bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of MoStBioDat for Rapid Screening of Molecular Diversity
Authors: Bak Andrzej , Polanski Jaroslaw , Kurczyk Agata
Published: September 2009

MoStBioDat is a uniform data storage and extraction system with an extensive array of tools for structural similarity measures and pattern matching which is essential to facilitate the drug discovery process. Structure-based database screening has recently become a common and efficient technique in early stages of the drug development, shifting the emphasis from rational drug design into the probability domain of more or less random discovery. The virtual ligand screening (VLS), an approach based on high-throughput flexible docking, samples a virtually infinite molecular diversity of chemical libraries increasing the concentration of molecules with high binding affinity. The rapid process of subsequent examination of a large number of molecules in order to optimize the molecular diversity is an attractive alternative to the traditional methods of lead discovery. This paper presents the application of the MoStBioDat package not only as a data management platform but mainly in substructure searching. In particular, examples of the applications of MoStBioDat are discussed and analyzed.
Image-Based Airborne Sensors: A Combined Approach for Spectral Signatures Classification through Deterministic Simulated Annealing
Authors: Guijarro María , Pajares Gonzalo , Herrera P. Javier
Published: September 2009

The increasing technology of high-resolution image airborne sensors, including those on board Unmanned Aerial Vehicles, demands automatic solutions for processing, either on-line or off-line, the huge amountds of image data sensed during the flights. The classification of natural spectral signatures in images is one potential application. The actual tendency in classification is oriented towards the combination of simple classifiers. In this paper we propose a combined strategy based on the Deterministic Simulated Annealing (DSA) framework. The simple classifiers used are the well tested supervised parametric Bayesian estimator and the Fuzzy Clustering. The DSA is an optimization approach, which minimizes an energy function. The main contribution of DSA is its ability to avoid local minima during the optimization process thanks to the annealing scheme. It outperforms simple classifiers used for the combination and some combined strategies, including a scheme based on the fuzzy cognitive maps and an optimization approach based on the Hopfield neural network paradigm.
The OMERACT-ICF Reference Group: Integrating the ICF into the OMERACT Process: Opportunities and Challenges
Authors: BOONEN ANNELIES , STUCKI GEROLD , MAKSYMOWYCH WALTER , RAT ANNE CHRISTINE , ESCORPIZO RUBEN , BOERS MAARTEN ,   the OMERACT-ICF Reference Group
Published: September 2009

At OMERACT 8 in May 2006 in Malta, the International Classification of Functioning, Disability and Health (ICF) was introduced as a universal model and a universal classification to describe human functioning. The potential usefulness of the ICF for the OMERACT process was highlighted and reported in a position paper following the OMERACT 8 meeting. Since then representatives of several OMERACT working groups with an interest in the ICF joined an OMERACT-ICF reference group. Most members had experience with the ICF and worked further to integrate the ICF into OMERACT. We describe the main roles of the ICF in the OMERACT process and the challenges when practice confronts theory.
Patient Perspective on Outcomes in Rheumatology — A Position Paper for OMERACT 9
Authors: KIRWAN JOHN R. , NEWMAN STANTON , TUGWELL PETER S. , WELLS GEORGE A.
Published: September 2009

The inclusion of patient participants at OMERACT has resulted in direct incorporation of the patient perspective in the development of outcome assessments in rheumatology. Fatigue has been adopted as a recommended measure in all studies, and further work is now under way on the assessment of sleep, effective healthcare consumers, and the effects of psychological or educational interventions. This position paper draws this work together in preparation for the Patient Perspective Workshop at OMERACT 9, and introduces the concept that other core outcomes relevant to patients might be required in assessing interventions designed to help patients live with their disease.
Measuring Worker Productivity: Frameworks and Measures
Authors: BEATON DORCAS , BOMBARDIER CLAIRE , ESCORPIZO REUBEN , ZHANG WEI , LACAILLE DIANE , BOONEN ANNELIES , OSBORNE RICHARD H. , ANIS ASLAM H. , STRAND C. VIBEKE , TUGWELL PETER S.
Published: September 2009

Worker productivity is a combination of time off work (absenteeism) due to an illness and time at work but with reduced levels of productivity while at work (also known as presenteeism). Both can be gathered with a focus on application as a cost indicator and/or as an outcome state for intervention studies. We review the OMERACT worker productivity groups’ progress in evaluating measures of worker productivity for use in arthritis using the OMERACT filter. Attendees at OMERACT 9 strongly endorsed the importance of work as an outcome in arthritis. Consensus was reached (94% endorsement) for fielding a broader array of indicators of absenteeism. Twenty-one measures of at-work productivity loss, ranging from single item indicators to multidimensional scales, were reviewed for measurement properties. No set of at-work productivity measures was endorsed because of variability in the concepts captured, and the need for a better framework for the measurement of worker productivity that also incorporates contextual issues such as job demands and other paid and unpaid life responsibilities. Progress has been made in this area, revealing an ambivalent set of results that directed us back to the need to further define and then contextualize the measurement of worker productivity.
Guerra, pueblo y cultura: Antonio Machado en el congreso de Valencia (1937)
Authors: Escalera Cordero Matías
Published: September 2009

