bluuebunny/crossref_metadata_2025 huggingface dataset:
Diseño y construcción de muros en el primer gótico cordobés
Authors: García Ortega A. J.
Published: December 2009

Las primeras iglesias cristianas de Córdoba constituyen un homogéneo conjunto, comenzado además en un corto período de tiempo a finales del siglo XIII. Esto ofrece una plataforma idónea para estudiar sus soluciones constructivas tipo, entre las que son trascendentales los sistemas de muros. Utilizando magnífica sillería, se construyen sabiendo adaptar las técnicas cristianas nortepeninsulares a las tradiciones locales y al aprovechamiento de los sillares de acarreo islámicos. Esto incidiría en el aparejo a soga y tizón mayoritariamente utilizado, aunque el muro sigue siendo el gótico de tres hojas, con dos paramentos y relleno interior. Estas características, así como la solución de cimentación, el mortero utilizado o el posible uso de la vara burgalesa como unidad de medida, suponen una manera de proceder nueva en la ciudad, apuntando a la más que probable intervención de canteros castellanos.
El análisis dimensional del conjunto permite también detectar la lógica y coherencia en la asignación de espesores a los muros. Existe gradación de los mismos según sus circunstancias y posición en el organismo arquitectónico, e igualmente coincidencias dimensionales entre los distintos edificios para un mismo tipo de muro; todo esto apunta al uso de reglas preestablecidas, posiblemente muy sencillas. Por último, el conocimiento y objetivación de todos estos aspectos aporta interesantes datos sobre el proceso edificatorio, que, frecuentemente, priorizaría las cabeceras; y también, en edificios casi destruidos como la iglesia de S. Andrés, incluso es posible elaborar hipótesis fundadas para su reconstrucción.
Anexos 1 y 2: Relación de DIT, DIT plus y DITE concedidos por el IETcc, durante el año 2008
Authors: Editorial Equipo
Published: December 2009

No disponible
Development of Murine Lupus Involves the Combined Genetic Contribution of the SLAM and FcγR Intervals within the Nba2 Autoimmune Susceptibility Locus
Authors: Jørgensen Trine N. , Alfaro Jennifer , Enriquez Hilda L. , Jiang Chao , Loo William M. , Atencio Stephanie , Bupp Melanie R. Gubbels , Mailloux Christina M. , Metzger Troy , Flannery Shannon , Rozzo Stephen J. , Kotzin Brian L. , Rosemblatt Mario , Bono María Rosa , Erickson Loren D.
Published: December 2009

Autoantibodies are of central importance in the pathogenesis of Ab-mediated autoimmune disorders. The murine lupus susceptibility locus Nba2 on chromosome 1 and the syntenic human locus are associated with a loss of immune tolerance that leads to antinuclear Ab production. To identify gene intervals within Nba2 that control the development of autoantibody-producing B cells and to determine the cellular components through which Nba2 genes accomplish this, we generated congenic mice expressing various Nba2 intervals where genes for the FcγR, SLAM, and IFN-inducible families are encoded. Analysis of congenic strains demonstrated that the FcγR and SLAM intervals independently controlled the severity of autoantibody production and renal disease, yet are both required for lupus susceptibility. Deregulated homeostasis of terminally differentiated B cells was found to be controlled by the FcγR interval where FcγRIIb-mediated apoptosis of germinal center B cells and plasma cells was impaired. Increased numbers of activated plasmacytoid dendritic cells that were distinctly CD19+ and promoted plasma cell differentiation via the proinflammatory cytokines IL-10 and IFNα were linked to the SLAM interval. These findings suggest that SLAM and FcγR intervals act cooperatively to influence the clinical course of disease through supporting the differentiation and survival of autoantibody-producing cells.
Peroxiredoxin 1 Stimulates Secretion of Proinflammatory Cytokines by Binding to TLR4
Authors: Riddell Jonah R. , Wang Xiang-Yang , Minderman Hans , Gollnick Sandra O.
Published: December 2009

Peroxiredoxin 1 (Prx1) is an antioxidant and molecular chaperone that can be secreted from tumor cells. Prx1 is overexpressed in many cancers, and elevation of Prx1 is associated with poor clinical outcome. In the current study, we demonstrate that incubation of Prx1 with thioglycollate-elicited murine macrophages or immature bone marrow-derived dendritic cells resulted in TLR4-dependent secretion of TNF-α and IL-6 and dendritic cell maturation. Optimal secretion of cytokines in response to Prx1 was dependent upon serum and required CD14 and MD2. Binding of Prx1 to thioglycollate macrophages occurred within minutes and resulted in TLR4 endocytosis. Prx1 interaction with TLR4 was independent of its peroxidase activity and appeared to be dependent on its chaperone activity and ability to form decamers. Cytokine expression occurred via the TLR-MyD88 signaling pathway, which resulted in nuclear translocation and activation of NF-κB. These findings suggest that Prx1 may act as danger signal similar to other TLR4-binding chaperone molecules such as HSP72.
Gene Expression Analysis of Macrophages That Facilitate Tumor Invasion Supports a Role for Wnt-Signaling in Mediating Their Activity in Primary Mammary Tumors
Authors: Ojalvo Laureen S. , Whittaker Charles A. , Condeelis John S. , Pollard Jeffrey W.
Published: December 2009

