bluuebunny/crossref_metadata_2025 huggingface dataset:
Bacterial Flagella: Flagellar Motor
Authors: Wadhams George H , Sowa Yoshiyuki
Published: September 2009

The bacterial flagellar motor is a complex biological rotary molecular motor which is situated in the cell envelopes of bacteria. Whereas most biological motors use adenosine triphosphate (ATP) as their energy source, the rotation of the flagellar motor is driven by a flow of charged ions across the bacterial plasma membrane. The motor powers the rotation of helical flagellar filaments at speeds of up to several hundred hertz. These rotating filaments act like propellers, pushing the cells through their environment. The motors are regulated by one of the best‐characterized biological signalling pathways, the chemotaxis pathway. This pathway changes the swimming pattern of the bacteria in response to changes in the concentration of external chemicals so that they move into environments which are optimal for their growth.

Key concepts:

Bacteria swim using a small biological rotary motor which is powered by the movement of charged ions across the plasma membrane.

The flagellar motor consists of a rotor which rotates against stator units that are anchored to the peptidoglycan cell wall.

Torque is generated by the interaction of the stator units, MotA and MotB, with FliG in the rotor.

Despite the fact that the driving ions always flow in one direction through the stator units, many flagellar motors can switch between clockwise and counterclockwise rotation.

A complex signalling pathway regulates the motor output in response to environmental signals ensuring that bacteria swim towards nutrient rich environments.
Secoviridae: The Amalgamation of the Families
Sequiviridae
and
Comoviridae
Authors: Sanfaçon Hélène
Published: September 2009

Several plant viruses share features with animal and human viruses of the family
Picornaviridae
, including a conserved structure of both the virus particle and the viral genome, expressing viral proteins by proteolytic cleavage of large polyproteins and encoding replication proteins with conserved sequence motifs. Members of the family
Comoviridae
were originally described as the only plant picorna‐like viruses. Other plant picorna‐like viruses were later discovered and classified in the family
Sequiviridae
.
Sequiviridae
and
Comoviridae
are related to each other in phylogenetic studies and share the common property of encoding specialized proteins to enable their movement in the plant. Recently, it was proposed to regroup plant picorna‐like viruses into a single family termed ‘secoviridae’. The proposed family amalgamates the families
Comoviridae
and
Sequiviridae
, and incorporates other plant picorna‐like viruses currently classified in the genera

Sadwavirus

and

Cheravirus

, and the proposed genus ‘

Torradovirus

’.

Key concepts:

Many plant viruses are related to the animal and human picornaviridae and to other picorna‐like viruses infecting algae and arthropods.

A recent update in the taxonomy of plant picorna‐like viruses has lead to the creation of the family ‘secoviridae’ which amalgamates the families
Comoviridae
and
Sequiviridae
as well as the existing genera
Cheravirus
,
Sequivirus
and the proposed genus ‘torradovirus’.

Secoviridae share many common characteristics including having both similar virus particle structures and genomic organizations, and requiring a specialized protein to facilitate their movement within the host plant.

Secoviridae produce their proteins in the form of large polyproteins that are cleaved at specific sites by a viral proteinase.

Replication of the viral RNA occurs in large protein complexes in association with intracellular membranes from the host.

Plant cells infected with secoviridae generally display tubular structures that are composed of the viral movement protein, contain virus‐like particles and traverse the cell wall. These tubular structures are probably involved in the movement of the virus from cell to cell.

Secoviridae can be transmitted through seeds and pollen or with the help of nematode or arthropod vectors and their spread in the field is largely dependent on their mode of transmission.
Lysozyme
Authors: Imoto Taiji
Published: September 2009

Lysozymes are lytic enzymes that hydrolyse glycosidic bonds and are widely distributed in nature. Hen egg‐white lysozyme is the best characterized of all proteins and, as well as serving as a model protein for study, its antibacterial and immune function properties are exploited in medicines and food additives. Basic concepts of enzyme reaction, structure and function of protein, protein chemistry and stability of protein are described. Evolution and diversity in structure and function of lysozyme are also stated.

Key concepts

Fundamental concept on an enzyme reaction is elucidated in an atomic level.

Lysozyme is a model protein for studying on structure and function of protein.

The diversities in structure and function make lysozymes interesting.
m
RNA
Turnover
Authors: Dickson Alexa M , Wilusz Carol J , Wilusz Jeffrey
Published: September 2009

Messenger ribonucleic acid
(mRNA) decay is an important cellular mechanism for regulating gene expression in both bacteria and eukaryotes. The enzymes involved and the factors that modulate their activity have been well‐characterized. Enzymes responsible for mRNA turnover attack either the 5′ or 3′ ends (exoribonucleases) or cleave the RNA in the middle (endoribonucleases). Transcripts generally have specific modifications at their ends, such as the 5′ cap and 3′ poly(A) tail in eukaryotes, to protect them from exonucleolytic decay. RNA‐binding proteins can modulate decay rates by recruiting mRNA degradation enzymes or by altering messenger ribonucleoprotein (mRNP) conformation to favour or impede decay. Here, we describe the enzymes and regulatory factors of the mRNA decay pathways in bacteria and eukaryotes, highlighting similarities between the two. We also discuss how mRNA degradation is regulated by RNA‐binding proteins, and how mRNA turnover pathways are used to identify and degrade aberrant mRNAs.
Cytokines
Authors: Wilson Heather M , Barker Robert N
Published: September 2009

