bluuebunny/crossref_metadata_2025 huggingface dataset:
Eukaryotic Replication Origins and Initiation of
DNA
Replication
Authors: DePamphilis Melvin L , Aladjem Mirit I
Published: September 2010

Eukaryotic
deoxyribonucleic acid
(DNA) replication begins at specific genomic sites called replication origins that serve as assembly sites for prereplication complexes (preRCs). PreRCs include proteins that recognise origin sequences,
helicases
that separate the two strands of DNA and accessory proteins that facilitate
helicase
binding and interaction with cell cycle regulatory pathways. Assembly of preRCs is required for initiation of DNA replication which occurs after those complexes recruit additional proteins including
DNA polymerases
. The sequence requirements for replication origins vary but they all include several distinct DNA elements that act synergistically to facilitate preRC assembly. The number of potential replication origins is higher than the number of actual replication initiation sites. Epigenetic processes and metabolic conditions dynamically select the location of replication initiation events of each cell cycle to insure complete and accurate replication of the entire genome in coordination with gene expression and chromatin condensation.

Key Concepts:

Replication initiates at distinct chromosomal locations that recruit prereplication (preRC) complexes.

PreRCs are recruited sequentially, each step subject to strict regulation to prevent rereplication.

Cyclin‐dependent kinases (CDK) levels change during the cell cycle. Low CDK activity is required for preRC assembly as cells exit mitosis. High CDK activity is required for activation of existing preRCs and initiation of DNA synthesis, while simultaneously suppressing assembly of new preRCs.

Replication origin sequences vary among metazoans, but the functions of proteins that bind replication origins are conserved.

Eukaryotic origins exhibit a modular structure. Modularity is detectable in single‐cell eukaryotes such as yeast and is more pronounced in metazoans, in which replication origins often cluster.

Not all potential replication origins are activated in each cell cycle. Utilisation of replication origins is regulated dynamically to facilitate coordination with other metabolic processes occurring on chromatin.

Either hyperactivation or suppression of replication origins can damage DNA and cause chromosomal rearrangements, suggesting that spacing replication initiation events at defined intervals facilitates genomic stability.
Blastoderm Formation and Cellularisation inDrosophila melanogaster
Authors: Kotadia Shaila , Crest Justin , Tram Uyen , Riggs Blake , Sullivan William
Published: September 2010

Immediately following fertilisation inDrosophilaand many other arthropods, the embryo undergoes a series of rapid syncytial nuclear divisions. These divisions are driven by maternally supplied components and occur in the absence of zygotic transcription. Unlike typical cell divisions, these divisions alternate between S and M phases, resulting in cell cycles that last only from 10 to 25 min. After four rounds of division, the nuclei undergo axial expansion, a process that relies on microfilaments. Subsequently migration of the nuclei to the cortex relies on microtubules. Once at the cortex, the nuclear divisions occur on a single plane and rely on partial cleavage furrows to maintain an even distribution. The cortical nuclear divisions continue until the mid‐blastula transition (MBT), at which time cellularisation results in the formation of a multicellular embryo.

Key Concepts:

Fertilisation triggers a series of events that induces the first mitotic cycle, a gonomeric division between the male and female pronucleus.

After fertilisation, the embryo undergoes 13 synchronous divisions within a syncytium.

Divisions 10–13 occur at the cortex of the embryo and require reorganisation of actin and membrane into metaphase furrows.

At cycle 14, the cell cycle pauses and cellularisation occurs forming individual somatic cells.

Cellularisation, a key feature of the mid‐blastula transition, marks the time at which zygotic transcription occurs and maternal products are degraded.
Autoimmune Disease: Pathogenesis
Authors: Bellone Matteo
Published: September 2010

Autoimmune diseases are a vast array of organ‐specific as well as systemic diseases, whose pathogenesis stems from the activation of B‐ and T lymphocytes reacting against antigens of the body's own tissues (defined as ‘self’). T‐ and B lymphocytes are the main components of the adaptive arm of the immune system, and their major task is to rapidly and efficiently remove pathogens (e.g. viruses or bacteria) in the absence of relevant tissue damage and self‐recognition. In physiologic conditions, the ability of the immune system to avoid responsiveness to self‐antigens is obtained by the cooperative efforts of central and peripheral tolerance mechanisms. Alteration of either one of the two mechanisms favours the induction of autoimmune diseases that may either cause complete and irreversible loss of function of the targeted tissue or its hyperfunction.

Key Concepts:

Autoimmune diseases are the result of specific immune responses directed against structures of the self.

Autoimmune diseases are the consequence of an altered function of the immune system.

Autoimmune disease may involve a single tissue or multiple organs.

Consequences of an autoimmune reaction may either be the loss of function or the hyperfunction of the target tissue.