Este artículo analiza, una a una, las ideas claves del discurso que Antonio Machado pronuncia en la última de las sesiones celebradas en Valencia, en el mes de julio de 1937, ante los intelectuales y escritores antifascistas que se han reunido en España en el II Encuentro de Escritores en Defensa de la Cultura, con el fin de apoyar a la República española en combate contra las fuerzas golpistas interiores y contra las potencias fascistas exteriores. Además, muestra cómo Antonio Machado sintetiza en ese discurso las líneas esenciales de su pensamiento expresado tanto en los artículos de la serie de Mairena, como en sus numerosas intervenciones públicas durante la guerra.
Ensayo en Lima (Perú) de edificio de adobe sismorresistente construido con el sistema de albañilería integral
Authors: Orta B. , Adell M. , Bustamante R. , García A. , Vega S.
Published: September 2009

Este artículo presenta una aplicación del Sistema de Albañilería Integral (SAI), desarrollado en Europa bajo la marca “AllWall System” para muros de albañilería de ladrillo o bloque, cerámico o de hormigón, empleando sólo mortero. En este caso el sistema se modifica para adaptarlo al adobe y permitir la construcción de viviendas sismorresistentes en países en desarrollo.Cuando el relleno empleado es de adobe, es imposible transferir las tensiones de los refuerzos por adherencia de las barras debido a que estas estructuras carecen de mortero. Se hace necesario que las armaduras transmitan los esfuerzos entre sí. Las armaduras, en forma de cercha, se pueden cruzar en las tres direcciones del espacio, lo que permite la construcción de muros y forjados. De esta manera sólo se necesita un posterior relleno con bloques de adobe o el tablero del forjado para que el conjunto tenga la rigidez suficiente. Para verificar la seguridad de este nuevo tipo de edificación para su construcción en zonas sísmicas del tercer mundo, se ha ensayado a sismo un prototipo realizado con el sistema SAI con adobe, de 6x6x6 m y dos plantas a escala 1/2 en la PUCP (Pontificia Católica Universidad del Perú) de Lima en colaboración con la UPM (Universidad Politécnica de Madrid). Los resultados de este ensayo muestran que el SAI con adobe permanece estable sin grietas significativas ante un sismo severo de 130 mm de desplazamiento (equivalente a un sismo de 10º en la escala de Richter).
Beliggaamde realisme en ekobillike godskonstrukte
Authors: Venter Philip P.
Published: September 2009

Embodied realism and congruent God constructs The findings of modern cognitive sciences have far-reaching implications for the philosophical framework within which theological texts have been and could be interpreted. In this regard, the body presents itself as an important epistemological agent. Body-critical analysis of Bible texts provides insight into the societal and cultural factors that brought about those texts, and presents a philosophical approach of embodied realism congruent with the embodiment of thought, the cognitive subconscious and the methaphorical nature of abstract concepts. By taking the body ideology fundamental to the concepts and constructs in religious texts seriously, a new discourse can be stimulated that will bring about new embodied perspectives on the relationship between humans, the environment and other �others�. A society that is serious about ecojustice as far as the interrelatedness of all creatures is concerned should shoulder the responsibility continuously to consider and revise its hierarchical normative paradigms. The purpose of this article is to investigate the role and place of the body in the establishment of God constructs as normative paradigms.
Spectroscopic Properties of Protein‐Bound Cofactors: Calculation by Combined Quantum Mechanical/Molecular Mechanical (
QM
/
MM
) Approaches
Authors: Sundararajan Mahesh , Riplinger Christoph , Orio Maylis , Wennmohs Frank , Neese Frank
Published: September 2009

In this article, we discuss some aspects of the combined quantum mechanics/molecular mechanics (QM/MM) method for the calculation of energetics and spectroscopic parameters of protein‐bound cofactors. Following a brief introduction to the theory of the QM/MM approach, some selected examples are discussed that illustrate the use of this methodology in theoretical spectroscopic studies. The examples cover the following: (i) excitation energies for the
S
0
 → 
S
1
transition in bacteriorhodopsin; (ii) electron paramagnetic resonance (EPR) and absorption spectra of plastocyanin; and (iii) the spin Hamiltonian parameters of compound I in cytochrome
P
450
cam
.
Quantum‐Chemistry‐Centered Normal Coordinate Analysis (
QCC
‐
NCA
): Application of
NCA
for the Simulation of the Vibrational Spectra of Large Molecules
Authors: Lehnert Nicolai
Published: September 2009

