bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimalarials
Authors: Smithson David C. , Armand Guiguemde W. , Kiplin Guy R.
Published: September 2010

While the treatment of malaria has until recently relied upon a small number of therapeutic agents with a few mechanisms of action, the past decade has seen a huge growth in the number of targets being addressed and new agents being pushed to the clinic. This chapter briefly reviews existing agents and close homologs in development and then carefully explores new targets and new chemotypes being developed.
HIVReverse Transcriptase Inhibitors
Authors: De Clercq Erik
Published: September 2010

The first antiviral compound ever shown to be activein vitroagainst HIV (human immunodeficiency virus) (originally referred to as HTLV‐III (human lymphotropic virus type III) and LAV‐1 (lymphadenopathy‐associated virus type 1)) was suramin; suramin was also the first antiviral found to be effectivein vivoin the treatment of HIV infections. Suramin was explored as a potential strategy for the therapy of AIDS because it has been recognized as a potent inhibitor of the reverse transcriptase (RT) associated with a number of animal retroviruses. Later, it became evident that suramin primarily acts against HIV infections as an inhibitor of virus adsorption rather than an RT inhibitor.
Approaches to Amyloid Therapies for the Treatment of Alzheimer's Disease
Authors: Robichaud Albert J. , Kim Ji‐In , Jacobsen J. Steven
Published: September 2010

Recognized as the most common of the neurodegenerative disorders, Alzheimer's disease (AD) affects greater than 18 million people worldwide and is predicted to become the largest socioeconomic burden of the twenty‐first century. The underlying mechanism of Alzheimer's disease is as yet unknown, but the growing body of pathophysiologic evidence is beginning to point to two main causes, the formation of β‐amyloid plaques and neurofibrillary tangles. This review will cover approaches to disease modification that are based on the amyloid hypothesis; that being, the prevention of the accumulation, aggregation, and deposition of β‐amyloid peptide (Aβ) monomers, leading first to multiple oligomeric species and then to fibrils and ultimately senile plaques, is the center of focus for an approach to disease modification. There is a wealth of evidence to implicate this peptide and its subsequent aggregation in the etiology of the disease and approaches, both small molecule and biopharmaceutical, to prevent its accumulation have been the subject of much research. The vast majority of this research over the last decade has been, and continues to be, focused on these disease‐modifying, antiamyloidogenic approaches to AD. It is this subject, and the various approaches, past and present to amelioration of AD through the various agents being explored, that will be the focus of this chapter.
Electrical Properties
Authors: Mathes Kenneth N.
Published: September 2010

Polymers, both uncompounded and compounded, are used in many electrical applications, often as primary electrical insulation. In other cases, such plastics may have primarily a structural function, but also an electrical function. The electrical behavior of insulating materials is influenced by temperature, time,mositure, and other contaminants, geometric relationships, mechanical stress and electodes, and frequency and magnitude of the applied voltage. These factors interact in a complex fashion. These article covers theoretical aspects, electric breakdown, conductive resistance, alternating current characteristics, and special electrical characteristics. The electrical properties of plastics are measured to determine performance capability in electrical applications; evaluate characteristics other than electrical; provide quality assurance; to serve as a means of identification and research tool; and to provide a basis for the buyer‐seller relationship.
Self‐Healing Polymers
Authors: Wilson Gerald O. , Andersson H. Magnus , White Scott R. , Sottos Nancy R. , Moore Jeffrey S. , Braun Paul V.
Published: September 2010

Increasing demand for petroleum and the effect of the use of petroleum products on the environment continue to create the need for more sustainable technologies. Self‐healing technologies present an opportunity to quickly add a sustainable dimension to materials that are already being used in a wide variety of applications. The present work is a discourse that includes the classification of self‐healing and related technologies into autonomic and non‐autonomic approaches and further sub‐classification into the various types of self‐healing systems including one‐capsule, dual‐capsule, and microvascular. The varying chemistries that have been evaluated in the disparate classes of self‐healing systems are also discussed along with the compartmentalization of the reactants, self‐healing performance, and evaluation in relevant applications.
Olfaction
Authors: Wilson Donald A , Chapuis Julie , Wesson Daniel W
Published: September 2010

Olfaction, the ability to recognise and discriminate myriad airborne molecules with great accuracy and sensitivity, is one of the most remarkable but least understood senses. It permits continuous monitoring of the surroundings for small volatile molecules, including chemical signals that identify territories, food, predators and mates; thus, olfaction plays a key role in survival and adaptation. Recent work suggests that in mammals, odour perception begins through volatile molecules binding to a subset of several hundred G protein‐coupled receptors on the olfactory sensory neurons in the nose. The identity of the odorant is encoded by a spatiotemporal pattern of activity within the first central relay, the olfactory bulb. The olfactory cortex then functions as a combinatorial array that allows recognition of those odorant‐specific patterns, and forms synthetic odour percepts. This pattern recognition process is experience‐dependent, and thus odour discrimination and perception can be affected by a variety of memory and cognitive disorders.

