bluuebunny/crossref_metadata_2025 huggingface dataset:
Roman and byzantine layers at Umm el-Tlel : ceramics and other finds
Authors: Majcherek Grzegorz , Taha Ahmed
Published: September 2009

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Une lame en croissant de lune de Tell Chagar Bazar
Authors: Quenet Philippe
Published: September 2009

The aim of this article is to publish a crescentic axehead exhibited in the Aleppo National Museum that remained unnoticed up to now. It was probably found or acquired by Max Mallowan while he was digging at Tell Chagar Bazar. On this occasion the author reconsiders the chrono-typology of this well-known type of EBA axeheads which first appeared in Northern Syria during the EB II Period and spread to the adjacent regions later on.
Il "Migdol" di Ramesse III a Medinet Habu fra originalità ed influssi asiatici
Authors: Cavillier Giacomo
Published: September 2009

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>jJA\ «A* cJU lil j&j itllii Jl O
Traslatio Studii: Contribución de los exilios al establecimiento de la Sociología y la Historia del arte en Gran Bretaña, 1933-1960
Authors: Burke Peter
Published: September 2009

Este ensayo es una pequeña parte de una historia más amplia, la gran diáspora de intelectuales del Centro y Este de Europa en los años treinta, hacia Gran Bretaña, EEUU, Francia, América latina, etc. El exilio puede ser observado como una escuela, una forma de educación de adultos, no sólo para los propios exiliados sino también para algunos de los nativos que llegaron a conocerlos. De forma más precisa, consideramos las consecuencias intelectuales de la diáspora en una cultura insular, con mención especial a dos disciplinas relativamente nuevas y pequeñas. La sociología y la historia del arte estaban en los años treinta mucho más desarrolladas en Europa central de lo que lo estaban en las islas Británicas, permitiendo a algunos destacados inmigrantes realizar una desproporcionada contribución si tenemos en cuenta su número. ¿Cómo se establece una nueva disciplina? Lo que se ofrece en este ensayo es una suerte de historia social o de sociología histórica tanto de la Historia del Arte como de la misma Sociología, sugiriendo que la contribución de los exiliados puede ser vista no como una simple transferencia de conocimiento, sino más bien como un encuentro cultural que supuso cambios en ambas partes, en una especie de hibridización cultural.
Las canciones de Hanns Eisler: lucha, exilio y autonomía del arte
Authors: Arribas Sonia
Published: September 2009

En este artículo se describen y analizan las técnicas y letras empleadas por Hanns Eisler en algunas de las canciones que compuso durante la República de Weimar y posteriormente durante su exilio en los Estados Unidos. Si las primeras composiciones fueron creadas con el objetivo de contribuir a la lucha política de los trabajadores y por tanto reflejan el rechazo de Eisler a la autonomía del arte, o al arte como un fin en sí mismo, las últimas pueden ser interpretadas como síntomas de lo que aquí denomino la autonomía “forzada” del arte.
“Ser devorado no duele”. Th. W. Adorno y la experiencia americana
Authors: Maiso Jordi
Published: September 2009

El presente texto pretende desentrañar la experiencia americana de Theodor W. Adorno como un proceso de aprendizaje decisivo en la formulación de su Teoría Crítica. A partir de su exilio en Nueva York y de su participación en el Princeton Radio Research Project, Adorno no sólo adquiere un conocimiento directo del funcionamiento de la industria de la cultura y formula una decisiva aproximación teórica a la música radiofónica, sino que también toma conciencia de un cambio en la función social de la teoría que le permite llevar a cabo una aguda autorreflexión sobre la situación del intelectual emigrado.
Elipses y parábolas de la experiencia. La obra de Franz Kafka según Walter Benjamin
Authors: García Roldán Daniel
Published: September 2009

Walter Benjamin define la obra de Franz Kafka como una elipse cuyos focos son la experiencia de la tradición mística y la experiencia de la modernidad. En el siguiente ensayo se dilucida esta interpretación de Benjamin y se exploran las correspondencias históricas, sociales e intelectuales existentes entre ambos autores.
Eugenio Ímaz y la Guerra contra la Guerra
Authors: Sánchez Cuervo Antolín
Published: September 2009

Eugenio Ímaz fue uno de los filósofos del exilio español del 39 que mayor atención dedicó a la crítica del fascismo y de sus implicaciones belicistas. En el horizonte de la guerra española, apeló en este sentido al compromiso del intelectual ante la barbarie como piedra de toque de toda experiencia filosófica radical, esbozó una genealogía moderna del nazi-fascismo y señaló las suicidas contradicciones ideológicas de las democracias liberales europeas.
Las revistas técnicas como base documental para la recuperación de un patrimonio olvidado: el caso de las salas de cine españolas
Authors: Castillo A. , Azorín V.
Published: September 2009

