bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endogenous Retroviral Sequences; Their Evolutionary Contribution to the Human Genome
Authors: Mayer Jens 
Published: April 2013

Abstract

Endogenous retroviruses (ERVs) comprise approximately 8% of the human genome. They stem from germ cell invasions of exogenous retroviruses in the evolutionary past. Human ERV transcripts are found in every human tissue, and their expression patterns seem to be regulated by complex mechanisms. HERV transcription is often deregulated in diseased tissue and cells. By introducing numerous regulatory elements into the genome ERVs profoundly influence quite a number of cellular genes regarding gene structure and expression patterns. Although most ERV sequences in the human genome are coding defective, some HERVs still encode proteins that appear to have become essential human genes or that appear to be involved in human diseases. A HERV encoded protein is essentially involved in placenta development. Other HERV encoded proteins may serve as biomarkers for certain tumour types or may be involved in tumour development.

Key Concepts:

Most vertebrate genomes harbour significant amounts of repetitive sequences.

Human endogenous retroviruses are remnants of ancient retroviral infections of the germ line.

Approximately 8% of the human genome are of retroviral origin.

HERV sequences are often severely mutated due to long‐time presence in the genome.

HERV transcripts are found in every human tissue.

HERV transcription is deregulated in some diseases including tumours.

HERV loci can influence transcription of nearby genes.

A HERV encoded protein is essentially involved in placental development.

Other HERV proteins may be involved in tumour development.
Evolution of X‐Chromosome Inactivation
Authors: Shevchenko Alexander I , Zakian Suren M 
Published: April 2013

AbstractX‐chromosome inactivation is a transcriptional silencing of one of the two X chromosomes that occurs in females of marsupial and eutherian mammals. The process arose and developed as a part of dosage compensation mechanism during differentiation of mammalian X and Y chromosomes. X inactivation started from being imprinted and unstable in marsupials and then was transformed to random and stable in eutherians. The transformation included replacement of the key noncoding nuclearribonucleic acidmaster switch genersxtoxist, and emergency of the X‐inactivation centre responsible for random choice of one of the two X chromosomes. Presumably, further involvement of thexist‐dependent repressive histone modifications together withdeoxyribonucleic acidmethylation and enrichment of the X chromosome with LINE1 mobile elements, allowed for more efficient spread and maintenance of an inactive state and has made the X‐chromosome inactivation process more complete and stable. During eutherian evolution, X‐chromosome inactivation mechanisms have tended to accumulate the taxon‐ and species‐specific differences.Key Concepts:X‐chromosome inactivation emerged as part of dosage compensation mechanism caused by differentiation of mammalian X and Y chromosomes.X‐chromosome inactivation is unique for marsupial and eutherian mammals.X‐chromosome inactivation has evolved from imprinted, incomplete, and unstable to random, complete, and efficiently maintained.The long noncoding nuclear RNA controlling X‐chromosome inactivation, initiallyrsxin marsupials, has been replaced forxistin eutherians.The noncoding nuclear RNA genexist, responsible for initiation of inactivation in eutherians, emerged from a protein coding gene and a set of mobile elements.Xistand the surrounding genes regulating its expression have formed the inactivation centre that regulate a random choice of one of the two X chromosomes to be transcriptionally silent.Presumably, the main steps leading to complete and stable X‐chromosome inactivation are involvement of thexist‐dependent repressive histone modifications in gene rich clusters together with DNA methylation of the promoters and enrichment of X chromosome with the mobile elements LINE.During eutherian evolution, X‐chromosome inactivation mechanisms mainly accumulated taxon‐ and species‐specific differences.
Population Genetics of Lactase Persistence and Lactose Intolerance
Authors: Ingram Catherine JE , Liebert Anke , Swallow Dallas M 
Published: April 2013

