bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trypsinogen Genes: Insights into Molecular Evolution from the Study of Pathogenic Mutations
Authors: Chen Jian‐Min , Cooper David N , Férec Claude 
Published: April 2013

Abstract

The basic fuel for evolution is genetic variation that is subsequently acted on by natural selection. Selection may either act conservatively so as to ensure that features of structural or functional importance are retained (purifying selection), or it may act so as to favour those changes, which confer some advantageous characteristics (positive selection). Insights into these divergent evolutionary processes are sometimes generated through the study of pathogenic mutations, an archetypal example being the human trypsinogen genes. The integration of data gleaned from the functional characterisation of pathogenic missense mutations in the human cationic trypsinogen gene (
PRSS1
) with information obtained from comparative sequence analysis has provided evidence for stepwise selective pressures acting against prematurely activated trypsin within the human pancreas. Studies of
PRSS1
mutations have also revealed evidence for past gene conversion events between the various trypsinogen gene family members and have helped to improve our understanding of the evolutionary history of these genes.

Key Concepts:

Trypsinogen plays an important role in digestion.

Prematurely activated trypsin within the pancreas, if not inhibited and/or inactivated, has the potential to trigger the pancreatic zymogen activation cascade, leading to pancreatic autodigestion and pancreatitis.

Gain‐of‐function mutations in the human cationic trypsinogen gene (
PRSS1
) cause chronic pancreatitis.

Pathogenic
PRSS1
mutations have been exploited to understand the molecular evolution of the human trypsinogen family.

Pathogenic mutations in
PRSS1
have revealed the molecular footprints of gene conversion occurring between the highly homologous human trypsinogen genes.

The integration of data gleaned from the functional characterisation of pathogenic
PRSS1
missense mutations with information obtained from comparative sequence analysis has provided evidence for stepwise selective pressures acting against prematurely activated trypsin within the human pancreas.

Genetic data have also helped to improve our understanding of the evolutionary history of the different human trypsinogen genes.
Mitochondrial
DNA
Polymorphisms
Authors: Passarino Giuseppe , Rose Giuseppina 
Published: April 2013

Abstract

The analysis of genetic variation occurring in human
mitochondrial deoxyribonucleic acid
(mtDNA) has characterised the field of human population genetics since this small molecule has been sequenced in 1981. First analyses were carried out by restriction analysis, and they immediately suggested that mtDNA polymorphisms could allow a phylogenetic reconstruction of the human populations. The technical improvements, which made subsequently easier sequence analyses, allowed to refine the previous results and to understand many aspects of the human origin and of the dispersal of human populations in the world. Interestingly, the variability of mtDNA turned out not to be neutral but to affect the adaptation to the environmental factors (such as climate and diet) and many complex traits such as aging and degenerative diseases.

Key Concepts:

The analysis of mitochondrial DNA polymorphisms has characterised the last three decades of human genetics.

The lack of recombination in mitochondrial DNA leads mtDNA polymorphisms to accumulate sequentially along independent lineages.

The availability of a great number of mitochondrial DNA sequences has allowed to find numerous mtDNA polymorphisms.

The phylogenesis of mitochondrial DNA polymorphisms allowed to understand many aspects of human evolution and many aspects of the dispersal of human populations.

The analysis of mitochondrial DNA polymorphisms in groups of subjects with different complex traits has allowed to highlight that mtDNA polymorphisms are not neutral but they affect many phenotypic traits.
Limits of Proteomics: Protein Solubilisation Issues
Authors: Rabilloud Thierry 
Published: April 2013

AbstractBecause of their tremendous chemical heterogeneity, many proteins, such as membrane proteins, are poorly soluble in aqueous solvents. This precludes their analysis by classical proteomics techniques, whether these techniques are based on protein separation (e.g. two‐dimensional gel‐based proteomics) or on peptide separation after in‐solution digestion. For techniques based on peptide separation, the issue is to couple on the one side a complete solubilisation of proteins, a good efficiency of the protease used to produce the peptides, and on the other side minimal interference with the techniques used to separate the peptides. For techniques based on protein separation, the issue is to solubilise the proteins and to keep them soluble under the conditions used for the protein separation. For both type of technologies, combinations of detergents and chaotropes often provide the most performing solution to the protein solubilisation problem, although complete solubilisation can never be guaranteed.Key Concepts:Proteins must be extracted from their cellular context into an aqueous‐based solvent for their analysis.Surfactants/detergents provide the adequate medium to mimic a lipid‐like environment in water.The structural variety of detergents provides the various solubilisation performances that can be adapted to many proteomics methods.Chaotropes are often used in conjunction with detergents to improve protein/peptide solubility.
Protein Characterisation in Proteomics
Authors: Meri Seppo , Baumann Marc 
Published: April 2013

