scholarly journals Linking functional and molecular mechanisms of host resilience to malaria infection

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Tsukushi Kamiya ◽  
Nicole M Davis ◽  
Megan A Greischar ◽  
David Schneider ◽  
Nicole Mideo
Keyword(s):  
Malaria Infection ◽  
Molecular Mechanisms ◽  
Parasite Clearance ◽  
Mouse Strains ◽  
Cross Sectional ◽  
Host Interactions ◽  
Proximate Mechanisms ◽  
Longitudinal Measurements ◽  
Host Mortality ◽  
Functional Mechanisms

It remains challenging to understand why some hosts suffer severe illnesses, while others are unscathed by the same infection. We fitted a mathematical model to longitudinal measurements of parasite and red blood cell density in murine hosts from diverse genetic backgrounds to identify aspects of within-host interactions that explain variation in host resilience and survival during acute malaria infection. Among eight mouse strains that collectively span 90% of the common genetic diversity of laboratory mice, we found that high host mortality was associated with either weak parasite clearance, or a strong, yet imprecise response that inadvertently removes uninfected cells in excess. Subsequent cross-sectional cytokine assays revealed that the two distinct functional mechanisms of poor survival were underpinned by low expression of either pro- or anti-inflammatory cytokines, respectively. By combining mathematical modelling and molecular immunology assays, our study uncovered proximate mechanisms of diverse infection outcomes across multiple host strains and biological scales.

Recent approaches for isolating and culturing mouse bone marrow-derived mesenchymal stromal stem cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Basem M. Abdallah ◽  
Hany M. Khattab
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Molecular Mechanisms ◽  
Replicative Senescence ◽  
Cellular Heterogeneity ◽  
High Yield ◽  
Mouse Strains ◽  
Mouse Bone Marrow ◽  
Differentiation Potential ◽  
Stromal Stem Cells

: The isolation and culture of murine bone marrow-derived mesenchymal stromal stem cells (mBMSCs) have attracted great interest in terms of the pre-clinical applications of stem cells in tissue engineering and regenerative medicine. In addition, culturing mBMSCs is important for studying the molecular mechanisms of bone remodelling using relevant transgenic mice. Several factors have created challenges in the isolation and high-yield expansion of homogenous mBMSCs; these factors include low frequencies of bone marrow-derived mesenchymal stromal stem cells (BMSCs) in bone marrow, variation among inbred mouse strains, contamination with haematopoietic progenitor cells (HPCs), the replicative senescence phenotype and cellular heterogeneity. In this review, we provide an overview of nearly all protocols used for isolating and culturing mBMSCs with the aim of clarifying the most important guidelines for culturing highly purified mBMSC populations retaining in vitro and in vivo differentiation potential.

scholarly journals Utilization of key preventive measures for pregnancy complications and malaria among women in Jimma Zone, Ethiopia

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Mariame Ouedraogo ◽  
Jaameeta Kurji ◽  
Lakew Abebe ◽  
Ronald Labonté ◽  
Sudhakar Morankar ◽  
...  
Keyword(s):  
Health Services ◽  
Pregnant Women ◽  
Malaria Infection ◽  
Preventive Measures ◽  
Health Sector ◽  
Maternal Health Services ◽  
Cross Sectional Survey ◽  
Wealth Status ◽  
Cross Sectional ◽  
Jimma Zone