AbstractVariation in the ability of adult humans to digest the lactose in milk is a genetically determined trait that has excited the interest of many for the past 50 years. The trait seems to have risen to high frequencies by one of the strongest selection pressures ever described. This section describes the phenotypic polymorphism and the evidence that the genetic trait involves regulation of expression of the lactase gene and is caused by multiple independent mutations that have reached high frequencies in different populations, because of the benefits of drinking milk. The evolutionary history in Europe and Africa are rather different; there being a single high‐frequency allele in Europe, in contrast to multiple alleles in Africa. Also the selective forces, which are likely to include both the nutritional and water content of milk, may have been different in these regions.Key Concepts:The enzyme, lactase, is restricted to the small intestine where it digests lactose in the milk of suckling mammals.Lactase persists into adult life in some, but not all, people.Lactase persistence is a genetic trait, which varies in frequency in different populations of the world.Mutations in an enhancer sequence, at a distance from the lactase gene, appear to be responsible for lactase persistence.These alleles arose in the last few thousand years and have been under strong positive selection.The selection may be attributable to one of the nutrients or water in fresh milk and/or its calorific value.
Modelling Cancer in
Drosophila
: The Next Generation
Authors: Cheng Louise Y , Parsons Linda M , Richardson Helena E 
Published: April 2013

Abstract

Drosophila melanogaster

, the vinegar fly, has been utilised as a genetic amenable model organism for more than 100 years. In recent years, its use in modelling human cancer has been greatly expanding. In this article, an update of the recent advances in
Drosophila
research towards understanding cancer development is provided. Genetic analysis in
Drosophila
has provided considerable insight into the mechanisms controlling tissue growth and cell invasion/metastasis during tumourigenesis, as well as the importance of stem cells in tissue regeneration and cancer, and how genes cooperate in tumourigenesis. Several evolutionarily conserved signalling pathways are emerging as playing key roles in many of these processes, including the Jun kinase, Notch, Wnt, Jak/Stat and the Hippo tissue growth control pathway.
Drosophila
has also been specifically utilised to model certain human cancers, by expression of the human versions of cancer‐causing genes, including multiple endocrine neoplasia type 2, glioblastoma and acute myeloid leukaemia. Finally, the use of
Drosophila
as a vehicle for anticancer drug discovery is beginning to make an important impact in combating human cancer.

Key Concepts:

Drosophila
is a useful system for modelling human cancer due to the high conservation of critical cancer‐causing genes between humans and flies.

Many signalling pathways contribute to tissue growth; however, the Hippo growth control pathway is emerging as playing a major role.

The Jun kinase signalling pathway plays a context‐dependent role in invasion/metastasis.

Cell polarity and differentiation factors play important roles in controlling the behaviour of stem cells, which can be usurped in cancer.

Cell competition mechanisms are important in removing damaged cells, and the perturbation of this control contributes to tumourigenesis.

Cancer is a cooperative process and
Drosophila
research has revealed many cooperating oncogenes and tumour suppressors.

Drosophila
provides a useful model system to investigate specific human cancers including multiple endocrine neoplasia type 2, glioblastoma and acute myeloid leukaemia.

Drosophila
can be utilised to screen for anticancer drugs.
Quality Control of Protein Folding in the Cytosol
Authors: McClellan Amie J 
Published: April 2013

Abstract

In order to function properly, newly synthesised proteins must rapidly and efficiently attain their native conformations. If they fail to do so, the cell may be adversely affected due to loss of function or toxic gain of function effects of misfolded polypeptides. Effective quality control mechanisms to recognise and eliminate misfolded proteins are thus critical for cell viability. The primary means by which misfolded proteins are selectively removed from the cell is via the ubiquitin–proteasome system. Although much is known about regulated proteolysis, how any given protein, which could potentially misfold, is recognised and targeted for proteasome‐mediated degradation has been challenging to decipher. Recent progress, much of it in yeast, has identified specific E3 ligases involved in this process, clarified or added to our knowledge of the roles of molecular chaperones, and identified multiple cellular locations where degradation, or failing that, aggregation, occurs.