Este trabajo consiste en una valoración de las revistas técnicas españolas como fuentes de información para la recuperación del Patrimonio Cultural. Para mostrarla, se han seleccionado como caso de estudio las salas de cine, que como construcciones singulares se desarrollaron especialmente entre los años 20 y 60 del siglo recién terminado. El método de trabajo para valorar estas obras ha consistido en realizar una revisión bibliográfica y documental de las revistas- así como de otros trabajos vinculados con la Historia de estos inmuebles-, para finalmente seleccionar tres de ellas; Cortijos y Rascacielos, Arquitectura/Revista Nacional de Arquitectura e Informes de la Construcción, puesto que a lo largo de las décadas citadas son las que dedican más páginas a este tipo de arquitectura. A través de un estudio comparativo de estas publicaciones periódicas, hemos podido comprobar la importancia que su uso puede tener para el tratamiento del Patrimonio Cultural, observando cuáles son las características y peculiaridades que más se resaltan sobre las obras realizadas desde el punto de vista constructivo, inclusive, sobre otros aspectos relacionados con las características que definen y diferencian entre ellas a cada una de estas publicaciones periódicas.
Simulación por el método de Monte Carlo para generar criterios de aceptación en el control de calidad de productos de construcción
Authors: Garrido A. , Conesa E. M.
Published: September 2009

En el Sector de la Construcción es habitual realizar operaciones de control de la calidad de aquellos productos o procesos prescritos por los reglamentos. Raramente, por tanto, se llevan a cabo operaciones de recepción de productos por pactos espontáneos entre las partes. Esto último no ocurre, fundamentalmente, porque los que toman decisiones empresariales o técnicas a este respecto no conocen las bases estadísticas del control de conformidad y, por tanto, no conocen cómo operar en consecuencia. Este artículo propone un método para que los agentes involucradas en la recepción de productos, una vez fijado el riesgo asociado al control estadístico que les corresponde, definan el criterio de aceptación más adecuado.
Interpreting the parables of the Galilean Jesus: A social-scientific approach
Authors: Van Eck Ernest
Published: September 2009

This article proposes a methodology for interpreting the parables of Jesus. The methodology put forward has as starting point two convictions. Firstly, the difference between the context of Jesus’ parables as told by Jesus the Galilean in 30 CE and the literary context of the parables in the gospels has to be taken seriously. Secondly, an effort has to be made to at least try to avoid the fallacies of ethnocentrism and anachronism when interpreting the parables. In an effort to achieve this goal it is argued that social-scientific criticism presents itself as the obvious line of approach. Operating from these two convictions, the method being proposed is explained by using 12 statements (or theses) which are discussed as concisely and comprehensively as possible. It is inter alia argued that the central theme of Jesus’ parables was the non-apocalyptic kingdom of God, that the parables are atypical stories (comparisons), and that the parables depict Jesus as a social prophet.
Scandium, Yttrium and the Lanthanides: Applications
Authors: Cotton Simon A.
Published: September 2009

New applications are increasingly found for scandium, yttrium, and the lanthanides and their compounds. Among reagents in synthetic organic chemistry, LaNi
5
is a versatile hydrogenation catalyst. SmI
2
is an important one‐electron reducing agent, and lanthanide triflates, Ln(CF
3
OSO
3
)
3
(Ln = Sc, Y, or lanthanide), are recyclable Lewis acid catalysts, which operate in aqueous conditions. Organocerium compounds are valuable, mild alkylating agents, while using cerium chloride in combination with NaBH
4
and LiAlH
4
permits a range of reductions to be carried out. (NH
4
)
2
[Ce(NO
3
)
6
] is an established oxidant for which new applications are being found. The alloys SmCo
5
and Sm
2
Co
17
have been used to produce magnetic materials that are very powerful for their size, though partly superseded by cheaper Nd
2
Fe
14
B material, while strongly paramagnetic salts of Dy
3+
or Gd
3+
permit attainment of extremely low temperatures through adiabatic demagnetization. The mixed metal oxide YBa
2
Cu
3
O

7−
x

was the first material to superconduct above 77 K, revolutionizing understanding; new materials are being developed, most recently fluoride‐doped oxypnictides LaFeAsO. In addition to gadolinium complexes as MRI contrast agents, other lanthanide compounds find medicinal application, including cerium compounds in wound and burn treatment. In terms of quantity, the most important application of lanthanide compounds is lanthanide‐exchanged zeolites as catalysts in the petrochemical industry, notably in cracking, but cerium oxide is an important component of catalytic converters in automobile exhausts. The ability of LaNi
5
to absorb hydrogen reversibly has been vital to nickel–metal hydride (NiMH) batteries, while yttrium aluminum garnet (Y
3
Al
5
O
12
) is widely used as a host material in lasers and phosphors. Yttria‐stabilized zirconia (YSZ) is a ceramic material used as the electrolyte material in solid oxide fuel cells (SOFCs) and in sensors in car exhaust systems.
Spectroscopic Properties Obtained from Time‐Dependent Density Functional Theory (TD‐DFT)
Authors: Autschbach Jochen
Published: September 2009

This article summarizes basic aspects of time‐dependent density functional theory (TD‐DFT) and its applications in inorganic chemistry. Sections titled TD‐DFT and Spectroscopic Properties outline some of the theoretical formalism and explain how excitation energies can be obtained from TD‐DFT linear response theory. Common approximations in density functional theory (DFT) exchange‐correlation (XC) potentials that might have adverse effects on the accuracy of computed results are explained. Sections titled Benchmark Data and Some Case Studies discuss a number of case studies, with emphasis on TD‐DFT excitation spectra computations in coordination chemistry. Computations of spectra and other properties of metals clusters are also discussed. Apart from excitation spectra, this section also describes TD‐DFT computations of Raman intensities (including resonance Raman and surface‐enhanced Raman spectra (SERS)), magnetic circular dichroism, optical rotatory dispersion (CD and ORD), and concludes with some comments on relativistic effects.
Calculation of Bonding Properties
Authors: Frenking Gernot , von Hopffgarten Moritz
Published: September 2009