An autoimmune response may be primarily T‐ or B‐cell‐mediated, or both.
Evolution: History
Authors: Bowler Peter J
Published: September 2010

The modern theory of evolution was founded by Charles Darwin, but an overview of the history of evolutionism shows that ideas of the transformation of species predated the publication of hisOrigin of Speciesin 1859. Various theories of progressive and purposeful change in the organic world had begun to circulate even before Darwin's more radical theory was injected into the debate. Natural selection was regarded as a materialistic idea, and through the late nineteenth century naturalists searched for alternatives that would allow them to believe that the history of life had an ultimate purpose. A complex series of developments in the early twentieth century was needed to create the genetical theory of natural selection accepted by most biologists today.
Plant Tracheary Elements
Authors: Fukuda Hiroo
Published: September 2010

The plant tracheary element is the constituent of vessels and tracheids. Tracheary elements are characterised by patterned secondary wall thickenings and programmed cell death (PCD) at maturity. Their differentiation is induced by plant hormones such as
auxin
, cytokinin and brassinosteroids, and suppressed by a small peptide, tracheary element differentiation inhibitory factor (
TDIF
), secreted from phloem cells. The final determination of tracheary element differentiation is initiated by master transcription factors,
VAD6
and
VND7
(vascular‐related NAC‐domain 7). The secondary wall pattern is formed by guiding the movement of
cellulose synthase
complex in the plasma membrane by the cortical microtubules. The PCD during tracheary element differentiation is initiated by the rupture of the central vacuole in which cell death‐related hydrolytic enzymes have been accumulated. Thus the process of tracheary element differentiation is well understood, so that tracheary element differentiation is an excellent model of cell differentiation in plants.

Key Concepts:

The xylem, which is tissue specific to the vascular plants, is composed of tracheary elements (TEs), parenchyma cells and fibres.

Procambial cells produce the primary xylem containing protoxylem and metaxylem TEs
in planta
.

Typical characteristics of TEs are patterned secondary wall thickenings and programmed cell death (PCD).

TE differentiation is regulated by plant hormones such as auxin, cytokinin and brassinosteroids.

A small peptide secreted from phloem cells prevents procambial cells from differentiating into TEs.

VND6 and VND7 are master transcription factors that initiate TE differentiation.

Microtubules determine the secondary wall pattern by guiding the movement of cellulose synthase complex in the plasma membrane.

During the formation of secondary walls, levels of cellulose and hemicellulose increase and the deposition of pectin ceases, and a little later lignin deposition starts.

The central vacuole plays a crucial role in TE PCD.

A
Zinnia
xylogenic culture is an excellent model system of TE differentiation.
Glycosylation and Disease
Authors: Rhodes Jonathan , Campbell Barry J , Yu Lu‐Gang
Published: September 2010

Glycosylation is the process of attachment of sugar molecules, usually in chains (oligosaccharides), to proteins and lipids to form the glycoproteins and glycolipids found in eukaryotic and some prokaryotic organisms. The presence of oligosaccharides on a protein can have substantial effects on its size, stability, charge and antigenicity. The varying structure, branching and substitution of the carbohydrates in an oligosaccharide results in much greater diversity than would be achieved for a peptide with an equivalent number of residues. Acquired alterations in glycosylation occur in cancer and inflammation and may have particularly important functional consequences when they affect mucosae. They also have the potential to affect pathogen–host and other cell–cell interactions. Congenital glycosylation disorders most commonly affectN‐glycosylation and affect development in diverse ways. There is increasing evidence of the importance of interactions between carbohydrate structures and carbohydrate‐binding proteins (lectins) which may be extrinsic (dietary or microbial) or intrinsic (mammalian galectins or siglecs).

Key Concepts:

Glycosylation occurs asN‐ andO‐linked (mucin type) oligosaccharides (glycans) on glycoproteins and as glycolipids.

Variation in sequence, linkage and substitution of carbohdrates in a glycan means that a relatively short glycan can have many more variations (glycoforms) than a peptide with an equivalent number of amino acids.

Variations in glycan structure can result from a range of different mechanisms that include altered glycosyltransferase and glycosidase activity, Golgi acidification and structure, donor and acceptor availability.

Cell–cell and cell–microbe interactions are often driven by interactions between lectins on one cell and the relevant carbohydrate (glycan) receptor on the other cell.

Mucins are heavily glycosylated, particularly withO‐linked glycans and this gives them their protective properties.

Mammalian lectins include a family of galactose‐binding lectins called galectins that interact with some of the glycans that show increased expression in epithelial cancers with increased cancer cell to endothelial adherence and increased metastasis as a consequence.

Foodstuffs, particularly legumes, contain lectins some of which resist digestion and may have biologically significant interactions with the intestinal epithelium.

A wide range of rare congenital dosorders of glycosylation have been recognised – these have many and varied developmental consequences.