Key Concepts:

Molecular chaperones facilitate the folding of newly synthesised proteins to their native states and thus are critical for the maintenance of cellular proteome integrity.

Cellular proteostasis reflects the balance between protein folding and degradation.

Proteins that fail to fold properly must be eliminated via cellular quality control systems to avoid potentially damaging effects on the cell.

The ubiquitin–proteasome system is the primary means for the selective removal of misfolded proteins.

Molecular chaperones can tip the balance between protein folding and degradation, and facilitate the destruction of misfolded proteins.

E3 ligases have been identified that either cooperate with chaperones, or that directly interact with nonnative proteins to target them for degradation.

The degradation of misfolded cytosolic proteins in eukaryotes occurs in multiple cellular locations.
Ciona
: A Model for Developmental Genomics
Authors: Satoh Noriyuki 
Published: April 2013

Abstract

The ascidian

Ciona intestinalis

is an excellent model system for studying developmental biology due to the simplicity of its embryogenesis and genomics. The
Ciona
tadpole larva is composed of only 2600 cells and possesses the basic body plan of chordates. The 117‐Mbp‐long euchromatic genome encodes approximately 320 core transcription factors and 125 major signal transduction molecules, the expression profiles of which have been described at the single‐cell level in
Ciona
embryos. Not only the function of developmentally relevant genes can be explored by means of suppressed and/or ectopic expression, but also a convenient electroporation method of reporter gene constructs has been developed to identify
cis
‐regulatory modules. High throughput and genome‐wide approaches can be used to uncover gene regulatory networks involved in cell specification and differentiation. Transposon‐mediated transgenesis also provides a new strategy for elucidating the mechanisms of gene expression and function. These and other advantages of the
Ciona
system recommend future developmental biology studies with this model.

Key Concepts:

The
Ciona
tadpole larva represents the basic and most simplified chordate body plan, and its embryogenesis is well characterised.

The
Ciona intestinalis
genome has been decoded. The 117‐Mbp euchromatic genome, which is packaged into 14 pairs of chromosomes, contains 15 254 genes including ∼320 core TF genes and 125 major signalling molecule genes.

Most of these developmentally relevant genes have been chromosomally mapped.

The spatial and temporal expression profiles of these developmentally relevant genes have been elucidated.

Gene function can be easily studied by suppressed and/or ectopic expression.

A convenient electroporation method allows quantitative and qualitative examination of
cis
‐regulatory modules responsible for gene expression.

The regulatory networks of TF and signalling molecule genes that establish the blueprint of the chordate body plan have been uncovered.

The short generation time allows forward genetics of
Ciona
, a first for a marine invertebrate.

Transgenic lines have been established using
Minos
transposons to reveal gene function and expression.
Micro
RNAs
and Their Role in Cancer
Authors: Ferracin Manuela , Negrini Massimo 
Published: April 2013

Abstract

Microribonucleic acids (miRNAs)
are short, noncoding RNAs that act as post‐transcription regulators and are able to modulate the expression of hundreds of target genes. In the past few years, they gained a very important role in oncology. Indeed, many of them can be now considered tumour suppressor genes or oncogenes. In cancer, they appeared to have a dysregulated expression due to genetic aberrations, altered methylation or irregular processing that finally lead to an altered modulation of their target genes.

Each cancer type displayed specific alterations of specific miRNAs, and their exceptional stability confer to miRNAs a strong potential as cancer therapeutics. Finally, miRNAs are stable and detectable as circulating molecules in blood of cancer patients. For this reason they are going to become useful biomarkers in cancer diagnostics.

Key Concepts:

In the last few years, miRNAs have produced a micro‐revolution in cancer research because of their action as oncogenes or tumour suppressor genes.

miRNA expression profiling may be used for cancer classification and for the identification of cancer subtypes.

A promising role of miRNA in prognosis stratification has been proposed.