The bonding situation in four classes of compounds is analyzed with modern charge and energy decomposition methods. The nature of the bonding in the diatomic species H
2
, N
2
, CO, and BF is investigated with the energy decomposition analysis (EDA). The electronic structure of the heavy‐atom homologs of acetylene HEEH (E = SiPb) is investigated with the help of an orbital analysis and EDA calculations. Metal–ligand bonding in isoelectronic metal hexacarbonyls TM(CO)
6
q
(TM
q
 = Hf
2−
, Ta
−
, W, Re
+
, Os
2+
, Ir
3+
) is the subject of a detailed EDA study. The bonding situation in the unusual 12‐fold coordinated transition‐metal compound [Mo(ZnH)
12
] is analyzed with the AIM (atoms in molecules), EDA, and MO methods. The results of the electronic structure analyses build a bridge between the heuristic bonding models, which are ubiquitously used in inorganic chemistry and accurate quantum chemical calculations.
Calculation of Reduction Potential and
p

K

a
Authors: Jensen Jan H. , Li Hui
Published: September 2009

Three methods, quantum mechanical and molecular mechanical polarizable continuum model (QM/MM/PCM), QM/PCM, and empirical, were developed and applied to calculate protein reduction potential (
E
0
) and p
K
a
values. In the QM/MM/PCM calculation of Lys55 p
K
a
of turkey ovomucoid third domain (OMTKY3), the MP2/6‐31 + G(2d,p) method was used to describe the QM region consisting of ∼45 atoms; the rest of the protein was modeled either with ab initio‐derived electric multipole points or atomic charges from standard force field methods; and the aqueous solvation effect was described with the polarizable continuum model (PCM). The calculated Lys55 p
K
a
values are in good agreement with experiments. QM/PCM methods were used to calculate p
K
a
values of various proteins and the
E
0
of type‐1 Cu centers. For solvent‐exposed p
K
a
sites, QM/PCM (MP2/6‐31 + G(2d,p) for ∼100 atoms, PCM with dielectric = 78.39 for aqueous solution) methods can often reproduce experimental p
K
a
values. For type‐1 Cu
E
0
, because of protein burial, the desolvation effect becomes significant: it was found that Cu‐ligand interactions and desolvation can potentially change the
E
0
by ∼300 and ∼400 mV, respectively, using the CPCM/B3LYP/6‐311++G(2df,p) method and model molecules of ∼100 atoms. An empirical method, PROPKA, was developed for protein p
K
a
calculation and analysis, which is able to calculate the p
K
a
values of a protein within ∼1 s.
Broken Symmetry States of Iron—Sulfur Clusters
Authors: Noodleman Louis , Case David A.
Published: September 2009

After presenting a general introduction to the structures and physical properties of dinuclear and polynuclear iron sulfur clusters, we discuss the relationship between the broken symmetry model within density functional theory (DFT), and the energies and properties of related pure spin states. The methodology for calculating and the physical significance of Heisenberg coupling parameters (J) and spin‐dependent delocalization parameters (B) are developed. The interaction energy of the active site quantum cluster with the protein and solvent environment is treated with a single step procedure based on the classical Poisson–Boltzmann (PB equation). Redox potentials of various high‐potential 4Fe4S and ferredoxin proteins are calculated with DFT/PB methods. The electronic and spin‐coupling structure of oxidized high‐potential (HIPIP) proteins is examined, and it is shown that two distinct electronic structures are possible. These contrasting electronic structures may have implications for the structural stability of oxidized HIPIP. For the Fe protein of nitrogenase, the redox potential and spin state of the super‐reduced form are calculated, and it is argued that this all‐ferrous state is probably not physiologically accessible. The redox potential and electronic structure of the FeMo cofactor of the MoFe protein of nitrogenase are examined for the “resting” state. A very small spin density at the central atom is very feasible. The central atom could be XC, N, O, but C, N are most probable, despite the absence of an observable ENDOR signal for the central atom. The spin‐density for a central atom should be much higher for the 2e‐reduced FeMo cofactor when a ligand is bound, and we have tested this for bound allylic alcohol. Three different ligand‐cluster binding structures are characterized by geometry, energy, and spin distribution.
Electronic Structure Calculations: Dinitrogen Reduction in Nitrogenase and Synthetic Model Systems
Authors: Tuczek Felix
Published: September 2009

Theoretical studies on the binding and reduction of dinitrogen and alternative substrates at the iron‐molybdenum cofactor (FeMoco) of nitrogenase are reviewed. Before considering the enzymatic pathways, the available mechanistic scenarios for N
2
reduction in small‐molecule model systems are discussed. These systems are divided into those involving an end‐on terminal (Sections 2.1 and 2.2) and those involving a bridging coordination of N
2
(Section 2.3). For the enzyme, calculations of Noodleman
et al
., Nørskov
et al
., Blöchl
et al
., Dance, and others are reviewed and compared to each other. Conclusions are drawn with respect to the most probable scenario of N
2
reduction at the FeMoco and the open mechanistic questions in this research area.
Hydrogenases: Theoretical Investigations Towards Bioinspired
H
2
Production and Activation
Authors: Bruschi Maurizio , Zampella Giuseppe , Greco Claudio , Bertini Luca , Fantucci Piercarlo , De Gioia Luca
Published: September 2009

Hydrogenases catalyze the reduction of protons, and have great biotechnological relevance in light of the key role played by H
2
in several industrial processes. Moreover, the industrial and social relevance of H
2
stems also from the observation that dihydrogen could be an efficient and cost‐attractive energy carrier for the future.

