1,354 research outputs found
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Anthelmintic activities against Haemonchus contortus or Trichostrongylus colubriformis from small ruminants are influenced by structural features of condensed tannins
Plants containing condensed tannins (CTs) may hold promise as alternatives to synthetic anthelmintic (AH) drugs for controlling gastrointestinal nematodes (GINs). However, the structural features that contribute to the AH activities of CTs remain elusive. This study probed the relationships between CT structures and their AH activities. Eighteen plant resources were selected based on their diverse CT structures. From each plant resource, two CT fractions were isolated and their in vitro AH activities were measured with the Larval Exsheathment Inhibition Assay, which was applied to Haemonchus contortus and Trichostrongylus colubriformis. Calculation of mean EC50 values indicated that H. contortus was more susceptible than T colubriformis to the different fractions and that the F1 fractions were less efficient than the F2 ones, as indicated by the respective mean values for H.contortus F1 = 136.9 ± 74.1 µg/ml; and for H.contortus F2 = 108.1 ± 53.2 µg/ml and for T colubriformis F1 = 233 ± 54.3 µg/ml and F2=166 ± 39.9 µg/ml. The results showed that the AH activity against H. contortus was associated with the monomeric subunits that give rise to prodelphinidins (P < 0.05) and with CT polymer size (P < 0.10). However, for T. colubriformis AH activity was correlated only with prodelphinidins (P < 0.05). These results suggest that CTs have different modes of action against different parasite species
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Synergistic inhibition of Haemonchus contortus exsheathment by flavonoid monomers and condensed tannins
This study investigated the separate and combined anthelmintic (AH) effects of different phenolic compounds, including condensed tannins and flavonoids, all of which are known to occur in willow leaves, a potentially valuable dry season feed. A range of contrasting model tannins, which span the whole range of willow tannins, were isolated from tilia flowers, goat willow leaves, black currant leaves and red currant leaves. All together, the tested compounds represented the major tannin types (procyanidins and prodelphinidins) and flavonoid types (flavonols, flavones and flavanones). The larval exsheathment inhibition assay (LEIA) was used to assess their in vitro effects on Haemonchus contortus third stage larvae. Arbutin, vanillic acid, and taxifolin proved to be ineffective whereas naringenin, quercetin and luteolin were highly effective at 250 ÎĽM concentrations. Procyanidin (PC) tannins tended to be less active than prodelphinidin tannins (PD). Experiments with combinations of tannins and quercetin or luteolin revealed for the first time the existence of synergistic AH effects between tannins and flavonoid monomers. They also provided evidence that synergistic effects appear to occur at slightly lower concentrations of PC than PD. This suggests that the AH activity of condensed tannins can be significantly enhanced by the addition of quercetin or luteolin. This information may prove useful for plant breeding or selection and for designing optimal feed mixtures
Chasing Lions: Co-Designing Human-Drone Interaction in Sub-Saharan Africa
Drones are an exciting technology that is quickly being adopted in the global
consumer market. Africa has become a center of deployment with the first drone
airport established in Rwanda and drones currently being used for applications
such as medical deliveries, agriculture, and wildlife monitoring. Despite this
increasing presence of drones, there is a lack of research on stakeholders'
perspectives from this region. We ran a human-drone interaction user study
(N=15) with experts from several sub-Saharan countries using a co-design
methodology. Participants described novel applications and identified important
design aspects for the integration of drones in this context. Our results
highlight the potential of drones to address real world problems, the need for
them to be culturally situated, and the importance of considering the social
aspects of their interaction with humans. This research highlights the need for
diverse perspectives in the human-drone interaction design process.Comment: To be published in the ACM conference on Designing Interactive
Systems (DIS '20
Peripheral nervous system: A promising source of neuronal progenitors for central nervous system repair
