Phenotype-genotype comorbidity analysis of patients with rare disorders provides insight into their pathological and molecular bases

An emerging poplar canker caused by the gram-negative bacterium, Lonsdalea populi, has led to high mortality of hybrid poplars Populus × euramericana in China and Europe. The molecular bases of pathogenicity and bark adaptation of L. populi have become a focus of recent research. This study revealed the whole genome sequence and identified putative virulence factors of L. populi. A high-quality L. populi genome sequence was assembled de novo, with a genome size of 3,859,707 bp, containing approximately 3434 genes and 107 RNAs (75 tRNA, 22 rRNA, and 10 ncRNA). The L. populi genome contained 380 virulence-associated genes, mainly encoding for adhesion, extracellular enzymes, secretory systems, and two-component transduction systems. The genome had 110 carbohydrate-active enzyme (CAZy)-coding genes and putative secreted proteins. The antibiotic-resistance database annotation listed that L. populi was resistant to penicillin, fluoroquinolone, and kasugamycin. Analysis of comparative genomics found that L. populi exhibited the highest homology with the L. britannica genome and L. populi encompassed 1905 specific genes, 1769 dispensable genes, and 1381 conserved genes, suggesting high evolutionary diversity and genomic plasticity. Moreover, the pan genome analysis revealed that the N-5-1 genome is an open genome. These findings provide important resources for understanding the molecular basis of the pathogenicity and biology of L. populi and the poplar-bacterium interaction.

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First approach to pod dehiscence in faba bean: genetic and histological analyses

Scientific Reports ◽

10.1038/s41598-020-74750-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

David Aguilar-Benitez ◽

Inés Casimiro-Soriguer ◽

Ana M. Torres

Keyword(s):

Faba Bean ◽

Linkage Mapping ◽

Genetic Basis ◽

Genomic Analysis ◽

Fiber Layer ◽

Dehiscence Zone ◽

Molecular Bases ◽

Insight Into ◽

Pod Dehiscence ◽

Comprehensive Study

Abstract Pod dehiscence causes important yield losses in cultivated crops and therefore has been a key trait strongly selected against in crop domestication. In spite of the growing knowledge on the genetic basis of dehiscence in different crops, no information is available so far for faba bean. Here we conduct the first comprehensive study for faba bean pod dehiscence by combining, linkage mapping, comparative genomics, QTL analysis and histological examination of mature pods. Mapping of dehiscence-related genes revealed conservation of syntenic blocks among different legumes. Three QTLs were identified in faba bean chromosomes II, IV and VI, although none of them was stable across years. Histological analysis supports the convergent phenotypic evolution previously reported in cereals and related legume species but revealed a more complex pattern in faba bean. Contrary to common bean and soybean, the faba bean dehiscence zone appears to show functional equivalence to that described in crucifers. The lignified wall fiber layer, which is absent in the paucijuga primitive line Vf27, or less lignified and vacuolated in other dehiscent lines, appears to act as the major force triggering pod dehiscence in this species. While our findings, provide new insight into the mechanisms underlying faba bean dehiscence, full understanding of the molecular bases will require further studies combining precise phenotyping with genomic analysis.

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Novel Components of the Flagellar System in Epsilonproteobacteria

mBio ◽

10.1128/mbio.01349-14 ◽

2014 ◽

Vol 5 (3) ◽

Cited By ~ 27

Author(s):

Beile Gao ◽

Maria Lara-Tejero ◽

Matthew Lefebre ◽

Andrew L. Goodman ◽

Jorge E. Galán

Keyword(s):

