Monomorphic Trypanozoon: towards reconciling phylogeny and pathologies

Trypanosoma brucei evansi and T. brucei equiperdum are animal infective trypanosomes conventionally classified by their clinical disease presentation, mode of transmission, host range, kinetoplast DNA (kDNA) composition and geographical distribution. Unlike other members of the subgenus Trypanozoon, they are non-tsetse transmitted and predominantly morphologically uniform (monomorphic) in their mammalian host. Their classification as independent species or subspecies has been long debated and genomic studies have found that isolates within T. brucei evansi and T. brucei equiperdum have polyphyletic origins. Since current taxonomy does not fully acknowledge these polyphyletic relationships, we re-analysed publicly available genomic data to carefully define each clade of monomorphic trypanosome. This allowed us to identify, and account for, lineage-specific variation. We included a recently published isolate, IVM-t1, which was originally isolated from the genital mucosa of a horse with dourine and typed as T. equiperdum. Our analyses corroborate previous studies in identifying at least four distinct monomorphic T. brucei clades. We also found clear lineage-specific variation in the selection efficacy and heterozygosity of the monomorphic lineages, supporting their distinct evolutionary histories. The inferred evolutionary position of IVM-t1 suggests its reassignment to the T. brucei evansi type B clade, challenging the relationship between the Trypanozoon species, the infected host, mode of transmission and the associated pathological phenotype. The analysis of IVM-t1 also provides, to our knowledge, the first evidence of the expansion of T. brucei evansi type B, or a fifth monomorphic lineage represented by IVM-t1, outside of Africa, with important possible implications for disease diagnosis.

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Monomorphic Trypanozoon: towards reconciling phylogeny and pathologies

10.1101/2021.04.14.439642 ◽

2021 ◽

Author(s):

Guy Oldrieve ◽

Mylène Verney ◽

Kamil S. Jaron ◽

Laurent Hébert ◽

Keith Matthews

Keyword(s):

Trypanosoma Brucei ◽

Geographic Distribution ◽

Disease Diagnosis ◽

Mammalian Host ◽

Tsetse Flies ◽

Supplementary File ◽

Type B ◽

Sequencing Data ◽

Specific Variation ◽

Mode Of Transmission

2.AbstractTrypanosoma brucei evansi and Trypanosoma brucei equiperdum are animal infective trypanosomes conventionally classified by their clinical disease presentation, mode of transmission, host range, kDNA composition and geographic distribution. Unlike other members of the subgenus Trypanozoon, they are non-tsetse transmitted and predominantly morphologically uniform (monomorphic) in their mammalian host. Their classification as independent species or subspecies has been long debated and genomic studies have found that isolates within T. b. evansi and T. b. equiperdum have polyphyletic origins. Since current taxonomy does not fully acknowledge these polyphyletic relationships, we re-analysed publicly available genomic data to carefully define each clade of monomorphic trypanosome. This allowed us to identify, and account for, lineage specific variation. We included a recently published isolate, IVM-t1, which was originally isolated from the genital mucosa of a horse with dourine and typed as T. equiperdum. Our analyses corroborate previous studies in identifying at least four distinct monomorphic T. brucei clades. We also found clear lineage specific variation in the selection efficacy and heterozygosity of the monomorphic lineages, supporting their distinct evolutionary histories. The inferred evolutionary position of IVM-t1 suggests its reassignment to the T. b. evansi type B clade, challenging the relationship between the Trypanozoon species, the infected host, mode of transmission and the associated pathological phenotype. The analysis of IVM-t1 also provides the first evidence of the expansion of T. b. evansi type B, or a 5th monomorphic lineage represented by IVM-t1, outside of Africa, with important possible implications for disease diagnosis.3.Impact statementTrypanosoma brucei are unicellular parasites typically transmitted by tsetse flies. Subspecies of T. brucei cause human African trypanosomiasis and the animal diseases, nagana, surra and dourine. T. b. evansi and T. b. equiperdum have branched from T. brucei and, by foregoing tsetse transmission, expanded their geographic range beyond the sub-Saharan tsetse belt. These species can only reproduce asexually and exhibit morphological uniformity in their host (‘monomorphism’). T. b. evansi and T. b. equiperdum have historically been classified based on fragmentary information on the parasites’ transmission routes, geographic distribution, kDNA composition and disease phenotypes. Our analysis of genome sequencing data from monomorphic T. brucei supports at least four independent origins with distinct evolutionary histories. One isolate, IVM-t1, typed as T. equiperdum, is a closer relative to T. b. evansi, highlighting the risk of using pathognomonic descriptors for subspecies assignment. We show clear lineage specific variation in the selection efficacy in monomorphic T. brucei. Using the evolutionary relationships between lineages, we suggest it would be beneficial to reconcile phylogeny and pathology in monomorphic trypanosomes.4.Data summaryThe data used in this study is available from the Sequence Read Archive or the Wellcome Sanger Institute. The accessions can be found in Supplementary file 1.