Some of the developmental glycosylation disorders can be screened for by isoelectric focusing of serum glycoproteins.
Atopy and Asthma
Authors: Yates Anne B , de Shazo Richard D
Published: September 2010

Atopy is the genetic propensity to develop an
immunoglobulin E
antibody response to common allergens. The most common clinical manifestations of atopy are allergic rhinitis, asthma and atopic dermatitis. Asthma is a complex disorder of the airways, involving airway hyperresponsiveness, airflow obstruction that is at least partially reversible, and inflammation of the airways. Although atopy has been identified as the strongest predisposing factor for the development of asthma, not all asthma is allergic in nature. The overall prevalence of asthma has been increasing worldwide for the past few decades, and continues to increase globally. Guidelines for the evaluation and treatment of asthma were developed in the early 1990s, and are revised periodically as research into effectiveness of available medications emerges, and development of new therapies arise.

Key Concepts:

Asthma is a common but complex disorder of the airways, involving variable and recurrent symptoms, airway obstruction, inflammation and bronchial hyperresponsiveness.

Symptoms of asthma include coughing, wheezing, shortness of breath and feelings of chest tightness or pain with breathing.

Onset of asthma usually begins early in life, although adult‐onset of asthma may occur.

Genetic predisposition, as well as environmental factors, play a role in the development of asthma.

Treatment of asthma centres around control of chronic inflammation, avoidance of triggering factors and treatment of acute bronchospasm when needed.

Individuals over 65 may have a decreased perception of breathlessness and air hunger. Therefore, the use of clinical symptoms to diagnose and treat seniors may underestimate the severity of airways obstruction.
Mixed
T
‐ and
B
Lymphocyte Deficiency Disorders
Authors: Vihinen M
Published: September 2010

Mixed immunodeficiency diseases are intrinsic defects of the immune system affecting both B and T cells and thus the adaptive immune system. Mixed or combined immune deficiencies may also be associated with or secondary to other diseases. Patients have severe symptoms and the condition can be fatal unless properly treated. Early and reliable diagnosis is in many instances crucial for the efficient treatment of these diseases since delayed diagnosis and management can cause severe and irreversible complications, even the death of the patient. Combined immunodeficiencies, which are a heterogeneous disease group, appear throughout the immune system and affect several crucial genes and proteins. The symptoms and signs vary significantly between the different forms of combined immunodeficiencies.

Key Concepts:

Combined immunodeficiency affects both B and T cells.

Lymphocytes are white blood cells including B and T cells.

Haematopoietic stem cell transplantation, the intravenous infusion of autologous or allogeneic stem cells collected from bone marrow, peripheral blood or umbilical cord blood, reestablishes haematopoietic function in patients.

V(D)J recombination is genetic recombination which randomly selects and assembles segments of genes encoding specific proteins in the immune system.
Galen of Pergamum
Authors: Nutton V
Published: September 2010

G
alen
,
ad
129–216, Greek physician, anatomist and physiologist, was the most influential of ancient doctors. His combination of erudition, logic and practical skills convinced many contemporaries of his supreme merits, and his theories came to dominate learned medicine in medieval Europe and in the Islamic world. He saw himself as continuing the work of Hippocrates of Cos in medicine, and of the physicians of early Alexandria in anatomy, systematising the notion that health and disease depended on an individual balance or imbalance of four fluids, or humours, blood, bile, black bile and phlegm. He was a prolific dissector, almost entirely of animals, and his description of the body, bolstered by an exuberant rhetoric, remained largely unchallenged until the sixteenth century CE.
Tetrahymena
Cell Culture
Authors: Zhang Siwei , Ling Zihui , Wang Shulin , Nozawa Yoshinori , Umeki Shigenobu
Published: September 2010

Tetrahymena

, a free‐living unicellular eukaryote, is a ciliate considered to be the most highly developed protozoan, because it possesses specialised organelles that perform each of the cell functions. This pear‐shaped microorganism (30×50 μm) can be found in almost all freshwater environments, including even natural hot springs in which a thermotolerant strain can live. One distinct feature that sets ciliate apart from other multicellular eukaryotes is the possession of two functionally different nuclei – macronucleus, which is transcriptionally active and responsive for the somatic function of cells, and micronucleus, which is transcriptionally silent and serves as germinal nucleus during mating.

Tetrahymena

grows easily to high density. Its relatively large size, nuclear dimorphism and other unique genetic characteristics make it a good model system to study the molecular, cellular and genetic processes of cells.

Key Concepts:

Ciliates are unicellular organisms that execute many biological activities observed in multicellular organisms.

Tetrahymena
cells can survive under extremely dangerous conditions such as cold, pH alterations and osmotic stress.

Tetrahymena
cells possess rapid adaptation machineries to regulate biological processes including cell division, conjugation and cell death against intracellular and extracellular stresses.
Mitochondria: Methods for Preparation
Authors: Mühlenhoff Ulrich
Published: September 2010

Mitochondria are the main energy providers of the cell. Procedures developed for the isolation of pure and intact mitochondria have contributed considerably to the understanding of the complex biochemical functions of mitochondria, as they permit the application of detailed biochemical and biophysical techniques to the investigation of this organelle. This article describes the principles underlying the procedures for the isolation of mitochondria from a large variety of tissues and the techniques for assessing the quality of mitochondrial preparations. Special emphasis is given to cell fractionation protocols for the isolation of mitochondria from model organisms, includingSaccharomyces cerevisiae,Arabidopsis thaliana, cultured mammalian cells, and for the isolation of hydrogenosomes and mitosomes from amitochondriates. The special requirements for the determination of the mitochondrial proteome by high‐throughput mass spectrometry are discussed.