Cytokines are small secreted ‘messenger proteins’ that allow communication between cells. They contribute to a chemical signalling language that controls many processes in multicellular organisms including haematopoiesis, chemoattraction, tissue repair, embryogenesis and virtually all aspects of immunity and inflammation. Cytokine functions are mediated by their binding to specific receptors to initiate intracellular signalling cascades that increase or decrease expression of transcription factors and genes regulating, for example, secretion of effector molecules (including other cytokines), cell proliferation and expression of membrane receptors. They play an important role in many pathologies and indeed measurement of cytokine profiles in patients provides a useful indicator of disease. Due to their multiple functions in disease, therapeutic interference of cytokines, cytokine receptors and their signal transduction pathways offer new treatment options for a range of disorders.

Key concepts

Cytokines are extremely potent, acting at picomolar or femtomolar concentrations.

Cytokines are not produced constitutively but are expressed on stimulation usually acting in an autocrine or paracrine fashion.

Individual cytokines can have many functions and can act synergistically or antagonistically.

Chemokines are a family of cytokines that are principally involved in chemoattraction but also participate in cell activation and angiogenesis.

Cytokine receptors can have similar subunit structures that divide them into families.

Most cytokine receptors are heterodimers but some can be homodimers or heterotrimers.

Cytokines exert their effects by activating specific intracellular signalling pathways.

By sharing receptor subunits and signal transducing molecules, many cytokines are known to play redundant and pleiotropic roles.

T‐helper cell subsets are distinguished based on their cytokine secretion whereas the cytokine environment determines which subset will develop.

Excessive cytokine production or activity can lead to several pathologies and cytokine modifiers are showing to be therapeutically effective in modifying cytokine‐mediated diseases.
Cleavage and Gastrulation in Sea Urchin
Authors: McClay David R
Published: September 2009

Cleavage in the sea urchin initially is highly stereotypic and during this time cells are specified transcriptionally to obtain unique molecular identities. A complex series of intercellular signals assist in this diversification of the cells and coordinate their location in the blastula stage embryo. Once the cells are programmed by these early nuclear events the process of gastrulation follows. Gastrulation is characterized by a dramatic morphogenetic rearrangement of cells to form the basic body plan of the organism. In the sea urchin embryo gastrulation occurs in two phases: ingression of the skeletogenic cells and then invagination of the archenteron or the primitive gut.

Key Concepts:

Cleavage is the stage encompassing the earliest cell divisions after fertilization during which cells divide without an increase in embryo mass.

During cleavage, in each cell a combination of transcription factors and signalling between cells establishes gene regulatory networks.

Gene regulatory network states become different in subpopulations of cleaving cells through asymmetric signaling and/or asymmetric inheritance of cytoplasmic determinants, and this process is causal for cell diversification.

Gastrulation in the sea urchin embryo involves two separable morphogenetic processes: ingression of primary mesenchyme cells and invagination of the archenteron, or the primitive gut.

As a consequence of gastrulation, cells of the embryo are rearranged to establish the early body plan of the larval stage.

Most sea urchin embryos develop indirectly. That is, embryogenesis leads to a feeding larval stage, and the larva later metamorphoses into a juvenile, which grows into an adult.
Regeneration of the Urodele Limb
Authors: Stocum David L
Published: September 2009

Urodele limbs regenerate via a blastema of progenitor cells derived from differentiated limb cells by a process of dedifferentiation. The blastema grows by mitosis of the progenitor cells under the influence of factors supplied by the wound epidermis and nerves, and is patterned into the new limb structures by molecular interactions between blastema cells.
The Role of Insulators in Genome Organization and Gene Expression
Authors: Baxley Ryan M , Geyer Pamela K
Published: September 2009

Transcription of eukaryotic genomes is regulated by enhancer and silencer input at a gene promoter. These regulatory elements act over large distances and demonstrate limited target specificity, suggesting that constraints exist to increase specificity. Insulators are
deoxyribonucleic acid
(DNA) elements that limit enhancer and silencer action, establishing independent transcriptional domains. Eukaryotic genomes contain a variety of widely distributed insulators. The best characterized are the

Drosophila

Su(Hw)‐dependent insulators and the vertebrate CCCTC‐binding factor (CTCF)‐dependent insulators. Emerging evidence suggests that insulators are not impassable barriers, but are active players in many nuclear functions. Insulator action depends on the organization and properties of local enhancers, promoters and insulators. Two models describing insulator action include (1) formation of independent structural domains that have a global impact on transcription and (2) direct participation in transcriptional regulation that confers specificity to regulatory interactions. Further studies of insulators will provide a richer understanding of transcriptional regulation in eukaryotes.
Natural Antibodies
Authors: Zouali Moncef
Published: September 2009

Natural antibodies are essentially antibodies of the immunoglobulin M (IgM) isotype present in the circulation of normal humans and other mammalian species that have not been previously exposed to deliberate immunization. They are often directed against highly conserved epitopes and often bind to ligands of varying chemical composition with low affinity. This antibody subset contrasts with immune antibodies, which are produced in response to the introduction of antigen to the immune system. Natural antibodies are frequently directed to intracellular structures, rather than to cell‐surface antigens. They have been found to play a role in protection against infectious agents and to exert homeostatic functions. Other investigations suggest that natural antibodies might play a pathogenic role.

