bluuebunny/crossref_metadata_2025 huggingface dataset:
La distinción entre Ugandapithecus y Proconsul
Authors: Pickford M. , Senut B. , Gommery D. , Musiime E.
Published: December 2009

La decisión de crear el género Ugandapithecus por Senut et al. (2000) ha sido criticada, tanto directamente y en detalle por Maclatchy & Rossie (2005b) que argumentan que es una sinonimia de Proconsul, o indirectamente sin ninguna argumentación, primero por Harrison (2001) que no lo considera como distinto de Proconsul, y después por Suwa et al. (2007) que emplean el nombre de “Ugandapithecus” entre comillas, implicando algún grado de duda sobre su validez como género. Recientemente Harrison & Andrews (2009) han reconocido la muestra de Meswa como una especie diferente, pero argumentando que debería ser mantenida en Proconsul, a pesar de las diferencias morfológicas que posee con respecto a otras especies del género. En este trabajo reexaminamos el problema, por un lado comparando, el maxilar holotipo de Proconsul africanus, especie tipo del género, con la dentición superior de Ugandapithecus major y por otro lado, con la dentición inferior y mandíbulas previamente atribuidas a Proconsul africanus. La conclusión de estas comparaciones es que las diferencias entre las denticiones superiores e inferiores conocidas de P. africanus y U. major son de tal grado que los dos taxones necesitan una separación genérica, y que las diferencias no están relacionadas con dimorfismo sexual. Tanto como Proconsul difiere de Ugandapithecus major , se aproxima a Proconsul nyanzae y Proconsul heseloni de Rusinga.
Además, el rango de variación morfométrica en la muestra previamente atribuida a Ugandapithecus es tan grande que sobrepasa de lejos la variación conocida en cualquier hominoideo, fósil o actual. Previamente esta importante variación fue interpretada como debida a que U. major era extremadamente dimórfico, con enormes machos y pequeñas hembras, pero si esto fuese verdad, entonces U. major sería único entre los hominoideos al tener hembras cuya dentición cae completamente fuera del rango de variabilidad de la dentición de los machos. En todos las otras especies conocidas de hominoideos, machos y hembras poseen rangos dentarios cuyas dimensiones se solapan ampliamente. Los gráficos bivariantes de los dientes atribuidos a Ugandapithecus revelan tres agrupaciones independientes para los ejemplares del Mioceno inferior, que nosotros interpretamos como representantes de tres especies diferentes. Una cuarta especie del género, U. gitongai fue previamente definida en el yacimiento Mioceno Medio de Kipsaraman, Kenia. Nosotros podemos concluir que Ugandapithecus constituyó una línea de grandes simios distintos de Proconsul, en los que su principal tendencia evolutiva fue el incremento en talla desde Ugandapithecus meswae de la base del Mioceno Inferior (21,5-19 Ma) hasta las especies final del Mioceno Inferior, Ugandapithecus legetetensis (20-19 Ma) y Ugandapithecus major (19-18 Ma), culminando en Ugandapithecus gitongai del final del Mioceno medio (ca. 14,5 Ma).
Rehabilitación de las instalaciones eléctricas en los edificios destinados principalmente a viviendas
Authors: Toledano J. C. , De las Casas J. Mª. , Bedoya C.
Published: December 2009

Este trabajo tiene como objetivo difundir la complejidad que conlleva la rehabilitación de las instalaciones eléctricas de un edificio dentro de la rehabilitación integral de los mismos, así como la normativa que la regula y que el proyectista, y posteriormente el instalador electricista que realiza la obra, deben de cumplir.
A la hora de pensar en la rehabilitación de la instalación eléctrica de un edificio debemos plantearnos que es lo que se va a rehabilitar y cual va a ser el uso de esas instalaciones después de la rehabilitación, teniendo presente que el trabajo que se realice tiene que ser de utilidad al menos para 30 – 50 años.
Se hace un repaso de todas las partes que componen las instalaciones eléctricas de enlace de un edificio, normativa a aplicar y forma de ejecución. En las instalaciones interiores de las viviendas se describen los circuitos que como mínimo se deben ejecutar de acuerdo con el reglamento electrotécnico para baja tensión de 2002, actualmente en vigor, y que habilitan a esas viviendas para el nivel de electrificación que requieren actualmente las viviendas.
Los trabajos de rehabilitación de instalaciones eléctricas requieren un manejo importante de la legislación actual, tanto a nivel nacional como autonómica, y una gran experiencia en cómo aplicar esta norma en los edificios, por cuyas características debemos conservar, haciendo unas instalaciones que no deterioren el edificio en su conjunto ni en sus partes más significativas.
La evolución de la construcción del Templo de la Sagrada Familia
Authors: Espel R. , Gómez J. , Grima R. , Aguado A.
Published: December 2009