Key Concepts:

Cell fractionation is a summary term for the isolation of cell organelles and subcellular fractions from tissues and cultivated cells.

Equilibrium centrifugation, a centrifugation technique by which particles are separated by virtue of their different densities in density gradients, is the most common technique for the preparation of highly enriched mitochondrial fractions.

Differential centrifugation, a centrifugation technique by which subcellular particles are separated by virtue of their differences in sedimentation rates, is the most common technique of cell fractionation protocols.

The mitochondrial proteome represents the whole set of proteins found within mitochondria.

Mitosomes and hydrogenosomes are mitochondria‐related organelles from protists.

A model organism is an experimental organism that is representative for a whole group of species. Models that are easy to manipulate tend to be the most widely used.

A subcellular marker is a selected biomolecule that is confined to a specific organelle or suborganellar compartment and that may be used to determine the presence of this compartment in a subcellular fraction.

The subfractionation of mitochondria involves techniques that allow the physical separation of individual mitochondrial compartments.

The quality of a mitochondrial preparation is determined by the degree of other contaminating organelles, the level of specific mitochondrial activities and the degree of mitochondrial integrity.
Microinjection into
Xenopus
Oocytes
Authors: Sigel E
Published: September 2010

Microinjection of genetic information in the form of complimentary
ribonucleic acid
(cRNA) into the

Xenopus

oocyte leads to the functional expression of the encoded proteins. In this novel environment, exogenous proteins may be functionally characterised under well‐defined conditions. Complimentary
deoxyribonucleic acid
(cDNA) coding for the protein may be mutated, the altered cDNA transcribed and polyadenylated

in vitro

to the corresponding cRNA and the function of the resulting altered protein is compared with that of the wild‐type protein. The oocyte is a major expression system used in membrane protein structure–function studies. It is especially popular for expression of membrane transport proteins such as carriers and ion channels. In another approach, total messenger RNA (mRNA) may be prepared from a tissue of choice, microinjected into oocytes, the encoded functions characterised and the encoding genetic information isolated.

Key Concepts:

Proteins can be ‘transplanted’ into the
Xenopus
oocyte.

The
Xenopus
oocyte may be used as a test tube for newly introduced protein functions.

Genetic information in the form of cRNA may be prepared
in vitro
from the coding cDNA.

The
Xenopus
oocyte translates foreign microinjected cRNA.

The
Xenopus
oocyte is favourite expression system for structure–function studies.

Expression cloning can identify genes purely based on protein function.
Crystallisation of Nucleic Acids
Authors: Holbrook Elizabeth L , Holbrook Stephen R
Published: September 2010

High‐resolution three dimensional structure analysis by X‐ray diffraction requires large, well‐ordered, single crystals. The crystallisation of nucleic acids has become the limiting step in their structural analysis by X‐ray crystallography. Nucleic acids may be isolated from native sources or synthesised chemically or enzymatically. Purification to homogeneity may be achieved by thin layer chromatography, polyacrylamide gel electrophoresis, column chromatography or combinations of these methods. Approaches to crystallisation have included batch methods, dialysis, evaporation, interface diffusion and vapour diffusion. The most widely and successfully used technique is hanging‐drop vapour diffusion. Sparse matrix screening has allowed exploration of the vast crystallisation space with the limited amount of nucleic acid available. Developments in synchrotron radiation and cryocrystallography have allowed use of smaller crystals for structure determination. High‐throughput robotic crystallisation uses less material thus allowing more crystallisation experiments from a given amount ofdeoxyribonucleic acid(DNA) orribonucleic acid(RNA).

Key Concepts:

The most complete structural description of a DNA or an RNA molecule is achieved through high resolution X‐ray crystallography.

Nucleic acid crystallisation depends on synthesis of large quantities of homogeneous DNA or RNA.

Material for crystallisation can be prepared by purification of native material, chemical synthesis or enzymatic synthesis.

Purification to homogeneity implies a single form of oligomeric state and modification in addition to a single species.

Purification methods include thin layer chromatography (TLC), polyacrylamide gel electrophoresis (PAGE) and liquid chromatography (LC).

The most widely used method for crystallisation is vapour diffusion in either a hanging drop or sitting drop format.

High‐throughput robotic crystallisation allows setup of a greater number of experiments while using less nucleic acid material.

The size of crystal needed for X‐ray diffraction analysis has been sharply reduced with the use of powerful synchrotron radiation and computer programs.