Key concepts

A natural antibody is an antibody present in the circulation of an animal or a subject that had not been previously exposed to the corresponding antigen.

Certain B‐lymphocyte subsets, such as B‐1a cells, are committed to natural antibody production.

The antibody repertoire expressed in B‐cell malignancies exhibits several features in common with those of the natural antibody repertoire of healthy subjects.

It is possible that natural antibody production is driven by microorganisms indigenous to the organism, such as bacteria living in the intestine.

Natural antibodies play a role in shaping the B‐cell repertoire and may represent the precursors of antibodies to pathogens.

Natural antibodies could serve as innate recognition receptors, recognizing various bacterial cell wall components or parasites.

Studies of rodents rendered deficient in natural antibodies suggest that this antibody subset is endowed with a homeostatic potential and housekeeping functions, such as recognition and removal of senescent cells and other self‐antigens.

Circumstantial evidence suggests that natural antibodies can be associated with protection against Alzheimer disease, atherosclerosis or cancer development.

B lymphocytes secreting natural antibodies could represent a reservoir capable of mutating their immunoglobulin variable region genes to give rise to high‐affinity pathogenic autoantibodies.
Photosynthesis
Authors: Ort Donald R , Kramer David
Published: September 2009

Photosynthesis is the process that enables higher plants, algae and a broad class of bacteria to transform light energy and store it in the form of energy‐rich organic molecules. In plants and algae, as well as some species of bacteria, photosynthesis removes carbon dioxide from the atmosphere, produces the molecular oxygen we breath and stores energy in biomass. In addition some bacteria use light energy to create energy‐rich molecules, but do not split water to produce oxygen. Photosynthesis is finely regulated to avoid damage caused by excess solar energy. At the same time, though, this regulation also decreases the efficiency of photosynthesis. Current research is aimed at understanding these responses to improve photosynthetic efficiency, thus increasing the production of food and fuel.

Key Concepts:

Photosynthesis is the transformation of light energy to chemical energy by higher plants, algae and certain bacteria.

In higher plants, the initial capture of light energy and conversion to the stable, high‐energy products of NADPH and ATP occurs within and around the thylakoid membranes of the chloroplast. The NADPH and ATP produced are used by enzymes in the stroma to ‘fix’ carbon dioxide and produce carbohydrates.

Although photosynthesis is driven by light, the photosynthetic apparatus must protect itself from excess solar energy which causes a decrease in photosynthetic efficiency.
Nuclear‐Cytoplasmic Transport
Authors: Lange Allison , Corbett Anita H
Published: September 2009

In eukaryotic cells, the genomic
deoxyribonucleic acid
(DNA) in the nucleus is separated from the translational machinery in the cytoplasm by the nuclear envelope. Transport of macromolecules such as proteins and
ribonucleic acid
(RNA) across this membrane is essential for cellular function and requires active nuclear–cytoplasmic transport systems. These systems consist of soluble transport receptors, which recognize and bind cargo in one compartment, mediate transport through nuclear pore complexes embedded in the nuclear envelope and deliver cargo in the target compartment. Disruption of this highly regulated process results in abnormal cell function and is linked to human disease etiology. Understanding the contribution of nuclear protein and RNA transport to cellular organization is one of the major challenges in cell biology.

Key Concepts

Transport into and out of the nucleus occurs through nuclear pore complexes (NPCs), which are large proteinaceous channels that perforate the nuclear membrane.

Proteins destined for import into the nucleus contain a nuclear localization signal (NLS) and proteins destined for export from the nucleus contain a nuclear export signal (NES), each of which targets them for transport.

Soluble transport receptors called importins and exportins or karyopherins recognize and bind macromolecular cargos and facilitate transport through the nuclear pore.

The asymmetric distribution of RanGDP in the cytoplasm and RanGTP in the nucleus controls the directionality of nuclear transport.

Nuclear protein import can be regulated through inter‐ or intramolecular occlusion of the NLS or NES; posttranslation modification of the targeting signal; compartmental sequestration of the cargo protein or altering properties of the nuclear transport machinery including receptors and nuclear pores.

Many classes of RNA are transported via Ran‐regulated, karyopherin‐dependent pathways.

Messenger
ribonucleic acid
(mRNA) export is highly coupled to mRNA processing and is mediated by distinct receptors.