The tumor microenvironment modifies the malignancy of tumors. In solid tumors, this environment is populated by many macrophages that, in genetic studies that depleted these cells from mouse models of breast cancer, were shown to promote tumor progression to malignancy and increase metastatic potential. Mechanistic studies showed that these tumor-promoting effects of macrophages are through the stimulation of tumor cell migration, invasion, intravasation, and enhancement of angiogenesis. Using an in vivo invasion assay, it was demonstrated that invasive carcinoma cells are a unique subpopulation of tumor cells whose invasion and chemotaxis is dependent on the comigration of tumor-associated macrophages (TAMs) with obligate reciprocal signaling through an epidermal growth factor–CSF-1 paracrine loop. In this study, these invasion-promoting macrophages were isolated and subjected to analysis of their transcriptome in comparison with TAMs isolated indiscriminately to function using established macrophage markers. Unsupervised analysis of transcript patterns showed that the invasion-associated TAMs represent a unique subpopulation of TAMs that, by gene ontology criteria, have gene expression patterns related to tissue and organ development. Gene set enrichment analysis showed that these macrophages are also specifically enriched for molecules involved in Wnt-signaling. Previously, it was shown that macrophage-derived Wnt molecules promote vascular remodeling and that tumor cells are highly motile and intravasate around perivascular TAM clusters. Taken together, we conjecture that invasive TAMs link angiogenesis and tumor invasion and that Wnt-signaling plays a role in mediating their activity.
Continuing theological training at the University of Pretoria
Authors: Nel Malan
Published: December 2009

Around the world, most professional people are requested and expected to participate in continuing training, which is often referred to as �continuing professional development�. Many denominations expect their pastors and other clergy to participate in such training. The Dutch Reformed Church has an official policy, in terms of which it expects such continuing theological training and ministry development of its ordained pastors. The introduction to this article offers some insight into the rationale behind such an expectation. After describing the history and programme of one of the first centres that offers such training, the history and programme of the ecumenical Centre for Contextual Ministry, Faculty of Theology at the University of Pretoria is described.�
The story of the Department of Practical Theology
Authors: B�chner Elsje P. , M�ller Julian C.
Published: December 2009

This article tells the story of the development of the Department of Practical Theology of the Faculty of Theology at the University of Pretoria. The story goes back to the start of the Faculty in 1938, although the Department of Practical Theology was only established in 1966 when Professor H.D.A. du Toit applied himself fully to the subject and Professor C.W.H. Boshoff became the first full-time lecturer for Missiology. The article is written mainly from the perspective of the Dutch Reformed Church, but with the acknowledgement of the appointments of Professor Yolanda Dreyer from the Nederduitsch Reformed Church of Africa and Professor Maake Masango from the Uniting Presbyterian Church of Southern Africa.
Translational Components in Prokaryotes: Genetics and Regulation of Ribosomes
Authors: Wagner Rolf
Published: December 2009

The regulation of the biosynthesis of ribosomes, which constitute the catalytic organelles for the translation reaction, is central for the adaptation of bacteria to different growth conditions. The synthesis of the different ribosomal
ribonucleic acid
(rRNA) and ribosomal protein (RP) components is controlled and coordinated by a complex network of regulatory mechanisms to adjust the translational capacity to the required cell demands. Regulation of rRNA transcription plays a key role in ribosome formation. Quality control steps are operated during processing and assembly to ensure functionally competent particles and to avoid the accumulation of defective products and waste of energy and resources.

Key concepts:

Bacterial growth rates depend on the number of ribosomes.

Ribosome synthesis is adapted to environmental changes.

Biosynthesis of ribosomes involves quality control steps.

Ribosome synthesis is determined by the rate of rRNA transcription.

Synthesis of many ribosomal proteins is adjusted to the amount of free rRNA by a translational feedback mechanism.

Many ribosomal proteins have extra‐ribosomal functions in the cell.

A limited number of sequence heterogeneities in the redundantly encoded rRNA genes provide the potential for the formation of specialized ribosomes.

The stringent control is one of the major mechanisms for the adaptation of ribosomes in response to nutritional changes.
DNAInterstrand Crosslink Repair
Authors: Siede Wolfram
Published: December 2009

Crosslinking agents such as psoralens, nitrogen mustards or cisplatin are bifunctionally acting chemicals that generate a fraction of their adducts as covalent linkages between complementary deoxyribonucleic acid strands. Since many of these agents are of importance in genetic toxicology and cancer therapy, repair of interstrand crosslinks (ICL) has been studied extensively in prokaryotes and in lower and higher eukaryotes. The main repair pathway inE. coliinvolves the sequential action of nucleotide excision repair and recombinational repair. In eukaryotes, several repair pathways play important roles not only in repair including nucleotide excision repair, translesion synthesis, recombination, but also mismatch repair. Relative contributions of the various pathways depend on cell cycle position and agent used. Eukaryotic proteins that specifically enhance resistance to crosslinking agents have been identified (SNM1,FANCfamily of proteins).