Hydrogenases invariably contain a transition metal ion (Fe and in some case Ni) in their active site, and therefore have attracted the attention of experimental and theoretical bioinorganic chemists, which have given fundamental contributions to the elucidation of structure‐activity relationships in this class of enzymes. In addition, the recent elucidation of the X‐ray structure of [NiFe]‐ and [FeFe]‐hydrogenases has prompted synthetic chemists to design and characterize bioinspired coordination compounds, with the aim of obtaining efficient catalysts for H
2
production/activation.

Here, we briefly review the contributions given by quantum chemistry to the characterization of key forms of the enzymes, the elucidation of reaction pathways and catalytic mechanisms, as well as the complementation of experimental data in the investigation of synthetic models. Emphasis is mainly given to underline the kind of insights that can be obtained using quantum chemical methods when investigating coordination compounds related to the hydrogenases active site, and to highlight some strengths and limitations of density functional theory, which currently is the most frequently used quantum chemical method to investigate metalloenzymes.
Computational Methods: Modeling of Reactivity in Zn‐Containing Enzymes
Authors: Mujika Jon I. , Mulholland Adrian J. , Harvey Jeremy N.
Published: September 2009

Computation is increasingly well placed to offer insight into a range of structural and spectroscopic properties of Zn‐containing enzymes, as well as into their reactivity. The latter aspect is the focus of this article. Molecular dynamics simulations provide insight into substrate binding and active‐site relaxation around the metal and substrate. A significant challenge in such studies is the representation of the zinc center. Quantum mechanical methods, either on their own using small active‐site models, or for whole enzymes using hybrid techniques, provide insight into reaction paths and hence into transition states and intermediates. Examples of these applications are reviewed for carbonic anhydrase, carboxypeptidase A, thermolysin, type B β‐lactamase, and farnesyltransferase.
Combined Density Functional Theory (
DFT
) and Electrostatics Study of the Proton Pumping Mechanism in Cytochrome

C

Oxidase
Authors: Quenneville Jason , Popović Dragan M. , Stuchebrukhov Alexei A.
Published: September 2009

Cytochrome
c
oxidase is a redox‐driven proton pump which converts atmospheric oxygen to water and couples the oxygen reduction reaction to the creation of a membrane proton gradient. The structure of the enzyme has been solved; however, the mechanism of proton pumping is still poorly understood. Recent calculations from this group indicate that one of the histidine ligands of the enzyme's Cu
B
center, His291, may play the role of the pumping element. Here, we discuss results of calculations that combined first principles density functional theory (DFT) and continuum electrostatics to evaluate the energetics of the key energy generating step—the transfer of the chemical proton to the binuclear center of the enzyme, where the hydroxyl group is converted to water, and the concerted expulsion of the proton from d‐nitrogen of the His291 ligand of the Cu
B
center.
Computational Methods: Lanthanides and Actinides
Authors: Dolg M. , Cao X.
Published: September 2009

First‐principles and semiempirical relativistic quantum chemical methods applicable to molecular systems containing lanthanides and actinides are briefly reviewed. Selected recent applications of some of these methods are discussed.
Nature of the Catecholate—
Fe
(
III
) Bond: High Affinity Binding and Substrate Activation in Bioinorganic Chemistry
Authors: Solomon Edward I. , Pau Monita Y. M. , Hocking Rosalie K.
Published: September 2009

Catecholate‐Fe(III) (high‐spin) bonds are important in many areas of bioinorganic chemistry. These exhibit low‐energy, intense ligand‐to‐metal charge transfer (LMCT) transitions reflecting highly covalent bonds. This high covalency can make a major contribution to function. In this review, we develop the method of metal L‐edge X‐ray absorption spectroscopy (XAS) as a probe of differential orbital covalency (DOC), the amount of ligand character in the different d orbitals of a metal site in a highly covalent environment. We then apply this method to experimentally determine the covalency of the ligand‐metal bonds related to the siderophores and computationally evaluate this contribution to their high stability constants. We then use variable‐temperature, variable‐field, magnetic circular dichroism (VTVH MCD) spectroscopy to assign the LMCT transitions of the catecholate‐, substrate‐bound Fe
III
site of the intradiol dioxygenases. A reaction coordinate is presented where this charge transfer can overcome the spin‐forbidden nature of the reaction of the bound catecholate (singlet) with dioxygen (triplet).
Calcium and Neurotransmitter Release
Authors: Delaney Kerry R , Stanley Elise E
Published: September 2009

Information is coded in the brain as patterns of electrical impulses that are transmitted along nerve processes. These impulses are passed from one neuron to the next primarily at chemical synapses where the electrical event is converted to the release of a neurotransmitter substance that activates the next neuron in the pathway. Neurotransmitter release is triggered by the opening of ‘voltage‐sensitive’ calcium channels, the admission of a small pulse of Ca
2+
ions and the binding of these ions to the neurotransmitter secretion apparatus culminating in the fusion and discharge of a transmitter‐filled secretory vesicle. Increasing evidence suggests that most synapses an individual release site is gated by ion influx through one or more nearby calcium channels. In this section, we explore the physiology of this impulse‐to‐secretion gating mechanism.