Abstract Background In Ethiopia, malaria infections and other complications during pregnancy contribute to the high burden of maternal morbidity and mortality. Preventive measures are available, however little is known about the factors influencing the uptake of maternal health services and interventions by pregnant women in Ethiopia. Methods We analyzed data from a community-based cross-sectional survey conducted in 2016 in three rural districts of Jimma Zone, Ethiopia, with 3784 women who had a pregnancy outcome in the year preceding the survey. We used multivariable logistic regression models accounting for clustering to identify the determinants of antenatal care (ANC) attendance and insecticide-treated net (ITN) ownership and use, and the prevalence and predictors of malaria infection among pregnant women. Results Eighty-four percent of interviewed women reported receiving at least one ANC visit during their last pregnancy, while 47% reported attending four or more ANC visits. Common reasons for not attending ANC included women’s lack of awareness of its importance (48%), distance to health facility (23%) and unavailability of transportation (14%). Important determinants of ANC attendance included higher education level and wealth status, woman’s ability to make healthcare decisions, and pregnancy intendedness. An estimated 48% of women reported owning an ITN during their last pregnancy. Of these, 55% reported to have always slept under it during their last pregnancy. Analysis revealed that the odds of owning and using ITNs were respectively 2.07 (95% CI: 1.62–2.63) and 1.73 (95% CI: 1.32–2.27) times higher among women who attended at least one ANC visit. The self-reported prevalence of malaria infection during pregnancy was low (1.4%) across the three districts. We found that young, uneducated, and unemployed women presented higher odds of malaria infection during their last pregnancy. Conclusion ANC and ITN uptake during pregnancy in Jimma Zone fall below the respective targets of 95 and 90% set in the Ethiopian Health Sector Transformation Plan for 2020, suggesting that more intensive programmatic efforts still need to be directed towards improving access to these health services. Reaching ANC non-users and ITN ownership and use as part of ANC services could be emphasized to address these gaps.

scholarly journals Physiology of a Microgravity Environment Invited Review: Microgravity and skeletal muscle

2000 ◽  
Vol 89 (2) ◽  
pp. 823-839 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Thin Filament ◽  
Molecular Mechanisms ◽  
Skeletal Muscle Atrophy ◽  
Microgravity Environment ◽  
Type I ◽  
Fiber Types ◽  
Maximal Velocity ◽  
Cross Sectional

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

scholarly journals The Function of the PRRSV–Host Interactions and Their Effects on Viral Replication and Propagation in Antiviral Strategies

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 364
Author(s):  
Jun Ma ◽  
Lulu Ma ◽  
Meiting Yang ◽  
Wei Wu ◽  
Wenhai Feng ◽  
...  
Keyword(s):  
Immune Response ◽  
Molecular Mechanisms ◽  
Immune Escape ◽  
Rna Virus ◽  
Economic Losses ◽  
Respiratory Syndrome Virus ◽  
Swine Industry ◽  
Live Virus ◽  
Virus Challenge ◽  
Host Interactions

Porcine reproductive and respiratory syndrome virus (PRRSV) affects the global swine industry and causes disastrous economic losses each year. The genome of PRRSV is an enveloped single-stranded positive-sense RNA of approximately 15 kb. The PRRSV replicates primarily in alveolar macrophages of pig lungs and lymphatic organs and causes reproductive problems in sows and respiratory symptoms in piglets. To date, studies on how PRRSV survives in the host, the host immune response against viral infections, and pathogenesis, have been reported. PRRSV vaccines have been developed, including inactive virus, modified live virus, attenuated live vaccine, DNA vaccine, and immune adjuvant vaccines. However, there are certain problems with the durability and effectiveness of the licensed vaccines. Moreover, the high variability and fast-evolving populations of this RNA virus challenge the design of PRRSV vaccines, and thus effective vaccines against PRRSV have not been developed successfully. As is well known, viruses interact with the host to escape the host’s immune response and then replicate and propagate in the host, which is the key to virus survival. Here, we review the complex network and the mechanism of PRRSV–host interactions in the processes of virus infection. It is critical to develop novel antiviral strategies against PRRSV by studying these host–virus interactions and structures to better understand the molecular mechanisms of PRRSV immune escape.

scholarly journals The Relationship between Body Mass Index, Obesity, and LINE-1 Methylation: A Cross-Sectional Study on Women from Southern Italy

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Giuliana Favara ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Smoking Status ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
The Relationship

