scholarly journals Mapping of host-parasite-microbiome interactions reveals metabolic determinants of tropism and tolerance in Chagas disease

2020 ◽  
Vol 6 (30) ◽  
pp. eaaz2015 ◽  
Author(s):  
E. Hossain ◽  
S. Khanam ◽  
D. A. Dean ◽  
C. Wu ◽  
S. Lostracco-Johnson ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Large Scale ◽  
Scale Effects ◽  
Parasite Burden ◽  
Acute Stage ◽  
Metabolic Disturbances ◽  
Spatially Resolved ◽  
Cardiac Strain ◽  
Host Parasite ◽  
The Impact

Chagas disease (CD) is a parasitic disease caused by Trypanosoma cruzi protozoa, presenting with cardiomyopathy, megaesophagus, and/or megacolon. To determine the mechanisms of gastrointestinal (GI) CD tissue tropism, we systematically characterized the spatial localization of infection-induced metabolic and microbiome alterations, in a mouse model of CD. Notably, the impact of the transition between acute and persistent infection differed between tissue sites, with sustained large-scale effects of infection in the esophagus and large intestine, providing a potential mechanism for the tropism of CD within the GI tract. Infection affected acylcarnitine metabolism; carnitine supplementation prevented acute-stage CD mortality without affecting parasite burden by mitigating infection-induced metabolic disturbances and reducing cardiac strain. Overall, results identified a previously-unknown mechanism of disease tolerance in CD, with potential for new therapeutic regimen development. More broadly, results highlight the potential of spatially resolved metabolomics to provide insight into disease pathogenesis and infectious disease drug development.

scholarly journals 3D mapping of host-parasite-microbiome interactions reveals metabolic determinants of tissue tropism and disease tolerance in Chagas disease

2019 ◽  
Author(s):  
Ekram Hossain ◽  
Sharmily Khanam ◽  
Chaoyi Wu ◽  
Sharon Lostracco-Johnson ◽  
Diane Thomas ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Large Intestine ◽  
Large Scale ◽  
Scale Effects ◽  
Parasitic Infection ◽  
Parasite Burden ◽  
Acute Stage ◽  
Disease Tolerance ◽  
Chronic Stage ◽  
Spatially Resolved

AbstractChagas disease (CD) is a parasitic infection caused by Trypanosoma cruzi protozoa. Over 8 million people worldwide are T. cruzi-positive, 20-30% of which will develop cardiomyopathy, megaoesophagus and/or megacolon. The mechanisms leading to gastrointestinal (GI) symptom development are however poorly understood. To address this issue, we systematically characterized the spatial impact of experimental T. cruzi infection on the microbiome and metabolome across the GI tract. The largest microbiota perturbations were observed in the proximal large intestine in both acute and chronic disease, with chronic-stage effects also observed in the cecum. Strikingly, metabolomic impact of acute-to-chronic stage transition differed depending on the organ, with persistent large-scale effects of infection primarily in the oesophagus and large intestine, providing a potential mechanism for GI pathology tropism in CD. Infection particularly affected acylcarnitine and lipid metabolism. Building on these observations, treatment of infected mice with carnitine-supplemented drinking water prevented acute-stage mortality with no changes in parasite burden. Overall, these results identified a new mechanism of disease tolerance in CD, with potential for the development of new therapeutic regimens. More broadly, these results highlight the potential of spatially-resolved metabolomic approaches to provide insight into disease pathogenesis, with translational applications for infectious disease drug development.

scholarly journals The Impact of Neurofeedback on Effective Connectivity Networks in Chronic Stroke Patients

2020 ◽  
Author(s):  
Lioi Giulia ◽  
Veliz Adolfo ◽  
Coloigner Julie ◽  
Duché Quentin ◽  
Butet Simon ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Large Scale ◽  
Scale Effects ◽  
Self Regulation ◽  
Chronic Stroke ◽  
Causal Modeling ◽  
Stroke Recovery ◽  
Functional Improvement ◽  
Stroke Patients ◽  
The Impact