To date, over 2000 DNA and 1000 RNA crystal structures have been reported in public databases such as the Nucleic Acid Database and the Protein Data Bank. Most of these structures are nucleic acid complexed with protein or ligands.
Duve, Christian Rene De
Authors: Fry Iris
Published: September 2010

Born in 1917, Belgian cytologist and biochemist who in 1974 was awarded the Nobel Prize for Physiology or Medicine for his discoveries of the cellular organelles, the lysosome and the peroxisome. Since the 1980s, De Duve contributed to the theoretical understanding of the origin and evolution of life.
Phosphorimager
Authors: Van Kirk C , Feinberg LA , Robertson DJ , Freeman WM , Vrana KE
Published: September 2010

Phosphorimaging is a form of solid‐state liquid scintillation where radioactive material can be both localised and quantified. Similar to traditional autoradiographic techniques (in that it relies on high‐energy particle decay), phosphorimaging can recognise radiolabelled
deoxyribonucleic acid
(DNA),
ribonucleic acid
(RNA) and protein targets in a variety of sample preparations, such as gels, blots, homogenised tissues, cell populations, arrays and tissue slices. Although more expensive than traditional X‐ray film technology, phosphorimaging is more sensitive, develops images more rapidly and has a greater dynamic range than X‐ray film, which has made it a popular choice for several applications in molecular biology. Current applications include, but are not limited to,

in situ

hybridisation, ligand‐binding pharmacology, as well as Southern, northern and western blotting.

Key Concepts:

Phosphorimaging allows for both localisation and quantification of targets.

Potential targets include radiolabelled DNA, RNA, proteins and posttranslational protein modifications.

Phosphorimaging can be performed on media including gels, homogenised samples, cell populations, arrays and tissue slices.

Phosphorimaging identifies and quantifies its target through the measurement of light emitted from excited electrons returning to their ground state. These electrons are stimulated to higher energy levels by radioactivity emitted from the target and light is released as the electrons return to their ground state.

Although phosphorimaging is more expensive and has lower resolution than traditional X‐ray film detection and quantification methods, phosphorimaging affords greater sensitivity, faster image development, reusable detection plates and enhanced linear dynamic range.
Sexual Conflict
Authors: Bonduriansky Russell
Published: September 2010

Although females and males share a common interest in successful reproduction, the sexes often maximise their reproductive success (fitness) in mutually incompatible ways. Two basic forms of sexual conflict are recognised:
Interlocus sexual conflict
reflects a conflict of interest over the outcome of an interaction between sexes (e.g. to mate or not?), with some genetic loci evolving to enhance male fitness at females’ expense and other loci evolving to promote female fitness by mitigating male‐imposed harm. This conflict drives the evolution of sexually antagonistic male strategies such as coercive behaviours and morphologies, toxic ejaculates and infanticide, and female counter‐adaptations that confer resistance to such strategies.
Intralocus sexual conflict
reflects divergent selection on a shared trait whose expression is influenced by the same loci in both sexes, such that selection on one sex can displace the other sex from its phenotypic optimum. It selects for genomic adaptations that permit the evolution of sexual dimorphism.

Key Concepts:

Sexual conflict arises because strategies that maximise the fitness of one sex can reduce the fitness of the other sex.

Two basic forms of sexual conflict are recognised:
interlocus
(between genetic loci) and
intralocus
(within a genetic locus).

Interlocus sexual conflict is a conflict of interest over the outcome of some interaction (e.g. to mate or not?), mediated by different genetic loci in each sex.

Sexual conflict can lead to sexually antagonistic coevolution and sexual ‘arms races’, whereby adaptations that benefit males at females’ expense select for counter‐adaptations in females that mitigate male‐imposed harm.

Interlocus sexual conflict is manifested in a variety of traits that increase male reproductive success but harm females in the process, including behavioural harassment and coercion, morphological armaments such as genital spines and chemical manipulation via ejaculate components or pheromones.

Intralocus sexual conflict is a conflict of interest over the expression of a shared trait that is subject to sex‐specific patterns of selection but influenced by the same genetic loci in both sexes.

Intralocus sexual conflict selects for modifications to the genetic basis of trait expression that allow each sex to evolve towards its phenotypic optimum, resulting in sexual dimorphism.

Intralocus sexual conflict challenges the ‘good genes’ model of sexual selection because females that mate with high‐quality males may produce low‐quality daughters.

Sexual conflict may increase the costs of sexual reproduction, reduce mean fitness in populations and (in theory) even promote population extinction.

The study of sexual conflict has become one of the most important and dynamic areas in evolutionary biology.
In VitroFertilisation: Regulation
Authors: Pynes Christopher A
Published: September 2010

In vitrofertilisation (IVF) is a fertility treatment, sometimes referred to more generically as an assisted reproductive technology (ART), designed to help couples who cannot get pregnant in the normal manner, establish a pregnancy. IVF treatment requires the creation of multiple pre‐embryos for implantation into the patient's uterus. The development of IVF techniques has prompted the use of several regulatory models, such as free market approaches, industry self‐regulation, laissez‐faire legislation and prohibitive licensing systems. Each regulatory model has strengths and weaknesses in dealing with different types of moral concerns within the IVF debate, including reproductive autonomy, safety and dignity of the unborn, the creation and destruction of waste embryos, surrogacy and ownership issues. With varying models of regulation and conflicting moral views on the matter, international harmonisation of IVF regulations is unlikely.