Mutations in nuclear targeting signals and nuclear transport receptors have been linked to several human diseases.
Amino Acid Degradation
Authors: Sawers R Gary
Published: September 2009

Amino acids are valuable metabolic fuels, providing a supply of both nitrogen and carbon for intermediary metabolism and energy for growth. Controlled degradation of amino acids is important in the maintenance of the carbon–nitrogen balance. It is becoming increasingly apparent that imbalance of amino acid degradation can have important consequences for both development and disease. Generally, the first step in degradation of amino acids results in the amino group either being incorporated into other nitrogenous compounds or being excreted as ammonia or urea, whereas the carbon skeleton is catabolized to one of a few common metabolic intermediates. Thus, an understanding of amino acid degradation provides knowledge of the interrelationships between metabolic pathways and helps explain some of the clinical features when deficiencies in amino acid metabolism occur.

Key concepts

Amino acids are important growth substrates for microorganisms.

Tight control of amino acid degradation and cycling maintains the C–N balance.

Glutamate is a key central amino acid in maintenance of the C–N balance.

The first step in amino acid degradation is removal of the α‐amino group.

Key steps in amino acid degradation include deamination, catalysed by pyridoxal phosphate‐dependent transaminases, oxidoreductases or carbon–oxygen lyases, decarboxylase reactions and carbon skeleton rearrangements catalysed by isomerases.

Carbon skeletons arising from amino acid breakdown are channelled into central metabolism.

Production and excretion of urea and uric acid by animals and birds and reptiles, respectively, avoids the accumulation of toxic levels of ammonia in blood and tissues.

Metabolic products derived from
l
‐serine are essential for cell proliferation and a functional nervous system.

Absence of key enzymes or imbalance in amino acid degradation leads to severe disease states, such as phenylketonuria and methylmalonic aciduria.
Bioinformatics
Authors: Tramontano A
Published: September 2009

Bioinformatics is a discipline at the intersection of biology, computer science, information technology and mathematics. It aims at integrating and analysing a wealth of biological data with the aim of identifying and assigning a function to each of the parts list of a living organism and understanding the incredibly complex processes that define life at a systems level. It is applied, for example, in the construction of genetic and physical maps of genomes, gene discovery, the inference of the molecular function and three‐dimensional structure of their products, the interpretation of the effect of gene variations on the phenotype, the reconstruction of interaction and signal transduction pathways and the simulation of biological systems. Bioinformatics is an essential part of modern biology and a key player in the quest for a complete systems‐level understanding of a living cell and of an organism.

Key concepts

Biological data are being produced at an unprecedented speed and need to be organized and integrated.

Bioinformatics, or computational biology, is the discipline that uses computational tools for analysing biological data and adds ‘biological’ value to them.

The complete DNA sequences of many genomes, including
Homo sapiens
, have been elucidated and need to be annotated, that is, associated to their biological function.

Proteins, the products of genes, perform most of the functions of life.

The function of a protein can be deduced by its evolutionary history or by analysing the three‐dimensional shape that it assumes.

The evolutionary history of a protein (a gene) can be deduced by comparing its sequence with those of all other known proteins (or genes).

The number of possible three‐dimensional structures of a protein is almost infinite and the correct one cannot be selected, as of today, on the basis of first principles.

Empirical methods, based on evolution or on the body of experimental knowledge on protein structures, can be used to infer the unknown structure of a protein.

The future challenge of bioinformatics is to use and combine available data on sequences, three‐dimensional structures, interactions, abundance and temporal patterns of expression to obtain a systems level understanding of life.
Lipoproteins: Genetic Disorders
Authors: Soutar Anne K
Published: September 2009

The primary function of plasma lipoproteins is to transport newly synthesised or dietary lipids in the circulation; these water‐insoluble substances include triacylglycerol, cholesterol and fat‐soluble vitamins. Mutations in genes for the many enzymes, receptors and structural proteins that regulate lipoprotein metabolism and transport are often detrimental to health, and may increase the amount of normal lipoproteins, result in accumulation of abnormal lipoproteins or cause lipoprotein deficiencies. Some defects increase the risk of coronary heart disease, whereas other deficiency disorders cause neurological and/or gastrointestinal symptoms. Genetic disorders of lipoprotein metabolism highlight the importance of lipid transport and metabolism in normal human physiology.

Key Concepts

Normal regulation of plasma lipoprotein metabolism is critical for transport of lipids and fat‐soluble vitamins in the circulation.

Once secreted from cells in the liver or intestine, lipoproteins undergo many complex metabolic changes in the blood circulation brought about by enzymes and their cofactors, exchange factors and cell‐surface receptors.

Variation in the genes for these proteins can alter their function and cause changes in the composition, concentration and/or function of plasma lipoproteins that are frequently deleterious to health.

Several defects in lipoprotein metabolism result in increased risk of premature coronary heart disease because of cholesterol deposition in the blood vessels, whereas others lead to neurological symptoms due to deficiency of fat‐soluble vitamins.