Key concepts:

Chemicals with two or more correctly spaced reactive groups can covalently link opposing DNA strands.

Several repair or tolerance pathways such as nucleotide excision repair, recombination and translesion synthesis can work together to overcome such complex damage.

Cell cycle stage may determine the choice of repair pathway combinations.

A seemingly deleterious consequence of complex DNA damage (replication fork collapse at a crosslinked site) can be an important integrated part of damage tolerance and repair.

A heritable human syndrome with multiple diverse phenotypes (Fanconi anaemia) can be associated with a specific DNA repair deficiency (crosslink repair).
DNAReplication: Mammalian
Authors: Snider Brandy M , Phipps Elizabeth A , Smith Shanna J , Herbert Brittney‐Shea , Hickey Robert J , Malkas Linda H
Published: December 2009

It is well known thatdeoxyribonucleic acid(DNA) replication occurs at the replication fork, whereby the parent strand of DNA unwinds and two daughter strands are formed, which are subsequently synthesized in a leading and lagging strand manner. Furthermore, many proteins and enzymes are involved in initiation of DNA replication, and the synthesis of DNA, as well as the structural component of the nuclear matrix, which allows for attachment of replication proteins. It is also known that replication of mammalian DNA is a very complicated and highly regulated process, requiring strict regulation, along with many different proteins and enzymes. Although there is a wealth of information regarding basic DNA synthesis, there is still much more information to learn regarding the machinery involved in initiation of DNA replication, DNA synthesis and, ultimately, DNA replication.

Key Concepts:

The proteins thus far identified in mammalian cell DNA replication include the MCM helicase complex, DNA pol α‐primase, PCNA, RFC, DNA pol δ, FEN1, RPA, DNA ligase I, topoisomerase I and II and RNAse H.

The manner and timing by which mammalian DNA replication occurs is highly regulated and occurs mostly in the G1 phase of the cell cycle.

Telomeres maintain the integrity of the genome by protecting the ends of the chromosomes from degradation and preventing end‐to‐end fusions of chromosomes.

Mammalian cells have many levels of tight regulation for the replication of telomeres to maintain genome stability and cell survival.

The nuclear matrix plays a vital role in initiation, chromosome replication and regulation.

Proteins necessary for DNA replication come together to form ‘replication factories’ within the nucleus.
EukaryoticDNAPolymerases
Authors: Cotterill Sue , Kearsey Stephen
Published: December 2009

Deoxyribonucleic acid(DNA) is replicated and repaired by a family of enzymes calledDNA polymerases. Eukaryotic cells have a diversity of these enzymes that, while sharing a common biochemical activity, are specialized for particular roles. Three polymerases are required for the replication of the nuclear genome, withpol αinvolved in priming and initial synthesis andpols δand ɛ involved in bulk DNA replication. These polymerases are dependent on a large number of other proteins which unwind the DNA and perform other functions essential for efficient DNA synthesis. Polymerases are also involved in DNA repair and many repair‐specific enzymes have been identified. Some repair polymerases can refill a gap generated by removal of damaged DNA, or copy a damaged template, allowing DNA synthesis to proceed across a damaged template. Repair polymerases can also have tissue‐specific functions in lymphoid cells, where they contribute to somatic hypermutation of immunoglobulin genes.

Key concepts:

Catalytic function of DNA polymerases.

Concepts of ‘proofreading’ and ‘processivity’.

Roles of replicative DNA polymerases needed for chromosome replication and organization at the replication fork.

Function of accessory proteins needed for polymerase function in chromosome replication.

Different modes of action of specialized polymerases involved in DNA repair.

Catalytic mechanism of polymerases.

Assays used to detect polymerase functionin vitro.
Cleavage and Gastrulation in Avian Embryos
Authors: Stern Claudio D
Published: December 2009

Avian embryos differ from those of other vertebrates in several respects – among them, they have a large mass of yolk, the cells initially divide from the centre of a disk with cleavage planes that open into the yolk, and the embryo has great ability to regulate until very late stages of development. After approximately 20 000 cells have been generated, gastrulation begins. This process generates the primitive streak which defines bilateral symmetry, and through which cells from the superficial layer (epiblast) ingress to generate two new layers of embryonic cells (mesoderm and endoderm). This period of development starts to define the three axes of the future embryo (head–tail, dorsoventral and left–right), and it is at this time that many cell fates start to be fixed.

Key concepts:

Avian embryos cleave meroblastically: the cleavage planes are initially open to the yolk and generate a disc with smaller cells in the middle and larger, yolky cells outside.

Gastrulation is the process by which the embryo generates three germ layers: ectoderm, mesoderm and endoderm. It involves massive cell movements as well as specification of cell fates through differential gene expression.

As cells move around the embryo, they change their patterns of gene expression according to their current position. Therefore during early development, gene expression marks cell states rather than cell fates.

The mechanisms of early development are largely conserved between different vertebrate classes but there are also some differences.

Amniote (reptiles, birds and mammals) embryos have a unique capacity toregulate, meaning that when an embryo is cut into half or smaller pieces each piece can generate a whole embryo. Embryos retain this ability right up to the start of gastrulation and this is probably one of the processes responsible for generating identical twins.