Several studies indicated miRNAs as predictors of drug response.

miRNA polymorphisms may modify innate genetic susceptibility to cancer: SNPs in miRNAs and their gene targets may alter cancer susceptibility.

miRNAs as cancer biomarkers detected in plasma or serum of patients seem to be very promising in terms of efficacy and specificity.

miRNA may represent important therapeutic targets and can be effectively targeted
in vivo
.
Molecular Basis of Complex Traits
Authors: Polychronakos Constantin 
Published: April 2013

Abstract

Most genetically determined differences between individuals, including (but not limited to) susceptibility to specific diseases, depend on functional variation at multiple genes (loci). The frequency of these variants (alleles) in the general population varies from common to rare. The contribution of most common alleles, each in isolation, to disease risk is weak. Most uncommon and rare alleles have not been studied to date and some may have strong effects on disease risk even if they contribute to disease cause each in a small subset of cases. This mixture of strong and weak effects by common and rare alleles is referred to as allelic architecture. Defining the allelic architecture of each disease will be the first step towards using an individual's genetic profile to individualise the molecular diagnosis within a group of cases that all bear the same clinical diagnostic label.

Key Concepts:

Most diseases and other human traits have statistically significant familial clustering, indicating the involvement of genetic susceptibility.

Genetic susceptibility to most diseases is determined by a large number of gene variants (loci).

Disease‐associated variants may change the sequence of the protein product, or the control of its transcription, RNA stability or translational efficiency.

Most known loci have a weak genetic association with the disease or trait.

A genetic association may be weak because of weak biology, or because the associated allele is merely an imperfect marker for an untested rare allele with strong effect.

The discovery, among low‐frequency alleles, of those that have the strongest effects, is the next frontier in the genetics of complex traits and the greatest promise to personalised medicine.
Genetic Determinants of Human Life‐Span
Authors: Jylhävä Juulia , Hurme Mikko 
Published: April 2013

Abstract

The contribution of genetic factors to human life‐span and longevity is recognised although the mediators and their molecular mechanisms are currently far from completely understood. However, significant advances have been recently made to unveil the genes and pathways involved in life trajectory determination in humans as well as in model organisms. In humans, more than 100 longevity candidate genes have been presented; however, with the exception of a few loci, the results tend to suffer from a lack of replication. Nevertheless, genetics appears to have moderate control over human life‐span and the impact is known to increase towards the old ages. Currently, the pathways with the most potential for harbouring longevity genes include the insulin/insulin‐like growth factor (IGF) signalling (IIS) and lipid metabolism. It remains to be seen whether future studies can pinpoint additional pathways and elucidate the remaining unexplained genetic variation in human life‐span.

Key Concepts:

Human life‐span is an extremely complex entity with genetic, environmental and stochastic factors modulating the longevity phenotype.

The majority of the proposed longevity gene candidates appear to be population‐ and/or sex‐specific.

Consistent association with human life‐span or longevity has thus far been observed for only the
APOE
,
FOXO3
and
ATK1
loci.
Cardiofaciocutaneous (
CFC
) Syndrome
Authors: Denayer Ellen , Legius Eric 
Published: April 2013

Abstract

Cardiofaciocutaneous (CFC) syndrome is a rare genetic disorder that is characterised by facial dysmorphism, cardiac defects, mental retardation, typical ectodermal abnormalities and short stature. It is caused by germline mutations in
BRAF
,
MEK1
,
MEK2
or
KRAS
and shows phenotypical overlap with other conditions caused by mutations in the RAS‐MAPK pathway such as neurofibromatosis type 1, Noonan, LEOPARD, Costello and Legius syndromes. The identification of the underlying genetic defect opens new windows for therapeutic strategies in these RASopathies including CFC syndrome.

Key Concepts:

Mutations in genes coding for key components of the RAS‐MAPK pathway are responsible for a group of inherited disorders (RASopathies).

The RASopathies are clinically and molecularly related disorders characterised by variable cognitive deficits, growth retardation, facial dysmorphy, and congenital cardiopathies.