Key Concepts:

Odorants are transduced by olfactory sensory neurons through a large family of G protein‐coupled receptors, with individual sensory neurons expressing a single type of receptor.

Olfactory sensory neurons project axons directly into the mammalian forebrain targeting the olfactory bulb, and are continually replaced throughout life.

Odorant identity is encoded by odour‐specific spatiotemporal patterns of activity in the olfactory bulb which emerge due to highly specific sensory neuron axonal projections.

In contrast to other sensory systems, the direct projection to the primary olfactory cortex does not pass through the thalamus, although there is an olfactory thalamocortical pathway.

Information about internal state, emotion, expectation and past experience can influence odour processing as early as the first central synapse, and odour learning can influence processing through the entire olfactory pathway.

Given that most natural odours are mixtures of many volatile components, odour perception is based on an experience‐dependent combinatorial process resulting in perception of synthetic odour objects.

Odour habituation is a central phenomenon involving changes in the strength of connections between specific neurons within the olfactory bulb and cortex.

Through extensive interaction with other sensory systems, olfaction plays a critical role in the perception of flavour and food.

Impairment in olfactory perception is a prevalent problem which is associated with a wide variety of neurological disorders.
Nicotinic Acetylcholine Receptors
Authors: Lindstrom Jon
Published: September 2010

Nicotinic acetylcholine receptors (AChRs) bind the neurotransmitter acetylcholine, triggering the opening of a cation channel. AChRs are part of a gene superfamily of transmitter gated ion channels that include receptors for glycine and γ‐amino butyric acid which have anion channels. Muscarinic AChRs are part of a gene superfamily of metabotropic G protein‐linked receptors. AChRs are formed from five homologous subunits arranged like barrel staves to form the channel. Subtypes of AChRs are defined by their subunit composition. Studies of AChR subunits in knockout and transgenic mice reveal much about the normal physiological roles of AChR subtypes and their roles in disease. AChRs are the targets of nicotine in addiction to tobacco, of auto‐antibodies and disease‐causing mutations. They are also the targets of drug development for treatment of addiction and diseases of mood, cognition and neurodegeneration.

Key Concepts:

Nicotinic AChRs are the archetype for a superfamily of receptors which includes receptors for GABA and glycine.

AChR are formed by five homologous subunits organised around a central cation channel.

AChR subtypes are defined by their subunit composition.

AChRs serve many roles in excitatory intercellular signalling: as pre‐, post‐ and extra‐synaptic neurotransmitter receptors and as autocrine AChRs in nonneuronal tissues.

Nicotine acting on AChRs causes addiction to tobacco.

AChRs are involved in several diseases and are the targets of drug development for treatment of addiction, alcoholism, depression, schizophrenia, Alzheimer and Parkinson diseases and others.

The effects of nicotine and agonist drugs are complex because they can act on many AChR subtypes causing activation, desensitisation and upregulation.

Antibody‐mediated autoimmune responses to α1
*
AChRs cause myasthenia gravis and to α3
*
AChRs cause autonomic neuropathy. These diseases are models for the pathological mechanisms of autoantibodies to other receptors.

Mutations in α1
*
AChRs cause congenital myasthenic syndromes, and mutations in α4β2
*
AChRs cause autosomal dominant nocturnal frontal lobe epilepsy.
Archaea
Authors: Oren Aharon
Published: September 2010

Analysis of nucleotide sequences of ribosomalribonucleic acid(RNA) led in the 1970s to the recognition of the existence of three domains of life, named Eukarya (Eukaryotes), Bacteria (Eubacteria) and Archaea (Archaebacteria). This classification replaced the earlier accepted Eukaryotes–Prokaryotes dichotomy. The Archaea resemble the Bacteria in cell size and cell structure, but possess many distinguishing features, including lack of peptidoglycan in their cell wall, presence of unique membrane lipids not found in the other domains of life and other unique biochemical and genetic properties. Most cultured Archaea were recovered from extreme environments (high salt concentrations, high temperatures and acidic hot springs). The unique properties of these extremophiles can be exploited in biotechnology. The strictly anaerobic methanogenic prokaryotes also belong to the archaeal domain. Culture‐independent studies show that Archaea are also widespread in nonextreme environments such as seawater and soil, and the properties of a few nonextremophilic Archaea are now being elucidated.

Key Concepts:

The Archaea form a second lineage of prokaryotes, evolutionarily distant from the Bacteria.

Most Archaea are classified within the phyla Crenarchaeota and Euryarchaeota; other archaeal phyla proposed are the Korarchaeota, the Nanoarchaeota, and the Thaumarchaeota.

Archaea resemble Bacteria in cell size, morphology and ultrastructure, but differ from the Bacteria in many biochemical, physiological and genetic features.

The cell membrane lipids of the Archaea are based on branched (isoprenoid) hydrophobic carbon chains linked to glycerol by ester bonds.