El Templo de la Sagrada Familia (Barcelona, 1882–hoy) es, aun inacabado, una de las obras más importantes de Gaudí y uno de los máximos exponentes de la arquitectura modernista catalana. Este artículo hace un recorrido en la evolución de la construcción del Templo, haciendo hincapié en los retos constructivos que han supuesto las formas de Gaudí.
A lo largo de la historia los materiales se han adaptado a las necesidades de cada parte a realizar. A finales del s. XIX, Gaudí empezó construyendo principalmente a base de mampostería tradicional, pero dedicó años al estudio del resto del Templo y a los diferentes materiales con los que podía construirse. El texto continúa describiendo cómo los colaboradores de Gaudí siguieron las obras tras su muerte y cómo, en los últimos años, se han introducido en el Templo los últimos avances en los procesos constructivos y en los materiales. Buen ejemplo de ello son los hormigones de prestaciones especiales utilizados en la actualidad y las técnicas de dibujo asistido por ordenador más avanzadas del mercado.
Prostaglandin E2 Inhibits IFN-α Secretion and Th1 Costimulation by Human Plasmacytoid Dendritic Cells via E-Prostanoid 2 and E-Prostanoid 4 Receptor Engagement
Authors: Fabricius Dorit , Neubauer Marina , Mandel Birgit , Schütz Catharina , Viardot Andreas , Vollmer Angelika , Jahrsdörfer Bernd , Debatin Klaus-Michael
Published: December 2009

Plasmacytoid dendritic cell (PDC)-derived IFN-α plays a central role in antiviral defense and in Th1-driven autoimmune diseases, such as systemic lupus erythematosus (SLE). In the current study, we explored how PGE2 effects the phenotype of PDCs from healthy and SLE subjects. Although PGE2 is considered to mediate mainly proinflammatory effects, we show that PGE2 and PG analogs potently inhibit secretion of IFN-α by TLR-activated PDCs. This effect is mainly mediated by PG receptors E-prostanoid 2 and E-prostanoid 4 and involves inhibition of IFN regulatory factor 7 expression. Of note, profound IFN-α inhibition by PGE2 is also seen in PDCs from SLE subjects, independent of age, disease activity, and therapy. We show that TLR9-activated PDCs treated with PGE2 exhibit DC2-like characteristics with enhanced expression of CD86 and CD62L, and decreased expression of CD80 and MHC class I. Consequently, PGE2-treated PDCs suppress secretion of Th1 cytokines by T cells while increasing the secretion of Th2 cytokines. Prevention of CpG-induced CD62L downregulation by PGE2 suggests that it may induce the retreat of PDCs from inflamed tissues. Our data on the effects of PGE2 on PDCs may explain occasional reports about the induction of SLE-like symptoms by cyclooxygenase inhibitors as well as improvement of such symptoms by treatment with PG analogs. In conclusion, our data suggest that PGE2 and certain PG analogs, some of which are already in clinical use, should be evaluated as a novel and inexpensive treatment approach for patients with SLE and other IFN-α–dependent, Th1-driven autoimmune diseases.
Granzyme A- and B-Cluster Deficiency Delays Acute Lung Injury in Pneumovirus-Infected Mice
Authors: Bem Reinout A. , van Woensel Job B. M. , Lutter Rene , Domachowske Joseph B. , Medema Jan Paul , Rosenberg Helene F. , Bos Albert P.
Published: December 2009

