bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of Alpha‐Satellite
DNA
Authors: Ugarković Đurđica
Published: April 2013

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

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

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

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

For 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.
Ecosystem Services
Authors: Patterson Trista M
Published: April 2013

Ecosystem services represent all the things that functioning ecosystems do for people that people generally do not have to pay for. Examples include a forested hillside filtering water and retaining topsoil/sediments, how trees remove carbon from the atmosphere, or how a mangrove buffers surrounding low‐lying lands from wave action and storm surge. When ecosystem services are lost, the human‐made substitutes (such as a water filtration plant, erosion retaining walls, etc.) are often costly, and costly to maintain. Environmental management decisions are increasingly incorporating estimates of ecosystem service values as part of the cost–benefit evaluations. The intent of many ecosystem service efforts are to internalise ecosystem contributions into decision‐making, thus stemming ecosystem service loss. However, accomplishing this requires not only stemming the loss of ecosystem services, but also addressing the increasing human demands for them.

Key Concepts:

Ecosystem services are those processes of ecosystems that support (directly or indirectly) human well‐being.

The concept of ecosystem services is of interest to economists, ecologists and many other disciplines for its ability to create cross‐discipline dialog.

Ecosystem services provide valuable social benefits, which are often not accounted in standard economic currencies. Left unaccounted, they are vulnerable to loss. Numerous tools are emerging to visualise this value, supporting protection and/or restoration of ecosystem services.

Much of the current focus on ecosystem service work bases its emphasis on thesupplyof ecosystem services. For this concept to support sustainability objectives however, growingdemandsfor ecosystem services must be addressed through changes in behaviour, technology, governance and design.
Molecular Genetics of Sleep Disorders
Authors: Caylak Emrah
Published: April 2013

Common sleep disorders include narcolepsy, restless legs syndrome, obstructive sleep apnea syndrome, circadian sleep disorders and parasomnias. They are influenced by genes and several research groups to attempt to identify susceptibility genes of sleep disorders through the sequential analysis of genetic linkage and association. Strong evidence has now emerged for the presence of genes influencing sleep disorders at several chromosomal loci and for at least one of these, there is evidence implicating specific genes. This review highlights the genetic contribution to sleep disorders and current molecular genetic researches aimed at identifying susceptibility genes for sleep disorders.

Key Concepts:

Sleep disorders result in sleep deprivation and interfere with work, driving and social activities. Management of sleep disturbances is important to inhibit secondary to mental, medical, or substance abuse disorders.

Genetic factors are important in sleep disorders.

The association and linkage studies of sleep disorders identify genetic causes of heritable sleep disorder.

Molecular genetic researches should be aimed to identify susceptibility genes for sleep disorders.

Molecular advances in narcolepsy (NRCLP), restless legs syndrome (RLS), obstructive sleep apnea syndrome (OSAS), circadian sleep disorders (CSD) and parasomnias will help to set the research agendas for future studies to follow.

Gene‐mapping studies may help us to understand the biological basis of normal sleep variation, in addition to sleep disorders.
Molecular Genetics of Coeliac Disease
Authors: Mistry Vanisha , van Heel David
Published: April 2013

Coeliac disease (CD) is a common inflammatory disease of the small intestine. It has a prevalence of 1% in the population and is strongly heritable. Current germline disease risk variants explain ∼50% of known heritability, the majority contributed by a strong human leukocyte antigen (HLA)‐DQ association. The role of HLA‐DQ in the immunology of CD is well understood, for example the role of tissue transglutaminase and HLA‐DQ in modifying and binding immuno‐dominant dietary cereal (gluten) peptides. Genome‐wide association studies have found 39 loci with risk variants of more modest effect. The use of high‐throughput sequencing technologies to locate rare variants of larger effect may aid in the complete resolution of this complex trait, as well as in other autoimmune diseases, which show considerable overlap in immunological pathways.

Key Concepts:

Coeliac disease has a strong genetic component with an environmental trigger, gluten.