Peptidoglycan, the characteristic cell wall constituent of the Bacteria, does not occur in the Archaea.

All known methane‐forming prokaryotes belong to the Archaea.

Most cultured Archaea are extremophiles that live at high temperatures, low or high pH values or high salt concentrations.

Archaea are also widespread in environments not characterised by environmental extremes, but their function in aquatic and soil ecosystems is still poorly understood.

Archaea contribute to the autotrophic oxidation of ammonia to nitrite in different ecosystems.

Thanks to their unique biochemical features, the Archaea have considerable potential for biotechnological applications.
Glycoproteins
Authors: Merry Tony , Astrautsova Sviatlana
Published: September 2010

Glycoproteins are proteins that contain covalently bound oligosaccharides (glycans). Although there are structural features ofN‐ andO‐linked glycans common to all eukaryotes, species‐specific glycosylation reactions create a wide diversity of structures. This is particularly relevant to cell surface glycoproteins although intracellular and even nuclear proteins may be glycosylated. The factors controlling glycosylation are complex and include the protein sequence and structure, specificity of relevant transferase enzymes, availability of donor sugars and other environmental factors. These may all interact so it is not surprising that there is great variety in glycosylation even on the same protein. Glycosylation of proteins is important in such areas as development and interaction with pathogens and provides a means of modifying the function of proteins that is not directly dependent on theirdeoxyribonucleic acid(DNA) template. Interest in the field is growing and advances in analytical technology now make the field accessible to a wider community.

Key Concepts:

Proteins are frequently modified posttranslationally, the most frequent modification being glycosylation.

Glycosylation may play an important role in protein folding through interaction with the chaperones calnexin and calreticulin.

It has been calculated that as many as 70% of all proteins may be glycosylated.

The glycosylation of a protein may vary extensively depending on the cell in which it is produced which may enable the same protein to function in different ways depending where it is expressed.

On the cell surface, glycoprotein glycans are frequently involved in cell–cell interactions.

Glycosylation of the same protein may change during development or in maturation, for example in cells of the immune system.

Glycosylation differs between species even if they are closely related, for example between great apes and man.

Analysis of glycosylation has progressed in recent years and is now almost a routine procedure.

Particular features of glycosylation may only have functional significance in a particular time and place but can be widely distributed which can make assignment of function to glycan structure difficult.
Plant Volatiles
Authors: Qualley Anthony , Dudareva Natalia
Published: September 2010

Plants produce an amazing number of chemical compounds that can disperse in the air at ambient temperature. These plant volatiles have served mankind, perhaps since pre‐Neolithic times, as perfumes and flavour compounds. In nature, these compounds attract pollinators and seed dispersers, protect plants through repulsion or intoxication of attacking herbivores, entice predator or parasitoid insects that prey on herbivores, prime defences of neighbouring plants against imminent attack, confer antimicrobial properties critical to defence against pathogens, and mitigate oxidative stresses. Plant volatiles are typically classified into four major categories: terpenoids, fatty acid derivatives, amino acid derivatives and phenylpropanoid/benzenoid compounds, though a number of species‐ or genus‐specific volatile compounds, such as those found in select species of Alliaceae and Brassicaceae, fall outside these categories. This enormous variety is represented by more than 1700 compounds from 90 species.

Key Concepts:

Plant volatiles are critical in the attraction of pollinators and seed dispersers.

Plants use volatiles to protect themselves from pests and pathogens.

Plants under herbivore attack can alert neighbouring plant species, priming their chemical defences.

Plant volatiles are classified according to their metabolic origins as terpenoids, phenylpropanoids/benzenoids, fatty acid derivatives and amino acid derivatives.

Biosynthesis of plant volatiles is spatially, developmentally and temporally regulated.

Modern techniques for the collection and trapping of plant volatiles (SPME, dynamic headspace sampling) provide sensitive and representative samples for analysis.

Plant volatiles serve humankind as perfumes and aroma compounds, natural flavour constituents, food additives/preservatives, and chemotherapeutics and anaesthetics.
Immune Responses: Primary and Secondary
Authors: Ademokun Alexander A , Dunn‐Walters Deborah
Published: September 2010

Immune responses to antigens may be categorised as primary or secondary responses. The primary immune response of the body to antigen occurs on the first occasion it is encountered. Depending on the nature of the antigen and the site of entry this response can take up to 14 days to resolve and leads to the generation of memory cells with a high specificity for the inducing antigen. The humoral response, mediated by B cells with the help of T cells, produces high‐affinity and antigen‐specific antibodies. This is in contrast with the CD8 T‐cell response which leads to the generation of large numbers of antigen‐specific cells that are capable of directly killing infected cells. Antigen‐specific CD4 T cells, which provide help to B cells in the form of cytokines and other stimulatory factors, can also be expanded upon antigenic stimulation.

The secondary response of both B‐ and T cells is observed following subsequent encounter with the same antigen and is more rapid leading to the activation of previously generated memory cells. This has some quantitative and qualitative differences from the primary response.

