bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Morphogenetic Proteins and Their Receptors
Authors: de Gorter David Jan Jozef , van Bezooijen Rutger Leo , ten Dijke Peter 
Published: September 2009

Abstract

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

AbstractThe 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

Abstract

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

AbstractAptamers 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 ConceptsAptamers 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

Abstract

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

Abstract

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

AbstractFeminism 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

Abstract

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

AbstractBiological 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 ConceptsBiological 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

AbstractBioethics 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

AbstractThe 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 conceptsThe 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

Abstract

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.