With a steadily aging population there is an increasing prevalence of neurological disorders. Given the lack of effective treatment strategies and a limited ability for the central nervous system (CNS) to regenerate endogenously, there is a critical need to better understand exogenous strategies for nervous system repair. Stem cell therapy offers a promising approach to promote the repair of neurologic tissue and function, however studies to date have been limited by various factors including challenges in harvesting donor cells from the CNS, ethical concerns regarding use of embryonic or fetal tissue, tumorigenic potential of induced pluripotent stem cells, and immune-mediated rejection of non-autologous cell sources. Here we review and propose two alternative sources of autologous cells derived from the peripheral nervous system (PNS) for CNS repair: enteric neuronal stem cells (ENSCs) and neural crest-derived Schwann cells found in subcutaneous adipose tissue (termed SAT-NSCs). ENSCs can be successfully isolated from the postnatal enteric nervous system, propagated in vitro, and transplanted successfully into models of CNS injury via both direct intracerebral injection and systemic tail vein injection. Similarly, SAT-NSCs can be readily isolated from both human and mouse adipose tissue and, although not yet utilized in models of CNS injury, have successfully been transplanted and restored function in models of colonic aganglionosis and gastroparesis. These unique sources of PNS-derived autologous cells offer an exciting option for stem cell therapies for the CNS as they have proven neurogenic potential and eliminate concerns around tumorigenic risk, ethical considerations, and immune-mediated rejection
Strategies for Understanding and Reducing the Plasmodium vivax and Plasmodium ovale Hypnozoite Reservoir in Papua New Guinean Children: A Randomised Placebo-Controlled Trial and Mathematical Model
The undetectable hypnozoite reservoir for relapsing Plasmodium vivax and P. ovale malarias presents a major challenge for malaria control and elimination in endemic countries. This study aims to directly determine the contribution of relapses to the burden of P. vivax and P. ovale infection, illness, and transmission in Papua New Guinean children.; From 17 August 2009 to 20 May 2010, 524 children aged 5-10 y from East Sepik Province in Papua New Guinea (PNG) participated in a randomised double-blind placebo-controlled trial of blood- plus liver-stage drugs (chloroquine [CQ], 3 d; artemether-lumefantrine [AL], 3 d; and primaquine [PQ], 20 d, 10 mg/kg total dose) (261 children) or blood-stage drugs only (CQ, 3 d; AL, 3 d; and placebo [PL], 20 d) (263 children). Participants, study staff, and investigators were blinded to the treatment allocation. Twenty children were excluded during the treatment phase (PQ arm: 14, PL arm: 6), and 504 were followed actively for 9 mo. During the follow-up time, 18 children (PQ arm: 7, PL arm: 11) were lost to follow-up. Main primary and secondary outcome measures were time to first P. vivax infection (by qPCR), time to first clinical episode, force of infection, gametocyte positivity, and time to first P. ovale infection (by PCR). A basic stochastic transmission model was developed to estimate the potential effect of mass drug administration (MDA) for the prevention of recurrent P. vivax infections. Targeting hypnozoites through PQ treatment reduced the risk of having at least one qPCR-detectable P. vivax or P. ovale infection during 8 mo of follow-up (P. vivax: PQ arm 0.63/y versus PL arm 2.62/y, HR = 0.18 [95% CI 0.14, 0.25], p < 0.001; P. ovale: 0.06 versus 0.14, HR = 0.31 [95% CI 0.13, 0.77], p = 0.011) and the risk of having at least one clinical P. vivax episode (HR = 0.25 [95% CI 0.11, 0.61], p = 0.002). PQ also reduced the molecular force of P. vivax blood-stage infection in the first 3 mo of follow-up (PQ arm 1.90/y versus PL arm 7.75/y, incidence rate ratio [IRR] = 0.21 [95% CI 0.15, 0.28], p < 0.001). Children who received PQ were less likely to carry P. vivax gametocytes (IRR = 0.27 [95% CI 0.19, 0.38], p < 0.001). PQ had a comparable effect irrespective of the presence of P. vivax blood-stage infection at the time of treatment (p = 0.14). Modelling revealed that mass screening and treatment with highly sensitive quantitative real-time PCR, or MDA with blood-stage treatment alone, would have only a transient effect on P. vivax transmission levels, while MDA that includes liver-stage treatment is predicted to be a highly effective strategy for P. vivax elimination. The inclusion of a directly observed 20-d treatment regime maximises the efficiency of hypnozoite clearance but limits the generalisability of results to real-world MDA programmes.; These results suggest that relapses cause approximately four of every five P. vivax infections and at least three of every five P. ovale infections in PNG children and are important in sustaining transmission. MDA campaigns combining blood- and liver-stage treatment are predicted to be a highly efficacious intervention for reducing P. vivax and P. ovale transmission.; ClinicalTrials.gov NCT02143934
Coronary Artery Remodeling in a Model of Left Ventricular Pressure Overload is Influenced by Platelets and Inflammatory Cells