Coeliac disease shows strong HLA association, which is necessary but not sufficient for disease development.

Genome‐wide association studies have located common variants of modest effect size.

Rare variants with larger effect are hypothesised to contribute to common complex disease.

Exome sequencing a large number of individuals from multigenerational families might isolate precise causal variants.
Molecular and Cellular Basis of Learning Difficulties in Genetic Disorders
Authors: Crego Cortney , Landreth Anthony , Silva Alcino J
Published: April 2013

Recent advances have revealed a plethora of genes, signalling pathways, cellular and circuit processes involved in learning and memory. Convergent evidence demonstrates that molecular mechanisms that regulate long‐lasting changes in synaptic function are critical for learning and memory. This evidence has had a key role in unraveling mechanisms responsible for learning disabilities. For example, mutations in the neurofibromatosis type I (
NF1
) gene are a common genetic cause for learning disabilities. Studies in mice revealed that these learning deficits are caused by increases in Ras signalling leading to enhancements in synaptic inhibition and synaptic plasticity deficits. These deficits can be reversed by manipulations that target Ras signalling or inhibition. Current clinical trials are testing the efficacy of these treatments in
NF1
. Studies in other genetic causes for learning disabilities have shown that it is possible to develop mechanism‐based treatments for these disorders in mice that are effective even when they are started in adulthood.

Key Concepts:

The molecular mechanisms that regulate long‐lasting changes in synaptic function are critical for learning and memory.

Our growing understanding of mechanisms of memory has been effectively used to unravel the causes for memory deficits associated with animal models of several key genetic disorders, including NF1, tuberous sclerosis and fragile X.

It is possible to develop mechanism‐based treatments for developmental disorders that are effective even when treatment is started in adulthood.
Next‐generation Sequencing in Clinical Molecular Diagnostics
Authors: ten Bosch John R , Deignan Joshua L , Grody Wayne W
Published: April 2013

Next‐generation sequencing is based upon the concept of massively parallel chemical reactions in which millions of independent DNA sequencing events occur simultaneously, and this is achieved using a relatively similar concept across all of the currently available platforms. Current clinical molecular genetics labs offer testing mainly for single‐gene defects and a few multigene panels. However, for whole‐exome and whole‐genome sequencing, as the cost per sample continues to fall, there is little question that the clinical application of this technology will soon become abundant in diagnostic labs. Before that happens, we will need to prepare ourselves to handle certain types of unexpected and potentially unwanted information, since this technology should prove to be of tremendous value for the practice of medicine in the future.

Key Concepts:

Next‐generation sequencing is based upon the concept of massively parallel chemical reactions in which millions of independent DNA sequencing events occur simultaneously.

There are several commercial vendors of next‐generation sequencing instruments, though the market is currently dominated by Roche, Illumina and Life Technologies.

Most clinical labs prefer to sequence multiple samples or many regions of the genome in one run, and there are several methods that can be used to accomplish this.

Next‐generation sequencing can also be used to effectively detect both large and small chromosome aberrations.

Next‐generation sequencing has the potential to increase the scope of tests for sequence variants in the areas of infectious disease testing and oncology.

Clinical laboratories are currently observing caution in the adoption of this new technology.
Evolution of Genetic Resistance/Susceptibility to Malaria Infection
Authors: Ghosh Kanjaksha , Ghosh Kinjalka
Published: April 2013

Severe malaria infection still kills more than 2.7 million people across the globe every year. Of the few infections which has shaped human genome over the millennia through the process of natural selection, malaria infection has left its imprints on human genome. Genetic studies on malarial resistance started in the late 1940s with demonstration of protection against malaria in carriers of several haemoglobinopathy genes and further demonstration of increasing prevalence of such genes across the malarious areas of the world. As malaria parasites pass a significant period of its life inside the red cell, many red cell proteins and their genes were studied for polymorphic variants which offers protection against such infection. Total absence of

Plasmodium vivax

malaria in Western Africa and its linkage with total absence of red cell Duffy antigen is a case in point. Subsequently as a rational extension of the above idea, association of resistance or susceptibility to severe malarial infection were studied with relation to genes of innate immunity, adoptive immunity, cytokine genes, adhesion molecules, coagulation proteins, proteins involved in systemic inflammatory reactions etc. Innumerable studies have shown various kinds of association. However, at present the interest has shifted towards genome wide association studies with malarial infection. Present review stops short of genome wide association and presents a snapshot view of genome association with malaria infection.