Lower respiratory tract infection by the human pneumovirus respiratory syncytial virus is a frequent cause of acute lung injury in children. Severe pneumovirus disease in humans is associated with activation of the granzyme pathway by effector lymphocytes, which may promote pathology by exaggerating proapoptotic caspase activity and proinflammatory activity. The main goal of this study was to determine whether granzymes contribute to the development of acute lung injury in pneumovirus-infected mice. Granzyme-expressing mice and granzyme A- and B-cluster single- and double-knockout mice were inoculated with the rodent pneumovirus pneumonia virus of mice strain J3666, and were studied for markers of lung inflammation and injury. Expression of granzyme A and B is detected in effector lymphocytes in mouse lungs in response to pneumovirus infection. Mice deficient for granzyme A and the granzyme B cluster have unchanged virus titers in the lungs but show a significantly delayed clinical response to fatal pneumovirus infection, a feature that is associated with delayed neutrophil recruitment, diminished activation of caspase-3, and reduced lung permeability. We conclude that granzyme A- and B-cluster deficiency delays the acute progression of pneumovirus disease by reducing alveolar injury.
Cutting Edge: Sympathetic Nervous System Increases Proinflammatory Cytokines and Exacerbates Influenza A Virus Pathogenesis
Authors: Grebe Kristie M. , Takeda Kazuyo , Hickman Heather D. , Bailey Adam M. , Embry Alan C. , Bennink Jack R. , Yewdell Jonathan W.
Published: December 2009

Although the sympathetic nervous system innervates the lung, little is known about its participation in host immunity to pulmonary pathogens. In this study, we show that peripheral sympathectomy reduces mouse morbidity and mortality from influenza A virus-induced pneumonia due to reduced inflammatory influx of monocytes, neutrophils, and NK cells. Mortality was also delayed by treating mice with an α-adrenergic antagonist. Sympathectomy diminished the immediate innate cytokine responses, particularly IL-1, which was profoundly reduced. These findings demonstrate an unexpected role for the sympathetic nervous system in innate antiviral immunity and in exacerbating the pathology of a virus of great significance to human and animal health.
Sharing in God�s surprise: The place and role of the Department of Science of Religion and Missiology at the University of Pretoria
Authors: Meiring Pieter G.J.
Published: December 2009

During the centenary year of the University of Pretoria (2008), the Department of Science of Religion and Missiology took stock of its activities during the past 55 years, since the first professor in Missiology, H.D.A. du Toit, was appointed. In his wake a number of missiologists followed � C.W.H. Boshoff, D. Crafford, P.G.J. Meiring, J.J. Kritzinger, P.J. van der Merwe, A.S. van Niekerk and C.J.P. Niemandt � each of whom has contributed to the formation of hundreds of ministers and missionaries, as well as to the development of missiology and science of religion in South Africa through their research and writings. In this article, the place of missiology among the other theological disciplines at the University of Pretoria is discussed, together with an analysis of the nature and the mandate of missiology and science of religion in South Africa in our day. This article discusses five specific challenges to missiology at the beginning of the third millennium, namely to maintain its theological �roots�; to operate in close relationship with the church; to focus on our African context; to concentrate on a relevant agenda; and to develop a responsible methodology. Attention is given to some of the more important publications by members of the Department.
Seventy years of dogmatics and Christian ethics at the University of Pretoria: A Dutch reformed perspective
Authors: Wethmar Conrad
Published: December 2009

This article provides a brief analysis and evaluation of the work done by the Department of Dogmatics and Christian Ethics at the University of Pretoria during its history of 70 years. The respective periods of tenure of the successive members of staff were extensive enough to serve as a basis for distinguishing between various phases in the development of the Department. In each of the phases, a significant and istinctive contribution was made to the academic enterprise of the Faculty of Theology, as well as to the work of the Dutch Reformed Church which was represented by the relevant members of staff.
Imaging Nervous System Activity
Authors: Fields R. Douglas , Shneider Neil , Mentis George Z. , O'Donovan Michael J.
Published: December 2009