Vibrational spectroscopy is a powerful spectroscopic method that provides detailed information about the geometric and electronic structural properties of materials, compounds, and biomolecules. In the case of transition‐metal complexes, for example, vibrational spectra allow for the determination of the oxidation and spin state of the metal. In addition, vibrational spectroscopy is of great value in monitoring the binding and activation of small molecules, especially diatomics X–Y (O
2
, N
2
, CO, NO, etc.) and their derivatives, by transition‐metal complexes. Here, the coordination, reduction, protonation, derivatization, etc., of the diatomic can be monitored via the X–Y and metal‐XY bond strengths. Usually, the corresponding X–Y and metal‐XY vibrational frequencies are used for such correlations. This, however, is problematic because the energies of normal modes in general do not correlate directly with bond strengths, as they also depend on mode mixing and atomic masses. Because of this, it is much better to compare the X–Y and metal‐XY force constants along a reaction coordinate or between different species to identify chemically important changes/differences in bond strengths. This poses one problem: force constants are obtained from normal coordinate analysis (NCA), but how can this type of analysis be performed routinely for large molecules with many vibrational degrees of freedom, especially if the interest is focused on a small subunit of the molecule (the metal‐XY bond), whereas the other organic ligands L of the metal are of limited interest? The quantum chemistry centered normal coordinate analysis (QCC‐NCA) provides a solution to this problem by using density functional theory (DFT) calculations to generate an initial force field, followed by refinement of the limited number of force constants of the metal‐XY subunit only, whereas all other force constants remain unchanged. The available QCC‐NCA software allows one to perform this kind of analysis with minimal effort. This article provides a general introduction to the QCC‐NCA method and the underlying principles of vibrational analysis, combined with illustrative examples for applications from the area of the transition‐metal mediated activation of N
2
, O
2
, and NO. Special focus is put on the electronic structures and reactivities of ferrous‐heme nitrosyls, where the Fe–NO and N–O force constants have provided key insight into the activation of NO as a function of the trans ligand. The latest development with respect to the QCC‐NCA method is the calculation of nuclear resonance vibrational spectroscopy (NRVS) intensities, which is described in the final sections of this article.
Quantum Mechanical/Molecular Mechanical (
QM
/
MM
) Methods and Applictions in Bioinorganic Chemistry
Authors: Ryde Ulf
Published: September 2009

The combination of quantum mechanics and molecular mechanics (QM/MM) methods is a promising approach to study the structure, function, and properties of proteins. The number of QM/MM applications on metalloproteins has been steadily increasing and it is the method of choice to study the influence of the protein onto the structure, spectroscopy, and energetics of an active site. In particular, it has been shown that QM/MM calculations can provide geometries of metal sites in proteins with an accuracy that is better than in low‐ and medium‐resolution crystal structures. However, it is quite hard to obtain reliable and converged energies. Therefore, QM/MM is still an area of method development and no consensus of the best treatment of a protein has yet been reached. This review covers various aspects of QM/MM studies of metalloproteins, including methods to incorporate experimental data in the calculations, methods to obtain reliable energies, as well as some examples of typical applications.
Multiconfigurational Quantum Mechanics (QM) for Heavy Element Compounds
Authors: Roos Björn O.
Published: September 2009

One frequently used quantum chemical approach for the studies of transition metal and other heavy element compounds is the complete active space self consistent field (CASSCF) method in combination with multiconfigurational second‐order perturbation theory (CASPT2). Here, we describe this method and some of its typical applications. The basic idea is to construct a wave function that gives a qualitatively correct description of the electronic structure already at the lowest level of theory. This should be possible for all sorts of electronic states independent of spin multiplicity and excitation level. Strong mixing of configurations makes it necessary to use a multiconfigurational approach in such cases. It should also be possible to use for all atoms of the periodic system. The CASSCF wave function fulfills, in principle, this requirement because it is full configuration interaction (CI), albeit in a limited space of active orbitals. The addition of dynamic electron correlation is necessary to give quantitative results. The suggested solution is to compute this energy using second‐order perturbation theory (CASPT2) because it is relatively simple and allows applications to a wide variety of systems and many electrons. Relativistic corrections are included using a Douglas‐Kroll‐Hess Hamiltonian. The method is scrutinized and illustrated by some applications in transition metal and actinide chemistry.
Structural Origins of Noninnocent Coordination Chemistry
Authors: Szilagyi Robert K.
Published: September 2009

A concise synthesis is provided for key electronic and geometric structural features, leading to noninnocent coordination chemistry as manifested by unprecedented reactivity, unusual coordination chemistry, and ligand‐based redox chemistry. These include ligand–ligand repulsion arising from steric rigidity, reduced effective nuclear charge of the ligand‐donor atoms, and increased effective nuclear charge of the metal centers in addition to suitable metal–ligand overlap for efficient intramolecular electron transfer. These features can contribute to considerable deviations from formal oxidation states by leading to effectively low‐valent, reduced metal centers and oxidized ligands that can have very different electronic and geometric structures from their uncoordinated forms. To demonstrate the influence of these structural factors, classical examples of dithiolene complexes are discussed, followed by pincer‐type ligands with late transition metals that show unexpected noninnocent behavior. Combined calibrated density functional theory and multi‐edge X‐ray absorption spectroscopy (XAS) has the potential for uncovering new families of noninnocent ligands that have importance in involving generally redox silent metals in electron‐transfer processes or inducing nucleophilic character for metals due to extreme ligand‐to‐metal electron donation.
Electronic Structure of Metal—Metal Bonds
Authors: McGrady John E.
Published: September 2009