Neural induction subdivides the ectoderm into neural (future nervous system) and non‐neural (future skin and sensory organs in the head) territories. Neural‐inducing signals in avian embryos arise from the ‘organizer’, Hensen's node.

The final head–tail axis of the embryo does not correspond to the axis of the primitive streak (which correlates better with axial and lateral fates). Mesodermal cells that will occupy more cranial positions emerge earlier from the streak than those that will end up in the trunk and tail. After gastrulation, the embryo has mechanisms that convert ‘time’ information into ‘positional identity’.
Schistosomiasis and Other Trematode Infections
Authors: Vennervald Birgitte J , Johansen Maria V
Published: December 2009

Trematodes, including schistosomes, are parasitic flatworms (flukes) infecting both humans and animals. Various freshwater snails are intermediate hosts. Human water contact is a key element in schistosomiasis transmission. Infection takes place when cercariae penetrate intact skin exposed to infested water. For all other trematodes, humans become infected by ingestion of metacercariae in crustacea, fish or plants, the second intermediate host, hence the term foodborne trematodes. Most of the trematodes are zoonotic and infect a wide range of domestic and wild animals as well as man. Based on the location of the adult worms, flukes can be grouped as blood (schistosomes), liver, lung or intestinal flukes. Infections can lead to serious diseases and are of economic importance owing to the high number of infections worldwide. Control strategies should include treatment of affected populations to reduce the burden of disease, health education and effective control of animal reservoir hosts.

Key concepts:

Schistosmiasis affects the general health and well being of millions of people.

Integration of schistosomiasis control measures into existing public health services are vital for long‐term success.

Agricultural development projects and irrigation can increase the risk of schistosomiasis transmission.

Domestic animals play an important role in the transmission of liver and intestinal trematodes.

Control of foodborne zoonotic trematodes requires effective control of the reservoir hosts.

Health education is an essential element in control of foodborne zoonotic trematodes.
Vesicle Transport Assay
Authors: Wöllert Torsten , Langford George M
Published: December 2009

Eukaryotic cells contain actin filaments and microtubules that function as cytoplasmic filaments for vesicle transport. The study of vesicle transport on these filaments

in vitro

advanced rapidly when vesicle transport assays were developed. High‐resolution multimode video‐enhanced microscopy is the method used for such assays to detect vesicles as small as 100 nm in diameter and microtubules 25 nm in diameter. Vesicle transport is recorded in real time on high‐capacity digital storage media. Motion analysis is performed to quantify different parameters of vesicle movement along cytoplasmic filaments including velocity, distances travelled and straightness of path.

In vitro

vesicle transport assays proved highly successful and enabled the identification of important factors that are essential for regulation of intracellular transport.

Key concepts

The cytoskeleton contains actin filaments and microtubules, both of which serve as tracks for vesicle transport.

Vesicle transport is the directed movement of membrane vesicles on filaments of the cytoskeleton.

Microtubules function as intracellular tracks for transport of vesicles by two classes of motor proteins, kinesins and dyneins.

Actin filaments serve as tracks for vesicle transport by myosin motors.

Motor proteins are mechanochemical nanomachines that use the energy of adenosine triphosphate (ATP) for muscle contraction, cell motility and transport of cargo along the cytoskeleton.

The superfamily of myosin motor proteins found in eukaryotic cells is known to contain over 20 different classes.

The kinesin superfamily is subdivided into 14 classes and the family of dyneins is grouped into axonemal and cytoplasmic dyneins.

Motor protein defects are associated with diseases including Griscelli syndrome, Usher syndrome, myopathies and deafness.

Differential interference microscopy, also known as Nomarski microscopy, uses polarized light to produce contrast in unstained biological specimens.

Cell‐free extracts are important tools for cell biologists and have a variety of applications including cell cycle studies, intracellular transport mechanisms, signal transduction events and maintenance of cell architecture.
Lederberg, Joshua
Authors: Morange Michel
Published: December 2009

Joshua Lederberg (1925–2008), American microbiologist, winner of the Nobel Prize in Physiology or Medicine in 1958, played a major role in the creation and development of bacterial genetics.
Protein Quaternary Structure: Symmetry Patterns
Authors: Stenkamp Ronald E
Published: December 2009

Protein molecules can assemble into larger, multisubunit oligomers that possess unique quaternary structures and biological properties. The properties of the oligomeric protein can be quite different from those of the individual subunits. The noncovalent protein–protein interactions giving rise to oligomers often result in symmetric complexes containing identical monomers in identical environments. The symmetry properties of these complexes are described, in particular with respect to the types of subunit–subunit interactions giving rise to the oligomers. Because the symmetry of the macromolecular assemblies is based on the symmetric interactions between the subunits, understanding the symmetry provides further insight into the functioning of the oligomers. Specific examples discussed include:
aspartate carbamoyltransferase
(where symmetry concepts are tied to allosteric control), multienzyme complexes (built along the lines of the Platonic polyhedra) and virus capsids (large macromolecular complexes formed making use of symmetry and quasi‐symmetry).
Protein Export from Endoplasmic Reticulum to the Cytosol:
In Vitro
Methods
Authors: Matsumura Yoshihiro , Skach William R
Published: December 2009

Newly synthesized proteins that fail to achieve their proper conformation in the endoplasmic reticulum (ER) are recognized by quality control machinery and degraded by the
ubiquitin
–proteasome pathway. This process is termed ER‐associated degradation (ERAD) and is implicated in a large number of inherited and acquired human diseases characterized by aberrant protein folding. Because
ubiquitin
, ubiquitination machinery and proteasomes are restricted to the cytosol and nucleus, ERAD substrates must be exported from the ER lumen and/or extracted from the ER membrane before or during degradation.