The inheritance pattern varies: most known lipoprotein disorders are monogenic, with either autosomal dominant inheritance, where heterozygous carriers are affected or autosomal recessive inheritance, where heterozygous carriers are apparently unaffected. Some dominantly inherited disorders have a gene dosage effect, where homozygous individuals are more severely affected than heterozygous ones.

Some gene variants only have a marked physiological effect in a particular genetic or environmental background, so not all carriers are affected.

Families exist who have a clinical phenotype characteristic of a known monogenic disorder, but who have no detectable defect in the known causal genes; this suggests that novel genes still remain to be identified that influence lipoprotein metabolism.

One of the commonest inherited disorders, familial combined hyperlipidaemia, is not monogenic and requires several gene variants to be present for symptoms to be manifest. These variants are also unlikely to be the same for all families.
Bone Morphogenetic Proteins and Their Receptors
Authors: de Gorter David Jan Jozef , van Bezooijen Rutger Leo , ten Dijke Peter
Published: September 2009

Bone morphogenetic proteins (BMPs) are important signalling molecules that were first identified by their ability to induce bone and cartilage, and subsequently were shown to be pleiotropic cytokines controlling a wide variety of biological responses during early development, skeletogenesis and homoeostasis of several tissues. In agreement with their crucial role in many biological processes, mutations in components of the BMP signalling pathway underlie several pathologies. BMPs transmit their signals from membrane to nucleus through distinct combinations of types I and II serine/threonine kinase receptors and their intracellular effectors the Smad proteins. Smad‐mediated transcription of target genes is regulated in a complex manner in which interactions with other transcription factors and signalling pathways define the final response.

Key Concepts

Bone morphogenetic proteins (BMPs) are important pleiotropic cytokines controlling a wide variety of biological responses ranging from early development, skeletogenesis and homeostasis of several tissues to suppression of tumorigenesis.

In agreement with their crucial role in many biological processes, mutations in components of the BMP signalling pathway underlie several pathologies, including primary pulmonary hypertension and fibrodysplasia ossificans progressiva.

BMPs transmit their signals from membrane to nucleus through distinct combinations of types I and II serine/threonine kinase receptors and their intracellular Smad effector proteins.

An essential step in most BMP receptor‐controlled responses is the phosphorylation of the receptor‐regulated Smads, Smad1, Smad5 and Smad8, which then associate with the co‐Smad, Smad4, and translocate to the nucleus where they control transcription of BMP target genes.

Besides the well‐established BMP/Smad pathway, BMPs can also activate alternative signalling routes, so‐called non‐Smad pathways, which in concert with the Smad pathway determine the BMP‐induced effects.

The pleiotropic characteristics of BMPs clearly implicate the need for a tight control of their activities, which is achieved via secreted antagonists which directly bind BMPs and prevent them from binding to their receptors, negative feedback loops mediated by the inhibitory Smads, Smad6 and Smad7, and crosstalk with many different signalling pathways.

Differential binding of BMP family members to receptors and extracellular antagonists, their ability to activate certain Smad‐independent signalling pathways, differences in signalling amplitude and duration of both Smad‐dependent and Smad‐independent pathways, and how these interact, define the final outcome of BMP‐induced cellular responses.
Signal Transduction Pathways in Development and Immunity:NFκB/Rel Pathways
Authors: Gilmore Thomas D , Tony Ip Y
Published: September 2009

The nuclear factor kappa B (NFκB)/Rel signal transduction pathway is conserved from simple multicellular eukaryotes, such as sponges and insects, to humans and controls a variety of processes involved primarily in immunity and development. The NFκB family of transcription factors includes several structurally related proteins that form dimers, which regulate the expression of numerous genes by binding to specificdeoxyribonucleic acid(DNA) sites near these genes. In mammals, the NFκB pathway is important in the control of innate and adaptive immunity, immune cell development, cell proliferation and cell survival. In insects, the NFκB pathway controls the establishment of dorsal–ventral polarity in the early embryo and an antimicrobial response. Activation of NFκB transcription factors occurs via a series of biochemical steps and involves translocation of NFκB from the cytoplasm to the nucleus where it can activate gene expression. Misregulation of the NFκB pathway is also implicated in several human disease states, including many types of cancer and inflammatory diseases.

Key concepts:

NFκB and Rel proteins are part of a family of transcription factors whose activity is controlled primarily by subcellular localization.

Many extracellular signals can activate a multicomponent signal transduction pathway that leads to nuclear localization of NFκB/Rel proteins where they control the transcription of many important effector genes.

NFκB/Rel transcription factors control a number of evolutionarily conserved developmental and immune processes.

InDrosophila, NFκB/Rel signalling controls the immune response of flies to fungal and bacterial infections.

In vertebrates, NFκB/Rel signalling controls the innate immune response, cell survival and the development of several specific cell types, such as liver cells, immune cells and skin cells.