Key Concepts:

Assisted reproductive technology (ART) is a general term used to describe a variety of fertility treatments fromin vitrofertilisation to sperm donation where the ultimate goal is to achieve pregnancy. There is currently no strict definition.

Conflicts of interest occur when an individual or group has multiple interests in a particular act or behaviour, which could unjustly influence the act or behaviour; common examples occur in law, medicine, business, politics and journalism.

Industry self‐regulation is where an industry or profession attempts to set up regulations to prevent, what the industry might think is, excessive governmental regulation of the industry. The auto industry in the USA is a prime example.

In vitrofertilisation literally mean ‘within the glass’ fertilisation and occurs when an ovum is fertilised outside the body in a glass or plastic container like a Petri dish or test‐tube. Hence, the phrase ‘test‐tube’ baby.

Laissez‐faire approaches to regulation refer to a ‘let it be’ attitude and is typically associated with free markets and less government involvement.

Pre‐embryos are fertilised ova up to 14 days old before they are implanted into a uterus.

Procreative (medical) tourism is the practice of travelling to a country other than one's own home country where a particular medical practice, in this case an ART of some kind, is legally permissible.
Neural Networks
Authors: Wu Cathy H , McLarty Jerry W , Liao Li
Published: September 2010

Artificial neural networks are a form of machine learning, inspired by biological neural networks, which can be trained by examples to recognise patterns, classify data and make predictions. They have been used in a wide variety of problems in the fields of life sciences, such as predicting protein secondary structures, classifying protein families and identifying single nucleotide polymorphism. Problems in life sciences in general and in bioinformatics in particular present challenges to the design and training of neural networks and to the interpretation of networks outputs as well, including complex structured data and limited amount of training examples. In addressing these issues and limitations, significant progress has been made, including ways to design the neural networks to incorporate prior knowledge, to make automatic formulation of network architecture for optimal performance and to construct hybrid systems to leverage advantages of various learning methods.

Key Concepts:

Artificial neural networks are a means of mapping input data to output data in such a manner as to perform complex functions such as pattern recognition, classification, prediction and knowledge extraction, that are increasingly useful in bioinformatics applications.

There are numerous kinds of neural networks, classified by their architecture (number of layers, number of processing units, interconnections, etc.) and how they are trained to perform.

Neural networks have been successfully applied to numerous areas of genomic and proteomic research; the number of such applications has grown explosively in the past few years.

One of the most difficult challenges in constructing and training neural networks is often in determining the content and features of data to be used for training and ultimately using the neural networks, that is feature extraction, preprocessing.

Hybrid systems, which combine neural networks with other artificial intelligence and statistical techniques, are a promising area of research.
Mammalian Phylogeny
Authors: Phillips Matthew J , Penny David
Published: September 2010

Living mammals can be divided into three subclasses (monotremes, marsupials and placentals) and within these, about 27 orders. Final resolution of the relationships between the orders is only now being achieved with the increased availability of
deoxyribonucleic acid
(DNA) sequences. Highlights include the deep division of placental mammals into African (Afrotheria), South American (Xenarthra) and northern hemisphere (Boreoeutheria) super‐orders, and the finding that the once considered primitive ‘Insectivora’ and ‘Edentata’ clades, in fact, have members distributed widely among these super‐orders. Another surprise finding from DNA studies has been that whale origins lie among the even‐toed ungulates (Artiodactyla). Our order, Primates is most closely related to the flying lemurs and next, the tree shrews. With the mammal phylogeny becoming well resolved, it is increasingly being used as a framework for inferring evolutionary and ecological processes, such as adaptive radiation.

Key Concepts:

A phylogeny describes the relationships of organisms with respect to their shared ancestry.

In the context of phylogenetics, molecular data refer to the genotype (DNA) and its direct translations (e.g. protein sequences).

Morphology refers to an organism's structural phenotype, sometimes limited to anatomy, but often also incorporating physiology.

Homoplasy describes character states that are similar for reasons other than shared ancestry, such as due to convergent or parallel evolution.

Retroposons are DNA sequences that can use the protein, reverse transcriptase to copy themselves and insert into new positions in the genome.

Molecular dating employs DNA or protein sequence differences between organisms to provide evolutionary time scales, with independent (especially fossil) information used to convert molecular differences into time.