This unit describes methods for loading ion‐ and voltage‐sensitive dyes into neurons, with a particular focus on the spinal cord as a model system. In addition, we describe the use of these dyes to visualize neural activity. Although the protocols described here concern spinal networks in culture or an intact in vitro preparation, they can be, and have been, widely used in other parts of the nervous system. Curr. Protoc. Neurosci. 49:2.3.1‐2.3.14. © 2009 by John Wiley & Sons, Inc.
Assessment of Parkinson Disease Manifestations
Authors: Perlmutter Joel S.
Published: December 2009

Parkinson disease (PD) is a progressive neurologic condition that causes motor and nonmotor manifestations. Treatment provides symptomatic benefit but no current treatment has been proven to slow disease progression. Research studies of PD require a means of rating the severity of disease by measurement of motor manifestations, assessment of ability to perform daily functional activities, and symptomatic response to medication. The most common rating scales are the Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr staging, and the Schwab and England rating of activities of daily living. Each of these rating scales are described, including detailed instructions on how to implement these ratings. Although these are the most widely applied rating scales of PD, there are still substantial limitations to these scales that must be considered when using them for research. Finally, some common applications of these scales are described. Curr. Protoc. Neurosci. 49:10.1.1‐10.1.14. © 2009 by John Wiley & Sons, Inc.
EEG Recording and Analysis for Sleep Research
Authors: Campbell Ian G.
Published: December 2009

The electroencephalogram (EEG) is the most common tool used in sleep research. This unit describes the methods for recording and analyzing the EEG. Detailed protocols describe recorder calibration, electrode application, EEG recording, and computer EEG analysis with power spectral analysis. Computer digitization of an analog EEG signal is discussed, along with EEG filtering and the parameters of fast Fourier transform (FFT) power spectral analysis. Sample data are provided for a typical night's analysis of EEG during NREM (non‐REM) and REM sleep. Curr. Protoc. Neurosci. 49:10.2.1‐10.2.19. © 2009 by John Wiley & Sons, Inc.
Neuropsychological Assessment in the Diagnosis of Alzheimer's Disease
Authors: Baldwin Sharelle , Farias Sarah Tomaszewski
Published: December 2009

Alzheimer's disease (AD) is the most common form of dementia in older adults. It represents a significant public health concern because of its associated personal, social, and economic burden. As such, AD is the focus of considerable research worldwide. This unit reviews the major cognitive and behavioral impairments associated with AD, and the practical application of current neuropsychological procedures used to assess these deficits.Curr. Protoc. Neurosci. 49:10.3.1‐10.3.8. © 2009 by John Wiley & Sons, Inc.
Bacterial Cell Division
Authors: Lutkenhaus Joe
Published: December 2009

Bacterial cell division or cytokinesis is the process in which a bacterial cell is split into two progeny cells, each with a copy of the chromosome. In most bacteria this process in initiated by the formation of the Z ring, a dynamic structure consisting of polymers of
FtsZ
, a
tublin
family member. The Z ring recruits additional division proteins to form the septal ring, also called the divisome, which leads to the synthesis of the septum separating the progeny cells. Spatial regulation of Z‐ring formation occurs primarily through negative regulators of
FtsZ
assembly that are positioned within the cell. The Z ring forms where the concentration of these negative regulators is at a minimum. A variety of regulators and mechanisms for positioning them have been identified in different bacteria. Among the mechanisms are the binding of a regulator to the segregating chromosome or the divisome itself and a self‐organizing system.

Key concepts:

Division depends on a cytoskeletal element (Z ring) that functions as a scaffold to recruit all the division proteins.

Spatial regulation of Z ring placement involves positioning inhibitors of FtsZ in the cell to prevent FtsZ polymers from coalescing into the ring.

Dynamic self‐organization – the ability of proteins to form dynamic structures and patterns fuelled by nucleotide hydrolysis; the Min system produces an oscillatory pattern and FtsZ filaments have the ability to form rings when attached to a lipid bilayer that has a cylindrical shape.
Ascomycota
Authors: Eriksson Ove E
Published: December 2009