Misregulation of NFκB/Rel activity occurs in a number of human diseases, including several chronic inflammatory diseases and cancers.
Immunofluorescence: Dyes and Other Haptens Conjugated with Antibodies
Authors: Härtig Wolfgang , Fritschy Jean‐Marc
Published: September 2009

Conjugation is the covalent attachment of a reporter molecule to a probe for the investigation of specific tissue constituents. Biotin, digoxigenin, fluorescent molecules (fluorochromes) and other haptens are applied for conjugation to antibodies and lectins. They enable the sensitive detection of a large variety of probes in cells and tissues by hapten–antihapten techniques. Fluorescently labelled probes are a prerequisite for the direct visualization of relevant markers not only in fixed tissues, but also

in vivo

and

in vitro

. The concomitant use of differently haptenylated antibodies facilitates bioanalytical approaches such as flow cytometry. Antibodies raised in the same animal species conjugated to various haptens are useful tools for specific multiple fluorescence labelling. Investigating pathologically altered tissues, haptenylated reagents allow for the omission of secondary antibodies avoiding undesired cross‐reactions with endogenous immunoglobulins in the tissues.

Key concepts

The fluorescence monitoring of biomolecules is enabled by chemically and genetically fluorochromated antibodies.

Large biomolecules can be modified by fluorescent haptens or by nonfluorescent haptens to be targeted with fluorescent hapten‐binding molecules.

Digoxigenylated, biotinylated and fluorochromated antibodies are useful tools for multiple labelling of antigens under physiological conditions and after pathological alterations, for example, in Alzheimer disease.

Differently haptenylated antibodies allow for the immunofluorescence and immunoperoxidase staining with antibodies from the same host species and without possibly cross‐reacting secondary antibodies.

Fluorescent primary antibodies are useful for the direct

in vivo

labelling.

Alternative approaches include the combined immuno‐ and lectin‐histochemical staining of neural markers.
Macromolecular Interactions: Aptamers
Authors: Warren Christopher L , Mohandas Appesh , Chaturvedi Ishan , Ansari Aseem Z
Published: September 2009

Aptamers are composed of nucleic acids or peptides and target many types of different molecules, including proteins and ligands, such as hormones and antibiotics. Nucleic acid aptamers can adopt diverse structures, including G‐quadruplexes, bubbles, bulges, multiway junctions and pseudoknots. Aptamers have been developed against a multitude of proteins and small molecules. The versatility of aptamers to recognize nearly any biomolecule in a very specific manner makes them effective as diagnostic tools and attractive as potential therapeutics. Currently, the systematic evolution of ligands by exponential enrichment (SELEX) technique is the standard method to isolate an aptamer to a specific molecule. However, recent advances in microarrays offer much potential for isolating aptamers in a more efficient and effective method than SELEX.

Key Concepts

Aptamers are nucleic acids or peptides designed to target a wide variety of molecules such as proteins and small molecules such as hormones and antibiotics, with exquisite precision.

Nucleic acid aptamers can adopt diverse structures, including G‐quadruplexes, bubbles, bulges, multiway junctions and pseudoknots.

Aptamers have been developed against a multitude of proteins and small molecules; an abridged table is included in this article.

The versatility of aptamers to recognize nearly any biomolecule in a very specific manner makes them effective as diagnostic tools and attractive as potential therapeutics.

Systematic evolution of ligands by exponential enrichment (SELEX) technique is the standard method to isolate an aptamer to a specific molecule.

Recent advances in microarrays present a new method for isolating aptamers in a potentially more efficient and effective manner than SELEX.
Environmental Impact of Genetically Modified Organisms (
GMOs
)
Authors: Hails Rosemary S
Published: September 2009

The intensification of agriculture has provided cheaper more plentiful food, but has also caused declines in farmland wildlife. The introduction of genetically modified (GM) crops may exacerbate this, or offer new ways of mitigating anthropogenic impacts. The potential consequences of the introduction of GM crops have been studied for over a decade, since commercialization. Although the specific issues depend on the crop and transgenes involved, one common theme that emerges is that the biggest effects will arise from the way in which the GM crop will be managed. Herbicide‐tolerant GM crops may allow better weed control, and this is a risk to biodiversity that should be mitigated. However, even herbicide‐tolerant crops have some environmental benefits through reduced production and application of herbicides. Insect and disease‐resistant crops will have fewer impacts on nontarget organisms than conventional crops and their management, and so may offer direct environmental benefits.

Key concepts

Farmland biodiversity
has been enhanced and maintained by agricultural land management over hundreds of years. Changes in the intensity of farming since the 1970s have caused its decline, and any future change may exacerbate or ameliorate this impact.

Global warming potential
(GWP) is the potential of a gas produced by a product or a process to contribute to global warming. It is measured over a specific time period, and on a scale relative to carbon dioxide. Different agricultural practices will have different GWP.

Life cycle assessment
is defined as an objective process to evaluate the environmental burdens associated with a product or a process by identifying energy and materials used and wastes released to the environment.

Meta‐analysis
involves retrieving and combining data from a number of studies to obtain a quantitative estimate of the overall effect which can be statistically analysed.

Refuge strategy
is the strategy employed to delay or prevent the build up of pests resistant to the GM crop. It involves a ‘refuge’ of approximately 20% of the crop in which susceptible individuals may survive, in contrast to the 80% of the crop in which the majority of the pest individuals fail to reach maturity. Any rare resistant individuals that do survive are then likely to mate with a susceptible individual and produce susceptible offspring.