In vitro

systems that reconstitute ERAD allow detailed mechanisms of ERAD to be studied independently of ongoing protein synthesis and compensatory feedback mechanisms present in cells. Evidence indicates that retrotranslocation (or dislocation) is tightly regulated via parallel pathways that are adapted to various substrates, molecular lesions and cellular needs and stresses.

Key concepts:

The endoplasmic reticulum (ER) utilizes a stringent quality control machinery for secretory and transmembrane proteins.

Misfolded proteins are recognized by the ER quality control components and degraded by the ubiquitin–proteasome pathway.

ER‐associated degradation (ERAD) is a multistep process.

Molecular chaperones and lectin‐like proteins play key roles in recognizing misfolded proteins.

Ubiquitin ligases modify ERAD substrates by covalent attachment of ubiquitin.

Two ATPase associated with various cellular activities, p97 and the 19S proteasome subunit, facilitate retrotranslocation of ERAD substrates and delivery to the 20S proteasome.

In vitro
systems reconstitute complex ERAD processes.

Mechanistic details of ERAD are readily amenable to
in vitro
manipulation and analysis.
Genetic Discrimination
Authors: Hoy Michael
Published: December 2009

Knowledge about the relationship between genes and health, as well as genes and behaviour, is expanding rapidly. Genetic and other predictive tests are becoming less expensive and so knowledge about individuals’ genetic backgrounds is likely to become commonplace. Although such information holds the promise of eventually being very useful in the context of improving health outcomes for individuals, it has long been recognized that this promise may be accompanied by the threat of increased genetic discrimination, most notably in insurance markets. Genetic discrimination may also arise in personal and social spheres of life. Each aspect creates different types of problems. Thus, different types of remedies or responses are in order. This article reviews the ethical and economic aspects of this new information from a variety of normative perspectives and considers the appropriateness of the sorts of regulations recently put in place to limit its adverse social implications.

Key Concepts:

Genetic information can lead to improved decision‐making and treatments for people's health but may also lead to discrimination in insurance markets and beyond.

Many academics and members of the public believe that charging different prices to different people based on genetic test results is unfairly discriminatory.

However, many insurance market analysts believe individuals at higher risk of death or higher need of health care should pay more for insurance regardless of what causes their higher risk status.

Economic arguments can be made that not charging risk‐relevant prices for insurance will discourage ‘better’ risks from participating in the market for insurance and this will lead to higher overall prices for insurance.

The conflicting views noted above have led to unresolved issues regarding the appropriate regulation of genetic information in the area of insurance pricing.

Genetic discrimination may also increase in areas of personal or social relations where market regulations are not effective remedies.

Education about genetic differences may be an appropriate alternative mechanism for dealing with genetic discrimination in the personal and social spheres.
Carrier Screening of Adolescents in Montreal
Authors: Scriver Charles R , Mitchell John J
Published: December 2009

A carrier screening programme for common genetic autosomal recessive diseases is described. The programme focuses on testing of adolescents in their last year of high school. The main purpose of this programme is to educate the population in high‐risk communities, to offer carrier screening of autosomal recessive diseases (Tay–Sachs and β‐thalassaemia diseases) and to provide counselling about reproductive options. The specific age range targeted allows for education and screening to occur before reproduction. This is a unique programme that was developed in conjunction with the community. Although there remains controversy regarding the screening of adolescents in other areas of the world, this programme is well accepted and has continued to flourish in our specific community for over 30 years.

Key concepts:

Genetic carrier screening programmes need education, effective counselling and support from the community to be successful.

Genetic screening of adolescents in our community is well accepted by the targeted populations.

Adolescents who obtain information through carrier testing understand their risks and later utilize this information when they consider their reproductive options.
Geneticization: Debates and Controversies
Authors: Hedgecoe Adam M
Published: December 2009

The term ‘geneticization’ describes a process where by there is an increasing tendency to use genetic explanations to describe differences between individuals and groups. Supporters of this position argue that the way in which genetics is described in the media and dealt with the medical profession risks increases inequality and discrimination on the basis of a belief in genetic determinism among policy‐makers and the public. While this ‘geneticization thesis’ has proved popular among social scientists and bioethicists, empirical research into the way in which people interpret media messages and how clinicians adopt genetic tests casts doubt on the simplistic, homogenous model underpinning the geneticization thesis, raising challenges to the way in which this process is researched.