Uncovering the relationship between body mass index (BMI) and DNA methylation could be useful to understand molecular mechanisms underpinning the effects of obesity. Here, we presented a cross-sectional study, aiming to evaluate the association of BMI and obesity with long interspersed nuclear elements (LINE-1) methylation, among 488 women from Catania, Italy. LINE-1 methylation was assessed in leukocyte DNA by pyrosequencing. We found a negative association between BMI and LINE-1 methylation level in both the unadjusted and adjusted linear regression models. Accordingly, obese women exhibited lower LINE-1 methylation level than their normal weight counterpart. This association was confirmed after adjusting for the effect of age, educational level, employment status, marital status, parity, menopause, and smoking status. Our findings were in line with previous evidence and encouraged further research to investigate the potential role of DNA methylation markers in the management of obesity.

scholarly journals Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine

2021 ◽  
Author(s):  
Leetah Senkpeil ◽  
Jyoti Bhardwaj ◽  
Morgan Little ◽  
Prasida Holla ◽  
Aditi Upadhye ◽  
...  
Keyword(s):  
Immune Activation ◽  
Malaria Infection ◽  
Protective Immunity ◽  
Molecular Mechanisms ◽  
Protective Efficacy ◽  
T Cell Response ◽  
Innate Immune ◽  
Transcriptional Analysis ◽  
Innate Immune Activation

Baseline innate immune signatures can influence protective immunity following vaccination. Here, we used systems transcriptional analysis to assess the molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole sporozoite PfSPZ Vaccine in African infants. Innate immune activation and myeloid signatures at pre-vaccination baseline correlated with protection from Plasmodium falciparum infection in placebo controls, while the same signatures predicted susceptibility to infection among infants who received the highest and most protective dose of the PfSPZ Vaccine. Machine learning identified monocytes and an antigen presentation signature as pre-vaccination features predictive of malaria infection after highest-dose PfSPZ vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against malaria infection in mice while diminishing the CD8+ T cell response to radiation-attenuated sporozoites. These data establish a dichotomous role of innate stimulation for malaria protection and induction of protective immunity of whole-sporozoite malaria vaccines.

Abstract MP13: TRPM7 Downregulation Contributes To Cardiovascular Injury And Hypertension Induced By Aldosterone And Salt

Hypertension ◽  
2020 ◽  
Vol 76 (Suppl_1) ◽  
Author(s):  
Francisco J Rios ◽  
ZhiGuo Zou ◽  
Karla B Neves ◽  
Sarah S Nichol ◽  
Livia L Camargo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cardiac Fibroblasts ◽  
Protective Role ◽  
Internal Diameter ◽  
Resistance Arteries ◽  
Cross Sectional ◽  
Vessel Structure ◽  
Cardiovascular Fibrosis ◽  
Fold Activation

TRPM7 has cation channel and kinase properties, is permeable to Mg 2+ , Ca 2+ , and Zn 2+ and is protective in the cardiovascular system. Hyperaldosteronism, which induces hypertension and cardiovascular fibrosis, is associated with Mg 2+ wasting. Here we questioned whether TRPM7 plays a role in aldosterone- induced hypertension and fibrosis and whether it influences cation regulation. Wild-type (WT) and TRPM7-deficient (M7+/Δ) mice were treated with aldosterone (600μg/Kg/day) and/or 1% NaCl (drinking water) (aldo, salt or aldo-salt) for 4 weeks. Blood pressure (BP) was evaluated by tail-cuff. Vessel structure was assessed by pressure myography. Molecular mechanisms were investigated in cardiac fibroblasts (CF) from WT and M7+/Δ mice. Protein expression was assessed by western-blot and histology. M7+/Δ mice exhibited reduced TRPM7 expression (30%) and phosphorylation (62%), levels that were recapitulated in WT aldo-salt mice. M7+/Δ exhibited increased BP by aldo, salt and aldo-salt (135-140mmHg) vs M7+/Δ-veh (117mmHg) (p<0.05), whereas in WT, BP was increased only by aldo-salt (134mmHg). Mesenteric resistance arteries from WT aldo-salt exhibited increased wall/lumen ratio (80%) and reduced internal diameter (15%) whereas vessels from M7+/Δ exhibited thinner walls by reducing cross-sectional area (35%) and increased internal diameter (23%) after aldo-salt. Aldo-salt induced greater collagen deposition in hearts (68%), kidneys (126%) and aortas (45%) from M7+/Δ vs WT. Hearts from M7+/Δ veh exhibited increased TGFβ, IL-11 and IL-6 (1.9-fold), p-Smad3 and p-Stat1 (1.5-fold) whereas in WT these effects were only found after aldo-salt. Cardiac expression of protein phosphatase magnesium-dependent 1A (PPM1A), a Mg 2+ -dependent phosphatase, was reduced (3-fold) only in M7+/Δ mice. M7+/Δ CF showed reduced proliferation (30%) and PPM1A (4-fold) and increased expression of TGFβ, IL-11 and IL-6 (2-3-fold), activation of Stat1 (2-fold), Smad3 (9-fold) and ERK1/2 (8-fold) compared with WT. Mg 2+ supplementation normalized cell proliferation and reduced protein phosphorylation in M7+/Δ CF (p<0.05). Our findings indicate a protective role of TRPM7 in aldosterone-salt induced cardiovascular injury through Mg 2+ -dependent mechanisms.