Adaptive radiation describes the (often) rapid diversification of closely related species into a wide variety of ecological niches.
Pulmonary Disorders: Hereditary
Authors: Marciniak Stefan J , Lomas David A
Published: September 2010

Hereditary lung diseases can affect the airways (asthma, COPD, cystic fibrosis and primary ciliary dyskinesia), parenchyma (pulmonary fibrosis, Birt Hogg Dube syndrome and tuberous sclerosis) and vasculature (hereditary heamorrhagic telangiectasia) of the lung. Such conditions include simple monogenic disorders such as Kartagener syndrome andα1‐antitrypsin, wherein mutations of critical genes are sufficient to induce well‐defined disease phenotypes. However, many are complex genetic traits in which inheritance subtly affects pathogenesis, for example asthma and idiopathic pulmonary fibrosis. A greater understanding of the genetic basis of pulmonary conditions has provided new insights into their underlying pathophysiology and helped in some cases to shed light on more common sporadic forms. Importantly, the identification of causative genes has also enabled prenatal diagnosis and genetic counselling to be introduced for many diseases.

Key Concepts:

Common diseases frequently have a genetic component, which with the advent of genome‐wide association studies can now be elucidated.

The study of rare monogenic disorders can provide important mechanistic clues to the pathogensis of more common sporadic disease.

Pulmonary manifestations can be the presenting feature of several important inherited diseases.
Porphyrias: Genetics
Authors: Elder George H
Published: September 2010

The porphyrias are a group of eight disorders of haem biosynthesis characterised by overproduction of haem precursors secondary to partial enzyme deficiencies or, in one porphyria, gain‐of‐function of the rate‐controlling enzyme of the pathway in erythroid cells. Patients suffer from acute neurovisceral attacks, always associated with overproduction of porphyrin precursors, skin lesions caused by photosensitisation by porphyrins or both together. All are inherited, apart from sporadic porphyria cutanea tarda. The three porphyrias in which acute attacks occur (acute intermittent porphyria, hereditary coproporphyria and variegate porphyria) and familial porphyria cutanea tarda are low penetrance autosomal dominant disorders and one is an X‐linked dominant disorder. All others are autosomal recessive. Most patients with erythropoietic protoporphyria, the commonest inherited cutaneous porphyria, are compound heterozygotes for a deleterious
ferrochelatase
mutation and a low expression
ferrochelatase
allele; the population frequency of the latter is a major determinant of the prevalence of erythropoietic protoporphyria.

Key Concepts:

The porphyrias are disorders of haem biosynthesis.

Each of the eight porphyrias is caused by an abnormality of a different enzyme of haem biosynthesis.

Each enzyme abnormality leads to overproduction of haem precursors in a specific pattern that defines the disorder.

Overproduction of porphyrin precursors leads to acute neurovisceral attacks which characterise the three autosomal dominant acute porphyrias and one rare recessive porphyria.

Overproduction of porphyrins leads to photosensitisation of the skin with either skin fragility and blisters or, when only protoporphyrin accumulates, acute painful photosensitivity.

All autosomal dominant porphyrias have low clinical penetrance.

Most patients with the commonest inherited cutaneous porphyria, erythropoietic protoporphyria, have inherited a low expression ferrochelatase allele
trans
to a deleterious ferrochelatase mutation.

The prevalence of erythropoietic protoporphyria and the proportion of families showing pseudodominant inheritance are determined by the population frequency of the low expression allele.
Autosomal Dominant Polycystic Kidney Disease
Authors: Arnaout M Amin
Published: September 2010

Autosomal dominant polycystic disease (ADPKD) is the most common monogenic disease in humans and is among the leading causes of kidney failure. Dominantly inherited germline mutations in 2 genes,PKD1andPKD2followed by a second somatic hit that annuls or reduces the function of the remaining normal allele lead to loss of tube diameter control, cyst formation and eventual kidney failure. The respective gene products,polycystin‐1andpolycystin‐2form a receptor–ion channel complex that transduces mechanical and/or chemical signals into a calcium entry signal that regulates cell polarity, proliferation and movement. Localisation of this complex in the primary cilium has linked this sensory organelle to the regulation of tube size. Here we review the recent advances made in elucidating pathogenesis, diagnosis and management of this disease and the experimental therapies targeting the implicated signalling pathways.

Key Concepts:

ADPKD presents with tubular dilatations/cysts mainly affecting the kidney, liver and cardiovascular system, reflecting a defect in tube diameter control. Arterial hypertension is common and occurs early. Current therapy is largely conservative.

ADPKD is caused by commonly inactivating germline mutations inPKD1orPKD2combined with a second somatic hit that abolishes or reduces function of the remaining normal allele, an event enhanced by the genomic instability associated with the haploid state.

Wide variations in onset and progression of the disease are caused by the type of the impaired gene, hypomorphic alleles, mosaicism, combining an inactivating germline mutation with an acquired hypomorphic allele, stochastic fluctuations in expression level of the remaining normal allele and the genetic background.

Cerebral aneurysms are more common in ADPKD patients, occur at an earlier age and tend to rupture at a smaller size when compared to the general population.

Progressive loss of renal function occurs before standard markers of renal function are abnormal. Measurement of kidney volume in patients with normal renal function using MR imaging (MRI), CT, or ultrasonography is a more sensitive approach for following disease progression at any age.