Key concepts:

The concept of geneticization has been widely used to critique the social impact of genetic testing.

Empirical research undermines claims about the ubiquity and nature of geneticization.

Differing attitudes towards the use of empirical data are underlined by different approaches to the study of geneticization.
Using Magic as a Vehicle to Elucidate Attention
Authors: Raz Amir , Zigman Philip
Published: December 2009

Attention, the awareness and selection of elements in our physical or mental environments, is a central concept in neuroscience. Michael I Posner and colleagues have proposed a three‐network model of attention. ‘Alerting’ involves increased readiness for immanent stimuli, ‘orienting’ refers to selecting amid various stimuli; whereas ‘executive attention’ links attention to decision making, planning and other higher cognitive functions. Though ignorant of the neural mechanisms underlying human attention, magicians are skilled at exploiting human attention to achieve their effects. Recent interest in the neuroscience of magic has built bridges between the practice of magic and the study of attention. However, beyond illustrating how our attention systems can be tricked, magic can be employed in research to explore otherwise unachievable conditions. Such methods provide a unique opportunity to study atypical attention, providing important insights into the function of human attention and other key cognitive domains.

Key Concepts

Attention refers to the preparedness for and selection of particular aspects of our environment or of ideas in our mind.

Attention can be overt, that is tied to fixation, or covert, like when we attend to something we are not looking at.

There are three attentional networks – alerting, orienting and executive – each with distinct neural correlates.

Magicians exploit change blindness, inattentional blindness and choice blindness to achieve many effects.

Neuroscientists have recruited magic as a tool for uncovering the nature of many cognitive processes, most notably attention.

Pushing healthy individuals towards atypical attention – via hypnosis, deception and other methods – introduces unique experimental opportunities.

Aside from helping direct investigations of attention, magic tricks can be effectively incorporated into certain experimental designs.
Neural Control of Birdsong
Authors: Schmidt Marc F
Published: December 2009

Birdsong is a learned behaviour that displays a remarkable level of acoustic and temporal complexity. It is controlled by a well‐defined neural circuit, known as the song system, which receives highly processed auditory information from specialized higher‐order auditory areas. Over the past decade, sophisticated new song analysis tools coupled with the ability to record from identified neurons in adult and juvenile singing birds have revealed many fundamental insights into the neural mechanisms that underlie vocal production, storage of auditory memories and sensorimotor learning. Some of these include an understanding of how sleep drives song acquisition and how circuits homologous to the mammalian basal ganglia generate the motor variability that enables sensorimotor learning. The tractable nature of this system coupled with its shared similarities with human speech make birdsong a unique model for understanding the neural bases of vocal production and learning.

Key Concepts:

Sophisticated new methodologies in song quantification have made it possible to provide quantitative descriptions of the entire vocal imitation process in juvenile birds.

Storage of the song template likely occurs in specialized higher‐order auditory forebrain areas rather than in the song system proper.

The song system is a specialized neural circuit that is necessary for song production and sensorimotor learning.

Neurons that form part of the descending motor pathway produce short (approximately 5 ms) bursts of action potentials that are precisely time locked to specific time segment of the song.

The portion of the song system necessary for song production is organized as a recurrent pathway with structures in the thalamus and respiratory brainstem projecting back up to the forebrain.

Neural variability from the basal ganglia circuit onto RA is thought to contribute to the observed motor variability in juvenile birds and likely enables the motor exploration strategy that is critical for song learning in juveniles.

Sleep plays a critical role in vocal learning by allowing offline processing of sensory and motor information.
HPVVaccine
Authors: Inglis Stephen
Published: December 2009

The discovery in the early 1970s that cervical cancer was caused by infection withhuman papillomavirus(HPV) stimulated a highly successful vaccine development programme based on the use of recombinantdeoxyribonucleic acid(DNA) technology to produce virus proteins in a form that can stimulate powerful and long lasting antibody responses. The vaccines have been designed as combinations to target the HPV virus types that are responsible for most human disease. Clinical trials have shown that it is possible to prevent both genital warts and the early stages of cervical cancer through vaccination and this has led to licensure and use of HPV vaccines in many countries throughout the world. Progression from initial virus infection to development of invasive cancer is often very slow, however, and so it will be many years before the impact of the vaccine on the overall disease burden is fully understood.

Key Concepts

Vaccine development

Virus‐like particles

Recombinant protein expression

Immunization against an epithelial infection

Prevention of papillomavirus‐induced disease
Caspases and Cell Death
Authors: Hernandez Lorraine D , Houde Caroline , Hoek Maarten , Butts Brent , Nicholson Donald W , Mehmet Huseyin
Published: December 2009

Caspases (
Cysteinyl ASPartate‐specific proteASE
) are
cysteine proteases
involved in cell death. The caspase family is comprised of 12 proteins in humans, seven in

Drosophila melanogaster

and a single protein in

Caenorhabditis elegans

. All caspases consist of three structural domains: a prodomain, a large subunit and a small subunit. The catalytically active enzymes are formed either by proteolytic cleavage of the subunits, or through a proximity‐induced activation process involving the prodomain. The cleavage site of caspase substrates is indicated by the positions P4, P3, P2 and P1. P1 is always aspartate, while amino acids in the other positions are highly variable. By cleaving over 1000 substrates in the cell, caspase activation results in the complete dismantling and ultimate death of the cell. Caspase activity can be regulated at a pharmacological level and has become a therapeutic target for the treatment of many diseases.