Helicobacter Pylori ◽

Campylobacter Jejuni ◽

Bacterial Pathogens ◽

Bacterial Species ◽

Flagellar Apparatus ◽

Genetic Screen ◽

Chemical Energy ◽

Content Type ◽

Molecular Bases ◽

Insight Into

ABSTRACT Motility is essential for the pathogenesis of many bacterial species. Most bacteria move using flagella, which are multiprotein filaments that rotate propelled by a cell wall-anchored motor using chemical energy. Although some components of the flagellar apparatus are common to many bacterial species, recent studies have shown significant differences in the flagellar structures of different bacterial species. The molecular bases for these differences, however, are not understood. The flagella from epsilonproteobacteria, which include the bacterial pathogens Campylobacter jejuni and Helicobacter pylori, are among the most divergent. Using next-generation sequencing combined with transposon mutagenesis, we have conducted a comprehensive high-throughput genetic screen in Campylobacter jejuni, which identified several novel components of its flagellar system. Biochemical analyses detected interactions between the identified proteins and known components of the flagellar machinery, and in vivo imaging located them to the bacterial poles, where flagella assemble. Most of the identified new components are conserved within but restricted to epsilonproteobacteria. These studies provide insight into the divergent flagella of this group of bacteria and highlight the complexity of this remarkable structure, which has adapted to carry out its conserved functions in the context of widely diverse bacterial species. IMPORTANCE Motility is essential for the normal physiology and pathogenesis of many bacterial species. Most bacteria move using flagella, which are multiprotein filaments that rotate propelled by a motor that uses chemical energy as fuel. Although some components of the flagellar apparatus are common to many bacterial species, recent studies have shown significant divergence in the flagellar structures across bacterial species. However, the molecular bases for these differences are not understood. The flagella from epsilonproteobacteria, which include the bacterial pathogens Campylobacter jejuni and Helicobacter pylori, are among the most divergent. We conducted a comprehensive genetic screen in Campylobacter jejuni and identified several novel components of the flagellar system. These studies provide important information to understand how flagella have adapted to function in the context of widely diverse sets of bacterial species and bring unique insight into the evolution and function of this remarkable bacterial organelle.

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Defects in cytochrome oxidase assembly in humans: lessons from yeastThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB — Membrane Proteins in Health and Disease.

Biochemistry and Cell Biology ◽

10.1139/o06-201 ◽

2006 ◽

Vol 84 (6) ◽

pp. 859-869 ◽

Cited By ~ 31

Author(s):

Jennifer M. Zee ◽

D. Moira Glerum

Keyword(s):

Molecular Mechanisms ◽

Inner Mitochondrial Membrane ◽

Yeast Saccharomyces Cerevisiae ◽

Assembly Pathway ◽

Complex Process ◽

Health And Disease ◽

Molecular Bases ◽

Near Future ◽

Insight Into ◽

Selection Of

The biogenesis of the inner mitochondrial membrane enzyme cytochrome c oxidase (COX) is a complex process that requires the actions of ancillary proteins, collectively called assembly factors. Studies with the yeast Saccharomyces cerevisiae have provided considerable insight into the COX assembly pathway and have proven to be a fruitful model for understanding the molecular bases for inherited COX deficiencies in humans. In this review, we focus on critical steps in the COX assembly pathway. These processes are conserved from yeast to humans and are known to be involved in the etiology of human COX deficiencies. The contributions from our studies in yeast suggest that this organism remains an excellent model system for delineating the molecular mechanisms underlying COX assembly defects in humans. Current progress suggests that a complete picture of COX assembly will be achieved in the near future.

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At-Risk Populations for Osteosarcoma: The Syndromes and Beyond

Sarcoma ◽

10.1155/2012/152382 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 27

Author(s):

George T. Calvert ◽

R. Lor Randall ◽

Kevin B. Jones ◽

Lisa Cannon-Albright ◽

Stephen Lessnick ◽

...

Keyword(s):

At Risk ◽

Effective Treatment ◽

Clinical Features ◽

Genetic Predisposition ◽

Molecular Pathogenesis ◽

Rare Disorders ◽

Primary Malignancy ◽

At Risk Populations ◽

Insight Into

Osteosarcoma is the most common primary malignancy of bone. Most cases are sporadic without a known genetic or environmental cause. Heritable genetic predisposition syndromes are associated with a small percentage of osteosarcomas. Study of these rare disorders has provided insight into the molecular pathogenesis of osteosarcoma. Screening of at-risk families and surveillance of affected individuals for these syndromes may permit earlier diagnosis and more effective treatment of osteosarcoma in these populations. This paper reviews the genetic and clinical features of the known osteosarcoma predisposition syndromes.