Key Concepts:

The immune system of man has evolved to fight pathogens like malaria parasite.

Pathogens have exerted intense selective pressures on the evolution of the immune system of man.

Key elements of the adaptive immune system, such as antigen receptors and major histocompatibility complex molecules, show evidence of such selective pressures.

Mutation is the key genetic mechanism underlying the co‐evolution of the immune system and pathogens.

Evolutionary adaptation to malaria involves many more aspects than modification of adoptive and Innate Immune system.

Owing to complex life cycle of the parasite and its specific requirements of nutrition and need for protection during its growth, the parasite vulnerability increases due to changes in Nutrient (haemoglobin), Host Enzyme system (Oxidant damage), changes in specialised receptors for entry into cells (Red cells, Hepatocytes) and its ability to adhere to Key cells (Endothelium).

Product of metabolism of malaria parasite (Hemozoin) exerts strong immunomodulatory effect.

As malaria parasite from different regions of the world exerted selection pressure on different population groups with different genetic endowment (polymorphisms), this resulted in evolution of different key resistant molecules against malaria in different parts of the world.
Molecular Genetics of Tourette Syndrome
Authors: Valenti Antoinette , Grados Marco
Published: April 2013

Tourette Syndrome (TS) is a neurodevelopmental disorder characterised by chronic motor and vocal tics, which fluctuate over time. The molecular genetics of TS is supported by genetic epidemiology studies, which strongly suggest the presence of susceptibility genes for TS. Epidemiologic family, segregation and linkage studies, as well as candidate gene studies, have yielded limited specific results to date, however, pathophysiology models that support a molecular genetics approach in TS are emerging. Whole‐genome approaches, including genome‐wide association studies (GWAS) and whole‐genome sequencing, may yield more definitive genomic findings. Uncovering the biological substrate of TS will spur the development of novel, more precisely targeted, treatments for this disabling disorder.
Optical Control of Neuronal Activity
Authors: de Lecea Luis , Carter Matthew E
Published: April 2013

Optogenetics has become an invaluable method to establish causal relationships between the activity of genetically defined neuronal circuits and behaviour.
Channelrhodopsin 2
is a light‐activated channel that, when introduced in neurons allows temporally precise control of the activity of genetically identified neuronal networks. Conversely, halorhodopsins are light sensitive ion pumps that allow us to reversibly inhibit neuronal transmission with single action potential resolution. These optical tools offer new approaches to deconstruct neuronal circuits in freely moving animals. New variants of light‐activated channels and pumps offer a menu of optogenetic tools that allow us to determine functional connectivities and dynamic properties of brain networks. The development of optogenetics has profound implications in our understanding of brain organisation and mechanisms of neuropsychiatric disease.

Key Concepts:

Introduction of Channelrhodopsin 2 in neurons allows millisecond optical control of genetically identified neurons.

Different mutants of ChR2 show different kinetic properties, spectral sensitivity.

Different gene delivery methods allow dissection of neuronal circuits even in the absence of genetic markers and in multiple model organisms.