Abstract

Proteomics refers to the comprehensive analysis of proteomes – the protein content of complex biological mixtures, that is, a whole proteome of a cell, microbe or a proteome of a certain tissue or just the proteome of the blood, saliva or cerebrospinal fluid. The aim is to separate and identify all the proteins of the chosen proteome and then to determine their interactome and with that their biological relevance and activity in that system at the moment of sample collection. Currently, such analyses would also include the characterisation of possible secondary modifications and determining the expression level of each protein. All this is performed by high‐end mass spectrometers that allow the identification and parallel quantification of several hundred proteins and several of their secondary modifications (e.g. phosphorylations, sumoylations, glycosylations

etc

.) in one analysis step. Thus, a big challenge is also to be able to deal with an enormous amount of complex data in order to make any sense of the results at the end. In this article, the authors will highlight some key issues for such analyses and describe some of the used technologies in greater detail.

Key Concepts:

Proteins are one of the key elements of life.

Proteome is the full content of proteins in a given biological sample.

Proteome content can change dynamically according to, for example, time, location and environmental conditions.

Meaningful results from proteomic analysis can be obtained if the analysis is restricted to a well‐defined and targeted goal.

Main methods include two‐dimensional gel separation, enzyme digestion and multidimensional liquid chromatography mass spectrometry.

Along the flow of proteomic analysis it is important to choose the most appropriate approach (top‐down vs. bottom‐up, focused vs. broad, quantitative vs. qualitative, comparative, selective).

Protein analysis can be subjected to positive and negative selection procedures for desired features.

Post‐translational modifications can change protein characteristics and function.

Large depositories of data are available for comparative analysis.
Biofuels: Ethanol Producers
Authors: Darku Irene D , Richard Thomas L 
Published: April 2013

AbstractTwo groups of microbes, saccharolytic and ethanologenic, are important in ethanol production. The former makes sugar utilisation possible and the latter converts the sugar to ethanol. Many promising or potential ethanologenic and saccharolytic microbes fall within the respective phyla Ascomycota and Neocallimastigomycota for fungi, and Proteobacteria and Fibrobacteres for bacteria.Saccharomycessp. (Ascomycota) andZymomonas mobilis(Proteobacteria) are the only microbes naturally capable of producing ethanol close to theoretical maximum, withSaccharomyces cerevisiaepredominant for current ethanol production based on starch and sugar feedstocks. To enable cellulosic ethanol technologies, microbial capability and efficiency must be enhanced by appropriately designed mixed‐culture systems and/or genetically modified microbes. As cellulosic ethanol nears commercialisation, these two approaches are key to sustainable and economical production.Key Concepts:Ethanol producers are known as ethanologens.Currently, commercial production of bioethanol depends on yeast, especially species ofSaccharomyces cerevisiae, for fermentation of hexose (6‐carbon) sugars.Zymomonas mobilisis the only bacteria naturally capable of producing ethanol as the sole product and the only ethanologen that uses a nonglycolytic metabolic pathway.Saccharolytic or hydrolytic microbes are an important complement to ethanologens in ethanol production.Production of ethanol from carbohydrate oligomers (2–10 monosaccharide units) or polymers (>10 monosaccharide units) usually requires hydrolysis to simple hexose or pentose sugars.Of the ten major phylogenetic phyla of fungi, only two are currently identified as relevant to ethanol production.Thermophilic microorganisms and species of the genusclostridiumare expected to play greater roles in future ethanol production.Microbial consortia, comprising different saccharolytic and diverse sugar fermenting microbes, provide one promising strategy for cellulosic ethanol production.Other cellulosic ethanol strategies are genetically modifying microbes capable of producing hydrolytic enzymes as well as co‐fermenting 5‐carbon and 6‐carbon sugars.
Biofuels: Fungal, Bacterial and Insect Degraders of Lignocellulose
Authors: Sethi Amit , Scharf Michael E 
Published: April 2013

