Mast Cell Chymase/Mcpt4 Suppresses the Host Immune Response to Plasmodium yoelii, Limits Malaria-Associated Disruption of Intestinal Barrier Integrity and Reduces Parasite Transmission to Anopheles stephensi

An increase in mast cells (MCs) and MCs mediators has been observed in malaria-associated bacteremia, however, the role of these granulocytes in malarial immunity is poorly understood. Herein, we studied the role of mouse MC protease (Mcpt) 4, an ortholog of human MC chymase, in malaria-induced bacteremia using Mcpt4 knockout (Mcpt4(-/-)) mice and Mcpt4(+/+) C57BL/6J controls, and the non-lethal mouse parasite Plasmodium yoelii yoelii 17XNL. Significantly lower parasitemia was observed in Mcpt4(-/-) mice compared with Mcpt4(+/+) controls by day 10 post infection (PI). Although bacterial 16S DNA levels in blood were not different between groups, increased intestinal permeability to FITC-dextran and altered ileal adherens junction E-cadherin were observed in Mcpt4(-/-) mice. Relative to infected Mcpt4(+/+) mice, ileal MC accumulation in Mcpt4(-/-) mice occurred two days earlier and IgE levels were higher by days 8-10 PI. Increased levels of circulating myeloperoxidase were observed at 6 and 10 days PI in Mcpt4(+/+) but not Mcpt4(-/-) mice, affirming a role for neutrophil activation that was not predictive of parasitemia or bacterial 16S copies in blood. In contrast, early increased plasma levels of TNF-alpha, IL-12p40 and IL-3 were observed in Mcpt4(-/-) mice, while levels of IL-2, IL-10 and MIP1 beta (CCL4) were increased over the same period in Mcpt4(+/+) mice, suggesting that the host response to infection was skewed toward a type-1 immune response in Mcpt4(-/-) mice and type-2 response in Mcpt4(+/+) mice. Spearman analysis revealed an early (day 4 PI) correlation of Mcpt4(-/-) parasitemia with TNF-alpha and IFN-gamma, inflammatory cytokines known for their roles in pathogen clearance, a pattern that was observed in Mcpt4(+/+) mice much later (day 10 PI). Transmission success of P. y. yoelii 17XNL to Anopheles stephensi was significantly higher from infected Mcpt4(-/-) mice compared with infected Mcpt4(+/+) mice, suggesting that Mcpt4 also impacts transmissibility of sexual stage parasites. Together, these results suggest that early MCs activation and release of Mcpt4 suppresses the host immune response to P. y. yoelii 17XNL, perhaps via degradation of TNF-alpha and promotion of a type-2 immune response that concordantly protects epithelial barrier integrity, while limiting the systemic response to bacteremia and parasite transmissibility

Miniaturization optimized weapon killing power during the social stress of late pre-contact North America (AD 600-1600)

Before Europeans arrived to Eastern North America, prehistoric, indigenous peoples experienced a number of changes that culminated in the development of sedentary, maize agricultural lifeways of varying complexity. Inherent to these lifeways were several triggers of social stress including population nucleation and increase, intergroup conflict (warfare), and increased territoriality. Here, we examine whether this period of social stress co-varied with deadlier weaponry, specifically, the design of the most commonly found prehistoric archery component in late pre-contact North America: triangular stone arrow tips (TSAT). The examination of modern metal or carbon projectiles, arrows, and arrowheads has demonstrated that smaller arrow tips penetrate deeper into a target than do larger ones. We first experimentally confirm that this relationship applies to arrow tips made from stone hafted onto shafts made from wood. We then statistically assess a large sample (n = 742) of late pre-contact TSAT and show that these specimens are extraordinarily small. Thus, by miniaturizing their arrow tips, prehistoric people in Eastern North America optimized their projectile weaponry for maximum penetration and killing power in warfare and hunting. Finally, we verify that these functional advantages were selected across environmental and cultural boundaries. Thus, while we cannot and should not rule out stochastic, production economizing, or non-adaptive cultural processes as an explanation for TSAT, overall our results are consistent with the hypothesis that broad, socially stressful demographic changes in late pre-contact Eastern North America resulted in the miniaturization–and augmented lethality–of stone tools across the region

Identifying areas at risk of drought-induced tree mortality across South-Eastern Australia

South-East Australia has recently been subjected to two of the worst droughts in the historical record (Millennium Drought, 2000–2009 and Big Dry, 2017–2019). Unfortunately, a lack of forest monitoring has made it difficult to determine whether widespread tree mortality has resulted from these droughts. Anecdotal observations suggest the Big Dry may have led to more significant tree mortality than the Millennium drought. Critically, to be able to robustly project future expected climate change effects on Australian vegetation, we need to be able to assess the vulnerability to drought of Australian trees. Here, we implemented a model of plant hydraulics into the Community Atmosphere Biosphere Land Exchange (CABLE) land surface model. We parameterised the drought response behaviour of five broad vegetation types, based on a common garden dry-down experiment with species originating across a rainfall gradient (188–1125 mm yr1 ) across South-East Australia. The new hydraulics model significantly improved (~35–45 % reduction in root mean square error) CABLE’s previous predictions of latent heat fluxes during periods of water stress at two eddy covariance sites in Australia. Landscape-scale predictions of the greatest percentage loss of hydraulic conductivity (PLC), 40–60 %, were broadly consistent with satellite estimates of regions of the greatest change in both droughts. In neither drought did CABLE predict that trees would have reached critical PLC in widespread areas (i.e. it projected a low mortality risk), although the model highlighted critical levels near the desert regions of South-East Australia where few trees live. Overall, our experimentally constrained model results imply significant resilience to drought conferred by hydraulic function, but also highlight critical data and scientific gaps. Our approach presents a promising avenue to integrate experimental data and make regional-scale predictions of potential drought-induced hydraulic failure