Combination of optogenetics with gene deficiencies and imaging systems will allow significant improvements in our understanding of circuit dynamics and mechanisms of disease.
Advanced Techniques for Cell Lineage Labelling in Drosophila
Authors: Hafezi Yassi , Nystul Todd G
Published: April 2013

The ability to mark and genetically manipulate clonally related cells in live organisms is invaluable for investigating the mechanisms of tissue development, homeostasis and repair. A wide variety of techniques have been developed in

Drosophila melanogaster

for this purpose. These cell lineage labelling techniques range from simple methods for randomly marking cells to complex schemes for differentially labelling and genetically altering specific cells or more than one clone at a time. For example, coupled MARCM makes it possible to simultaneously label both halves of a cell lineage with positive markers; FINGR uses a combinatorial approach, using Gal4 and Gal80, to provide finer spatial control over clone induction; Flybow and Drosophila Brainbow increase the resolution and efficiency of clonal analysis through multicolour labelling; and G‐trace differentially marks cells that currently express a driver from cells that expressed the driver in the past. These labelling techniques each have their own advantages and disadvantages. But together they create a powerful arsenal of tools for the study of many diverse topics in tissue biology.

Key Concepts:

Cell lineage labelling is a technique, which allows populations of clonally related cells to be traced
in vivo
.

Modern cell lineage labelling techniques in Drosophila allow cells to be labelled and genetically modified without invasive procedures.

Cell lineage labelling has become the gold standard for the identification of stem cells in Drosophila.

Recently developed cell lineage labelling techniques offer more flexibility, precision and control.
Cilia and Human Disease
Authors: Albee Alison J , Dutcher Susan K
Published: April 2013

Cilia and centrioles are highly conserved organelles that have hundreds of proteins associated with them. Studies in mice have shown that these organelles are essential for mammalian development and mice that cannot assemble them die

in utero

. However, mutations in many cilia and centriole genes cause human diseases that show a great range in defects. Defects in centrioles are associated with microcephaly and mental retardation. The reduction in brain size is related to the loss of neuronal progenitor cells. Defects in centrioles may also be associated with Sjögren syndrome, an autoimmune disease, because of defects in formation of the immunological synapse. Defects that cause immotile cilia result in chronic respiratory infections, infertility, and congenital heart defects. Defects in primary cilia share various symptoms that include loss of vision, obesity, diabetes, cystic kidney disease, mental retardation, polydactyly, and short bones. Many of these diseases are associated with the transport and sorting of receptors onto the ciliary membrane for sensing the environment.

Key Concepts:

Cilia perform functions in many different tissues and during development.

Many ciliary mutations affect multiple tissues and organs.

Key signalling pathways require cilia.

Orientation of the spindle during mitosis requires functional centrioles.
Selection of Phylogenetic Models of Molecular Evolution
Authors: Posada David
Published: April 2013

The use of different models of molecular evolution can change the conclusions derived from the evolutionary analysis of
deoxyribonucleic acid (DNA)
and protein sequence alignments. Several methods have been developed for the selection of the probabilistic model of nucleotide substitution or amino acid replacement that best fits the particular data at hand. Simulation studies indicate that these techniques work very well, and in recent years these methods have been implemented in a number of programs such as ModelTest, ProtTest and recently jModelTest. These programs also provide various tools for quantifying uncertainty in model selection, model averaging or multimodel inference.

Key Concepts:

Models of molecular evolution allow us to calculate probabilities of change between nucleotide and amino acid sequences.

The use of different models of evolution can change the outcome of the phylogenetic analysis.

Different datasets can be best‐fitted by distinct models.

Model selection techniques are quite accurate at identifying the generating model in simulations.

Programs like jModelTest and ProtTest facilitate the routinary selection of models of evolution in phylogenetics.
Evolution of Transcription Factors inCaenorhabditis
Authors: Jovelin Richard
Published: April 2013

Transcription factors (TFs) are regulatory proteins controlling gene expression by binding specific motifs associated with their target genes and playing essential roles during development and physiological response to stimuli. The evolution of transcriptional regulation is an important source of phenotypic diversity. The genome of the nematodeCaenorhabditis elegansencodes a similar proportion of TFs as the human genome, although TF families show different patterns of expansion in human and in worm. The TF repertoire ofC. elegansis well diversified with over 50 TF families. Alternative splicing and gene duplication contribute to the functional diversity of TFs and the rapid evolution of TF protein sequence suggests that TF evolution plays important roles in developmental evolution. Many of the principles that guided the diversification of the worm TFs are likely to be applicable to the evolution of TFs in other organisms.