AbstractLignocellulose is the main structural component of plant cell walls and can be degraded into simple sugars with the help of hydrolytic enzymes. Lignocellulose is composed of three polymers: cellulose, hemicellulose and lignin. Certain fungi, bacteria and insects have evolved the ability to degrade lignocellulose. Cellulose is degraded to glucose by the synergistic action of three distinct classes of enzymes: endoglucanases, exoglucanases and β‐glucosidases. Owing to its variable structure and organisation, hemicellulose degradation requires various enzymes with diverse modes of action, which include endoxylanases, endomannanases, β‐xylosidases, β‐mannosidases, β‐galactosidases, α‐glucuronidases, α‐arabinofurnosidases, α‐galactosidases, acetyl xylan esterases, feruloyl esterases and glucuronyl esterases. Lignin degradation is much more difficult due to its complex structure and bonding to carbohydrate complexes. It requires oxidative enzymes, such as lignin peroxidases, manganese peroxidases, versatile peroxidases, laccases, and several other auxiliary enzymes. Commercial biofuel production from lignocellulosic materials can be achieved by artificially producing these cellulases, hemicellulases and lignases in recombinant form.Key Concepts:Lignocellulose is the most abundant renewable resource of energy on the Earth.Lignocellulose is a general term referring to a natural complex of three biopolymers: cellulose, hemicellulose and lignin.Simple sugar can be released from lignocellulose using three categories of enzymes: cellulases, hemicellulase and lignases.Released sugars from lignocellulose can be fermented into biofuel (ethanol).Wood‐rotting fungi such as white‐rot, brown‐rot and soft‐rot fungi can degrade lignocellulose.Aerobic and anaerobic bacteria such asBacillus, Streptomyces, CellulomonasandClostridiumpossess lignocellulose‐degrading enzymes.Wood and plant‐feeding insects such termites, roaches, longhorn beetles and grasshoppers are rich sources of novel lignocellulases genes.Lignocellulases of fungal, bacterial and insect origin can be artificially/recombinantly produced in various protein expression systems.Fungal, bacterial and insect lignocellulases are expected to play important roles in the development of successful lignocellulose conversion technologies.
Evolution of Alpha‐Satellite
DNA
Authors: Ugarković Đurđica 
Published: April 2013

Abstract

Alpha satellite
deoxyribonucleic acid
(DNA) is based on 171 bp tandem repeats located in the centromeric and pericentromeric regions of all primate chromosomes. In humans, most of the alpha satellite repeats are organised in a hierarchical fashion, creating complex units called higher order repeats, composed of 2 to more than 30 diverged monomers in length. Monomeric alpha satellite DNA predates higher order arrays of alpha satellite and may represent direct descendant of the ancestral primate centromere sequence. Comparison of centromeric alpha satellite DNA sequences in different primate species reveals that alpha satellite DNA evolves through a series of amplification events resulting in the spreading of ‘new’ subfamilies, which replace the ‘old’ ones and confer centromere function. Transcripts of alpha satellite play an important role in kinetochore formation and the establishment of pericentromeric heterochromatin and are indispensable for the proper cell division.

Key Concepts:

Complex higher order repeats (HORs) are predominant form of alpha satellite DNA in the great ape and humans.

Alpha satellite HORs evolve much faster than monomers and contribute substantially to divergence between chromosomes of primates.

Two distinct chromosomal domains, the centromere and heterochromatin are assembled and maintained on the alpha satellite DNA sequence.

Alpha satellite DNA evolves through proximal amplification events occurring within the central active region of the centromere.

Transcription of alpha satellite DNA is crucial for centromere/kinetochore assembly and function during cell division.
Selection against Amino Acid Replacements in Human Proteins
Authors: Subramanian Sankar 
Published: April 2013

Abstract

The vast majority of mutations occurring in the coding regions of human genes alter the encoded amino acids of proteins. A significant proportion of these mutations are known to disrupt the structure and/or function of human proteins. The similarity of a large fraction of amino acid residues of human protein sequences with that of other species implies that the amino acid altering mutations were purged through natural selection during the evolution of the human lineage. In contrast, due to the effects of genetic drift, amino acid replacement mutations are present within human populations at low frequencies and a high proportion of such mutations are harmful to humans. Therefore, understanding the contrasting patterns of long‐term and short‐term evolutionary histories of human proteins are vital in identifying the amino acid mutations associated with human genetic diseases.

Key Concepts:

Natural selection eliminates a high proportion of amino acid changing mutations over time.

Selection against amino acid replacement mutations can be quantified at the level of whole proteome, specific protein or individual amino acid residue.

The intensity of selection is high for proteins performing essential housekeeping functions.

Selection intensity not only varies between proteins but also between amino acid residues within a protein.

Mutations involving changes between biochemically dissimilar amino acids are under high selection pressure.

Amino acid polymorphisms are abundant in human population due to genetic drift.

Evolutionary history, structure and functional properties of human proteins are useful to identify amino acid mutations associated with genetic diseases.
Ficolins
Authors: Takahashi Kazue , Thiel Steffen 
Published: April 2013

Abstract

Ficolins are innate immune pattern‐recognition molecules. The name of ficolin was derived from its basic structure, consisting of a collagen‐like domain and a fibrinogen‐like domain (FBG). The FBG preferably recognises acetylated compounds. Humans have three homologous proteins: H‐ficolin (or ficolin‐3), L‐ficolin (or ficolin‐2) and M‐ficolin (or ficolin‐1). Mice have ficolin‐A and ficolin‐B, which are homologous to L‐ficolin and M‐ficolin, respectively, whereas a murine homologue of H‐ficolin is absent. Ficolin genes are germinally present and, therefore, their proteins are expressed at healthy state and are circulating in blood or localised in organs, affording an instant host protection. Ficolins are homologous to collectins structurally and functionally but has a difference in target recognition. Ficolins, like collectins, play important roles in innate immunity as activators of the lectin pathway of the complement system.