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Migraine: Genetic Variants and Clinical Phenotypes

Current Medicinal Chemistry ◽

10.2174/0929867325666180719120215 ◽

2019 ◽

Vol 26 (34) ◽

pp. 6207-6221 ◽

Cited By ~ 1

Author(s):

Innocenzo Rainero ◽

Alessandro Vacca ◽

Flora Govone ◽

Annalisa Gai ◽

Lorenzo Pinessi ◽

...

Keyword(s):

Genetic Variants ◽

Association Studies ◽

Mthfr Gene ◽

Genome Wide Association Studies ◽

Clinical Phenotypes ◽

Network Analyses ◽

Genome Wide ◽

Genomic Studies ◽

The Common ◽

The Relationship

Migraine is a common, chronic neurovascular disorder caused by a complex interaction between genetic and environmental risk factors. In the last two decades, molecular genetics of migraine have been intensively investigated. In a few cases, migraine is transmitted as a monogenic disorder, and the disease phenotype cosegregates with mutations in different genes like CACNA1A, ATP1A2, SCN1A, KCNK18, and NOTCH3. In the common forms of migraine, candidate genes as well as genome-wide association studies have shown that a large number of genetic variants may increase the risk of developing migraine. At present, few studies investigated the genotype-phenotype correlation in patients with migraine. The purpose of this review was to discuss recent studies investigating the relationship between different genetic variants and the clinical characteristics of migraine. Analysis of genotype-phenotype correlations in migraineurs is complicated by several confounding factors and, to date, only polymorphisms of the MTHFR gene have been shown to have an effect on migraine phenotype. Additional genomic studies and network analyses are needed to clarify the complex pathways underlying migraine and its clinical phenotypes.

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Modification of Type B Inclusions by Calcium Treatment in High-Carbon Hard-Wire Steel

Metals ◽

10.3390/met11050676 ◽

2021 ◽

Vol 11 (5) ◽

pp. 676

Author(s):

Linzhu Wang ◽

Zuobing Xi ◽

Changrong Li

Keyword(s):

Inclusion Size ◽

Type B ◽

Calcium Treatment ◽

High Carbon ◽

Fine Size ◽

Dispersed Inclusions ◽

Wire Steel ◽

Classical Thermodynamics ◽

The Relationship

To investigate the modification of type B inclusions in high-carbon hard-wire steel with Ca treatment, Si-Ca alloy was added to high-carbon hard-steel, and the composition, morphology, size, quantity, and distribution of inclusions were observed. The samples were investigated by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS). The experimental thermal results showed that the modification effect of inclusion was better in high-carbon hard-wire steel with Al of 0.0053% and Ca of 0.0029% than that in steel with Al of 0.011% and Ca of 0.0052%, in which the inclusions were mainly spherical semi-liquid and liquid CA2, CA, and C12A7. The inclusion size decreased from 3.2 μm to 2.1 μm. The degree of inclusions segregation was reduced in high-carbon hard-wire steels after calcium treatment. The results indicate that the modification of inclusions is conducive to obtaining dispersed inclusions with fine size. The ratio of length to width decreased and tended to be 1 with the increase in CaO content in the inclusion. When the content of CaO was higher than 30%, the aspect ratio was in the range of 1 to 1.2. The relationship between the activity of aluminum and calcium and the inclusions type at equilibrium in high-carbon hard-wire steel was estimated using classical thermodynamics. The calculated results were consistent with the experimental results. The thermodynamic software Factsage was used to analyze the effect of aluminum and calcium additions on the type and quality of inclusions in high-carbon hard-wire steels. The modification law and mechanism of type B inclusions in high-carbon hard-wire steels are discussed.

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The Relationship between AGAMOUS and Cytokinin Signaling in the Establishment of Carpeloid Features

Plants ◽

10.3390/plants10050827 ◽

2021 ◽

Vol 10 (5) ◽

pp. 827

Author(s):

Andrea Gómez-Felipe ◽

Daniel Kierzkowski ◽

Stefan de Folter

Keyword(s):

Regulatory Network ◽

Dependent Manner ◽

Mads Box ◽

Type B ◽

Cytokinin Signaling ◽

Reproductive Structures ◽

Carpel Development ◽

Gene Regulatory ◽

The Relationship ◽

Gynoecium Development

Gynoecium development is dependent on gene regulation and hormonal pathway interactions. The phytohormones auxin and cytokinin are involved in many developmental programs, where cytokinin is normally important for cell division and meristem activity, while auxin induces cell differentiation and organ initiation in the shoot. The MADS-box transcription factor AGAMOUS (AG) is important for the development of the reproductive structures of the flower. Here, we focus on the relationship between AG and cytokinin in Arabidopsis thaliana, and use the weak ag-12 and the strong ag-1 allele. We found that cytokinin induces carpeloid features in an AG-dependent manner and the expression of the transcription factors CRC, SHP2, and SPT that are involved in carpel development. AG is important for gynoecium development, and contributes to regulating, or else directly regulates CRC, SHP2, and SPT. All four genes respond to either reduced or induced cytokinin signaling and have the potential to be regulated by cytokinin via the type-B ARR proteins. We generated a model of a gene regulatory network, where cytokinin signaling is mainly upstream and in parallel with AG activity.