Key Concepts:

The genome ofC. elegansencodes 988 TFs belonging to 50 distinct families based on the type of DNA‐binding domain.

The worm and human genomes encode a similar proportion of TFs, and in both species a third of the TFs show tissue‐specific gene expression.

Alternative splicing increases the number of TF transcripts by 22%.

Gene duplication contributes significantly to the functional diversification of TFs, and several examples illustrate the different evolutionary trajectories taken by TF duplicates.

Tissue‐specific expression, alternative splicing, gene duplication and the combinatorial regulatory activity of TFs reduce the pleiotropic constraints operating on TF sequence evolution.

TF factor sequence evolution plays an unappreciated role in developmental evolution.

TFs can harbour high level of amino acid variation both between species and within populations.
Advances in High‐Throughput Crystallisation
Authors: Meijers Rob , Mueller‐Dieckmann Jochen
Published: April 2013

Molecular biologists attempt to understand the inner workings of the cell, the smallest unit of all life forms on earth. The constituents that perform cellular functions are the proteins, enzymes and nucleotides. A full appreciation of the chemical and biological functions of the cellular constituents, and therefore life itself, requires knowledge of their three‐dimensional structures. X‐ray crystallography is among the most powerful methods to derive structural information from biological macromolecules. Before the three‐dimensional structure of biological macromolecules can be determined by X‐ray crystallography, they have to be assembled into the regular and periodic arrangements, which define a crystal. Biological macromolecules are irregularly shaped and inherently flexible, which makes their crystallisation very difficult. It frequently implies the testing of many different sample variations under many hundred conditions. This is the reason for the establishment of automated high‐throughput crystallisation facilities.

Key Concepts:

Progress in the life sciences requires knowledge of the cellular processes at a molecular level.

The principal components of the cell are proteins and nucleic acids.

The three‐dimensional structures of the cellular components define their functions.

X‐ray crystallography is the method of choice to determine the structure of biological macromolecules.

Crystallisation of biological macromolecules for X‐ray crystallography requires the testing of hundreds to thousands of conditions.

Automation supports many processes in molecular biology, by performing routine operations with the help of robotics.

High‐throughput crystallisation has significantly improved success rates in crystallography through the rapid and comprehensive screening of many sample constructs under many different conditions.
Mechanism of Single‐Stranded
DNA
Transposition: A Structural Perspective
Authors: Barabas Orsolya
Published: April 2013

Transposons are mobile genetic elements that have shaped evolution and thus constitute much of modern genomes. Their movements cause diseases, change regulatory patterns and spread antibiotic resistance.
Single‐stranded deoxyribonucleic acid (ssDNA)
transposition, is carried out by a unique transposase protein that recognises a hairpin structure formed on ssDNA, excises the transposon as a single‐stranded circle, and integrates it specifically into ssDNA target. The use of ssDNA alleviates the cumbersome processing of the second DNA strand and implies a built‐in regulation of transposition via substrate limitation

in vivo

. Moreover, it allows selection of a specific sequence for integration via base‐pairing between transposon and target DNA. Due to this target site recognition strategy the transposon can be redirected to novel sites and may permit the development of programmable site‐specific genetic tools for research and gene therapy. Furthermore, unexpected similarities suggest that ssDNA transposons share mechanistic features with repetitive extragenic palindromes and
ribonucleic acid (RNA)
machines.

Key Concepts:

Transposons are mobile genetic parasites that can move from one location in the genome to another.

Transposons are abundant in most prokaryotic and eukaryotic organisms, where they contribute to genome structure, function and evolution.