The ascomycetes, the spore sac fungi, are accommodated in the phylum Ascomycota, the largest of the seven phyla of the true fungi with more than 60 000 species. Many are saprobes; others are parasites or live in symbiosis with other organisms. A majority of the lichens are ascomycetes. The ascomycetes are of great economic importance as decomposers of dead material, parasites on crops, producers of antibiotics and other industrial products in food production (bread, beer, wine, etc.).
TransferRNASynthesis and Regulation
Authors: Toh Yukimatsu , Hori Hiroyuki , Tomita Kozo , Ueda Takuya , Watanabe Kimitsuna
Published: December 2009

Transferribonucleic acid(tRNA) is primarily synthesized from tRNA gene through transcription byRNA polymeraseand becomes the mature form via several steps: processing, splicing, CCA addition and posttranscriptional modification. Primary transcripts of tRNA genes contain 5′ and 3′ extra sequences, which are removed by a set of responsible nucleases, and introns in some cases, which are spliced out by a specificendonuclease. The resultant two fragments are joined byRNA ligase. The CCA sequences present at 3′‐termini of all mature tRNAs are not encoded in tRNA genes in some species and posttranscriptionally added by a CCA‐adding enzyme. All mature tRNA molecules contain modified nucleotides made by modification enzymes and which are considered to be involved in stabilization of tRNA structure, in decoding properties and in correct processing. The concentration of individual tRNA molecules is controlled to maintain cellular functions.

Key concepts:

tRNA is synthesized from tRNA gene by RNA polymerase and matured through processing, splicing, CCA addition and posttranscriptional modification.

Synthesis of tRNA is regulated by promoter activity and specific factors (ppGpp and/or pppGpp in prokaryotes and Maf1 in eukaryotes) depending on the nutrient condition of the cells.

The relative amounts of tRNA are regulated by several factors; the copy number of the tRNA gene, transcriptional activity aforementioned and tRNA degradation by a number of nucleases.

Primary transcripts of tRNA genes contain 5′ and 3′ extra sequences, which are removed by a set of responsible nucleases.

In some cases tRNA transcripts contain introns, which are spliced out by a specific endonuclease and the resultant two fragments are joined by RNA ligase.

CCA‐adding enzyme regulates the amount of active tRNA by repairing CCA sequence at theC‐terminal of tRNA.

tRNA possesses a variety of modified nucleotides which are introduced by modification enzymes during or after the processing, splicing and transport steps.

Several modifications in tRNA play important roles in the translation process, such as enhancement, expansion, restriction and/or alteration of codon–anticodon interactions, stabilization of tRNA structure, recognition by aminoacyl‐tRNA synthetase, etc.
Methanogenesis Biochemistry
Authors: Lessner Daniel J
Published: December 2009

Methanogenesis is the biological production of methane mediated by anaerobic microorganisms from the Archaea domain commonly called methanogens. The production of methane is the energy‐yielding metabolism of methanogens and is unique to these organisms. Methane is produced by three major pathways: (1) reduction of carbon dioxide, (2) fermentation of acetate and (3) dismutation of methanol or methylamines. All three pathways have in common the demethylation of methyl–
coenzyme M
to methane and the reduction of the heterodisulfide of
coenzyme M
and
coenzyme B
catalysed by
methyl–coenzyme M
and
heterodisulfide reductases
. Investigations of the biochemistry of the pathways have revealed novel enzymes with metal and cofactor requirements that have introduced new principles of biochemistry.

Key Concepts

Methanogenesis is the final step in the biological decomposition of biomass in the absence of oxygen.

Approximately 70% of biologically produced methane originates from conversion of the methyl group of acetate to methane.

The pathway of methanogenesis involves enzymes with novel cofactor and metal requirements.

Nickel is an essential metal that is found in the active site of carbon monoxide dehydrogenase, hydrogenase, and methyl–coenzyme M reductase, an enzyme which is common to all methanogenic pathways.

Methyltransferases involved in the metabolism of methylamines by
Methanosarcina
species contain pyyrolysine, the 22nd amino acid.

Comparative genomics combined with biochemical analyses have revealed variations in the enzymes involved in the energy‐conservation steps in methanogens.