The nature of bonding between two metal centres is extremely variable, spanning formal bond orders from 1 to 6, and this leads to a great diversity of chemical properties in metal cluster compounds. The bonds themselves have components with σ, π, δ, and ϕ symmetry, each of which has its own distinct properties. This article reviews the key features of these different bonding components.
Molecular Mechanics in Bioinorganic Chemistry
Authors: Deeth Robert J.
Published: September 2009

Molecular mechanics (MM) in bioinorganic chemistry separates into applications involving s‐block cations and those involving the d‐block elements. The former behave essentially as hard, charged spheres and can be treated efficiently and accurately with conventional force fields with little or no additional parameterization. The d‐block elements are significantly more challenging. The apparently complex electronic structures associated with the open d shell, the challenges of modeling reaction pathways within empirical methods, the lack of suitable software and MM parameters, and the rise of hybrid quantum mechanics/molecular mechanics (QM/MM) have all contributed to MM for transition metal systems being relatively underdeveloped. Given that metal‐ligand binding in coordination complexes and metalloenzyme active sites is essentially identical, this has significant consequences for bioinorganic applications. However, a critical handicap of any QM‐based method, including QM/MM, is that it is computationally expensive to carry out the configurational sampling or molecular dynamics necessary to get an accurate structure or reaction pathway. In contrast, MM is orders of magnitude faster and therefore has the potential to make a significant impact in bioinorganic chemistry. Encouraging progress is being made, especially with respect to d electron effects where ligand field molecular mechanics has demonstrated QM‐like performance at MM‐like speeds.
Spin‐Orbit Coupling: Effects in Heavy Element Chemistry
Authors: Kaltsoyannis Nikolas
Published: September 2009

Starting from the premise that the chemical consequences of scalar relativistic effects are by now largely understood, and may be incorporated more or less routinely into quantum chemical calculations, this contribution focuses on the historically less widely investigated part that spin‐orbit coupling plays in heavy element electronic structure. The effects of relativity are first summarized, followed by a discussion of the principal approaches to the calculation of molecular electronic structure and how relativistic effects may be incorporated into them. Two approaches for the calculation of spin‐orbit coupling effects are then presented; namely, the spin‐orbit coupled time‐dependent density functional theory technique of Wang
et al
. [Wang, F.; Ziegler, T.; van Lenthe, E.; van Gisbergen, S.; Baerends, E. J.
J. Chem. Phys.
2005
,
122
, 204103] and the spin‐orbit restricted active space state interaction method of Roos and coworkers [Roos, B. O.; Malmqvist, P. A.
Phys. Chem. Chem. Phys.
2004
,
6
, 2919]. Recent applications of both approaches to the electronic structure of p, d, and f block systems are then discussed, with emphasis on the improved understanding and agreement with experiment that these methods yield.
Algal Photosynthesis
Authors: Moroney James V , Ynalvez Ruby A
Published: September 2009

Algae are a very diverse group of predominantly aquatic photosynthetic organisms that account for almost 50% of the photosynthesis that takes place on Earth. Algae have a wide range of antenna pigments to harvest light energy for photosynthesis giving different types of algae their characteristic colour. Early work done with algae contributed much to what is presently known about the carbon dioxide fixation pathway and the light harvesting reactions. The processes of photosynthesis in algae and higher plants are very similar. From among the three types of carbon dioxide‐concentrating mechanisms known in photosynthetic organisms, two types are found in different types of algae. Algae are proposed to play a role in the global carbon cycle by helping remove excess carbon dioxide from the environment. Recently, algae are recognized as a promising biodiesel source due to its efficient absorption and conversion of solar energy into chemical energy.

Key Concepts:

Algal photosynthesis account for almost half of the photosynthetic carbon fixed every year.

Scientists have utilized different algal species including algal mutants to study different aspects of photosynthesis.

Algae's efficiency at pulling inorganic carbon out of the environment is dependent on growth condition which implies the presence of an inducible carbon dioxide‐concentrating mechanism in algal cells.

The proposed mechanism for carbon dioxide acquisition in algae includes active HCO3−accumulation, Rubisco packaging in specialized structures and the presence of a carbonic anhydrase near the location of Rubisco.

Carbonic anhydrase is an enzyme that interconverts carbon dioxide and hydrogencarbonate which supply Rubisco with carbon dioxide from the pool of HCO3−.

The major antenna pigments in algae include chlorophylls, phycobiliproteins and carotenoids and the variation in the composition and relative abundance of these pigments give algae their distinctive colour.

Antenna complexes are proteins with many bound antenna pigments which are important in absorbing light energy.

Algal photosynthesis is thought to increase with increase in nutrient, that is, N, P and Fe availability.

If the algal photosynthesis would increase more carbon dioxide would be removed from the environment.