Key Concepts

Information is transmitted between one neuron and the next at
synapses
where the nerve fibre terminal of the upstream (presynaptic) neuron contacts the surface membrane of the downstream (postsynaptic) one.

Most synapses transmit by secreting a chemical neurotransmitter across the narrow space between pre‐ and postsynaptic surface membranes.

Transmitter secretion is triggered by an electrical impulse that travels down the presynaptic nerve fibre to the terminal.

Neurotransmitter is stored in tiny membrane ‘packets’ called synaptic vesicles which can be triggered to secrete by fusing with the presynaptic membrane at the ‘transmitter release site’.

The synaptic vesicles are ‘docked’ at the release site ready for secretion.

Influx of calcium ions through selective voltage‐sensitive ion channels (calcium channels) plays a key role to link the action potential to the triggering of secretory vesicle discharge.

Calcium channels are positioned very close to the secretory vesicles so that when they open the spurt of entering calcium ions, called a ‘calcium domain’, can rapidly and effectively access the triggering sites for synaptic vesicle fusion.
Multiple Sclerosis
Authors: Preiningerova Jana , Bomprezzi Roberto , Vollmer Timothy L , Waxman Stephen G
Published: September 2009

Multiple sclerosis (MS) is the leading cause of neurological disability in young women in the USA and Europe and the second leading cause of such disability in young men. Major advances have been made in the past two decades in understanding the pathogenesis and immunobiology of MS resulting in major advances in the treatment of the disease over the past 15 years. These advances are the consequence of advanced neuroimaging, molecular biology and immunological techniques. However, the disease remains generally incurable. Further advances will depend on developing more selective immunotherapeutic strategies, particularly involving B cells and regulatory T cells as well as developing therapeutic strategies to prevent neurodegeneration and to induce repair in the central nervous system (CNS) of patients with MS.

Key Concepts:

MS is the leading cause of neurological disability in young women in North America and Europe.

Although there is good evidence that MS results from both genetic and environmental factors, the exact nature of those factors remains uncertain.

Although often classified as a disease of myelin, recent research clearly demonstrates the immune attack on the CNS destroys neurons, axons and oligodendroglia; therefore MS is more properly considered an inflammatory disease of the CNS.

Although classically considered an autoimmune disease driven by autoaggressive T cells, clinical data suggests B lymphocytes also play a key role in the pathogenesis of MS.

Mechanisms of immune attack on the CNS may vary from patient to patient but in general include both cellular and humoral mechanisms.

Brain magnetic resonance imaging (MRI) has fundamentally changed our understanding of disease activity in MS patients. It is now known that much of the damage to the CNS is not apparent clinically in the early phase of the disease, but contributes to the long‐term disability of the disease.

Recently, major advances have been made in developing therapies that can slow the progression of MS. However, no cure has yet been found.

Neurodegeneration appears to be a consequence of the immune attack on the CNS and may result in continued progression of disability even if the immune attack on the CNS is inhibited.

Recently it has become clear that the brain in MS patients is constantly attempting to repair the damage done by the immune attack both through remyelination and cortical remodelling. In fact, these processes appear to explain the clinical appearance of stability in MS patients at a time when the MRI demonstrates ongoing inflammation and damage.

Advances in our understanding of the pathogenesis and treatment of MS has significant implications for other inflammatory diseases of the nervous system.
Proteoglycans
Authors: Schwartz Nancy B
Published: September 2009

Proteoglycans are complex extracellular macromolecules consisting of a multidomain core protein to which are attached one or more glycosaminoglycan (GAG) chains. They are structurally very diverse, due to variations in length and sequence of the core proteins as well as abundance, distribution and composition of the GAG chains. Core proteins are often arranged in modules which have structural and functional significance, and the same module may be found in more than one core protein type. A single core protein type may have different GAG substituents and differing roles in different tissues. Proteoglycans have diverse, but often vital functions in a variety of tissue context. Genetic studies of proteoglycan core proteins and their modifying enzymes have elucidated numerous heritable diseases and syndromes. Much of our understanding of the structure, function, evolution, gene regulation and mutations causing heritable disorders of proteoglycans, in general, derives from the model proteoglycan, aggrecan.

Key Concepts

Glycosaminoglycans are linked to proteoglycan core proteins via a limited number of
O
‐ or
N
‐glycosyl bonds.

Synthesis of GAG chains proceeds by the sequential action of glycosyltransferases that catalyse transfer of a glycosyl unit from a nucleotide sugar to a protein or nonreducing end of a sugar acceptor.

Proteoglycans are abundant components of the extracellular matrix and associated with the cell surface.

Although there are only six major classes of proteoglycan types, there is great diversity in structure, size and composition.

Important functions have been attributed to both the protein backbone and glycosaminoglycan substituents.

Proteoglycans modulate numerous molecular interactions, for example, cell–cell signalling.