Energy conservation in methanogens is linked to the generation of a chemical gradient that drives ATP synthesis by an ATP synthase.
Immunoglobulin Gene Rearrangements
Authors: Lieber Michael
Published: December 2009

V(D)J and class switch recombination are two
deoxyribonucleic acid
(DNA) recombination processes that occur at immunoglobulin genes during the generation of B cells and the attendant rearrangement of immunoglobulin heavy and light chain loci. V(D)J occurs during early B‐ and T‐cell development whereas class switch recombination occurs exclusively in mature B cells. V(D)J recombination achieves the assembly of new exons that encode the portion of the antigen receptor that binds antigen. Class switch recombination changes the constant portion of the heavy chain of the antibody from IgM to IgG, IgA or IgE. V(D)J recombination occurs in the bone marrow for pre‐B cells and in the thymus for pre‐T cells. Class switch recombination occurs in the germinal centres in the spleen, lymph nodes and Peyer's patches.

Key Concepts:

V(D)J recombination occurs only in vertebrates, because these are the only organisms that have lymphocytes and that generate B and T cells with antigen receptors.

V(D)J recombination is done by the RAG1 and RAG2 proteins, which bind at recombination signal sequences (RSS) that consist of heptamer and nonamer recognition sequences.

The RAG complex (consisting of RAG1 and RAG2, along with HMGB1) is only expressed in pre‐B cells and pre‐T cells.

Class switch recombination requires activation‐induced deaminase (AID).

AID acts only on single‐stranded DNA.

For class switch regions, single‐stranded DNA is generated by the formation of R‐loops at the switch regions.

Switch regions consist of unit repeats (25–80 bp in length) that are 40–50% G on the nontemplate strand, making them prone to form R‐loops.

Occasionally, the RAG complex or AID act at off‐target sites, thereby triggering double‐strand breaks that can cause the chromosomal translocations that initiate many types of lymphomas or lymphoid leukaemias.
Protein Kinases: Signatures in Cancer
Authors: Sowadski Janusz M , Suto Robert K
Published: December 2009

Since the discovery of the first
protein kinase
crystal structure, structures of over 50
protein kinases
have been solved. This crystallographic tour‐de‐force has catalysed structure‐based design of specific inhibitors, resulting in over 100 000 patent protected molecules. One‐third of the pharmaceutical industry R&D worldwide is directed towards kinase inhibition. Concerted efforts resulted in Food and Drug Administration approval for several drugs including the most successful oncology drug – imatinib (Gleevec) developed by Novartis. The challenge now is to overcome drug resistance and increase drug efficacy through genetic patient stratification in clinical trials and clinical practice. Clinical data of
deoxyribonucleic acid
(DNA) sequences that contain key genes serve as the basis for establishing signatures for responding patients and allow the ‘tailoring’ of a particular drug to specific patient populations. Such a signature‐based approach can enhance the value of already approved drugs and may be used to treat patients with different cancer subtypes.

Key concepts:

All kinase inhibitors that are FDA approved as first in line oncology drugs compete with ATP binding to the kinase catalytic core.

Clinical responses of CML cancer patients to imatinib depend on the specific genetic signatures of the patients.

Resistance of CML patients to imatinib can be overcome by structure‐based redesigning of the inhibitor molecule.

Imatinib can treat cancer patients with very different cancer subtypes, such as CML and GIST.

CML and GIST patients responding to imatinib have common activating kinase mutations.

Only 10% of NSCLC patients respond to gefitinib or erlotinib; these responding patients have specific genetic signatures.

Activating mutants of responding NSCLC patients have a lower affinity to ATP.

There is a common site in the catalytic core of kinases where mutations can lead to higher affinity to ATP and this site can also be associated with patients who develop resistance to imatinib, gefinitib and erlotinib.
Polymerase Chain Reaction (
PCR
)
Authors: Metzker Michael L , Caskey C Thomas
Published: December 2009

Polymerase chain reaction (PCR) is a rapid,

in vitro

deoxyribonucleic acid
(DNA) synthesis process, which can amplify up to a billion copies of a given nucleic acid target. It has been extensively applied for the identification, detection and diagnosis of genetic and infectious disease. In the article, we provide a general overview of the PCR process, describe methods to identify and minimize exogenous contamination, and highlight limitations of product size and polymerase‐dependent errors. We present many of the applications for which PCR is used, particularly in creating recombinant DNA constructs, in detecting genetic variation, in preparing templates for DNA sequence analysis and in quantitating gene transcripts or viral copies. Whole genome amplification and the ligation chain reaction are also presented, which we believe this article provides the reader with a comprehensive viewpoint of the variety of amplification‐based methods used in molecular biology today.