Single‐stranded DNA (ssDNA) transposition is carried out solely on ssDNA substrates and intermediates.

ssDNA transposons alleviate the need for cutting and pasting two DNA strands and thereby preserve chemical energy.

The transposon encodes a transposase protein, which recognises, cleaves and integrates the two ends of the transposon in the context of a synaptic complex called the transpososome.

The ssDNA transpososome recognises its target site sequence specifically via base‐pairing interactions between a part of the transposon DNA and the cleavage site.

In vivo
, ssDNA transposition is limited by the availability of ssDNA, which provides a built‐in regulatory mechanism.

Their mechanism of target site recognition allows ssDNA transposons to be redirected to novel target site sequences, potentially allowing the development of unique genetic tools for research and medicine.

Repetitive extragenic palindromes (REPs) may have derived from ssDNA transposons.

In complex with a helper protein, ssDNA can form complex intertwined tertiary structures providing unique functions that were previously seen only for RNA.
Capsid‐Less
RNA
Viruses
Authors: Dolja Valerian V , Koonin Eugene V
Published: April 2013

Capsid‐less RNA viruses comprise an assemblage of diverse virus‐like agents with genomes of variable size that share only the gene encoding the RNA‐dependent RNA polymerase. Although double‐stranded
ribonucleic acid
(RNA) is the dominant form of virus‐specific RNA isolated from organisms infected by most capsid‐less viruses, these viruses probably have evolved independently from distinct positive‐strand RNA virus ancestors that have lost the ability to form capsids. The loss of capsid caused the loss of virus transmissibility via extracellular routes, limiting these agents to vertical transmission. The capsid‐less RNA viruses include the families
Narnaviridae, Hypoviridae
, and
Endornaviridae
as well as several viruses scattered among diverse viral lineages. The majority of the known capsid‐less viruses reproduce in fungi, and the rest in oomycetes and plants. The narnaviruses of the genus
Mitovirus
replicate within fungal mitochondria and show evolutionary affinity to RNA bacteriophages, suggesting their potential ancient origin from viruses of bacteria that gave rise to mitochondrial endosymbiont of the ancestral eukaryote. In contrast, it seems likely that the fungal hypoviruses and plant/fungal endornaviruses have emerged more recently, via reductive evolution of eukaryotic ancestral viruses of the Picornavirus‐like and Alphavirus‐like superfamilies, respectively.

Key Concepts:

Several groups of RNA viruses infecting fungi, plants and protists lack a capsid and replicate in the form of naked RNA.

Phylogenomic analysis shows that capsid‐less viruses have evolved on many independent occasions from different groups of typical positive‐strand RNA viruses.

The driving force behind the evolution of capsid‐less viruses appears the life style of their hosts such as fungi that hampers infectivity, even for viruses possessing a capsid, and restricts viruses to vertical transmission.

Numerous members of a widespread family of capsid‐less viruses, the
Narnaviridae
, replicate within the host mitochondria and are evolutionarily related to RNA bacteriophage, revealing a direct link between viruses of bacteria and eukaryotes.
Urban Biodiversity: Patterns, Processes and Implications for Conservation
Authors: Faeth Stanley H , Saari Susanna , Bang Christofer
Published: April 2013

As the world becomes increasingly urbanised, more and more species either reside in cities, suburbs and exurbs or are influenced by their growth. On the bases of our literature survey, species richness and diversity of animals, especially vertebrate animals, and plants usually declines in cities. However, contrary to the prevailing notion that bird abundances usually increase in cities, studies reporting increases or decreases of bird abundances are about equal. The mechanisms underlying patterns of urban biodiversity are complex and not well‐understood. Explanations for the observed changes in species diversity and composition in cities focus on local processes involving species responses to local abiotic environmental factors and interactions with other species and regional processes, such as dispersal. Recently, metacommunity theory has been applied to urban habitats to explore the relative importance of local and regional processes. This theory also provides insights into how biodiversity can be maintained and promoted in urban areas.