Research methods of Talking About The Smokes: an International Tobacco Control Policy Evaluation Project study with Aboriginal and Torres Strait Islander Australians

Objective: To describe the research methods and baseline sample of the Talking About The Smokes (TATS) project.Design: The TATS project is a collaboration between research institutions and Aboriginal community-controlled health services (ACCHSs) and their state and national representative bodies. It is one of the studies within the International Tobacco Control Policy Evaluation Project, enabling national and international comparisons. It includes a prospective longitudinal study of Aboriginal and Torres Strait Islander smokers and recent ex-smokers; a survey of non-smokers; repeated cross-sectional surveys of ACCHS staff; and descriptions of the tobacco policies and practices at the ACCHSs. Community members completed face-to-face surveys; staff completed surveys on paper or online. We compared potential biases and the distribution of variables common to the main community baseline sample and unweighted and weighted results of the 2008 National Aboriginal and Torres Strait Islander Social Survey (NATSISS). The baseline survey (Wave 1) was conducted between April 2012 and October 2013.Setting and participants: 2522 Aboriginal and Torres Strait Islander people in 35 locations (the communities served by 34 ACCHSs and one community in the Torres Strait), and 645 staff in the ACCHSs.Main outcome measures: Sociodemographic and general health indicators, smoking status, number of cigarettes smoked per day and quit attempts.Results: The main community baseline sample closely matched the distribution of the Aboriginal and Torres Strait Islander population in the weighted NATSISS by age, sex, jurisdiction and remoteness. There were inconsistent differences in some sociodemographic factors between our sample and the NATSISS: our sample had higher proportions of unemployed people, but also higher proportions who had completed Year 12 and who lived in more advantaged areas. In both surveys, similar percentages of smokers reported having attempted to quit in the past year, and daily smokers reported similar numbers of cigarettes smoked per day.Conclusion: The TATS project provides a detailed and nationally representative description of Aboriginal and Torres Strait Islander smoking behaviour, attitudes, knowledge and exposure to tobacco control activities and policies, and their association with quitting

A Groundbased Imaging Study of Galaxies Causing DLA, subDLA, and LLS Absorption in Quasar Spectra

We present results from a search for galaxies that give rise to damped Lyman alpha (DLA), subDLA, and Lyman limit system (LLS) absorption at redshifts 0.1 ~< z ~< 1 in the spectra of background quasars. The sample was formed from a larger sample of strong MgII absorbers (W_0^(2796) >= 0.3 A) whose HI column densities were determined by measuring the Ly-alpha line in HST UV spectra. Photometric redshifts, galaxy colors, and proximity to the quasar sightline, in decreasing order of importance, were used to identify galaxies responsible for the absorption. Our sample includes 80 absorption systems for which the absorbing galaxies have been identified, of which 54 are presented here for the first time. The main results of this study are: (i) the surface density of galaxies falls off exponentially with increasing impact parameter, b, from the quasar sightline relative to a constant background of galaxies, with an e-folding length of ~46 kpc. Galaxies with b >~ 100 kpc calculated at the absorption redshift are statistically consistent with being unrelated to the absorption system. (ii) log N(HI) is inversely correlated with b at the 3.0 sigma level of significance. DLA galaxies are found systematically closer to the quasar sightline, by a factor of two, than are galaxies which give rise to subDLAs or LLSs. The median impact parameter is 17.4 kpc for the DLA galaxy sample, 33.3 kpc for the subDLA sample, and 36.4 kpc for the LLS sample. (iii) Absorber galaxy luminosity relative to L*, L/L*, is not significantly correlated with W_0^(2796), log N(HI), or b. (iv) DLA, subDLA, and LLS galaxies comprise a mix of spectral types, but are inferred to be predominantly late type galaxies based on their spectral energy distributions. The implications of these results are discussed. (Abridged)Comment: Accepted for publication in MNRA

Massive migration from the steppe is a source for Indo-European languages in Europe