Natural enemy release
posits that natural enemies limit the growth or survival of plants. Resistance to these natural enemies could release a plant genotype from natural enemy regulation and lead to invasiveness.

Comparative sustainability assessment
is a matrix‐based approach to assess comparative sustainability, benefits and risks of the introduction of any novel agricultural products or practices. The purpose is to develop a more objective and comprehensive approach towards agricultural and rural policy.
RNA
Polymerase
II
Holoenzyme and Transcription Factors
Authors: Nicolas Moniaux , Jamila Faivre , Batra Surinder K
Published: September 2009

The transcription, which is the RNA (
ribonucleic acid
) biosynthesis, constitutes a tightly regulated multistep process involving the spatial and temporal recruitment of numerous protein complexes. The three main steps of the process are transcription initiation with the formation of the transcription preinitiation complex (PIC), elongation and termination. All these steps have in common the enzymatic activity of the protein complex known as the
RNA polymerase II
(RNAPII), which is an enzyme giving rise to the promoter‐specific protein complex called RNAPII holoenzyme. The composition of RNAPII holoenzyme (dependent on the extraction/purification process and the origin of the material) varies from laboratory to laboratory, but always includes RNAPII, general transcription factors (GTFs), protein mediators such as the suppressor of RNA polymerase B mutations (SRBs),
histone acethyl transferase
(HAT) and chromatin remodelling factors. This article focuses on the structure of RNAPII and the protein complex leading to the formation of RNAPII holoenzyme during the initiation step. The role of the main proteins allowing specific promoter recognition is detailed.

Key concepts:

The transcription is a regulated multistep process (initiation, elongation and termination) leading to RNA synthesis.

RNA polymerase synthesizes RNA in a DNA‐dependent manner.

Six RNA polymerases are known in eukaryote: RNAPI (synthesizing rRNAs), RNAPII (synthesizing mRNAs and snRNAs), RNAPIII (synthesizing tRNAs, 5S rRNA and some snRNAs), spRNAP‐IV (synthesizing mRNAs) and RNAP IV (synthesizing siRNA).

Transcription requires
cis
‐acting promoter elements (core and regulatory elements) and
trans
‐acting factors.

The core elements bind the transcription preinitiation complex (PIC) that include the GTFs (general transcription factor) and RNAPII.

Two main forms of RNAPII holoenzyme are identified, the SRB/MED‐containing and the PAF complex‐containing holoenzyme.
Feminist Perspectives on Human Genetics and Reproductive Technologies
Authors: Dickenson Donna L
Published: September 2009

Feminism offers three separate but equally important insights about human genetics and the new reproductive technologies. First, feminism is concerned with ways in which these new technologies have the potential to exploit women while seeming to offer women greater reproductive freedom. Second, feminism draws our attention to the ways in which decisions about genetic testing and reproductive choice take place in the context of relationship. Finally, feminist analysts and activists have been among the leaders in identifying the threats from commodification and commercialization in genetic research and patenting, which often affect women disproportionately. Although other authors have produced important critiques of commodification and patenting in this area, feminist writers have drawn specific attention to impacts on women that had not previously been considered. They have also produced concrete proposals for benefit‐sharing to compensate for harms women suffer from genetic research, particularly in Third World countries.

Key concepts:

Conventional bioethics frequently lacks a political dimension, which feminism corrects by focusing on power and justice issues in the new biotechnologies, including genetics.

A key insight of feminism has been that neither genetics nor new reproductive technology is gender‐neutral.

For example, if there were to be a general movement towards preimplantation genetic diagnosis (PGD) on the basis of minimizing hereditary genetic disorders, women would be asked routinely to undergo superovulation and egg extraction for the purpose ofin vitrofertilization (IVF).

More generally, it may be asked whether the wider availability of genetic tests will burden women disproportionately with moral quandaries, because typically it is women who are expected to assume responsibility not only for their own health but also for that of their families.

Women have also been disproportionately affected by the trend towards private firms taking out patents on human genes – with nearly 20 per cent of the human genome having been patented by 2005.

One instance of restrictive genetic patenting with particularly harmful impact on women has involved the fees levied for diagnostic tests on two genes implicated in some breast cancers,BRCA1andBRCA2.

According to a feminist analysis, genetics and new reproductive technologies (NRTs) pose a risk when they ignore or even worsen those differences in burdens between men and women that actually could be alleviated by modern biotechnology.
Genetic Carrier Testing
Authors: Henneman Lidewij , Cornel Martina
Published: September 2009

Genetic carrier testing includes tests for the heterozygous status of an inherited disorder in individuals who, although apparently healthy themselves, have a high risk of transmitting the genetic disorder to their offspring. Carrier testing will allow couples of childbearing age to make informed reproductive decisions. Genetic carrier tests are used by people who have a family history of an inherited disorder or carriership, reproductive partners of carriers and partners of individuals who have the disorder. A prerequisite for knowledge about a possible risk for relatives and the availability of testing is the dissemination of information in the family. Many factors impede the sharing of genetic information in families including lack of knowledge, persistent lay beliefs or poor relationships. In addition, several factors have been identified that interfere with decisions about genetic carrier testing, resulting in low uptake rates for carrier tests in high risk families.