Heritable proteoglycan disorders cause a wide range of phenotypes with examples from all clinical specialities.
Enzyme Kinetics: Steady State
Authors: Cleland W Wallace
Published: September 2009

The kinetics of enzyme‐catalysed reactions can be analysed in terms of steady state models if the substrate concentrations are more than an order of magnitude higher than the enzyme level. Such analysis yields Michaelis constants, maximum velocities and useful information on reaction mechanisms. Thus when there are two or more substrates, the number of terms in the denominator of the rate equation tells the type of mechanism. A sequential mechanism has a constant term plus ones in the concentration of each substrate and one including both concentrations. A ping pong mechanism has no constant term in the denominator. An ordered sequential mechanism where the binding of the first substrate is at equilibrium lacks a denominator term in the concentration of the second substrate. Other types of steady state studies include the use of inhibitors, determination of pH profiles and the effect of isotopic substitutions on the rates.

Key Concepts:

As long as substrate concentrations are more than an order of magnitude greater than the enzyme level, the reaction will be in a steady state.

Steady state rate equations are simple ratios of a numerator that is a function of substrate concentrations and a maximum velocity divided by a denominator that represents the distribution of the enzyme among all possible forms that are present in the steady state.

Steady state kinetic studies enable one to distinguish kinetic mechanisms and can also give information on rate limiting steps and in favorable cases, chemical mechanism.
Mammalian Embryo:HoxGenes
Authors: Alexander Tara B , Krumlauf Robb
Published: September 2009

Hoxgenes are evolutionarily conserved transcription factors that play important roles in establishing the basic body plan of animals. Mammals have 39Hoxgenes clustered into four chromosomal complexes. This gene family regulates the regional character and patterning of diverse structures along the anterior–posterior (A/P) axis of the embryo. Nested patterns ofHoxgene expression generate a Hox combinatorial protein code that orchestrates the morphogenesis of structures in the nervous system, axial skeleton, limbs, intestine and many other tissues. In light of their key role in regulating morphogenesis across animal species, modulation ofHoxexpression or function over the course of evolution is believed to have been important in generating diversity.

Key concepts:

Axial patterning is the process that generates different regional characteristics during the development of a tissue, such as the nervous system or skeleton.

Hoxgenes encode a family of transcription factors that regulate the identity of structures along the anterior–posterior axis of embryos.

Colinearity is the correlation between the order ofHoxgenes along a chromosome and their expression along the axis of an embryo.

The collection of Hox proteins expressed in a region provides a combinatorial code for specifying diversity.

Posterior prevalence is a model for explaining why some Hox proteins dominate over others when they are coexpressed.

Selector genes control the identity of a tissue.

Homeotic transformation is the conversion of one structure into another due to loss or gain of selector gene activity.

Segmentation subdivides a developing tissue, such as the hindbrain or skeleton, into repeating units that ultimately generate different structures along an axis.

Subfunctionalization is the partitioning of function and regulation between duplicated genes compared with the ancestral gene.

Changes inHoxexpression or function may be important for generating differences in structures during evolution of vertebrates.

Cooption refers to the redeployment or coupling of a common molecular pathway to multiple patterning processes.
Mammalian Embryo: Branching Morphogenesis
Authors: Davies Jamie A
Published: September 2009

Branched structures are common in mammals and exist mainly to solve problems of transport. Branched architectures allow a surface area to be packed into a small volume, minimize the distance of cells from transport systems and from the entrance of a system to its end. For development and evolution, branched structures offer the advantage of being scaleable: tree‐shaped systems can grow and add branches without altering their basic nature. Branching morphogenesis takes place by four methods: fusion, clefting, sprouting and intussusception. All are controlled by paracrine factors and take place through changes in the behaviours of cytoskeleton‐adhesion systems.

Key concepts:

The internal anatomy of mammals involves many branched structures.

Branched architectures optimize transport in compact organisms.

Branched architectures can be scaleable, which has evolutionary and developmental implications.

Branching can be by fusion, clefting, sprouting and intussusception.

The largest branches tend to be stereotypical and under precise genetic control, but the finest ones are pseudo‐fractal and quite variable.

Branching depends on ramogenic signals from surrounding cells.

Branching structures have endogenous mechanisms to ensure appropriate spacing; at least some rely on repulsive autocrine cues.
Follicular Dendritic Cells (
B
Lymphocyte Stimulating)
Authors: El Shikh Mohey Eldin M , El Sayed Rania M , Tew John G , Burton Gregory F
Published: September 2009

Follicular dendritic cells (FDCs) are unique immune system cells that contribute to the maintenance of humoral (i.e. antibody) immune responses. These cells are located in the follicles of secondary lymphoid tissues (e.g. lymph nodes and spleen), where they trap and retain antigens in the form of highly immunogenic immune complexes (ICs). FDC‐ICs are composed of antigen plus specific antibody and/or complement proteins. These trapped antigens, combined with other soluble and membrane‐bound signals contributed by FDCs, are essential to the development and maintenance of the germinal centre reaction and IgG and IgE responses respectively. FDCs also appear to contribute to initial IgM responses. In addition to their positive effects on humoral immunity, FDCs may promote diseases including HIV/AIDS (
human immunodeficiency virus
/acquired immunodeficiency syndrome), prion diseases and follicular lymphomas. A better understanding of FDCs should permit better regulation of antibody responses and may also allow the amelioration of some disease states.