We generated genome-wide data from 69 Europeans who lived between 8,000-3,000 years ago by enriching ancient DNA libraries for a target set of almost four hundred thousand polymorphisms. Enrichment of these positions decreases the sequencing required for genome-wide ancient DNA analysis by a median of around 250-fold, allowing us to study an order of magnitude more individuals than previous studies and to obtain new insights about the past. We show that the populations of western and far eastern Europe followed opposite trajectories between 8,000-5,000 years ago. At the beginning of the Neolithic period in Europe, ~8,000-7,000 years ago, closely related groups of early farmers appeared in Germany, Hungary, and Spain, different from indigenous hunter-gatherers, whereas Russia was inhabited by a distinctive population of hunter-gatherers with high affinity to a ~24,000 year old Siberian6 . By ~6,000-5,000 years ago, a resurgence of hunter-gatherer ancestry had occurred throughout much of Europe, but in Russia, the Yamnaya steppe herders of this time were descended not only from the preceding eastern European hunter-gatherers, but from a population of Near Eastern ancestry. Western and Eastern Europe came into contact ~4,500 years ago, as the Late Neolithic Corded Ware people from Germany traced ~3/4 of their ancestry to the Yamnaya, documenting a massive migration into the heartland of Europe from its eastern periphery. This steppe ancestry persisted in all sampled central Europeans until at least ~3,000 years ago, and is ubiquitous in present-day Europeans. These results provide support for the theory of a steppe origin of at least some of the Indo-European languages of Europe

XPS characterization of (copper-based) coloured stains formed on limestone surfaces of outdoor Roman monuments

Limestone basements holding bronzes or other copper alloys artefacts such as sculptures, decorations and dedicatory inscriptions are frequently met both in modern and ancient monuments. In outdoor conditions, such a combination implies the corrosion products of the copper based alloy, directly exposed to rainwater, will be drained off and migrate through the porous surfaces, forming stains of different colours and intensities, finally causing the limestone structures to deteriorate

Jumping into the deep-end: results from a pilot impact evaluation of a community-based aquatic exercise program

This multi-center quasi-experimental pilot study aimed to evaluate changes in pain, joint stiffness, physical function, and quality of life over 12 weeks in adults with musculoskeletal conditions attending ‘Waves’ aquatic exercise classes. A total of 109 adults (mean age, 65.2 years; range, 24–93 years) with musculoskeletal conditions were recruited across 18 Australian community aquatic centers. The intervention is a peer-led, 45 min, weekly aquatic exercise class including aerobic, strength, flexibility, and balance exercises (n = 67). The study also included a control group of people not participating in Waves or other formal exercise (n = 42). Outcomes were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and EuroQoL five dimensions survey (EQ-5D) at baseline and 12 weeks. Satisfaction with Waves classes was also measured at 12 weeks. Eighty two participants (43 Waves and 39 control) completed the study protocol and were included in the analysis. High levels of satisfaction with classes were reported by Waves participants. Over 90 % of participants reported Waves classes were enjoyable and would recommend classes to others. Waves participants demonstrated improvements in WOMAC and EQ-5D scores however between-group differences did not reach statistical significance. Peer-led aquatic exercise classes appear to improve pain, joint stiffness, physical function and quality of life for people with musculoskeletal conditions. The diverse study sample is likely to have limited the power to detect significant changes in outcomes. Larger studies with an adequate follow-up period are needed to confirm effects

Adult asthma and traffic exposure at residential address, workplace address, and self-reported daily time outdoor in traffic: A two-stage case-control study

<p>Abstract</p> <p>Background</p> <p>Most epidemiologic studies use traffic at residential address as a surrogate for total traffic exposure when investigating effects of traffic on respiratory health. This study used GIS (Geographical Information Systems) to estimate traffic exposure, not only on residential, but also on workplace address, in addition to survey questions on time spent in traffic during commuting or other daily activities.</p> <p>The aim was to investigate 1) if there is an association between traffic exposure and prevalence of adult asthma and asthma symptoms, and 2) if so, does this association become stronger using more complete traffic exposure information.</p> <p>Methods</p> <p>This study was conducted in two stages: A first cross-sectional survey in Southern Sweden 2004 (n = 24819, 18-80 years, response rate 59%) was followed by a case-control study in 2005 to obtain more detailed exposure and confounder information (n = 2856, asthmatics and controls (1:3), 86% response rate). In the first survey, only residential address was known. In the second survey, questions about workplace addresses and daily time spent in traffic were also included. Residential and workplace addresses were geocoded and linked with GIS to road data and dispersion modelled outdoor concentrations of NO_x(annual mean, 250 × 250 m resolution).</p> <p>Results</p> <p>Living within 50 m of a road (measured by GIS) with traffic intensity of >10 cars/minute (compared with no road within this distance) was associated with an increased prevalence of asthma, (OR = 1.8, 95% CI = (1.1-2.8), and with asthma symptoms last 12 months. No statistically significant effects were seen for traffic exposure at workplace address, daily time spent in traffic, or commuting time to work, after adjustment for confounders. A combined total exposure estimate did not give a stronger association with asthma prevalence or asthma symptoms.</p> <p>Conclusions</p> <p>Traffic exposure at close proximity to residential address showed association with asthma prevalence and asthma symptoms last 12 months, among adults in southern Sweden. The associations were not stronger when accounting for total traffic exposure. This could reflect exposure misclassfication at workplace address and for other daily time in traffic, but also that residential address remains the main determinant for traffic exposure among adults.</p