Key Concepts:

Ficolins are molecules of innate immunity, which is the first line of host defence mechanism and is fully functional throughout the body and life regardless of health.

Ficolins are similar to collectins in their structures and biologic functions with a major difference that target recognition is through fibrinogen‐like domain unlike carbohydrate recognition domain of collectins.

Ficolins are pattern‐recognition molecules, which are able to identify invading pathogens and abnormal cells and tissues, in addition to normal cells, which are not recognised by collectins.

Selected genetic mutations affect functions of ficolins and are associated with reduced host defence mechanisms.

Some ficolins may be a disease modifier as deficiency itself may cause no problem, whereas it may have adverse effect depending on types of disease, infection or injury.

Ficolins have structural and functional homology to collectins and may share and substitute functions in host defence.
Molecular Genetics of Endometriosis
Authors: Painter Jodie N , Zondervan Krina T , Missmer Stacey A , Montgomery Grant W 
Published: April 2013

Abstract

Endometriosis is a gynaecological disease that affects 6–10% of women of reproductive age. Symptoms vary but commonly include severe menstrual and pelvic pain and infertility, all of which can have major impacts on the lives of affected women. Linkage studies have identified several chromosomal regions but the genes contributing to these linkage signals have yet to be identified. Candidate gene studies on over 80 genes have not shown robust evidence of association, mostly due to the limited power to detect individual risk variants of small effects. Four groups have now conducted genome‐wide association studies for endometriosis, revealing a number of intriguing candidates that may contribute to disease risk. Further research aimed at increasing our understanding of the genes and biological pathways underlying endometriosis may provide better and more targeted diagnosis and treatment options in the future.

Key Concepts:

Endometriosis is a gynaecological disease that occurs when tissue resembling endometrium (the tissue that lines the inside of the uterus) attaches and grows on organs in the body cavity, including the ovaries, fallopian tubes, intestine and bowel.

Endometriosis affects 6–10% of women during their reproductive years and the symptoms, including severe menstrual and pelvic pain and sub‐ or infertility, can greatly impact an affected woman's physical and psychological wellbeing as well as her family and working life.

The financial cost of endometriosis is amongst the highest of all complex diseases, with direct (medical and surgical treatment) and indirect (loss of income, reduced productivity, infertility treatment and social withdrawal) health care costs estimated at >$15 billion annually in the US alone.

Linkage studies on large numbers of families have indicated chromosomal regions that may harbour endometriosis susceptibility genes but these are yet to be definitively identified.

Candidate gene association studies on over 80 genes have not produced convincing evidence of gene robustly associated with endometriosis susceptibility.

Genome‐wide association studies have identified a small number of chromosomal areas that harbour extremely interesting candidate genes that should be followed up in the future.

Understanding the genes and biological pathways underlying susceptibility to endometriosis may eventually lead to better diagnostic and treatment options for women affected by this common and often debilitating disease.
Amphioxus as a Model for Mechanisms in Vertebrate Development
Authors: Benito‐Gutiérrez Èlia 
Published: April 2013

AbstractFor the last two centuries, the cephalochordates, commonly known as lancelets or amphioxus, have been central to investigate the evolutionary genesis of vertebrates. At first, by classical morphologists fascinated by their odd but at the same time familiar anatomical traits and later by molecular biologists giving the first insights into their slow evolving nature. The present data available not only holds amphioxus as an organism of preternatural importance within the tree of life but also boosts its potential to untangle the molecular basis underlying the vertebrate complexity. This is a walk through the past and present of the amphioxus field merging morphological and molecular data in linkage with the fossil record and the modern vertebrates. The resulting picture is drawn together with comparative maps of genome organisation, gastrulation and the origin of the vertebrate organiser, neurulation and the origin of the neural crest, and shared signalling mechanisms between vertebrates and amphioxus during development. Special attention is also given to some of the most critical vertebrate novelties and how the pre‐duplicative amphioxus genetic toolkit might have contributed to set the basis for evolving complexity in the course of vertebrate evolution.Key Concepts:Cephalochordates occupy at present the key phylogenetic position to get insights into the invertebrate–vertebrate transition and the evolutionary genesis of vertebrates.Whole‐genome duplications in the lineage leading to modern vertebrates might have established the basis for molecular and morphological innovation.The amphioxus genome appears to be the best surrogate available for the ancestral chordate genome regarding the gene content, gene structure and chromosomal organisation.The amphioxus prototypical body plan with respect to vertebrates facilitates the comparative analysis and linkage between invertebrates and vertebrates.The pre‐duplicative genome of amphioxus offers the possibility of analysing vertebrate‐like gene regulatory networks in a simpler biological context with a reduced number of molecular players.