Stress and Bipolar Disorder

2020 ◽  
pp. 297-328
Author(s):  
Richard McCarty
Keyword(s):  
Bipolar Disorder ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Clock Genes ◽  
Mood State ◽  
Mouse Strains ◽  
Transporter Protein ◽  
Circadian Clock Genes ◽  
Dopamine Signaling ◽  
And Behavior

Animal models of bipolar disorder (BD) should capture the switching of mood states from mania to depression and vice versa. Dopamine signaling pathways in brain, including variations in the dopamine transporter protein, have been a focus of many animal models of BD. Another aspect of BD in humans is reflected in circadian and seasonal changes in onset of symptoms. Other animal models of BD include the Myshkin and Madison mouse strains, both of which display mania-like behavior that is reversed by treatment with lithium or valproic acid. Another experimental approach has been to manipulate circadian clock genes and examine effects on dopamine signaling and behavior. Finally, manipulations of risk genes for BD in laboratory mice have advanced our understanding of the molecular mechanisms involved in extreme alterations in mood state.

scholarly journals Targeted Disruption of the Plasmodium berghei Ctrp Gene Reveals Its Essential Role in Malaria Infection of the Vector Mosquito

1999 ◽  
Vol 190 (11) ◽  
pp. 1711-1716 ◽  
Author(s):  
Masao Yuda ◽  
Hiroshi Sakaida ◽  
Yasuo Chinzei
Keyword(s):  
Plasmodium Berghei ◽  
Malaria Infection ◽  
Molecular Mechanisms ◽  
Mammalian Host ◽  
Insect Vector ◽  
Wild Type ◽  
Mosquito Midgut ◽  
Parasite Plasmodium ◽  
Vector Mosquito ◽  
Stage 1

CTRP (circumsporozoite protein and thrombospondin-related adhesive protein [TRAP]-related protein) of the rodent malaria parasite Plasmodium berghei (PbCTRP) makes up a protein family together with other apicomplexan proteins that are specifically expressed in the host-invasive stage 1. PbCTRP is produced in the mosquito-invasive, or ookinete, stage and is a protein candidate for a role in ookinete adhesion and invasion of the mosquito midgut epithelium. To demonstrate involvement of PbCTRP in the infection of the vector, we performed targeting disruption experiments with this gene. PbCTRP disruptants showed normal exflagellation rates and development into ookinetes. However, no oocyst formation was observed in the midgut after ingestion of these parasites, suggesting complete loss of their invasion ability. On the other hand, when ingested together with wild-type parasites, disruptants were able to infect mosquitoes, indicating that the PbCTRP gene of the wild-type parasite rescued infectivity of disruptants when they heterologously mated in the mosquito midgut lumen. Our results show that PbCTRP plays a crucial role in malaria infection of the mosquito midgut and suggest that similar molecular mechanisms are used by malaria parasites to invade cells in the insect vector and the mammalian host.

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