Key Concepts

Polymerase chain reaction is an
in vitro
amplification method widely used in molecular biology.

PCR contamination can occur from a single molecule of foreign or exogenous DNA, which, if gone unchecked, can confound the interpretation of results.

PCR cloning of full‐length genes can be problematic because mutations can result in amino acid substitutions in wild‐type sequences.

PCR can reliably amplify target sizes up to 3–4 kb from a variety of source materials.

Recombinant PCR products can be created by mismatching sequences between the primer and the template DNA or by adding 5′ exogenous sequences to the primers.

PCR can detect human genetic variation associated with hereditary disease and cancer.

Degenerate PCR is a powerful tool for identifying novel gene family members that are important in drug development.

Quantitative PCR has been widely used for studying gene expression and estimating viral copy number.

Emulsion PCR is used to prepare templates in a cell‐free system for next‐generation sequencing platforms.

Whole genome amplification uses the highly processive φ29 DNA polymerase to amplify nanogram quantities of precious samples into microgram amounts.
Systemic Signalling in Plant Defence
Authors: Helliwell Emily E , Yang Yinong
Published: December 2009

Systemic signalling involves a complex network of signal transduction and amplification that leads to the activation of defence genes and establishment of systemic resistance throughout the entire plant. On microbial invasion, pathogen‐associated molecular patterns and effectors are frequently detected and recognized by plant receptors. Localized perception at the infection site rapidly triggers a cascade of early signalling events such as ion fluxes, protein phosphorylation and production of reactive oxygen species. Subsequently, secondary signal molecules are synthesized and involved in amplification of defence signalling and the establishment of systemic acquired resistance. In addition, crosstalks often occur among various signalling pathways, which further modulate host defence in response to different types of pathogen attack.

Key concepts:

Local resistance to pathogen infection generally results from PAMP (pattern‐associated molecular pattern)‐triggered immunity, otherwise known as basal defence, and microbial effector‐triggered immunity.

Microbial infection of local tissues often leads to systemic acquired resistance in distal tissues which provides long‐lasting broad‐spectrum resistance to a variety of pathogens.

Mobile signals for systemic acquired resistance are translocated via vasculature and may include small peptides such as AtPep1, methyl salicylate, jasmonate, azelaic acid and other lipid‐derived molecules.

Both local and systemic resistance involve a complex network of signal transduction which includes extensive crosstalks among reactive oxygen species (e.g. hydrogen peroxide and nitric oxide), salicylic acid, jasmonic acid, ethylene, abscisic acid, auxin and MAP kinase signalling pathways.
Cholesterol Metabolism and Vascular Disease
Authors: Olufadi R , Wild SH , Byrne CD
Published: December 2009

Cholesterol is packaged into lipoprotein particles in the liver and intestine and transported to peripheral tissues for normal cellular function. Reverse cholesterol transport is the mechanism by which excess cholesterol is transported back to the liver and is facilitated by high‐density lipoproteins (HDLs). Increased plasma concentrations of cholesterol within the low‐density lipoprotein (LDL) contribute to atherosclerotic vascular disease that commonly affects the coronary, cerebral and peripheral vascular circulation. Incontrovertible evidence now supports the use of the ‘statin’ class of drugs to decrease vascular disease. Statins inhibit hepatic cholesterol synthesis, increase hepatic low‐density lipoprotein cholestrol (LDLc) receptor expression and consequently decrease plasma LDLc, to reduce risk of myocardial infarction in people at widely varying risk of heart disease. At present, there is limited evidence to support the use of drugs that modify high‐density lipoprotein cholesterol (HDLc) to reduce risk of heart disease.

Key concepts

Endogenous and exogenous lipid pathways.

Hypercholesterolaemias.

Low‐density lipoprotein cholesterol (LDLc) and heart disease.

High‐density lipoprotein (HDL) metabolism.