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The relationship between the age of Schistosoma mansoni cercariae and their ability to penetrate and infect the mammalian host

Parasitology ◽

10.1017/s0031182000083001 ◽

1983 ◽

Vol 87 (3) ◽

pp. 481-492 ◽

Cited By ~ 10

Author(s):

J. Ruth Lawson ◽

R. A. Wilson

Keyword(s):

Schistosoma Mansoni ◽

Stratum Corneum ◽

Mass Mortality ◽

Mammalian Host ◽

Energy Reserves ◽

Age Related ◽

Abdominal Route ◽

Relationship Of ◽

The Relationship ◽

Related Mortality

SummaryThe ability of the cercariae of Schistosoma mansoni to penetrate the tails of mice was shown to remain constant throughout their lives. However, their capacity to establish themselves and then reach maturity decreased as they aged. The abdominal route of penetration produced consistently higher maturation rates than the tail route. Significantly different maturation rates were obtained by modifying the standard tail infection technique. Evidence is presented that age-related mortality of schisto-somula occurs within 24 h of penetration and may be associated with the exhaustion of energy reserves during the penetration of the stratum corneum. The relationship of this age-related mortality to ‘mass mortality’ is discussed.

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Type B trichothecenes-the relationship between slight structural changes and toxicity

JSM Mycotoxins ◽

10.2520/myco.66.45 ◽

2016 ◽

Vol 66 (1) ◽

pp. 45-55

Author(s):

Tadahiro Suzuki ◽

Yumiko Iwahashi

Keyword(s):

Structural Changes ◽

Type B ◽

The Relationship

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A retrospective, population-based cohort study of driving under the influence, Alzheimer’s disease diagnosis, and survival

International Psychogeriatrics ◽

10.1017/s1041610218001151 ◽

2018 ◽

Vol 31 (04) ◽

pp. 571-577 ◽

Cited By ~ 1

Author(s):

Margaret Miller ◽

Dennis Orwat ◽

Gelareh Rahimi ◽

Jacobo Mintzer

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cohort Study ◽

Law Enforcement ◽

Disease Diagnosis ◽

Population Based ◽

Alcohol Addiction ◽

Driving Under The Influence ◽

History Of ◽

The Relationship

ABSTRACTIntroduction:The relationship between Alzheimer’s Disease (AD) and alcohol addiction is poorly characterized. Arrests for driving under the influence (DUI) can serve as a proxy for alcohol addiction. Therefore, the potential association between DUI and AD could be helpful in understanding the relationship between alcohol abuse and AD.Materials and methods:A retrospective, population-based cohort study using state health and law enforcement data was performed. The study cross-referenced 141,281 South Carolina Alzheimer’s Disease Registry cases with state law enforcement data.Results:Of the 2,882 registry cases (1.4%) found to have a history of at least one DUI arrest, cases were predominantly White (58.7%) and male (77.4%). Results showed a correlation coefficient of 0.7 (p < 0.0001) between the age of first DUI arrest and the age of AD diagnosis. A dose-response relationship between the number of DUIs and age of AD onset was found to exist, where those with a history of DUI arrest were diagnosed an average of 9.1 years earlier, with a further 1.8 years earlier age at diagnosis in those with two or more arrests for DUI. A history of DUI arrest was also found to be negatively associated with survival after diagnosis, with a 10% decreased life expectancy in those with a DUI arrest history.Conclusions:Driving under the influence, a potential indicator of alcohol addiction, is associated with an earlier onset of AD registry diagnosis and shortened survival after diagnosis. This study contributes to the growing body of evidence suggesting that some cases of AD are alcohol related and, possibly, postponable or preventable.