Algae grow faster and are very efficient in absorbing and converting solar energy into chemical energy which is mainly in the form of triacylglycerols.
Aminoacyl‐t
RNA
Synthetases
Authors: Arnez John G , Moras Dino
Published: September 2009

Aminoacyl‐tRNA synthetases
catalyse a key reaction in protein biosynthesis. They match the 20 amino acids to the genetic code by specifically attaching them to their adaptors, transfer
ribonucleic acid
(tRNA) molecules. The reaction proceeds in two steps: the amino acid is first activated by adenosine triphosphate (ATP) to form aminoacyl adenylate, and then the aminoacyl group is transferred to the terminal ribose of tRNA. This family of enzymes is divided into two classes, based on the similarities in primary structure and architecture of the active site domains; the two architectures are characterized by two modes of binding of ATP, the intermediate aminoacyl adenylate and the acceptor end of tRNA, which result in two regioselectivities of amino acid attachment to the terminal ribose of the tRNA.
Aminoacyl‐tRNA synthetases
are modular enzymes; to the central active site module are attached various domains with diverse functions such as tRNA‐binding and amino acid editing. The primary subject of this article are structural and functional aspects of these enzymes.

Key Concepts

Aminoacylation is a key reaction in protein biosynthesis, as it matches the standard 20 amino acids to the genetic code.

Aminoacylation is generally catalysed by aminoacyl‐tRNA synthetases, a family of 20 enzymes, one for each standard amino acid and a set of corresponding (cognate isoacceptor) tRNAs.

Aminoacylation proceeds in two steps, where the amino acid is first activated by ATP to form aminoacyl adenylate, a mixed anhydride, and then transferred to form an ester bond with the terminal ribose of tRNA.

Aminoacyl‐tRNA synthetases are divided into two classes, based on the similarities in primary structure (sequence) and architecture of their active site domains.

Aminoacyl‐tRNA synthetases are modular enzymes; to the central active site module are attached various domains with diverse functions such as tRNA‐binding and amino acid editing.

Aminoacyl‐tRNA synthetases are highly specific enzymes, attaching the correct amino acids to the corresponding tRNAs with high fidelity.

Aminoacyl‐tRNA synthetases of the two classes generally bind the acceptor arm of tRNA in two ways that constitute mirror images of each other, resulting in two different regioselectivities of amino acid attachment to the tRNA.
Lectins
Authors: Sharon Nathan
Published: September 2009

Lectins, a class of sugar‐specific and cell‐agglutinating proteins of nonimmune origin that are devoid of enzymatic activity, are ubiquitous in nature. Plant lectins are invaluable tools for the study of carbohydrates, in solution and on cells, and are also employed for purging of bone marrow for transplantation into ‘bubble children’. Bacterial cell surface lectins mediate the attachment of the organisms to host cell surfaces in the initiation of infection; their blocking by suitable sugars can serve as a basis of antiadhesion therapy of bacterial diseases. Those of animals control the biosynthesis of glycoproteins, play key roles in cell interactions in the immune system and serve as innate immunity agents against microbial pathogens. They also monitor the migration of leucocytes in blood vessels and contribute to proliferation and metastasis of tumour cells.

Key concepts:

Antiadhesion therapy

Carbohydrate specificity

Cell recognition

Circular homology

Glycoarrays; lectin arrays

Lectin replacement therapy

Surface carbohydrates

Multisubunit proteins
Protein‐Coding Segments: Evolution of Exon–Intron Gene Structure
Authors: Rogozin Igor B
Published: September 2009

Many eukaryotic genes are disrupted by noncoding regions of
deoxyribonucleic acid
(DNA) of variable sizes called introns, giving the genes an exon–intron structure. Origin and evolution of introns is an important, long‐standing problem. The availability of multiple, complete genome sequences allows one to address many fundamental evolutionary questions. Analysis of orthologous genes from completely sequenced eukaryotic genomes revealed numerous shared intron positions in orthologous genes between animals, fungi, plants and protists. The data on intron positions were used as the starting point for evolutionary reconstruction with various phylogenetic methods. These methods reconstructed intron‐rich ancestors but in many cases inferred lineage‐specific high levels of intron loss and gain. These results indicate that numerous introns were present already at the earliest stages of evolution of eukaryotes and are compatible with the hypothesis that the original, catastrophic intron invasion accompanied the emergence of the eukaryotic cells.

Key concepts:

The exon–intron gene structure is highly dynamic.

Orthologous genes from distant eukaryotic species share up to 25–30% intron positions.

Intron gains and losses might occur during limited time spans.

The Last Eukaryotic Common Ancestor was intron‐rich.

In the course of evolution, the splice signal shifts from exons to introns.

The scenario of the origin and evolution of introns that is best compatible with the results of comparative genomics goes as follows: self‐splicing introns since the earliest stages of life's evolution followed by numerous spliceosomal introns invading genes of the emerging eukaryotes and subsequent lineage‐specific loss and gain of spliceosomal introns.
Hypersensitivity: Immunological
Authors: Thomas Wayne R , Cunningham Paula T
Published: September 2009

Immunological hypersensitivity reactions are immune responses that produce tissue damage. In 1963, a classification system was introduced by Gell and Coombs based on how immune reactions produced the damage, and to this day it has provided a framework for the understanding of immune effector mechanisms produced directly by antigen‐specific responses or by the activation of innate immune mechanisms. It was updated in 2001 to introduce type subcategories of the type IV delayed hypersensitivity to describe cell‐mediated allergy in the light of the recent knowledge of T‐cell function. Although the classification system remains useful for describing mechanisms of tissue damage, the damage produced in an individual hypersensitivity reaction is usually produced by a mixture of mechanisms. The type I hypersensitivity mediated by IgE antibody to allergens in asthma and hay fever is, for example, typically accompanied by eosinophils from the Th2 type IVb responses.