AbstractStroke is a complex motor disease that not only affects perilesional areas but also global brain networks in both hemispheres. Neurofeedback (NF) is a promising technique to enhance neural plasticity and support functional improvement after stroke by means of brain self-regulation. Most of the studies using NF or brain computer interfaces for stroke rehabilitation have assessed treatment effects focusing on motor outcomes and successful activation of targeted cortical regions. However, given the crucial role of large-scale networks reorganization for stroke recovery, it is now believed that assessment of brain connectivity is central to predict treatment response and to individualize rehabilitation therapies. In this study, we assessed the impact of EEG-fMRI NF training on connectivity strength and direction using a Dynamic Causal Modeling approach. We considered a motor network including both ipsilesional and contralesional premotor, supplementary and primary motor areas. Our results in nine chronic stroke patients indicate that NF upregulation of targeted areas (ipsilesional SMA and M1) not only modulated activation patterns, but also had a more widespread impact on fMRI bilateral motor networks. In particular, inter-hemispheric connectivity between premotor and primary motor regions decreased, and ipsilesional self-inhibitory connections were reduced in strength, indicating an increase in activation during the NF motor task. To the best of our knowledge, this is the first work that investigates fMRI connectivity changes elicited by training of localized motor targets in stroke. Our results open new perspectives in the understanding of large-scale effects of NF training and the design of more effective NF strategies, based on the pathophysiology underlying stroke-induced deficits.

The potential role of habitat on intestinal helminths of mountain hares, Lepus timidus

2001 ◽  
Vol 75 (4) ◽  
pp. 345-349 ◽  
Author(s):  
I.A.R. Hulbert ◽  
B. Boag
Keyword(s):  
Large Scale ◽  
Life History Strategies ◽  
Lepus Timidus ◽  
Kidney Fat ◽  
Potential Impact ◽  
Kidney Fat Index ◽  
Host Parasite ◽  
Forestry Plantations ◽  
The Impact

Over the last century in the uplands of Scotland, the extent of heather moorland which supports high densities of mountain hares Lepus timidus has diminished and has gradually been replaced by large-scale commercial forestry plantations or expanding natural woodlands. The potential impact of such a change in land use on host–parasite interactions was investigated by comparing the intensity and prevalence of infection of hares by parasites in two separate habitats: a large hare-fenced young forestry plantation and the adjacent open moorland. Carcasses were collected in November 1990 from within both habitats and after the woodland had been enclosed for nine months. Age, sex, fatness (kidney fat index) and degree of infection of hares were noted. Two parasites were recorded: the nematode Trichostrongylus retortaeformis and the cestode Mosgovoyia pectinata. Clear differences in the intensity of infection of adults occupying the different habitats had occurred in the nine months since woodland enclosure. Adult mountain hares in the woodland had levels of infections approaching four times that observed in hares occupying the open moorland and although not significant, the prevalence of infection was greater in hosts inhabiting the woodland than the open moorland. It is suggested that the parasite–host relationship differs between the two habitats and as heather-dominated moorland landscapes become more fragmented with the increasing establishment of woodlands, the impact of parasites on the life history strategies of mountain hares needs to be reconsidered.

scholarly journals Noise pollution: acute noise exposure increases susceptibility to disease and chronic exposure reduces host survival

2020 ◽  
Vol 7 (9) ◽  
pp. 200172
Author(s):  
Numair Masud ◽  
Laura Hayes ◽  
Davide Crivelli ◽  
Stephen Grigg ◽  
Jo Cable
Keyword(s):  
Noise Exposure ◽  
Animal Health ◽  
Parasite Burden ◽  
Aquatic Organisms ◽  
Noise Pollution ◽  
Parasitic Infections ◽  
Terrestrial Vertebrates ◽  
Host Parasite Interactions ◽  
Host Parasite ◽  
The Impact