Key Concepts:

The innate immune system is the first line of defence against infectious agents. When this is breached, the adaptive immune system provides a more efficient response to clearing pathogens.

The adaptive immune system has the capacity to ‘remember’ previous antigens, a process termed immunological memory.

Antigen‐specific T cells are selected during a primary immune response and expand to produce clones of T cells with high specificity for the activating antigen.

In a B cell primary response to a thymus‐dependent antigen, the immune system selects B cells with a high affinity and specificity for the antigen and these become memory cells.

The selection of B cells with a high affinity for a given antigen occurs in the germinal centres of secondary lymphoid follicles and requires the enzyme activation‐induced cytidine deaminase (AID) and interactions with other immune cells.

The ability to change the isotype of antibody produced (class switching) by a B cell also occurs in germinal centres and requires AID.

In a secondary response to the same antigen, memory cells are rapidly activated. This process is quicker and more effective than the primary response.
Picornaviruses
Authors: Rowlands David J
Published: September 2010

The name picornavirus is derived from
pico
for small and
ribonucleic acid
(RNA), denoting the chemical nature of the genome. Virions are nonenveloped icosahedral particles approximately 30 nM in diameter. The capsid is constructed from 60 copies of each of four structural proteins which account for 70% of the particle mass and enclose the single‐strand genome of 7500–8500 nucleotides. The positive strand genome acts directly as a messenger RNA to template a single polyprotein product. This is subsequently processed by virally encoded proteases into mature active proteins. Several intermediate products have distinct functions to the final fully processed proteins. Replication of the genome is initiated by an uridylated peptide and proceeds via a negative strand intermediate template. Picornaviruses are among the smallest pathogens of vertebrates and are responsible for many important diseases in humans and animals.

Key Concepts:

There are effective vaccines against polio, hepatitis A and foot‐and‐mouth disease viruses. In addition, movement control and slaughter is used to control foot‐and‐mouth disease. There are no licensed drugs for picornavirus infections.

Genome sequence comparisons have replaced biological and biophysical comparisons as the bases for classification within the family.

Picornavirus particles comprise 60 copies each of 4 structural proteins, which form a quasi T1 icosohedral capsid encasing the single strand RNA genome.

The picornavirus RNA genome functions as a messenger RNA to template the synthesis of a single polyprotein, which is posttranslationally processed by viral proteases.

Picornaviruses bind to cell specific surface receptors and this interaction is an important factor in determining host and tissue specificity of each virus.

Picornaviruses cannot gain entry to cells by membrane fusion, as is the case for enveloped viruses, and require special mechanisms to breach cellular membranes and safely deliver the genome into the host cell.

Genome replication occurs in association with virus modified cellular membranes. Viral RNA templates complementary negative strand molecules which in turn template multiple positive strand copies. The synthesis of all RNA molecules is initiated by an uridylated peptide primer.

The mechanisms of transmission of infection play key roles in the epidemiology of picornavirus infections.

Picornaviruses are responsible for a wide range of clinical diseases resulting from multiple factors such as receptor specificity, tissue‐specific susceptibility, virulence and the mechanisms of transmission.
Monoclonal Antibodies
Authors: Zola Heddy
Published: September 2010

Antibodies bind other molecules strongly and specifically and are therefore useful as reagents in research, diagnosis and therapy. Antibodies taken from the blood of immunised animals are a mixture of different antibodies produced by different cells (they are described as polyclonal). Monoclonal antibodies are antibodies with a unique specificity, generally made by cloning cells containing a particular antibody gene set to produce a population of identical cells, derived from a single cell, which all produce the same antibody. Monoclonal antibodies are therefore much more specific than polyclonal antibodies. Monoclonal antibodies can be made in cell culture and are therefore also more reproducible from batch to batch than polyclonal antibodies. Monoclonal antibodies have become the preferred reagents in many research and diagnostic applications and are increasingly used in therapy of cancer and immunological disorders, generating a multi‐billion dollar industry.

Key Concepts:

Antibodies form part of the mammalian immune response, binding to foreign molecules to neutralise or remove them.

By injecting an animal with a target molecule, we can make an antibody that binds the target molecules strongly and specifically.

One immune cell makes just one antibody, but from the blood, we get a mixture of the antibodies produced by many immune cells.

By isolating a single immune cell making a single antibody of interest and converting it to a dividing, growing clone of cells (cloning the cell), we can make large quantities of identical antibody – monoclonal antibody.

Monoclonal antibodies provide specific reagents for almost any molecular structure above a minimal size.

Monoclonal antibodies can be used to identify, quantify, isolate or remove the target molecule in complex biological mixtures or in tissues.

Monoclonal antibodies can be injected into patients to remove harmful components ranging from toxins to cancer cells.