Key Concepts

Type I hypersensitivity consists of the IgE‐mediated immediate hypersensitivity responses found in anaphylaxis and asthma attacks and slower responses caused by inflammatory cascades triggered by mediators released in the immediate reaction and by accompanying Th2 responses.

Type II hypersensitivity is mediated by the direct effects of antibody and complement‐mediated killing or opsonization.

Type III hypersensitivity is mediated by the formation of antigen–antibody complexes that either activate complement for direct toxic effects or attract inflammatory cells, especially neutrophils that bind the complexes by Fc receptors and cause tissue damage.

Type IV hypersensitivity can be subdivided depending on the type of T cell activated by the immune response.

Type IVa corresponds to the classical monocytic tuberculin‐type delayed hypersensitivity mediated by Th1 cells.

Type IVb corresponds to the eosinophilic inflammation produced by Th2 cells.

Type IVc corresponds to tissue damage produced by cytotoxic T cells and can have either granzyme B/perforin or Fas/FasL killing mechanisms.

Type IVd hypersensitivity produces tissue damage by the infiltration of neutrophils attracted by T cells producing IL‐8.

Type V hypersensitivity categorizes the damage caused by agonist effects of antibodies binding to endocrine receptors.

The tissue damage in individual hypersensitivity reactions is often caused by a mixture of the types of hypersensitivity reaction, for example, a combination of types I and IVa. IVb and IVc in contact hypersensitivity.
Arenaviruses
Authors: Kunz Stefan
Published: September 2009

The arenaviruses are a large and diverse group of enveloped
ribonucleic acid
(RNA) viruses that merit significant attention as powerful experimental models and important human pathogens. The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) has been instrumental in many landmark studies on virus–host interaction and antiviral immunity. Several arenaviruses, including

Lassa virus

in Africa and the South American arenaviruses such as

Junin virus

,

Guanarito virus

,

Machupo virus

and

Sabia virus

cause severe viral haemorrhagic fevers in humans and represent serious public health problems. Arenavirus haemorrhagic fevers are among the most devastating emerging human diseases with high fatality rates in hospitalized patients and a limited therapeutic repertoire available. Moreover, compelling evidence indicates that the worldwide‐distributed LCMV is a neglected human pathogen of clinical significance, especially in cases of congenital infection and immunocompromised individuals, as tragically illustrated by recent fatal cases of transplant‐associated infections.

Key concepts

Arenaviruses are zoonotic pathogens that are carried in nature by persistent infection of rodent hosts. The interaction of prototypic arenavirus LCMV with its host species, the mouse, provided fundamental concepts in virology and immunology. The current diversity of arenaviruses is the result of a remarkable long‐term co‐evolution between the viruses and their rodent hosts. When infecting humans as accidental hosts, some arenaviruses cause severe haemorrhagic fevers with high mortality. Arenavirus haemorrhagic fevers belong to the worst human diseases and represent important public health problems in many regions of the developing world. The epidemiology, clinical disease, diagnostics and current treatment for these diseases will be discussed. During the past decade much has been learned about the molecular and cell biology of the arenavirus life cycle. Cellular receptors for all major human pathogenic arenaviruses have been identified and first light has been shed on their mechanisms of cell entry. The advent of a powerful reverse genetic system for arenaviruses has allowed to elucidate the mechanisms of arenavirus replication, gene expression and assembly and release of progeny virions from infected cells. The investigation of the fundamental virology of arenaviruses will likely provide novel avenues for the development of efficacious therapeutic strategies against these important human pathogens.
Regeneration of Vertebrate Tissues: Model Systems
Authors: Stocum David L
Published: September 2009

Vertebrate animals exhibit three mechanisms of tissue regeneration. The most common mechanism is the proliferation and differentiation of adult stem cells, used by epithelia, muscle, bone and blood. Urodele salamanders are able to regenerate complex structures such as limbs by the dedifferentiation of adult cells to mesenchymal stem cell‐like cells at the site of amputation. Tissue lost from the vertebrate liver regenerates by compensatory hyperplasia. The mouse pancreas also regenerates by compensatory hyperplasia. The cellular activities in all these mechanisms are regulated by a wide variety of growth factors and hormones. Regenerative medicine aims to use three strategies based on regenerative mechanisms, transplants of stem cells or their derivatives, construction of bioartificial tissues composed of natural or synthetic biomaterials seeded with cells, and the pharmaceutical induction of regeneration at the site of injury by natural or synthetic regeneration‐promoting molecules.

Key Concepts

Regeneration restores the original structure and function of damaged or missing tissues.