DNA‐based diagnostics are useful when imaging studies are equivocal, in individuals with a negative family history, in the selection of a young transplant donor from an ADPKD family or to facilitate pre‐implantation genetic diagnosis.

The gene products ofPKD1andPKD2, polyctytsin‐1 (PC1) and polycystin‐2 (PC2), respectively, localise to primary cilia as well as to other membrane compartments. Defects in primary cilium structure causes cysts, as are mutations in several other ciliogenic genes supporting a critical role of the primary cilium in tube formation and maintenance.

PC1 and PC2 form a receptor‐ion channel complex that triggers calcium entry, which normally activates the planar polarity pathway and represses mitogenic pathways thus regulating tube diameter.

The abnormal mitogenesis and fluid secretion pathways that contribute to cyst growth are being targeted therapeutically.
Astromicrobiology
Authors: Davila Alfonso F
Published: September 2010

Astrobiology is the scientific discipline that focuses on the origin, evolution and distribution of life in the universe. Most efforts aiming at understanding the origin of life on Earth, and the possibility that life might exist elsewhere, are directed to the study of microorganisms. This is so because on Earth, microorganisms are the most abundant and widespread forms of life, and are seemingly able to colonise virtually every environment that can support life. Furthermore, small and relatively simple cells are more likely to originate first on a planet than large and complex multicellular organisms, and are also more likely to be transported from one planet to another in the process of panspermia. Hence the term Astro(micro)biology. In this article I introduce and summarise the main fields of research in Astro(micro)biology.

Key Concepts:

The study of life in the Universe requires an interdisciplinary approach.

Mars is the prime target for the search for life beyond the Earth.

The primary focus of planetary exploration is concerned with planets having liquid water.

Terrestrial analogue environments share physical, chemical, geological, mineralogical and any other type of environmental similarity with another planetary body.

Meteorites represent the main source of extraterrestrial material available to scientist.

Extrasolar planets are a likely candidate to provide the first evidence of life outside the Earth.
Microbial Inorganic Carbon Fixation
Authors: Sato Takaaki , Atomi Haruyuki
Published: September 2010

Carbon dioxide fixation is the biological process through which carbon dioxide is converted to organic compounds. Organisms that fix carbon dioxide provide the organic carbon necessary to support the existence of all heterotrophic life on our planet. This article provides an introduction to the various mechanisms of carbon dioxide fixation utilised by microorganisms. The Calvin–Benson–Bassham cycle is shared among plants, algae and many photo‐ and chemoautotrophic bacteria, and is probably the most well known carbon dioxide‐fixation pathway. However, a number of other pathways exist that are unique to the microbial world and the diverse chemistry and strategies they utilise are fascinating. Among the six carbon‐fixing pathways known at present, three pathways harbouring novel enzymes have just been established in the past few years. With the number and diversity of microorganisms still expanding, the possibilities are high that further novel pathways will be identified in the near future.

Key Concepts:

Carbon dioxide fixation is the biological process through which carbon dioxide is converted to organic compounds.

Organisms that fix carbon dioxide provide the organic carbon necessary to support the existence of all heterotrophic life on our planet.

In addition to the Calvin–Benson–Bassham cycle, which is also found in plants and microorganisms harbour a number of unique carbon dioxide‐fixing pathways.
Regeneration in Echinoderms and Ascidians
Authors: Carnevali M Daniela Candia , Burighel Paolo
Published: September 2010

The regenerative potential is expressed to a maximum extent in echinoderms and ascidians. They provide unique and valuable deuterostome models, closely related to vertebrates (man included), for an integrated approach exploring regeneration from tissue repair to asexual cloning. The comparison of results derived from different experimental models of echinoderms and ascidians and employing different approaches,in vivoandin vitro, provides an insight on specificity of regulatory mechanisms and processes governing large‐scale pattern formation and information signalling storage between cells and tissues allowing a living system to reliably regenerate and maintain a complex morphology. Since in these animals, regenerative phenomena involve progenitor cells present in the circulating fluids or in the tissues, the crucial questions opened are those related to (1) stemness properties of responsible cells, in terms of origin and derivation (stem cells or dedifferentiated cells) and (2) activities (proliferation and/or migration), plasticity and differentiation potential (derived cellular phenotypes).

Key Concepts:

Regeneration is a regulative and conservative developmental process complementary to asexual reproduction.

Asexual reproduction (cloning) represents the highest expression of the regenerative potential of an organism.

Regeneration processes generally imply the key‐contribution of pluripotential cells (stem cells or reprogrammed cells).

Echinoderms utilise regeneration processes at all stages of their life cycle (embryo, larva and adult).

Echinoderms can regenerate body parts and even complete individual from a fragment following self‐induced or traumatic amputation processes.

In ascidians the potential for asexual development is expressed during colony formation by developing functional individuals from adult tissues.

Ascidians are the unique adult chordates able to regenerate completely the ablated nervous system.