Advances in molecular biological technologies make it possible to modify monoclonal antibodies to achieve therapeutic objectives with minimal side effects.
Natural Killer (
NK
) Cells
Authors: Vivier Eric , Ugolini Sophie
Published: September 2010

Natural killer (NK) cells are a discrete subset of lymphocytes of the innate immune response. They are rapid mediators of cytotoxicity against a variety of ‘stressed cells’ that include microbe‐infected cells, transformed cells or cells in distress as a result of physical or chemical injuries. NK cells are also potent producers of a large spectrum of cytokines, including
interferon γ
(IFNγ) and
interleukin 10
(IL‐10). Through these functions, they act as both effector and regulatory cells of the immune response.

Key Concepts:

NK cells are lymphocyte of innate immunity that sense a variety of stressed cells and participate to their elimination.

NK cells are regulatory cells that contribute to the innate immune response and to the shaping of the adaptive immune response.

The study of NK cell biology has been instrumental in revealing various mode of immune detection: missing self‐recognition and stress‐induced cell recognition.

The manipulation of NK cell recognition strategies leads to the development of innovative therapeutic settings from allogeneic bone marrow transplantation to the injection of blocking anti‐KIR monoclonal antibodies.
Peptide Bonds, Disulfide Bonds and Properties of Small Peptides
Authors: Gilbert Hiram F
Published: September 2010

The peptide bond links amino acids into head‐to‐tail polymers in proteins as peptides. Chemically, the peptide bond is an amide with restricted rotation about the carbon–nitrogen bond. This restricted rotation combined with free rotation around the alpha carbon of the linked amino acids define the three‐dimensional structure of all proteins. The structure of a peptide or protein can be further stabilised by introducing disulfide crosslinks, a chemical oxidation between two sulfhydryl groups of the amino acid cysteine stabilise specific conformations of peptides and proteins. Small peptides, which often function biologically as hormones or other signalling molecules can also be useful model systems for investigating protein structure and function. The introduction of disulfide bonds and a change in conformation between thecisandtransconformations of the proline peptide bond may be a barrier to the rapid formation of the proper protein structure. In the cell, enzymes are present to catalyse these processes.

Key Concepts:

The conformational flexibility around the alpha carbon of peptides connected by peptide bonds accommodates an enormous number of structures depending on the protein sequence.

Disulfides are chemical crosslinks between or within polypeptides that adds stability to the overall structure.

Conformational transitions involving proline residues in a protein can slow protein folding due to a slow conformational transition.

The enzymes protein disulfide isomerase and peptidyl proline isomerase function in the cell to catalyse slow chemical and configuration changes that retard protein folding.
Membrane Lipid Biosynthesis
Authors: Vance Jean E
Published: September 2010

Biological membranes consist of a complex array of proteins and lipids that create selective permeability barriers in cells. Another function of membrane lipids is their degradation to generate ‘lipid second messengers’ that can regulate important cellular functions such as cell division and cell death. The major membrane lipids of eukaryotic cells are the glycerophospholipids, the sterols and the sphingolipids. The most abundant glycerophospholipids in eukaryotic cells are phosphatidylcholine and phosphatidylethanolamine, each of which is synthesised by two independent pathways. The glycosphingolipids consist of structures in which ceramide is attached to a variety of oligosaccharide chains to create an enormously diverse class of lipids that are highly enriched on the cell surface. In mammalian cells, cholesterol is the most abundant sterol in membranes, whereas plants and fungi do not contain cholesterol

per se

but instead contain sterols that are related to cholesterol; prokaryotic membranes do not contain sterols.

Key Concepts:

Lipid bilayers provide the fundamental architecture of biological membranes.

Cellular phospholipid levels are tightly regulated.

Major classes of phospholipids are made by more than one pathway.

Acyl chain composition of phospholipids can be modified by deacylation.

The cholesterol‐lowering statin drugs regulate cholesterol biosynthesis at the step catalysed by 3‐hydroxy‐3‐methylglutaryl‐CoA reductase.
Adrenaline and Noradrenaline
Authors: Goldstein David S
Published: September 2010

Noradrenaline and adrenaline are catecholamines that play major roles in regulation of the ‘inner world’ of the body by the brain. Noradrenaline (synonymous with norepinephrine), the main neurotransmitter of the sympathetic nervous system, is responsible for tonic and reflexive changes in cardiovascular tone. Adrenaline is a key determinant of responses to metabolic or global challenges to homeostasis, such as glucoprivation, and of manifestations of emotional distress. In contrast with the view that the sympathetic nervous and adrenomedullary hormonal systems function as a unit (the ‘sympathoadrenal system’) to maintain homeostasis in emergencies, across a variety of situations adrenaline responses are more closely linked to responses of the hypothalamic‐pituitary‐adrenocortical system than of the sympathetic nervous system. The sympathetic noradrenergic system is active even when the individual is at rest and maintains tonic levels of cardiovascular performance. Adrenoceptors in the membranes of effector cells determine the physiological and metabolic effects of catecholamines.

Key Concepts:

Noradrenaline and adrenaline are catecholamines.

Noradrenaline is the main neurotransmitter of the sympathetic nerves in the cardiovascular system.