Key Concepts

Antigens are trapped and retained for months on the surfaces of follicular dendritic cells (FDCs) in secondary lymphoid tissues (e.g. spleen and lymph nodes).

FDC‐trapped antigens maintain memory IgG and IgE immune responses.

FDC‐ICs are highly immunogenic and minute quantities are sufficient to generate significant antibody responses.

FDCs provide both antigen and other signals that are central to the induction and maintenance of specific antibody responses.

FDCs can play roles in both health and disease (e.g. HIV/AIDS, prion diseases and follicular lymphomas).
Evolution of Vertebrate Limb Development
Authors: Tanaka Mikiko
Published: September 2009

The origin and diversification of fins and limbs have long been a focus of interest to both palaeontologists and developmental biologists. Studies conducted in recent decades have resulted in enormous progress in the understanding of the genetic and developmental bases of the evolution of paired appendages in vertebrates. These discoveries in the areas of genetics and developmental biology have shed light on the mechanisms underlying the evolution of this key morphological innovation in vertebrates. In this article, I discuss recent advances in these fields and how they can provide a mechanistic explanation for the origin and evolution of paired appendages.

Key Concepts

According to the fossil record, single pair of fin‐like structures emerged in the bodies of certain ancestral jawless vertebrates, and two pairs of fins are unique to jawed vertebrates.

There are two separate phases/waves ofHoxdgene expression in tetrapod limbs. The first wave precedes the formation of the proximal parts of the limb, whereas the second wave corresponds to the most distal part of the limb (digits).

The earliest known amphibian fossils,AcanthostegaandIchthyostega, seem to have had more than five digits in their limbs. It has been proposed that regulatory changes inHoxand/orShhexpression modified the digit number during evolution.

Regulatory modifications of specific gene expression appear to account for the evolution of paired appendages, such as the increasing length of bat wings, the loss of limbs in pythons, and pelvic reduction in sticklebacks.
AIDS
: Clinical Manifestations
Authors: Boesecke Christoph , Dore Gregory J , Cooper David A
Published: September 2009

In the course of time
human immunodeficiency virus
(HIV) notably affects the host's immune system. As a result, HIV‐infected people can experience a wide range of clinical manifestations, especially if the infection is not being treated duly with combination antiretroviral therapy (cART). At such an advanced stage of the disease, patients eventually face severe illnesses. Of these, more than 20 conditions, including opportunistic infections and malignancies, have been classified as AIDS (acquired immune deficiency syndrome)‐defining illnesses to date. Recently, clinical research has also focused on serious non‐AIDS‐related events (SNAEs). This term refers to an increasing rate of illnesses such as cardiovascular, liver and renal diseases as well as neoplasms occurring in long‐term‐treated patients on the basis of longer life expectancy. However, there are still significant differences in access to and availability of antiretroviral therapy throughout the world which leads to contrasting patterns in the spectrum of AIDS‐defining illnesses in resource‐limited settings and developed countries.

Key concepts:

AIDS‐defining illnesses mainly occur at a very advanced stage of the HIV infection.

More than 20 conditions are currently listed as AIDS‐defining illnesses.

The spectrum of AIDS‐defining illnesses varies in developed and resource‐limited settings.

Pneumocystis jiroveci

pneumonia is the most common AIDS‐related illness in industrialized countries.

Tuberculosis is the most common AIDS‐related illness in developing countries.

Antiretroviral therapy has had a significant impact on the spectrum of AIDS‐defining illnesses.

Owing to the now longer life expectancy serious non‐AIDS‐related illnesses have become more important in clinical management.
Gene Conversion in Evolution and Disease
Authors: Chen Jian‐Min , Cooper David N , Chuzhanova Nadia , Férec Claude , Patrinos George P
Published: September 2009

Gene conversion involves the unidirectional transfer of genetic material from a ‘donor’ sequence to a highly homologous ‘acceptor’. Gene conversion is initiated by double‐strand breaks and can arise from mutually exclusive pathways. Over evolutionary time, gene conversion has homogenized the paralogous sequences within each species whereas diversifying the orthologous sequences between closely related species; interallelic gene conversion has generated a high level of allelic diversity at certain loci. Not only has gene conversion played a key role in fashioning extant human genes but it has also been implicated as the molecular cause of an increasing number of human genetic diseases.

Key concepts

Gene conversion involves the unidirectional transfer of genetic material from a ‘donor’ sequence to a highly homologous ‘acceptor’ and occurs in both meiosis and mitosis.

Gene conversion is initiated by DNA double‐strand breaks and appears to arise from different mutually exclusive pathways.

The rate of gene conversion is mainly determined by sequence homology and by the distance between the interacting sequences, but it may also be affected by specific sequence motifs or/and sequences capable of forming non‐B DNA structures.

Interallelic gene conversion events occur between alleles on homologous chromosomes whereas nonallelic or interlocus events can occur between paralogues on the same chromatid, sister chromatids or homologous chromosomes.

Interlocus gene conversion events have driven the concerted evolution of many human gene families whereas interallelic events have generated a high level of allelic diversity at certain loci.

Gene conversion has also been implicated as the cause of a variety of different human inherited diseases.