Left ventricular hypertrophy (LVH) is usually accompanied by intensive interstitial and perivascular fibrosis, which may contribute to arrhythmogenic sudden cardiac death. The mechanisms underlying the development of cardiac fibrosis are incompletely understood. To investigate the role of perivascular inflammation in coronary artery remodeling and cardiac fibrosis during hypertrophic ventricular remodeling, we used a well-established mouse model of LVH (transverse aortic constriction [TAC]). Three days after pressure overload, macrophages and T lymphocytes accumulated around and along left coronary arteries in association with luminal platelet deposition. Consistent with these histological findings, cardiac expression of IL-10 was upregulated and in the systemic circulation, platelet white blood cell aggregates tended to be higher in TAC animals compared to sham controls. Since platelets can dynamically modulate perivascular inflammation, we investigated the impact of thrombocytopenia on the response to TAC. Immunodepletion of platelets decreased early perivascular T lymphocytes\u27 accumulation and altered subsequent coronary artery remodeling. The contribution of lymphocytes were examined in Rag1(-/-) mice, which displayed significantly more intimal hyperplasia and perivascular fibrosis compared to wild-type mice following TAC. Collectively, our studies support a role of early perivascular accumulation of platelets and T lymphocytes in pressure overload-induced inflammation
Meta-modal Information Flow: A Method for Capturing Multimodal Modular Disconnectivity in Schizophrenia
Objective: Multimodal measurements of the same phenomena provide
complementary information and highlight different perspectives, albeit each
with their own limitations. A focus on a single modality may lead to incorrect
inferences, which is especially important when a studied phenomenon is a
disease. In this paper, we introduce a method that takes advantage of
multimodal data in addressing the hypotheses of disconnectivity and dysfunction
within schizophrenia (SZ). Methods: We start with estimating and visualizing
links within and among extracted multimodal data features using a Gaussian
graphical model (GGM). We then propose a modularity-based method that can be
applied to the GGM to identify links that are associated with mental illness
across a multimodal data set. Through simulation and real data, we show our
approach reveals important information about disease-related network
disruptions that are missed with a focus on a single modality. We use
functional MRI (fMRI), diffusion MRI (dMRI), and structural MRI (sMRI) to
compute the fractional amplitude of low frequency fluctuations (fALFF),
fractional anisotropy (FA), and gray matter (GM) concentration maps. These
three modalities are analyzed using our modularity method. Results: Our results
show missing links that are only captured by the cross-modal information that
may play an important role in disconnectivity between the components.
Conclusion: We identified multimodal (fALFF, FA and GM) disconnectivity in the
default mode network area in patients with SZ, which would not have been
detectable in a single modality. Significance: The proposed approach provides
an important new tool for capturing information that is distributed among
multiple imaging modalities
Asymptomatic Plasmodium vivax infections induce robust IgG responses to multiple blood-stage proteins in a low-transmission region of western Thailand
BACKGROUND: Thailand is aiming to eliminate malaria by the year
2024. Plasmodium vivax has now become the dominant species
causing malaria within the country, and a high proportion of
infections are asymptomatic. A better understanding of antibody
dynamics to P. vivax antigens in a low-transmission setting,
where acquired immune responses are poorly characterized, will
be pivotal for developing new strategies for elimination, such
as improved surveillance methods and vaccines. The objective of
this study was to characterize total IgG antibody levels to 11
key P. vivax proteins in a village of western Thailand. METHODS:
Plasma samples from 546 volunteers enrolled in a cross-sectional
survey conducted in 2012 in Kanchanaburi Province were utilized.
Total IgG levels to 11 different proteins known or predicted to
be involved in reticulocyte binding or invasion (ARP, GAMA, P41,
P12, PVX_081550, and five members of the PvRBP family), as well
as the leading pre-erythrocytic vaccine candidate (CSP) were
measured using a multiplexed bead-based assay. Associations
between IgG levels and infection status, age, and spatial
location were explored. RESULTS: Individuals from a
low-transmission region of western Thailand reacted to all 11 P.
vivax recombinant proteins. Significantly greater IgG levels
were observed in the presence of a current P. vivax infection,
despite all infected individuals being asymptomatic. IgG levels
were also higher in adults (18 years and older) than in
children. For most of the proteins, higher IgG levels were
observed in individuals living closer to the Myanmar border and
further away from local health services. CONCLUSIONS: Robust IgG
responses were observed to most proteins and IgG levels
correlated with surrogates of exposure, suggesting these
antigens may serve as potential biomarkers of exposure,
immunity, or both
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