Adrenaline is the main hormone secreted by the adrenal medulla.

The sympathetic noradrenergic system plays major roles in tonic and reflexive changes in cardiovascular tone.

Adrenaline is a major determinant of responses to metabolic or global challenges to homeostasis.

Adrenaline responses to stressors are more closely linked to responses of the hypothalamic‐pituitary‐adrenocortical system than of the sympathetic nervous system.

The sympathetic noradrenergic system is active even when the individual is at rest and maintains tonic levels of cardiovascular performance.

Adrenoceptors in the membranes of effector cells determine the physiological and metabolic effects of catecholamines.

Beta‐adrenoceptors mediate stimulatory effects of catecholamines on the rate and force of the heartbeat; stimulation of vascular alpha‐adrenoceptors produces vasoconstriction and increases blood pressure, and stimulation of vascular beta‐adrenoceptors – especially beta‐2 adrenoceptors in skeletal muscle – produces vasodilation.

Catecholamines affect cardiovascular functions by actions at adrenoceptors on cardiovascular cells, in the nervous system, and in the kidneys.
Tiering on Land – Trees and Forests (Late Palaeozoic)
Authors: Cleal Christopher Jonathan
Published: September 2010

Trees with woody trunks first appeared in Middle Devonian times (390 MYA). However, a number of other types of Palaeozoic plants also achieved large sizes, most notably the arborescent lycopsids. The tropical wetlands of late Carboniferous and early Permian age (320–280 MYA), often referred to as the coal swamps or coal forests, were dominated by the arborescent lycopsids. Because of the unusual growth and reproductive strategies of these plants, and the water‐logged and low pH substrates, the ecological structure of these forests was quite different from most modern‐day forests. Rather than there being a vertical stratification of the vegetation controlled by light availability, there was a lateral ecological partitioning of the habitats controlled mainly by substrate conditions.

Key Concepts:

The late Palaeozoic coal forests were relatively open habitats, and therefore, light levels were not significant in controlling their ecological partitioning.

Substrate conditions were most important for controlling plant distribution in the coal forests, resulting in a lateral ecological partitioning, rather than a vertical tiering as is typical in most modern‐day forests.

The rapid determinate growth of the arborescent lycopsids that dominated the coal forests meant that huge amounts of peat were generated, which are now preserved as coal.

The coal forests were a major carbon sink during the late Palaeozoic times and had a significant impact on levels of atmospheric carbon dioxide and global climates.
Sex: Advantage
Authors: Neiman Maurine , Jokela Jukka
Published: September 2010

One of the most important unanswered questions in evolutionary biology is why sexual reproduction is so common. In theory, sex is so costly that individuals that reproduce sexually should be at a major disadvantage relative to asexually reproducing competitors. This leads to the expectation that sex should lose in competition with asexual reproduction and thus be rare in nature, which is in striking contrast to its widespread occurrence. It is this profound disconnect between theory and reality that has motivated decades of research into potential advantages of sexual reproduction. While much progress has come from these efforts, why sex predominates is still unclear. It is likely that part of the answer is linked to an advantage of sex under pressure from coevolving parasites. Other important processes may be more efficient clearance of deleterious mutations and other costs associated with asexuality that are not direct consequences of the lack of recombination.

Key Concepts:

The fundamental difference between sexual and asexual reproduction is that sex produces offspring that have both unique combinations of alleles and different combinations of alleles than their parents and their siblings.

In theory, sex should be rare because it breaks up allele combinations that have proven to work well together and because sexual females waste resources on son production.

The predominance of sex in nature indicates that production of genetically distinct offspring must also generate profound benefits.

Comparing the geographic distribution of sexual and asexual populations can provide insights into the advantages and disadvantages of sex.

The most direct and powerful way to study sex is to compare coexisting sexual and asexual females that are phylogenetically close relatives and ecologically very similar with the exception of their reproductive mode.

Likely direct benefits of sex include evasion of biological enemies and clearance of harmful mutations.

The transition to asexuality may lower the fitness of asexual phenotypes and thus the cost of sex, in which case the maintenance of sex is easier to explain.
Species Concepts
Authors: Ghiselin Michael T
Published: September 2010

A species concept is roughly equivalent to a species definition. Considered in the abstract, the species is a class, or kind, of which particular species are concrete instances. So a species definition is a definition of species in general and not of a particular species. The biological species concept treats species as sexual populations, which are reproductively isolated from one another. The recognition species concept is a variant of the biological species concept that emphasises mate recognition of conspecifics. The evolutionary species concept stresses the point that species are historical lineages as well as populations. The various cladistic species concepts treat parts of biological species as species. Phenetic and morphological species concepts treat species not as populations or lineages but as classes or kinds of organisms that are similar to one another. Preference for one or the other concept often reflects differences among scientists as to what they consider important.

Key Concepts:

Species are fundamental units in evolution, classification and biodiversity.

Species are the products of the process of speciation.

Species concepts and definitions tell us what is meant by the term ‘species’ in the abstract.