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Respiratory Periodicity and Electroencephalogram Arousals During Sleep in Older Adults

Biological Research For Nursing ◽

10.1177/1099800406298072 ◽

2007 ◽

Vol 8 (4) ◽

pp. 249-260 ◽

Cited By ~ 3

Author(s):

Barbara Waag Carlson ◽

Virginia J. Neelon ◽

John R. Carlson ◽

Marilyn Hartman ◽

Sunil Dogra

Keyword(s):

Older Adults ◽

Exploratory Study ◽

High Variability ◽

Arterial Oxygenation ◽

Type B ◽

Breathing Patterns ◽

The Mean ◽

Relationship Of ◽

The Relationship ◽

Electroencephalogram Eeg

The aim of this exploratory study was to examine the relationship of electroencephalogram (EEG) arousals to breathing patterns and the relationship of both arousals and breathing patterns to arterial oxygenation during sleep in older adults. Five older adults were monitored using standard polysomnography. Records were divided into 5-min segments and breathing patterns identified based on the level of respiratory periodicity and the variability in the frequency of breathing cycles. Standard criteria were used to determine sleep states and occurrence of EEG arousals. High respiratory periodicity was seen in 23% of the segments, whereas 24% had low respiratory periodicity with minimal variability in the frequency of breathing (Type A low respiratory periodicity) and 53% had low respiratory periodicity with high variability in the frequency of breathing (Type B low respiratory periodicity). Nearly all (97%) segments with high respiratory periodicity had EEG arousals, whereas fewer segments (33%) with low respiratory periodicity had arousals, regardless of the stage of sleep. Desaturations occurred more often in segments with high respiratory periodicity, F (2,4) = 57.3, p < .001, but overall, the mean SaO2 of segments with high respiratory periodicity did not differ from levels seen in segments with low respiratory periodicity, F( 2,4) = 0.77, ns. Our findings suggest that high respiratory periodicity is a common feature of EEG arousals and, in older adults, may be important for maintaining oxygen levels during desaturations during sleep.

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Antigenic variation in its biological context

Philosophical Transactions of the Royal Society of London Series B Biological Sciences ◽

10.1098/rstb.1984.0106 ◽

1984 ◽

Vol 307 (1131) ◽

pp. 27-40 ◽

Cited By ~ 23

Keyword(s):

Salivary Glands ◽

Antigenic Variation ◽

Tsetse Fly ◽

Mammalian Host ◽

Full Understanding ◽

Anamnestic Response ◽

Insect Midgut ◽

The Relationship ◽

Biological Context

The biology of antigenic variation is discussed, and the problems that must be solved to provide a full understanding of antigenic variation are considered. These are (i) the induction of v.s.g. synthesis in the salivary glands of the tsetse fly; (ii) the nature of the restriction on v.s.g. genes that allows only some of them to be expressed in the salivary glands; (iii) the nature of ‘predominance’ in v.s.g. expression in the mammalian host, and the mechanism by which it operates; (iv) the repression of v.s.g. synthesis in the insect midgut; (v) the anamnestic response that produces expression of the ingested variant in the first patent parasitaemia in the mammalian host; (vi) the mechanism by which only one v.s.g. gene at a time is expressed; (vii) the relationship if any ofv.s.g. structure to v.s.g.-associated differences in growth rate and host range; (viii) the role of v.s.g. release within the life cycle and to pathogenesis.

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Boolean Implication Analysis Unveils Candidate Universal Relationships in Microbiome Data

10.21203/rs.3.rs-65519/v1 ◽

2020 ◽

Author(s):

Daniella Vo ◽

Shayal Charisma Singh ◽

Sara Safa ◽

Debashis Sahoo

Keyword(s):

Disease Diagnosis ◽

Biological Properties ◽

Weak Correlation ◽

Human Environment ◽

Asymmetric Data ◽

Therapeutic Properties ◽

Almost All ◽

Microbiome Data ◽

The Relationship ◽

Boolean Implication

Abstract Background: Microbiomes consist of bacteria, viruses, and other microorganisms, and are responsible for many different functions in both organisms and the environment. Some previous analyses of microbiomes focus on the relationships between specific microbiomes and a particular disease. These typically use correlation which is fundamentally symmetric with respect to pairs of microbes. Correlation focuses on the symmetry of the data distribution, and asymmetric data is often discarded as having a weak correlation. With all the data available on the microbiome, there is a need for a method that comprehensively studies microbiomes and how they are related to each other.Results: We collect publicly available datasets from human, environment, and animal samples to determine both symmetric and asymmetric Boolean relationships between a pair of microbes. We then find relationships that are potentially invariants, meaning they will hold in any microbe community. In other words, if we determine there is a relationship between two microbes, we expect the relationship to hold in almost all context. We discovered that certain pairs of microbes always exhibit the same relationship in almost all the datasets we studied, thus making them good candidates for universal relationships. Our results confirm known biological properties and seem promising in terms of disease diagnosis.Conclusions: Since the relationships are likely universal, we expect that they will hold in a clinical setting as well as in the general population. Strong universal relationships may provide insight on prognostic, predictive, or therapeutic properties of a clinically relevant disease. These new analyses may improve disease diagnosis and drug development in terms of accuracy and efficiency.

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