Key Concepts

Caspases (Cysteinyl ASPartate‐specific proteASE) are the key enzymes regulating and executing apoptosis. They include several proteases acting either at the upstream regulatory events, or in the effector phase of cell death.

Three groups of caspases have been classified and are involved either in inflammation or cell death.

Caspases cleave over 1000 proteins within the cell causing the morphological events of cell death.

Both natural (cellular, bacterial and viral) and pharmacological inhibitors of caspases have been identified offering novel therapeutic approaches to inflammatory and apoptotic pathways.
Engulfment of Apoptotic Cells and Its Physiological Roles
Authors: Hanayama Rikinari , Miyanishi Masanori , Yamaguchi Hiroshi , Suzuki Jun , Nagata Shigekazu
Published: December 2009

During development of animals, many cells undergo programmed cell death via apoptosis. In adult, senescent cells also undergo apoptosis and are replaced by newly generated cells. Apoptotic dying cells display an “eat‐me” signal(s) on their surface, and are recognized by macrophages and immature dendritic cells for engulfment. Phosphatidylserine, which is exposed on the cell surface in a caspase‐dependent manner, is the most likely candidate for the “eat‐me” signal. Phagocytes recognize phosphatidylserine through specific receptors or via bridging molecules that link them with the apoptotic cells. Phagocytes engulf the apoptotic cells in a Rac1‐dependent manner probably through specific portals. When apoptotic cells are not engulfed efficiently, they undergo secondary necrosis and release their cellular contents, which leads to local inflammation, production of autoantibodies, and SLE (systemic lupus erythematosus)‐type autoimmune diseases.

Key concepts:

Apoptotic cells are swiftly removed by phagocytes.

Phosphatidylserine on apoptotic cells plays an important role as an “eat‐me” signal.

Phosphatidylserine is recognized by both soluble molecules and surface receptors.

The engulfment of apoptotic cells leads to an anti‐inflammatory response by the immune system.

The inefficient removal of apoptotic cells leads to autoimmune diseases.
Autophagy
Authors: Isabel Colombo María , Simon Hans‐Uwe
Published: December 2009

Autophagy is a conserved proteolytic mechanism that degrades cytoplasmic material including cell organelles. Although the importance of autophagy for cell homeostasis and survival has long been appreciated, our understanding of how autophagy is regulated at a molecular level just recently evolved. The importance of autophagy for the quality control of proteins is underscored by the fact that many neurodegenerative and myodegenerative diseases are characterized by an increased but still insufficient autophagic activity. Similarly, if the cellular stress, leading to
deoxyribonucleic acid
(DNA) damage, mitochondrial damage and/or damaged proteins, does not result in sufficient autophagic repair mechanisms, cells seem to be prone to transform into tumour cells. Therefore, autophagy has multiple roles to play in the causation and prevention of human diseases.

Key concepts:

Autophagy is a cellular stress response induced to ensure cell survival, but excess autophagy may lead to cell death.

The kinases TOR (target of rapamycin) and PI3K (phosphatidyl inositol 3 kinase) are two essential components of the autophagy molecular machinery.

The family of genes or proteins called Atg (for
a
u
t
opha
g
y related) comprises the core of the molecular machinery of autophagy.

Upon autophagy induction the enwrapped cytoplasmic components and organelles are recycled by degradation in the autolysosome.

Autophagy can be dysregulated and may contribute to many pathologic processes.
Microtubule Organization inDictyostelium
Authors: Gräf Ralph
Published: December 2009

Dictyosteliumamoebae contain a radial array of microtubules emanating from a single microtubule‐organizing centre called centrosome that is bound to the cytosolic face of the nucleus. Their centrosome contains no centrioles but consists of a layered core surrounded by a corona harbouring microtubule nucleation centres. It duplicates in prophase of a closed mitosis and organizes a central spindle that drives centrosome separation and chromosome segregation. ThoughDictyosteliummicrotubules are quite dynamic during mitosis, their length appears to be very stable during interphase. Microtubules are associated with a couple of conserved proteins (microtubule‐associated protein,MAPs), which are involved in centrosome biogenesis and the crosstalk of microtubule tips with the actin cell cortex. The latter becomes evident in cytokinesis, when centrosomes with their attached microtubules participate in the positioning of cleavage furrows.

Key concepts:

Dictyosteliumamoebae contain a nucleus‐associated centrosome that serves as the only microtubule‐organizing centre.

TheDictyosteliumcentrosome contains no centrioles, but consists of a three‐layered core structure surrounded by a microtubule‐nucleating corona.

If compared to the three major plaques of the yeast spindle pole body, the entire core structure of theDictyosteliumcentrosome appears equivalent to the central plaque, whereas the corona plays a similar role as the inner and outer plaques.

Dictyosteliumcentrosomes duplicate at the onset of mitosis.