The species, in the abstract, forms a level in the Linnaean hierarchy used in formal classification (taxonomy). Like the genus and the family, it is a taxonomic category.

The groups that are called species are instances of the species category. They are taxa.

Populations and lineages are wholes composed of organisms, not kinds of organisms.

Species concepts may be difficult to apply to particular cases, in part because species speciate and get transformed.
Vestibular System Disorders
Authors: Fetter Michael
Published: September 2010

The vestibular system provides vital sensory information for the control of balance and posture. Vestibular end organs on each side sense linear and angular acceleration in three‐dimensional space: the saccule and the utricle (linear motion), and the anterior, posterior and lateral semicircular canals (angular motion) and transduce this information to electrochemical signals. The central nervous system integrates this information from the vestibular system with visual and proprioceptive information to a best possible estimate of the actual movement of the head and body to stabilise gaze during head motion by means of the vestibulo‐ocular reflex (VOR) and to control balance by modulation of muscle tone through the vestibulocollic and vestibulospinal reflexes. Disorders of the vestibular system, either peripheral or central, often give rise to the sensory illusion of rotation, vertigo, disequilibrium or imbalance, common symptoms in clinical practice.

Key Concepts:

The role of the vestibular sensory organs is to transduce the forces associated with head acceleration and gravity into a biological signal.

The control centres in the brain use this signal to develop a subjective awareness of head position and head movement in relation to the environment and to produce motor reflexes for equilibrium.

The two main motor reflexes are the vestibule‐spinal reflex (responsible for the stability of the body) and the vestibule‐ocular reflex (responsible for stabilising gaze in space).

Pathological dysfunction in the sensory organs or in the central pathways of the motor reflexes lead to the sensation of vertigo.

History together with a careful clinical neuro‐otological examination are the keys for most vestibular disorders and much more important than recordings of eye movements or brain imaging techniques.

Benign positional vertigo is the single most common cause of vertigo that can easily be diagnosed clinically and effectively treated by specific deliberation manoeuvres.

Vestibular migraine, a since recently much underestimated disorder, should be suspected when frequent attacks of fully reversible vertigo occur with or without headaches and can be treated successfully with classical migraine medication both for the acute attack as well as prophylactic treatment.
Acid–Base Balance Disorders
Authors: Hawfield Amret T , DuBose Thomas D
Published: September 2010

Abnormalities in maintaining the pH of the blood in a range that is incompatible with sustaining metabolic processes are known as acid–base balance disorders. Here, we define normal acid–base balance and describe the four basic acid–base balance disorders including metabolic acidosis, metabolic alkalosis, respiratory acidosis and respiratory alkalosis that occur. We suggest a diagnostic approach in defining the disorders and a differential diagnosis to their causes. Routine management of these disorders is also discussed.

Key Concepts:

Normal Physiologic function depends on the maintenance of a systemic arterial pH between 7.35 and 7.45.

The coordination of renal and respiratory regulatory mechanisms is responsible for maintaining physiologic pH.

The use of simple equations can differentiate between different acid–base disorders.

The causes of metabolic acidosis can be divided among those that lead to a high anion gap and those that present with a normal anion gap.

An approach to differentiating the causes of metabolic alkalosis is based on assessing volume status.

Respiratory acidosis develops in the setting of hypoventilation.

Respiratory alkalosis occurs when carbon dioxide output in the lungs exceeds its metabolic production in the tissues.

The ultimate treatment of acid–base disorders is focused on identifying and managing their underlying cause.
History of Oral Contraceptives
Authors: Djerassi Carl
Published: September 2010

Progesterone is the naturally occurring female sex hormone acting as nature's contraceptive by preventing women from conceiving during pregnancy. Since it is not orally active, progesterone cannot practically be used as an oral contraceptive. It required the efforts of organic chemists to synthesise steroids that mimic the biological activity of the natural hormone and that are effective by oral administration. The article concludes with the prognosis that the future prospects for developing fundamentally new contraceptives are dim, primarily because the priorities of the international pharmaceutical industry have shifted to diseases of the increasingly geriatric segments of the population of affluent countries.

Key Concepts:

The natural female sex hormone progesterone – nature's contraceptive – is not orally active.

New synthetic steroids had to be developed, which retained the biological activity of progesterone, but would be orally active.

The lead compound, norethindrone, was synthesised in 1951 and all but one of the subsequent steroid oral contraceptives are based on that chemical template.

Research in new approaches to contraception has declined dramatically as the pharmaceutical industry has shifted its attention to diseases of the geriatric segment of the population.