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Deciphering the molecular bases of Mycobacterium tuberculosis binding to the lectin DC-SIGN reveals an underestimated complexity

Biochemical Journal ◽

10.1042/bj20050709 ◽

2005 ◽

Vol 392 (3) ◽

pp. 615-624 ◽

Cited By ~ 74

Author(s):

Sylvain Pitarque ◽

Jean-Louis Herrmann ◽

Jean-Luc Duteyrat ◽

Mary Jackson ◽

Graham R. Stewart ◽

...

Keyword(s):

Dendritic Cells ◽

Mycobacterium Tuberculosis ◽

Human Monocyte ◽

Mycobacterial Species ◽

Mycobacterium Species ◽

Tuberculosis Complex ◽

Preferential Recognition ◽

Molecular Bases ◽

Slow Growing ◽

Insight Into

Interactions between dendritic cells and Mycobacterium tuberculosis, the aetiological agent of tuberculosis in humans, are thought to be central to anti-mycobacterial immunity. We have previously shown that M. tuberculosis binds to human monocyte-derived dendritic cells mostly through the C-type lectin DC-SIGN (dendritic-cell-specific intercellular molecule-3-grabbing non-integrin)/CD209, and we have suggested that DC-SIGN may discriminate between mycobacterial species through recognition of the mannose-capping residues on the lipoglycan lipoarabinomannan of the bacterial envelope. Here, using a variety of fast- and slow-growing Mycobacterium species, we provide further evidence that mycobacteria recognition by DC-SIGN may be restricted to species of the M. tuberculosis complex. Fine analyses of the lipoarabinomannan molecules purified from these species show that the structure and amount of these molecules alone cannot account for such a preferential recognition. We propose that M. tuberculosis recognition by DC-SIGN relies on both a potential difference of accessibility of lipoarabinomannan in its envelope and, more probably, on the binding of additional ligands, possibly including lipomannan, mannose-capped arabinomannan, as well as the mannosylated 19 kDa and 45 kDa [Apa (alanine/proline-rich antigen)] glycoproteins. Altogether, our results reveal that the molecular basis of M. tuberculosis binding to DC-SIGN is more complicated than previously thought and provides further insight into the mechanisms of M. tuberculosis recognition by the immune system.

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Molecular models of human visual pigments: insight into the atomic bases of spectral tuning

Bio-Algorithms and Med-Systems ◽

10.1515/bams-2016-0012 ◽

2016 ◽

Vol 12 (3) ◽

Author(s):

Francesca Centola ◽

Fabio Polticelli

Keyword(s):

Electrostatic Interactions ◽

Three Dimensional ◽

Visual Pigments ◽

Molecular Models ◽

Electronic Distribution ◽

Bovine Rhodopsin ◽

A Chain ◽

Green Pigments ◽

Molecular Bases ◽

Insight Into

AbstractThe cycle of vision is a chain of biochemical reactions that occur after exposure of the pigments to the light. The known mechanisms of the transduction of the light pulse derive mainly from studies on bovine rhodopsin. The objective of this work is to construct molecular models of human rhodopsin and opsins, for which three-dimensional structures are not available, to analyze the retinal environment and identify the similarities and differences that characterize the human visual pigments. One of the main results of this work is the identification of Glu102 as the probable second counterion of the Schiff base in M opsin (green pigments) and L opsin (red pigments). Further, the analysis of the molecular models allows uncovering the molecular bases of the different absorption maxima of M and L opsins with respect to rhodopsin and S opsin. These differences appear to be due to both an increase in the polarity of the retinal environment and specific electrostatic interactions, which determine a reorganization of the electronic distribution of retinal by selectively stabilizing one of the two resonance forms.