Anthropogenic noise is a pervasive global pollutant that has been detected in every major habitat on the planet. Detrimental impacts of noise pollution on physiology, immunology and behaviour have been shown in terrestrial vertebrates and invertebrates. Equivalent research on aquatic organisms has until recently been stunted by the misnomer of a silent underwater world. In fish, however, noise pollution can lead to stress, hearing loss, behavioural changes and impacted immunity. But, the functional effects of this impacted immunity on disease resistance due to noise exposure have remained neglected. Parasites that cause transmissible disease are key drivers of ecosystem biodiversity and a significant factor limiting the sustainable expansion of the animal trade. Therefore, understanding how a pervasive stressor is impacting host–parasite interactions will have far-reaching implications for global animal health. Here, we investigated the impact of acute and chronic noise on vertebrate susceptibility to parasitic infections, using a model host–parasite system (guppy– Gyrodactylus turnbulli ). Hosts experiencing acute noise suffered significantly increased parasite burden compared with those in no noise treatments. By contrast, fish experiencing chronic noise had the lowest parasite burden. However, these hosts died significantly earlier compared with those exposed to acute and no noise treatments. By revealing the detrimental impacts of acute and chronic noise on host–parasite interactions, we add to the growing body of evidence demonstrating a link between noise pollution and reduced animal health.

scholarly journals Early galaxy formation and its large-scale effects

2019 ◽  
Vol 15 (S352) ◽  
pp. 43-43
Author(s):  
Pratika Dayal
Keyword(s):  
Dark Matter ◽  
Galaxy Formation ◽  
Large Scale ◽  
Cold Dark Matter ◽  
Scale Effects ◽  
High Redshift ◽  
Early Galaxies ◽  
First Galaxies ◽  
The Impact ◽  
Early Galaxy

AbstractGalaxy formation in the first billion years mark a time of great upheaval in the history of the Universe: the first galaxies started both the ‘metal age’ as well as the era of cosmic reionization. I will start by reviewing the dust production mechanisms and dust masses for high-redshift galaxies which will be revolutionized in the ALMA era. I will then show how the JWST will be an invaluable experiment to shed light on the impact of reionization feedback on early galaxy formation. As we look forward towards the era of 21cm cosmology, I will highlight the crucial and urgent synergies required between 21cm facilities (such as the SKA) and galaxy experiments (JWST, E-ELT and Subaru to name a few) to understand the physics of the epoch of reionization that remains a crucial frontier in the field of astrophysics and physical cosmology. Time permitting, I will try to give a flavour of how the assembly of early galaxies, accessible with the forthcoming JWST, can provide a powerful testbed for Dark Matter models beyond ‘Cold Dark Matter’.

scholarly journals Spatial metabolomics identifies localized chemical changes in heart tissue during chronic cardiac Chagas disease

2020 ◽  
Author(s):  
Danya A. Dean ◽  
Gautham ◽  
Jair L. Siqueira-Neto ◽  
James H. McKerrow ◽  
Pieter C. Dorrestein ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Parasite Burden ◽  
Heart Tissue ◽  
Blood Transfusions ◽  
Organ Transplants ◽  
Chronic Stage ◽  
Congenital Transmission ◽  
Cardiac Symptoms ◽  
The Impact