Dictyosteliumamoebae show a closed‐type of mitosis with a persisting nuclear envelope.

Dictyosteliummicrotubules are quite dynamic during mitosis but show only little growth and shrinkage during interphase.

Microtubule plus ends influence actin dynamics at the cell cortex.

Dictyosteliumamoebae are a useful model to study the role of the centrosome and microtubules in cell dynamics and disease.
Sex Allocation in Hermaphrodites
Authors: Kazancioğlu Erem
Published: December 2009

Organisms in which individuals can reproduce both as males and females are called hermaphrodites. Sex allocation in hermaphrodites involves the division of reproductive resources between the male and female function, and presents an interesting contrast to species that alter sex allocation by adjusting offspring sex ratio. Theoretical and empirical research in the past four decades have largely attempted to explain when hermaphroditism is favoured, and how sex allocation in hermaphrodites is controlled. Furthermore, the application of endocrinological methods has elucidated some of the molecular processes that underlie hermaphroditic sex allocation, especially in sequential hermaphrodites. Despite significant advances in our understanding of hermaphrodites, some fundamental predictions such as the adaptiveness of changes in sex allocation have not been tested, and some basic questions on hermaphroditism have not been answered.

Key concepts:

In hermaphroditic organisms, individuals are capable of reproducing as both males and females.

Simultaneous hermaphrodites have male and female reproductive organs that are functional at the same time, and are both involved in a mating event.

Simultaneous hermaphroditism is favoured, when an increase in male and female reproduction yields diminishing fitness returns.

Factors such as limited mobility, low density or self‐fertilization can result in diminishing fitness returns for males, and favour simultaneous hermaphroditism. However, local resource competition and physiological limitations could saturate fitness through female function.

Simultaneous hermaphrodites can adjust sex allocation according to the social environment (e.g. mating group size), and the amount of resources available for reproduction (e.g. body size).

Sequential hermaphrodites, or sex changers, reproduce as one sex for a part of their lifetime, and then switch to reproducing as the opposite sex.

Sequential hermaphroditism is favoured in mating systems where individuals have consistently greater reproductive success as one sex earlier and as the other sex later in life.

Sequential hermaphrodites can adjust the optimal timing of sex change according to relative size or social status in a mating group.

There are also mixed hermaphroditic systems where individuals can repeatedly switch between sexes, or simultaneous hermaphrodites coexist with pure sexes.

Sex change in fishes involves complex behavioural and morphological changes that are regulated by an endocrine gland system conserved across all vertebrates.
Cornification Diseases (Skin Cell Death)
Authors: Candi E , McLean WH , Didona B , Terrinoni A , Melino G
Published: December 2009

The outermost layer of the skin is formed by the cornified envelope (CE), which is the end product of the process of keratinization. This forms a barrier that is essential to protect the internal homeostasis of the organism from the external environment. The process of keratinization proceeds according to a complex and elaborately controlled differentiation program with the coordinated expression of genes encoding specialized components, enzymes, and regulatory molecules. The CE is a specialized structure that replaces the plasma membrane of differentiating keratinocytes and consists of proteins crosslinked by covalent bonds and lipids to form a scaffold. Understanding of the pathologies associated with defects in CE components will help clarify the molecular mechanisms and the physiological endpoints of keratinization. Here, we describe some diseases of keratinization, and give a brief overview on animal models (transgenic and knockout) with defects in the CE formation.

Key concepts:

The outermost layer of the skin is formed by the cornified envelope (CE).

The CE is a specialized structure that replaces the plasma membrane of differentiating keratinocytes. It consists of proteins crosslinked by covalent bonds and lipids to form a scaffold.

The CE is essential to provide the barrier function of the epidermis.

The transglutaminase enzymes play a major role in the formation of the CE by catalyzing the formation of crosslinks between specific proteins.

Mutations in keratin genes cause a wide variety of epidermal and other epithelial disorders.

CE lipids contribute in a significant way to the establishment of barrier function of the epidermis by impermeabilizing the cornified cell and participating in the organization of the intercellular lipid lamellae.

Defects in proteases result in barrier function abnormalities or skin diseases.

The transcription factor p63 is crucial in epidermis formation, maintaining the progenitor‐cell populations that are necessary to sustain epithelial development and morphogenesis.
Philosophy of Biological Classification
Authors: Richards Richard A
Published: December 2009

The Linnaean hierarchy has long served as the basis for biological classification, but there have been other systems, and there are new systems in development. There are three main philosophical questions about biological classification. The first is theoretical: what is represented? The second is about the formal structure: what are the categories and how are they related? The third is operational: what principles are used to generate the classification? Historically there have been theoretical approaches based on pragmatic interests, natural kinds and essences, Divine ideas, evolutionary history, phenetics and the phylogenetic branching of the evolutionary tree. Currently there is some consensus that classification should represent evolutionary history in terms of phylogeny, but there are competing proposals both for the formal structure of classification, and operational methods to reconstruct phylogeny.

Key Concepts:

The theoretical basis of a classification is what it represents. The formal structure of a classification involves the nature and organization of the categories. The operational procedures of a classification are the rules for generating the classification.