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Genomic variation in the tea leafhopper reveals the basis of adaptive evolution

10.1101/2021.11.23.469662 ◽

2021 ◽

Author(s):

Qian Zhao ◽

Longqing Shi ◽

Weiyi He ◽

Jinyu Li ◽

Shijun You ◽

...

Keyword(s):

Balancing Selection ◽

Gene Families ◽

Genomic Variation ◽

Genomic Change ◽

Wide Range ◽

Evolutionary Success ◽

Genomic Signals ◽

Molecular Bases ◽

Key Pathways ◽

Insight Into

The tea green leafhopper (TGL), Empoasca onukii, is of biological and economic interest. Despite numerous studies, the mechanisms underlying its adaptation and evolution remain enigmatic. Here, we used previously untapped genome and population genetics approaches to examine how this pest so rapidly has adapted to different environmental variables and thus has expanded geographically. We complete a chromosome-level assembly and annotation of the E. onukii genome, showing notable expansions of gene families associated with adaptation to chemoreception and detoxification. Genomic signals indicating balancing selection highlight metabolic pathways involved in adaptation to a wide range of tea varieties grown across ecologically diverse regions. Patterns of genetic variation among 54 E. onukii samples unveil the population structure and evolutionary history across different tea-growing regions in China. Our results demonstrate that the genomic change in key pathways, including those linked to metabolism, circadian rhythms and immune system function, may underlie the successful spread and adaptation of E. onukii. This work highlights the genetic and molecular bases underlying the evolutionary success of a species with broad economic impact, and provides insight into insect adaptation to host plants, which will ultimately facilitate more sustainable pest management.

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Rational design of adjuvants targeting the C-type lectin Mincle

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1612421114 ◽

2017 ◽

Vol 114 (10) ◽

pp. 2675-2680 ◽

Cited By ~ 48

Author(s):

Alexiane Decout ◽

Sandro Silva-Gomes ◽

Daniel Drocourt ◽

Sophie Barbe ◽

Isabelle André ◽

...

Keyword(s):

Immune Responses ◽

Rational Design ◽

Biological Evaluation ◽

Subunit Vaccines ◽

Rational Development ◽

Dynamics Simulations ◽

Mycobacterial Cell Wall ◽

Molecular Bases ◽

Insight Into

The advances in subunit vaccines development have intensified the search for potent adjuvants, particularly adjuvants inducing cell-mediated immune responses. Identification of the C-type lectin Mincle as one of the receptors underlying the remarkable immunogenicity of the mycobacterial cell wall, via recognition of trehalose-6,6′-dimycolate (TDM), has opened avenues for the rational design of such molecules. Using a combination of chemical synthesis, biological evaluation, molecular dynamics simulations, and protein mutagenesis, we gained insight into the molecular bases of glycolipid recognition by Mincle. Unexpectedly, the fine structure of the fatty acids was found to play a key role in the binding of a glycolipid to the carbohydrate recognition domain of the lectin. Glucose and mannose esterified atO-6 by a synthetic α-ramified 32-carbon fatty acid showed agonist activity similar to that of TDM, despite their much simpler structure. Moreover, they were seen to stimulate proinflammatory cytokine production in primary human and murine cells in a Mincle-dependent fashion. Finally, they were found to induce strong Th1 and Th17 immune responses in vivo in immunization experiments in mice and conferred protection in a murine model ofMycobacterium tuberculosisinfection. Here we describe the rational development of new molecules with powerful adjuvant properties.

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Calibration problems in hydrogen luminosities

Symposium - International Astronomical Union ◽

10.1017/s0074180900053626 ◽

1966 ◽

Vol 24 ◽

pp. 322-330

Author(s):

A. Beer

Keyword(s):

Galactic Structure ◽

B Stars ◽

Insight Into

The investigations which I should like to summarize in this paper concern recent photo-electric luminosity determinations of O and B stars. Their final aim has been the derivation of new stellar distances, and some insight into certain patterns of galactic structure.

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