Key Concepts:

Urbanisation creates highly fragmented, heterogeneous and altered environments that act as selective filters for urban organisms and species.

Urbanisation is often associated with declines in animal and plant richness, abundance and diversity.

Studies showing increases or decreases in urban bird abundances are about equal, contrary to conventional wisdom of increased bird abundances in cities.

Various ecological concepts have been applied to explain urban biodiversity, including disturbance and productivity gradient hypotheses and island biogeography theory.

Metacommunity theory has been used recently to ascertain relative contributions of local and regional processes to urban biodiversity.

Understanding local and regional processes leads to better insights in conserving and promoting urban biodiversity.

Conservation efforts depend on connections to nature; therefore, it is important to engage city‐dwellers with their urban biotas.
Telomere Dysfunction in Human Genetic Disease
Authors: Morgan Garrett , Ly Hinh
Published: April 2013

Telomeres are specialised
deoxyribonucleic acid
(DNA) structures that cap the ends of chromosomes to protect genomic DNA. Telomerase is the enzyme that regulates telomere length to maintain the protective functions of telomeres. A major risk factor for some human diseases is telomere and telomerase dysfunction. Bone marrow deficiency syndromes as well as diabetes, hypertension and atherosclerosis have all been linked to alterations to telomeres or mutations in telomerase genes. The precise biological mechanisms involved in most of the diseases, however, are poorly understood. Research aimed at describing the biological processes that underlie these pathologies may elucidate the precise roles that telomeres and telomerase play in the progression of these diseases. Markers of telomere dynamics, such as telomere length and screening for telomerase mutations, may have some prognostic value related to these disorders.

Key Concepts:

Telomeres are repeats of the nucleic acid sequence TTAGGG.

T‐loop structure is composed of telomeric DNA and shelterin proteins.

Telomeres help maintain genomic stability in the cell.

Progressive telomeric repeat loss occurs due to the end‐replication problem and genotoxic stress.

Telomerase in an enzyme that adds TTAGGG repeats to 3′ ends of telomeres.

Bone‐marrow failure syndromes, such as dyskeratosis congenita, aplastic anaemia and idiopathic pulmonary fibrosis have been linked to telomere and telomerase dysfunctions.

Chronic diseases such as cardiovascular disease and diabetes have also been linked to telomere alterations.

In vitro
and
in vivo
research may demonstrate the precise role telomeres play in these disease processes.

In vivo
studies may lead to development of diagnostic markers and therapies for these diseases.
Protein Disorder and Human Genetic Disease
Authors: Uversky Vladimir N , Iakoucheva Lilia M , Dunker A Keith
Published: April 2013

Intrinsically disordered proteins (IDPs) are biologically active proteins that lack stable structure under physiological conditions. They are involved in crucial biological functions related to regulation, recognition, signalling and control of various events in the cell. Misbehaviour of IDPs is commonly associated with various human diseases. IDPs represent a prominent part of the human diseasome, a network that links the human disease phenome (which includes all the human genetic diseases) with the human disease genome (which contains all the disease‐related genes), where they could be grouped into a unique entity, the human‐genetic‐disease‐associated unfoldome. The exonic single nucleotide variations (SNVs) may induce a significant change in the tendency of a protein region to be structured or disordered, thereby causing malfunction of such a protein and contributing to the disease risk. Therefore, IDPs are abundant in genetic diseases, play crucial roles in pathogenesis of these maladies, and clearly require special attention.

Key Concepts:

Intrinsically disordered proteins (IDPs) are common in various proteomes, where they constitute functionally broad and densely populated unfoldomes.

IDPs have crucial biological functions and are responsible for regulation, recognition, signalling and control of various events in the cell.

Dysfunction, dysregulation and misbehaviour of IDPs are related to the pathogenesis of various diseases.

Mutations in IDPs are frequently associated with genetic diseases.

Mutations affecting the potential post‐translational modification sites (which are frequently located within the intrinsically disordered regions) are often related to various diseases.