In stark contrast to the frequent detection of pathogenic interlocus gene conversion events, the occurrence of interallelic gene conversion events causing human inherited disease is quite rare.

Only a few well‐documented examples of gene conversion events in cancer have been reported in the literature.

Gene conversion can account for the occurrence of some recurrent mutations on different chromosomal backgrounds in different ethnic groups.

Gene conversion may provide a possible future means to bring about ‘natural gene therapy’ by offering an important alternative to the introduction of an entire functional gene.
Genetic Counselling Profession in Europe
Authors: Skirton Heather
Published: September 2009

Genetic healthcare is developed as a speciality in Europe over the past five decades and initially services were provided by medical specialists. However, due to changes in awareness of the psychosocial impact of genetic conditions and the increase in options available to families, clinical genetic services are now frequently provided by multidisciplinary teams. In many European countries, nonmedical genetic counsellors are working as part of the clinical team, providing both information and support for individuals and families at risk of or affected by a genetic condition. Many genetic counsellors have a background in nursing or other allied health profession or have completed a Master level degree in genetic counselling. The European Network of Genetic Nurses and Counsellors is active in establishing genetic counselling as a profession in Europe through setting standards of competence and prescribing appropriate educational pathways for practitioners.

Key concepts

Awareness of human heredity was advanced in the nineteenth century through the work of Mendel and Galton.

Specialist clinical genetic services were established in Europe in the mid‐twentieth century.

Genetic counselling may be undertaken by practitioners from a range of health professions.

Genetic counsellors are practitioners have a background in one of the health professions or have undertaken a Master degree in genetic counselling.

Genetic counsellors provide information, discuss options, support adjustment and facilitate the client to make decisions.

Genetic counsellors are specially trained to offer the client psychological support.

There are disparities in the ways in which genetic counsellors work in different European countries.

The European Network of Genetic Counsellors is working to setting standards of competence and prescribing appropriate educational pathways for practitioners.

A set of core competences for genetic counsellors is available as a basis for setting educational standards.
Haemoglobin Disorders: Gene Therapy
Authors: Persons Derek A , Nienhuis Arthur W
Published: September 2009

The ability to transfer a globin gene into stem cells and achieve regulated expression during erythropoiesis following transplantation of genetically modified autologous cells could provide curative therapy for haemoglobin disorders such as sickle cell anaemia or β‐thalassaemia. Success has been achieved in several severe immunodeficiencies in which there is a selective advantage for gene corrected cells. The development of effective globin lentiviral vectors has resulted in resolution of the manifestations of sickle cell anaemia and β‐thalassaemia in mouse models of these diseases. However, a higher stem cell transduction efficiency must be achieved in humans than has been achieved in large animal models to date before success in treatment of haemoglobinopathies could be expected. Various strategies are being evaluated in animal models to increase the proportion of genetically modified, haematopoietic cells following infusion of transduced stem cells.
Nitrification
Authors: Arp Daniel J
Published: September 2009

Nitrification is the process whereby reduced forms of inorganic and organic nitrogen, particularly ammonium, are oxidized to nitrate. The process is mediated by microorganisms and contributes to the movement of nitrogen through the biogeochemical nitrogen cycle. Ammonia‐oxidizing bacteria first oxidize ammonia to nitrite, followed by the oxidation of nitrite to nitrate by the nitrite‐oxidizing bacteria. In both cases, these bacteria are able to derive energy for growth from the oxidation of these inorganic compounds and can use carbon dioxide as their sole carbon source.
Crenarchaeota
were recently shown to also be capable of deriving energy from the oxidation of ammonia to nitrite. Ammonia monooxygenase initiates the metabolism of ammonia and produces hydroxylamine. This intermediate is converted to nitrite by
hydroxylamine oxidoreductase
, a trimer of an octaheme subunit. Nitrite oxidation to nitrate is catalysed by
nitrite oxidoreductase
, a molybdenum‐containing enzyme.

Key Concepts

Nitrification is the process whereby reduced forms of inorganic and organic nitrogen, primarily ammonia, are oxidized to nitrate.

Nitrification is mediated by microorganisms including
Bacteria
and
Crenarchaeota
and occurs in two steps. In the first step, ammonia is oxidized to nitrite and in the second step nitrite is oxidized to nitrate.

Ammonia‐oxidizing bacteria and
Crenarchaeota
can derive energy for growth from the oxidation of ammonia to nitrite.

Nitrite‐oxidizing bacteria derive energy for growth from the oxidation of nitrite to nitrate.

Many ammonia‐ and nitrite‐oxidizing bacteria are autotrophs and assimilate carbon dioxide via the Calvin cycle.

Key enzymes involved in nitrification are ammonia monooxygenase, which catalyses the oxidation of ammonia to hydroxylamine, hydroxylamine oxidoreductase, which catalyses the oxidation of hydroxylamine to nitrite and nitrite oxidoreductase, which catalyses the oxidation of nitrite to nitrate.

Microorganisms involved in nitrification are broadly distributed in nature and found virtually everywhere that ammonia and oxygen are present.

The genomes of several representative ammonia‐ and nitrite‐oxidizing bacteria reveal the presence of genes consistent with the autotrophic lifestyle and only limited genes to support growth on organic compounds, again consistent with their lifestyle.