Tissues use three mechanisms to regenerate: adult stem cells sequestered during tissue development (epithelia, bone, muscle, blood), creation of stem cells by the dedifferentiation of differentiated cells (salamander limb regeneration) and proliferation of cells in their differentiated state (liver, pancreas).

Growth factors are important regulators of regeneration.

Regenerative medicine uses three strategies to regenerate damaged tissue: cell transplants, bioartificial tissue implants and pharmaceutical induction of regeneration directly at the site of damage by scaffolds or soluble molecules.

The source of cells for transplants and bioartificial tissues is a crucial issue for regenerative medicine. Induced pluripotent stem cells (iPSCs) may solve many of the problems presented by adult and embryonic stem cells.
Anaerobic Respiration
Authors: Oren Aharon
Published: September 2009

Many prokaryotes, Bacteria as well as Archaea, can obtain energy for growth in the absence of oxygen by anaerobic respiration. In this process, electrons are transferred to electron acceptors such as nitrate, sulfate, elemental sulfur, carbon dioxide, oxidized metal ions such as Fe(III) and Mn(IV) and a range of other compounds including fumarate, dimethylsulfoxide, trimethylamine
N
‐oxide, arsenate and selenate. In all these processes, respiratory electron transport is coupled to the generation of a transmembrane proton gradient and the formation of adenosine triphosphate (ATP). Anaerobic respiration processes are seldom encountered in eukaryotic organisms. Anaerobic respiration has an important impact on the cycle of matter in nature, including processes such as denitrification (dissimilatory reduction of nitrate and nitrite to gaseous nitrogen), dissimilatory sulfate reduction with the formation of sulfide, the formation of methane and acetate from carbon dioxide and different processes in the biogeochemical cycles of metals.

Key concepts

When oxygen is not available for respiration many prokaryotes can use alternative electron acceptors to obtain energy by respiration.

Anaerobic respiration is widespread in the two domains of prokaryotes: the Bacteria and the Archaea.

Some prokaryotes can perform both aerobic and anaerobic respiration; others are obligate anaerobes that cannot use oxygen as electron acceptor for respiration.

Denitrification, or dissimilatory reduction of nitrate to gaseous nitrogen, is an important process in the global nitrogen cycle.

In anaerobic environments sulfate serves as terminal electron acceptor and is reduced to sulfide, giving rise to both the formation of metal sulfides in sediments and the evolution of hydrogen sulfide gas.

Carbon dioxide is used as terminal electron acceptor by methanogenic Archaea for energy generation, yielding methane as final product and by different groups of prokaryotes to produce acetate.

Anaerobic respiration processes are involved in a wide range of reactions involving oxidized ions of metals (iron, manganese, chromium, uranium and others) and metalloids (arsenic, selenium).

Anaerobic respiration has important economic implications, both favourable (e.g. conversion of bound nitrogen to nitrogen gas in water purification plants) and unfavourable (e.g. loss of available nitrogen in agricultural soils, corrosion of steel pipes mediated by sulfate‐reducing bacteria).
Inbred Animal Strains
Authors: Kurosawa Tsutomu
Published: September 2009

There are four main genetic types of laboratory animal used in biomedical research animal breeding systems: inbred strains, mutant strains, closed colony and hybrid animals. An inbred strain is one created by at least 20 generations of brother–sister mating; members share a unique set of characteristics. Outbred animal strain is an antonym. The cloned animals are ultimate forms which are genetically identical. Congenic strain is produced from gene‐modified animals such as transgenic and knockout animals crossed to inbred strain for a precise analysis of modified genes. There are many disease model animals which are inbred to analyse the responsible gene of the target disease. For immunology, cancer research, transplantation technology and regenerative medicine, the usefulness of inbred animal strain is increased with the usage of embryonic stem (ES) and induced pluriopotent stem (iPS) cells. The quality control of inbred strain is made with genetic monitoring.

Key Concept

Inbred animal strain is part but main and key laboratory animals for fundamental biomedical research.

It is produced by brother–sister mating but its ultimate form is a cloned animal in which all of the genes are identical.

They are used for gene analysis and medicine as disease models.

There have been many incurable diseases which are caused by gene dysfunction are now treated using the fundamental knowledge found in inbred disease model animal strains.

The immunology and cancer research as fundamental medicine, and organ transplantation and regenerative medicine as modern medical technology have been advanced with its usage.

The knowledge of cell therapy will be advanced with the usage of inbred animal strain.

Before the application of ES and iPS cells for medical therapy, the fundamental research should be made on them.
Deafness
Authors: Terrinoni Alessandro , Melino Gerry , Serra Valeria , Alessandrini Marco , Napolitano Bianca , Bruno Ernesto
Published: September 2009

Recent statistical data indicate that in western countries, at least 1:1000 suffer of congenital hearing impairment. Genetic factors are responsible for more than 60% of the congenital cases. Sometimes, however, hearing loss is a multifactorial disorder caused by both genetic and environmental factors. Molecular genetics of deafness has experienced remarkable progress in the last decade. Genes responsible for hereditary hearing impairment are being mapped and cloned progressively. This article, while reporting some syndromic conditions related to deafness, focuses on nonsyndromic hearing loss. Genes involved in this type of pathologic condition have only recently begun to be identified. Owing to genetic heterogeneity, private nature of most mutations and large size of most deafness genes, the molecular diagnostic possibilities in recessive deafness are today limited only for a few genes. Facility and benefits of genetic tracking, in particular, should make it an important public health issue so that determinations of early diagnosis of hearing loss can be properly established.