The prediction is made that the ultimate direction of birth control in the affluent, geriatric countries will consist of cryopreservation of ‘young’ gametes (particularly relevant for females), followed by sterilisation, and recourse to IVF for reproduction, thus completing the divorce of sex from reproduction.
Splicing of
Pre
‐
m
RNA
Authors: Lu Yu‐Shiou , Tarn Woan‐Yuh
Published: September 2010

Eukaryotic messenger
ribonucleic acids
(mRNAs) are initially transcribed as intron‐containing precursor mRNAs (pre‐mRNAs). Removal of introns from each pre‐mRNA by splicing occurs concurrently with ligation of the two flanking exons to generate a mature mRNA. Pre‐mRNA splicing is catalysed by the spliceosome, a large ribonucleoprotein complex containing five small nuclear RNAs and numerous protein factors. In higher eukaryotes, alternative splicing provides a mechanism to generate multiple mRNA isoforms from a single gene. Alternative splicing not only increases proteome diversity but also regulates the level of gene expression posttranscriptionally. Moreover, alternative splicing has a substantial impact on regulation of many physiological processes such as cell differentiation and development. Defects in pre‐mRNA splicing underlie a considerable number of genetic diseases and cancers.

Key Concepts:

In most eukaryotic pre‐mRNAs, the coding sequences (exons) are interrupted by stretches of noncoding sequences (introns).

The spliceosome uses a two‐step transesterification reaction to remove introns and join exons of pre‐mRNAs.

The snRNAs and spliceosomal protein Prp8 are implicated in the key catalytic steps of splicing.

Alternative splicing extends proteome diversity and regulates gene expression levels.

Alternative splicing is determined by interplays between
trans
‐acting factors and
cis
‐elements of pre‐mRNAs.

Alteration of
cis
‐elements and aberrant control of
trans
‐acting factors lead to diseases.
Brain: Neurodevelopmental Genetics
Authors: Baker Kate D , Skuse David H
Published: September 2010

Genes expressed during development regulate the emergent structure and function of the growing brain. Genetic mechanisms interact with environmental influences to predispose individuals to structural and functional brain disorders. The embryological sequence of nervous system development is relatively well understood. Longitudinal neuroimaging studies have highlighted that prolonged postnatal brain change is associated with acquisition of higher level cognitive skills such as language, memory and executive function. However, understanding of developmental neurobiology has not yet been extensively integrated with systems neuroscience, to identify key molecular and cellular mechanisms relevant to human cognition. Furthermore, little is known about genetic variants that constrain embryological and later brain development to influence neurological and cognitive outcomes in developmental disabilities and psychiatric disorders. Following the completion of the Human Genome Project, new technologies have enabled an extraordinary expansion in knowledge of genetic sequence variation, gene expression and epigenetics. Establishing convergence between developmental biology, systems neuroscience and genomics to understand the neurobiological bases for neurodevelopmental disorders remains an exciting challenge for the next decades.

Key Concepts:

Brain development involves differentiation of highly specialised cell types, in predictable temporal sequences, and their organisation into precise spatial systems.

Genetic variation interacts with environmental influences to predispose individuals to structural and functional brain disorders, by influencing developmental mechanisms.

Major events in early nervous system development include induction of the neural plate, neurogenesis, differentiation of neuronal and glial cell types, and migration of cells into their correct position.

Postnatal brain development, including maturation of white matter tracts and synaptic pruning in response to stimulation and behaviour, is also important, but the neurobiology is much less well understood.

Both early and later developmental processes may be disrupted by genetic mutations or influenced by sequence variation, but links from gene to brain to cognitive functions are complex and require investigation by convergent methods.

New methods of investigating genomic organisation and the structure and function of the living human brain are increasingly being integrated to elucidate molecular and cellular mechanisms of relevance to neurodevelopmental disorders.
Twin Methodology
Authors: Snieder Harold , Wang Xiaoling , MacGregor Alex J
Published: September 2010

The classic twin study is established as the ideal study design with which to investigate the relative importance of genetic and environmental factors to traits and diseases in human populations. Twin methodology is concerned with analysis techniques that have been developed to estimate and quantify the relative contribution of genes and environment to the disease or trait of interest. The current chapter gives an overview of the most important approaches. Both concordance measures and variance components approaches are discussed. The latter include analysis of variance (ANOVA), the DeFries–Fulker regression method and structural equation modelling (or path analysis). Structural equation models for twin data have recently been extended to incorporate and evaluate gene–environment interaction. Twin studies continue to play an important role in the postgenomic era, especially in the study of complex traits and diseases.

Key Concepts:

Most phenotypes show large individual differences (i.e. variance), the source of which may be genetic or environmental.

The classic twin study is the ideal study design to investigate the relative importance of genetic and environmental factors to traits and diseases in human populations.

Concordance measures express the similarity of twins for dichotomous traits such as the presence or absence of a disease.

Heritability is defined as the proportion of phenotypic variation that can be attributed to genetic variation.

Structural equation modelling is a standard tool in twin research and involves solving a series of simultaneous linear structural equations to estimate genetic and environmental parameters that best fit the observed twin variances and covariances.

Structural equation models for twin data have recently been extended to incorporate and evaluate gene–environment interaction.

Twin studies have often provided the first crucial proof of the importance of genes in the aetiology of a disease or trait, justifying further search for the underlying genes.