Key concepts

Reproductive planning is the most important factor motivating genetic carrier testing.

Family disclosure of genetic information is a prerequisite to knowledge about the risk and availability of carrier testing.

Because of factors impeding the sharing of information in families and factors interfering with the decision about testing, the uptake for carrier testing in high‐risk families is often lower than expected.

To minimize (time) constraints and maximize reproductive options, carrier testing before conception is advocated.
Biological Complexity: Beyond the Genome
Authors: Salthe Stanley N , von Sternberg Richard
Published: September 2009

Biological development, evolution and behaviour are enormously complex processes. For instance, morphogenesis involves the emergence of tiers of organization that are not deterministically entailed by lower‐scale components. Such extensional (space–time) complexity can be detected at the level of chromatin states, where topologies are constrained by higher‐order pathways involving entire chromosomes or the nucleus. Once established, chromatin conformations can become heritable in mitosis and meiosis.Deoxyribonucleic acid(DNA) encodings are thus contained in a framework of epigenetic information, the complexity of which increases during ontogeny. Intensional (process and change) complexity is also evident, where genomes are shaped by cellular operations. Language and new representations need to be developed for representing such phenomena, because current reductive approaches to explaining complex systems, although useful in guiding observations, have become conceptually misleading when extrapolated to ontology. The approach we propose for constructing that language derives from hierarchy theory, involving both classes of complexity.

Key Concepts

Biological systems can be modelled as hierarchies.

Extensional complexity involves small‐scale functions being embedded within and contextualized by larger‐scale forms.

Dynamical complexity results from processes at different scalar levels mutually constraining each other, even though they cannot directly interact because they proceed at very different rates.

Phenotype construction is morphogenetic, with each event dependent on preceding ones and contextualized by collateral ones.

Chromatin states are an example of higher‐order cellular properties constraining lower‐level genomic events.

The cellular phenotype determines the activity of the genome via a series of informational channels across several scalar levels.

Genome structure is constrained by higher‐order boundary conditions, which is a type of intensional complexity.
Bioethics: Practice
Authors: Elliott Carl , Johnston Josephine
Published: September 2009

Bioethics is a multidisciplinary field that encompasses academic bioethics, clinical bioethics and health policy. Contemporary currents in bioethics emphasize the significance of practical experience for moral judgment, the influence of narrative and rhetorical style on ethical reasoning and the need to examine the social structures involved in the creation of power, authority and oppression.
Autonomy and Responsibility in Reproductive Genetics
Authors: Hellsten Sirkku K
Published: September 2009

The principle of respecting individual autonomy has traditionally been the most powerful of the four conventional principles of Western bioethics (the others being beneficence, benevolence and justice). It is rarely trumped by other ethical considerations such as an individual's personal responsibility, collective duties or even by the utilitarian maximization of the overall happiness or utility of a society. The new biotechnology has set the concept of autonomy in a new context challenging our traditional views on rights, responsibilities and humanity as a whole.

Key concepts

The concept of autonomy is one of the main conventional principles in bioethics.

The new scientific developments challenge our traditional views on autonomy, rights and responsibilities.

The concept of humanity is challenged by the new biotechnology.

Bioethics studies provide normative guidelines which sometimes appear value neutral.

Negative and positive rights are both central in policy considerations related to the development and use of new biotechnology.
Apoptosis: Regulatory Genes and Disease
Authors: Vince James E , Silke John
Published: September 2009

Apoptosis is essential for normal development and proceeds by the extrinsic death receptor pathway, or the intrinsic Bcl‐2 blockable pathway. Both pathways activate a class of proteases termed caspases that cleave intracellular substrates resulting in cell death. Excessive apoptosis may excerbate neurological diseases and the damage caused by heart attacks and strokes. Apoptosis is used by metazoans as a defence against pathogens that have, therefore, evolved mechanisms to block the apoptotic machinery. The involvement of apoptosis in disease states has led to the rational design of compounds that target this pathway which are already successfully used in the clinic.

Key concepts

Apoptosis can occur by the extrinsic death receptor pathway or by the intrinsic Bcl‐2 blockable pathway.

Perforin–granzyme‐mediated toxicity is important for NK and T‐cell destruction of pathogen‐infected cells and tumour cell surveillance.

p53 is a transcription factor that prevents tumourigensis by initiating the intrinsic cell death pathway.

The Bcl‐2 protein family is made up of pro‐ and antiapoptotic proteins that form the core components of the intrinsic cell death pathway and are often dysregulated in cancer.

Death receptors regulate immune cell function and development by inducing apoptosis and also by stimulating pro‐survival cellular responses.

Rationally designed compounds specifically targeting the intrinsic or extrinsic cell death regulators are hoped to provide new and highly specific cancer therapies.