbreaks nationally, regionally, and internationally. Findings: We found epidemic potential to vary within Africa, with regions where viral haemorrhagic fever outbreaks have previously occurred (eg, western Africa) and areas currently considered non-endemic (eg, Cameroon and Ethiopia) both ranking highly. Tracking transitions between stages showed how an index case can escalate into a widespread epidemic in the absence of intervention (eg, Nigeria and Guinea). Our analysis showed Chad, Somalia, and South Sudan to be highly susceptible to any outbreak at subnational levels. Interpretation Our analysis provides a unified assessment of potential epidemic trajectories, with the aim of allowing national and international agencies to pre-emptively evaluate needs and target resources. Within each country, our framework identifies at-risk subnational locations in which to improve surveillance, diagnostic capabilities, and health systems in parallel with the design of policies for optimal responses at each stage. In conjunction with pandemic preparedness activities, assessments such as ours can identify regions where needs and provisions do not align, and thus should be targeted for future strengthening and support. Funding Paul G Allen Family Foundation, Bill & Melinda Gates Foundation, Wellcome Trust, UK Department for International Development

2023 Altona Flat Rock Bird Survey Data

Data for "Differences in Avian Community Assemblages Across Forest Type, Age, and Time in a Disturbed Jack Pine Barrens" can be found here. Metadata for all data columns is also provided

Data from: Functional responses of an apex predator and a mesopredator to an invading ungulate: Dingoes, red foxes and sambar deer in south-east Australia

Biological invasions by large herbivores involve the establishment of novel interactions with the receiving mammalian carnivore community, but understanding these interactions is difficult due to the large spatiotemporal scales at which such dynamics would occur. We quantified the functional responses of a native apex predator (the dingo (Canis familiaris), which includes wild dogs and their hybrids) and a non-native mesopredator (red fox; Vulpes vulpes) to an invading non-native ungulate (sambar deer; Cervus unicolor) in Australia. We predicted that the apex predator would exhibit a stronger functional response to increasing sambar deer abundance than the mesopredator. We used a state–space model to link two 30-year time series: (i) sambar deer abundance (hunter catch-per-unit-effort); and (ii) percentages of sambar deer in dingo (N = 4531) and fox (N = 5002) scats. Sambar deer abundance increased over fourfold during 1984–2013. The percentages of sambar deer in dingo and fox scats increased during this 30-year period, from nil in both species in 1984 to 8.2% in dingoes and 0.5% in foxes in 2013. Dingoes exhibited a much stronger functional response to increasing sambar deer abundance than foxes. The prediction that invading deer would be utilized more by the apex predator than by the mesopredator was therefore supported. The increasing abundance of sambar deer during the period 1984–2013 provided an increasingly important food source for dingoes. In contrast, the smaller red fox utilized sambar deer much less. Our study demonstrates that prey enrichment can be an important consequence of large herbivore invasions and that the effect varies predictably with the trophic position of the mammalian carnivores in the receiving community

Data used in our analyses.

The file contains 8 columns and 31 rows. The first row contains the column headings and the remaining 30 rows are the data values arranged by year (i.e. one row for each of the 30 years of the study). The first column 'Year' is the year the data relate to (first year is 1984, last year is 2013). The second column 'HunterCPUE' is the mean number of sambar deer shot per hunter per day in each of the 30 years. The third column 'nDingoScats' is the number of dingo scats collected in each of the 30 years. The fourth column 'nRedFoxScats' is the number of red fox scats collected in each of the 30 years. The fifth column 'nSambDingoScats' is the number of dingo scats collected in each year that contained sambar deer. The sixth column 'nSambRedFoxScats' is the number of red fox scats collected in each year that contained sambar deer. The seventh column 'SambFoxScatsPerc' is the percentage of red fox scats collected in each year that contained sambar deer. The eighth column 'SambDingoScatsPerc' is the percentage of red fox scats collected in each year that contained sambar deer

Local, national and regional viral haemorrhagic fever pandemic potential in Africa

Predicting when and where novel and exotic pathogens will emerge is difficult, yet as recent Ebola and Zika epidemics demonstrate, despite progress in infectious disease interventions, effective and timely responses to emerging pathogens are still vital. In particular, it is critical to transition from relying on reactive responses to proactive management of these pathogens. To improve the identification of priority settings we present a cohesive framework to bring together disparate methodologies and data sources to assess subnational pandemic potential for four viral haemorrhagic fevers in Africa. Methods: We quantify three key stages that underlie the potential of a widespread epidemic. Stage 1 uses environmental factors that drive potential disease transmission and populations to define areas of possible spillover. Stage 2 assesses local outbreak receptivity by aggregating data on population vulnerabilities and infrastructural response capacities to identify areas of outbreak potential. Stage 3 utilises connectivity data to evaluate the potential for outbreak spread at both local and international scales. Findings: Epidemic potential varied within Africa, highlighting not only regions where viral haemorrhagic fever outbreaks have previously occurred (e.g. Western Africa), but also regions that are generally viewed as non-endemic. Differences by stage both across and within countries in Africa, highlighted where differnet preparedness or monitoring activities should be prioritised. Subnational levels of outbreak receptivity pointed to areas of particular vulnerability in much of Middle, Northern, and Eastern Africa. Interpretation: This study provides a unified assessment of potential trajectories of an epidemic, allowing national and international agencies to pre-emptively evaluate needs and target resources prior to any spillover event. Subnational regions can be identified for improving surveillance, diagnostic capabilities and health system strengthening in parallel with designing policies and guidelines for optimal response at each stage. In conjunction with pandemic preparedness activities, assessments such as this can help identify those regions where preparedness needs and provisions do not currently align. Funding: Paul G Allen Family Foundation, Bill & Melinda Gates Foundation, the Wellcome Trust, and the UK Department for International Development.JRC.E.1-Disaster Risk Managemen

Convergence of marine megafauna movement patterns in coastal and open oceans

Data and code used in Sequeira et al., "Convergence of marine megafauna movement patterns in coastal and open oceans", Proceedings of the National Academy of Sciences (2018).Peer reviewe