A more‐detailed understanding of the roles of intrinsically disordered proteins in genetic diseases might provide a basis for rational drug design against them.
Ecology and Social Organisation of Wasps
Authors: Bell Emily , Sumner Seirian
Published: April 2013

Understanding sociality is a general question in biology: it tells us how groups evolve and function, from cells to insect societies. The social wasps (Hymenoptera and Vespidae) display a wide range of diversity in their ecology and social organisation, providing insights into the origins of simple societies and the elaboration and maintenance of complex societies. Social wasps play an important role in our ecosystems and economies, for example, through their pollination and pest control services. Compared with other social insects (e.g. ants, termites and bees), the social wasps are understudied. Here the authors give a brief overview of the social wasps, their phylogenetic history, diversity in social organisation and explain how they offer important insights on the key innovations underpinning the evolution of sociality.

Key Concepts:

Wasps make up a huge group of social insects, yet only one‐fifth of them exhibit social behaviour.

Social wasps are ideal and unique models for studying social evolution as they show the full spectrum of social organisation and behaviours.

Across the social spectrum, wasp species show a number of key innovations that have contributed to their success, including the transition to group living, the evolution of castes, policing and swarm founding.

The evolution of caste differentiation has led to mutual dependency between phenotypes within species, and this is likely to have facilitated increased social complexity.

Studying both proximate and ultimate factors of social evolution will allow us to better understand the mechanisms of social evolution in wasps and reduce confusion in the theory of sociobiology.
Marine Protected Areas
Authors: Claudet Joachim
Published: April 2013

Human‐induced disturbance can affect the ecological functioning of coastal areas and reduce the associated goods and services required for human welfare. Major concerns are rising over observed declines in the abundance of particular species as well as reductions in functional diversity and changes in food web structure. As a result, the conservation and restoration of marine biodiversity and functions is a major concern. Marine protected areas are a useful management tool to mitigate some of the human‐induced changes in marine ecosystems. If properly managed and enforced, they can have several ecological, fisheries and socio‐economic benefits. Effects of marine protected areas are variable and context‐dependent but main drivers of change are now known. In recent years, MPA research made several important advances but some questions still remain unresolved.

Key Concepts:

Marine protected areas are a useful management tool.

Marine protected areas can have ecological, fisheries and socio‐economic benefits.

Partial protection confers less ecological benefits than full protection.

Effects of marine protected areas mainly depend on their design and age, on the socio‐cultural context in which they are established and on the life history traits of the species targeted by protection.

Effective marine protected areas need to be well enforced.

The global coverage of marine protected areas is still very low.
Diet, Changes in Gene Expression and Human Evolution
Authors: Luca Francesca
Published: April 2013

Changes in food availability and diet represent selective pressures that acted on multiple biological processes and anatomical features during human evolution. Anthropological studies have long investigated these dietary transitions; however, many questions are still open and aspects of these events are still strongly debated. More recently, evolutionary geneticists have provided evidence, both genome‐wide and from single‐gene studies, that diet is an important evolutionary force in humans. Changes in regulation of gene expression have played a major role during human evolution in response to a variety of selective pressures including dietary transitions. Furthermore, recent studies have highlighted the role of variation in gene regulation in risk for common diseases. Future studies promise to leverage the information from variation in gene expression to learn about adaptations to dietary shifts and disease predisposition in humans.

Key Concepts:

Changes in food availability and diet composition during hominin evolution created strong selective pressures on multiple biological processes and anatomical features.

Genes involved in metabolism carry a signature of selection in single‐gene and genome‐wide studies.

The two most interpretable examples of genetic adaptations to dietary shifts in humans have implied changes in the expression level of the lactase and amylase genes.

Adaptations to dietary changes may have acted on different molecular aspects of regulation of gene expression.

By gaining further knowledge on past human diets, it is possible to achieve a better understanding of potential adaptations to and clinical consequences of our current ones.