AbstractChagas disease (CD) is one of thirteen neglected tropical diseases caused by the parasite Trypanosoma cruzi. CD is a vector-borne disease transmitted by triatomines but CD can also be transmitted through blood transfusions, organ transplants and congenital transmission. While endemic to Latin America, T. cruzi infects 7-8 million people worldwide and can induce severe cardiac symptoms including apical aneurysms, thromboembolisms and arrhythmias during the chronic stage of CD. However, these cardiac clinical manifestations and CD disease pathogenesis are not fully understood. Using spatial metabolomics (chemical cartography), we sought to understand the localized impact of infection on the cardiac metabolome of mice chronically infected with two divergent T. cruzi strains. Our data showed chemical differences in localized cardiac regions upon chronic T. cruzi infection, indicating that parasite infection changes the host metabolome at select sites in chronic CD. These sites were distinct from the sites of highest parasite burden. In addition, we identified acylcarnitines and phosphocholines as discriminatory chemical families within each heart region, comparing infected and uninfected samples. Overall, our study indicated overall and positional metabolic differences common to infection with different T. cruzi strains, and identified select infection-modulated pathways. These results provide further insight into CD pathogenesis and demonstrate the advantage of a spatial perspective to understand infectious disease tropism.Author SummaryChagas disease (CD) is a tropical disease caused by the parasite Trypanosoma cruzi. CD originated in South America; however, there are now 7-8 million people infected worldwide due to population movements. CD is transmitted through a triatomine vector, organ transplants, blood transfusions and congenital transmission. It occurs in two stages, an acute stage (usually asymptomatic) and the chronic stage. Chronic stage CD presents with severe cardiac symptoms such as heart failure, localized aneurysms and cardiomyopathy. Unfortunately, what causes severe cardiac symptoms in some individuals in chronic CD is not fully understood. Therefore, we used liquid chromatography-tandem mass spectrometry to analyze the heart tissue of chronically T. cruzi-infected and uninfected mice, to understand the impact of infection on the tissue metabolome. We identified discriminatory small molecules related to T. cruzi infection. We also determined that regions with the highest parasite burden are distinct from the regions with the largest changes in overall metabolite profile; these locations of high metabolic perturbation provide a molecular mechanism to why localized cardiac symptoms occur in CD. Overall, our work gives insight to chronic cardiac CD symptom development and shapes a framework for novel treatment and biomarker development.

scholarly journals Land cover drives large scale productivity-diversity relationships in Irish vascular plants

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7035 ◽  
Author(s):  
Hannah J. White ◽  
Willson Gaul ◽  
Dinara Sadykova ◽  
Lupe León-Sánchez ◽  
Paul Caplat ◽  
...  
Keyword(s):  
Species Richness ◽  
Land Cover ◽  
Large Scale ◽  
Vegetation Index ◽  
Scale Effects ◽  
Spatial Scales ◽  
Vascular Plant ◽  
Regional Scale ◽  
The Impact ◽  
The Relationship

The impact of productivity on species diversity is often studied at small spatial scales and without taking additional environmental factors into account. Focusing on small spatial scales removes important regional scale effects, such as the role of land cover heterogeneity. Here, we use a regional spatial scale (10 km square) to establish the relationship between productivity and vascular plant species richness across the island of Ireland that takes into account variation in land cover. We used generalized additive mixed effects models to relate species richness, estimated from biological records, to plant productivity. Productivity was quantified by the satellite-derived enhanced vegetation index. The productivity-diversity relationship was fitted for three land cover types: pasture-dominated, heterogeneous, and non-pasture-dominated landscapes. We find that species richness decreases with increasing productivity, especially at higher productivity levels. This decreasing relationship appears to be driven by pasture-dominated areas. The relationship between species richness and heterogeneity in productivity (both spatial and temporal) varies with land cover. Our results suggest that the impact of pasture on species richness extends beyond field level. The effect of human modified landscapes, therefore, is important to consider when investigating classical ecological relationships, particularly at the wider landscape scale.

scholarly journals Structural and Efficiency Effects of Land Transfers on Food Planting: A Comparative Perspective on North and South of China

2021 ◽  
Vol 13 (6) ◽  
pp. 3327
Author(s):  
Zhihua Leng ◽  
Yana Wang ◽  
Xinshuo Hou
Keyword(s):  
Large Scale ◽  
Scale Effects ◽  
Division Of Labour ◽  
Market Mechanism ◽  
Small Scale ◽  
Structural Effects ◽  
The South ◽  
Operating Income ◽  
The North ◽  
The Impact