CFC syndrome is characterised by the most severe intellectual disabilities seen in the RASopathies.

Correcting cerebral RAS‐MAPK signalling is a potential targeted treatment for learning disabilities in patients with a RASopathy.
Bacterial Cell Wall Recycling
Authors: Mayer Christoph 
Published: April 2013

AbstractCell wall recycling is a process whereby bacteria degrade their own wall during growth, recover released constituents by active transport and reutilise them either to rebuild the wall or to gain energy. Most knowledge about cell wall recycling comes from studies with the Gram‐negative bacteriumEscherichia coli. Within one generation, this organism breaks down and efficiently recycles approximately 60% of the mature peptidoglycan of its side‐wall during cell elongation and approximately 30% of newly deposited septal peptidoglycan during cell division. The reason for the massive turnover of the peptidoglycan is still unclear, although many other bacteria, including Gram‐positives, have been reported to turnover their cell wall and release similar quantities of peptidoglycan fragments during growth and differentiation. Whether these fragments are also recycled is basically unknown. The presence of recycling genes on most bacterial genomes, however, suggests that cell wall recycling is a very common pathway of bacteria.Key Concepts:The peptidoglycan of the bacterial cell wall represents a single, giant, reticular macromolecule (i.e. the murein sacculus) that encases the entire bacterial cell.The peptidoglycan cell wall has to be cleaved continuously during growth to allow cell expansion by insertion of new wall material.Bacteria possess a huge and partially redundant set of cell wall lytic enzymes that potentially target every covalent bond connecting the amino acid and amino sugar building blocks within the peptidoglycan network (cell wall lytic complement).Many bacteria release a great amount of cell wall material during bacterial growth (cell elongation and division). The reason for the massive turnover of approximately 50% of the existing peptidoglycan in one generation is still unclear.Bacteria eventually recover cell wall turnover fragments. The pathways for the continuous recycling of peptidoglycan have been explored in great detail inEscherichia coli.Cell wall recycling in Gram‐positive bacteria has been appreciated just recently and apparently differs from theE. coliparadigm as well as between Gram‐positive species.Cell wall‐derived peptidoglycan fragments function as potent biological effectors. They are involved in sensing the cell wall and growth state, inducing expression of antibiotic resistance genes, and triggering cell differentiation and resuscitation of dormant cells.
Aerobic Methanotrophy and Nitrification: Processes and Connections
Authors: Stein Lisa Y , Roy Réal , Dunfield Peter F 
Published: April 2013

Abstract

Ammonia and methane are structurally similar molecules. Not surprisingly therefore, microorganisms that use methane as a sole energy source (methanotrophs) and microorganisms that use ammonia as a sole energy source (ammonia oxidisers or nitrifiers) share many similarities. They have several key enzymes in common, most especially the ammonia monooxygenase/particulate methane monooxygenase enzyme family. The two groups are proposed to have a common evolutionary history. They occupy similar ecological niches, and compete for nitrogen. Enzymatically, nitrifiers are capable of methane oxidation, and methanotrophs are capable of nitrification. Microbial ecologists have attempted to find specific inhibitors for either group in order to study their respective roles in the environment. The contribution of ammonia oxidisers to methanotrophy in natural systems appears to be very minor, however methanotrophs may sometimes have important roles in the nitrogen cycle.

Key Concepts:

Some bacteria and archaea are capable of using methane or ammonia as energy sources.

Methanotrophs and ammonia oxidisers are each highly specialised to living on their particular substrate.

Methanotrophs and ammonia oxidisers have several key enzymes in common, and may share a common evolutionary history.

Both groups must cope with toxic by‐products of ammonia oxidation.

Methanotrophs may be important in the environmental nitrogen cycle, but ammonia oxidisers do not affect the methane cycle.

Ammonia oxidising archaea appear to outcompete ammonia oxidising bacteria under ammonia‐limiting and acidic conditions.