Key concepts:

Deafness is the most common sensory deficit in humans, affecting 1 in 1000 new‐born, and to date more than 23 different DFNB proteins have been discovered.

DFNB proteins can be classified into two classes: (1) genes regulating potassium homeostasis and (2) genes producing proteins that are important in the formation of stereocilia.

Owing to genetic heterogeneity, the molecular diagnostic possibilities in recessive deafness are still limited. However, facility and benefits of genetic tracking should make them an important public health issue.
Terpenoids: Higher
Authors: Devarenne Timothy P
Published: September 2009

Terpenoids (or isoprenoids/isopentenoids) are a diverse group of compounds that are found throughout nature and are biosynthesized through the successive condensation of the five‐carbon compound isoprene. Higher terpenoids are complex structures that possess minimally between 20 and 40 carbon atoms. Although higher terpenoids are found in all organisms, plants produce the largest array of higher terpenoids in terms of number, structure and function. These plant‐derived higher terpenoids can be utilized by humans for purposes such as drugs to fight diseases or as feedstocks for biofuel production. The genes responsible for producing these plant of higher terpenoids are just now beginning to be identified and these studies are showing that higher terpenoids are essential for plant growth, development and defence against pathogens.

Key concepts:

Higher terpenoids contain at least 20 carbons and comprise many different structures and functions.

Triterpenoids originate from C
30
squalene which is directly cyclized in bacteria and oxygenated and then cyclized by eukaryotes.

Sterols are important regulators of membrane fluidity as well as the production of steroid hormones in both animals and plants.

Plants produce more higher terpenoids than any other organisms with many functions including defence against pathogens.
Macromolecular Interactions: Light Scattering
Authors: Folta‐Stogniew Ewa J
Published: September 2009

Static light scattering (SLS) is a spectroscopic technique for determination of molar masses (molecular weights) and radii of gyration for macromolecules in solution. Dynamic light scattering (DLS) measurement allows determination of translational diffusion coefficient and hydrodynamic radius. Measurement of molar mass from SLS experiment determines the oligomeric state and thus provides association stoichiometry for biological macromolecules such as native and modified proteins and their complexes, nucleic acids as well as phospholipid vesicles, viruses or drug delivering nanoparticles. Both static and DLS are routinely used to assess monodispersity (homogeneity with respect to molar mass or size) of protein stocks prepared for structural studies. Both homo‐ and hetero‐association of proteins can be detected and quantitatively characterized from light scattering measurements performed at various concentrations.
Berger, Hans
Authors: Borck Cornelius
Published: September 2009

Hans Berger (1873–1941), a German neuro‐psychiatrist, was the first to publish the human electroencephalogram, the recording of the electric activity of the human brain. The method kindled wide public interest for its alleged potential to read foreign minds. After its scientific soundness was confirmed, the method was quickly introduced in research for investigating the neuronal activity within the brain. In addition, it still is an important clinical tool, for example, for diagnosing epilepsy or other neurological conditions.
Intestinal Epithelial Cells: Immunological Aspects
Authors: Stadnyk Andrew W
Published: September 2009

Intestinal epithelial cells are the cell boundary between the external environment and tissues of the gastrointestinal tract. From this interface the epithelial cells have evolved processes that help guide whether inflammation or an immune response will occur in the intestines. Indeed intestinal epithelial cells are active participants in the inflammatory and immune response because they (1) secrete inflammatory mediators, including cytokines, when they detect certain microbes; (2) secrete mediators when they become detached from the basement membrane; (3) recruit and engage dendritic cells, professional antigen‐presenting cells which sample the intestinal lumen prior to presenting antigens to lymphocytes and (4) directly present antigens to T lymphocytes using a unique repertoire of molecules. Antigen presentation to lymphocytes is required for the initiation of a specific adaptive immune response, whether humoral (antibody) or cellular, and may be key to explaining many human chronic inflammatory diseases.

Key concepts

Intestinal epithelial cells form a monolayer of cells that define the boundary between tissues of the intestine and the external environment.

From this point of interface, intestinal epithelial cells receive and interpret insults/assaults from the intestinal lumen and signal to the tissues whether inflammation will ensue.

Intestinal epithelial cells communicate through the secretion of protein and glycoprotein mediators, some of which launch the inflammatory response including by recruiting leucocytes into the tissues.

Intestinal epithelial cells interact with and control lymphocyte activation using specialized molecules, some of which are used in antigen presentation.

Antigen presentation to lymphocytes is critical to launching the adaptive (humoral and cellular) immune responses.

Antigen presentation by intestinal epithelial cells most commonly results in the inhibition of activation of T lymphocytes, including CD8+ T lymphocytes.