This paper uses a multi-period PSM-DID model to explore the impact of land transfers on food production from a spatial perspective and analyses the income effects, scale effects, and structural effects of such transfers. The empirical results are as follows. (1) Land transfers have reduced the proportion of food crops planted by farmers, and the planting structure has shifted towards cash crops, which has obvious structural effects. (2) The impact of land transfers on the planting structure is spatially heterogeneous. Land transfers are more common in the south than in the north. Land transfers have reduced wheat planting in the north, while rice planting has been reduced in the south. (3) Land transfers have increased the operating income of farmers and have an income effect, but the income of farmers in the north is higher than that of farmers in the south. (4) Land transfers do not have scale effects. Current land transfers among farmers are mainly conducted on a small scale and do not improve farmers’ efficiency in planting food. The following suggestions are proposed. (1) A market mechanism for land transfers should be established to promote large-scale land transfers. (2) The trend towards non-grain cultivation due to land transfers should be halted to ensure food security. (3) The different impacts of urbanization in the northern and southern regions should be considered, and the division of labour in grain-producing areas should be strengthened. (4) Land transfer models should be developed, and the development of smart agriculture should be explored.

scholarly journals WAVE LOADS ON EXPOSED JETTIES: DESCRIPTION OF LARGE SCALE EXPERIMENTS AND PRELIMINARY RESULTS

2011 ◽  
Vol 1 (32) ◽  
pp. 18 ◽  
Author(s):  
Luca Martinelli ◽  
Alberto Lamberti ◽  
Maria Gabriella Gaeta ◽  
Matteo Tirindelli ◽  
John Alderson ◽  
...  
Keyword(s):  
Large Scale ◽  
Research Team ◽  
Scale Effects ◽  
Wave Loads ◽  
Large Wave ◽  
Preliminary Results ◽  
Wave Flume ◽  
Air Content ◽  
Wave Induced ◽  
The Impact

The large scale experiments described in this paper were carried out at the Large Wave Flume (GWK, Große Wellenkanal) in Hanover (Germany). The research team included Universities of Bologna (IT), Edinburgh (UK), Southampton (UK), Plymouth (UK), HR Wallingford (UK) and Coast & Harbor Engineering Inc (USA). Wave-induced loads on close-to-prototype scale jetties were measured, with particular attention to scale effects due to air content in water. The aim of the paper is to present the tests, describe the impact process and give preliminary results concerning uplift loads.

Kinetic Modeling of the Impact of Solar Wind Discontinuities on the Magnetopause

2021 ◽  
Author(s):  
Jean Berchem ◽  
Giovanni Lapenta ◽  
Robert L. Richard ◽  
Philippe Escoubet ◽  
Simon Wing
Keyword(s):  
Solar Wind ◽  
Kinetic Modeling ◽  
Large Scale ◽  
Scale Effects ◽  
Comprehensive Understanding ◽  
Global Simulation ◽  
Mhd Simulations ◽  
Dayside Magnetopause ◽  
Pic Code ◽  
The Impact

<p>An important step in comprehending the effects of solar wind structures on the magnetosphere is to develop an understanding of their impact on the dayside magnetopause.  While most of the time global magnetohydrodynamic (MHD) models describe adequately the large-scale effects of solar wind structures on the magnetopause, recent spacecraft observations in the near Earth solar wind indicate that solar wind discontinuities have plasma features that are often not accurately described by MHD.  In this presentation, we report our progress in gaining a comprehensive understanding of kinetic processes occurring at the magnetopause as solar wind structures impact the dayside magnetosphere. Our approach combines implicit PIC simulations with global MHD simulations of the solar wind-magnetosphere-ionosphere system. The global simulation sets the overall configuration of the magnetosphere, while fields and plasma moments of a sub-domain of the global simulation are used to set initial and boundary conditions of the PIC code. Results are discussed in the context of spacecraft observations.</p>

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