Modification of high‐density lipoprotein cholesterol (HDLc) and heart disease.

Pathophysiology of vascular disease in relation to lipid metabolism.
Calorimetry
Authors: Lewis Edwin A
Published: December 2009

In biology, particularly in studies relating the structure of biopolymers to their functions, two of the most important questions are: (1) how tightly does a small molecule bind to a specific interaction site and (2) if the small molecule is a substrate and is converted to a product, how fast does the reaction take place? Since almost any chemical reaction or physical change is accompanied by a change in heat or enthalpy, an isothermal titration calorimeter (ITC) is an ideal instrument to measure either how much of a reaction has taken place or the rate at which a reaction is occurring. In contrast to optical methods, calorimetric measurements can be done with reactants that are spectroscopically silent (a chromophore or fluorophore tag is not required), can be done on opaque, turbid or heterogeneous solutions( e.g. cell suspensions) and can be done over a range of biologically relevant conditions (temperature, salt, pH, etc).

Key Concepts

Almost all chemical reactions are accompanied by a change in heat or enthalpy.

Calorimetry can determine the complete set of thermodynamic parameters that characterize binding reactions, e.g. K, Δ
G
°, Δ
H
°, Δ
S
° and Δ
C
p
.

Binding reactions are typically pH, salt and temperature dependent.
Nature/Nurture – A Philosophical Analysis
Authors: Ariew André
Published: December 2009

The debate about whether some attribute is ‘by nature’ or ‘by nurture’ has a long history and it covers numerous topics. For instance, Socrates proposed that our ideas of complex concepts come from memories that are innate within us. Even today thinkers believe that some of our ideas are part of our nature rather than our nurture. This theory has social and policy implications. If intellectual quotient (IQ) is a fixed part of nature, is it worthwhile to contribute tax dollars to improve one's nurturing environment? Or, more generally, some think that understanding human nature might affect how we ought to live. Influenced by Darwin and developments in genetics, the nature/nurture debate has reduced to a debate about whether our attributes are ‘genetic’ or ‘environmental’. Yet, the implications of the genetic theories of human nature are not obvious since genes alone do not produce any attributes.

Key concepts:

‘Nativists’ employ ‘poverty of stimulus’ arguments to demonstrate that an idea or cognitive ability could not have been learned.

‘Empiricists’ believe that our beliefs about the world come from our perceptual connection to the world and not from our natures.

IQ is likely to be influenced by nurturing environments.

Likely, there is no such thing as the singular good life; rather there are numerous valid conceptions of the good life.

The gene/environment dichotomy is false but that does not mean we cannot distinguish between robust and plastic developmental events.
Human Cloning: Legal Aspects
Authors: Pynes Christopher A
Published: December 2009

Human cloning debates fall into two broad categories: reproductive and therapeutic. Both varieties of human cloning have important legal aspects from ownership of genetic material, stem cell research, the dignity and respect for human life, reproductive rights of individuals, among other things, to the rights of potentially cloned individuals. Two basic facts complicate the legal issues with cloning: the biological technology needed to achieve human cloning can be found in most good labs, and writing and enforcing laws on either kind of human cloning is difficult to achieve. And even though there is a general consensus about the need to ban reproductive cloning in the world community, the views concerning therapeutic cloning are varied and have complicated the legal matters internationally and in individual nations. It is certain that regulations will continue to change at a rate slower than the biological technology.

Key concepts:

Reproductive cloning is cloning where the live birth of another individual is intended, and has been consistently opposed by all government and most individuals.

Therapeutic cloning is cloning for purposes other than the live birth of an individual, and has seen support by some governments and many individuals.

UNESCO or the United Nations Educational, Scientific and Cultural Organization which functions as a mechanism that attempts to gain universal agreements on emerging ethical issues related to science and education.

The UK has a clear prohibition on reproductive human cloning, but works to keep laws current with and relevant to technological advances.

The EU supports funding for embryonic stem cell research, but has banned human cloning.

The USA has a complex mix of state and federal regulations and interlocutors often conflate the cloning issues with the abortion debate, which gives rise to strong objections to both types of cloning and to stem cell research.
Predictive Genetic Testing: The Huntington Disease Model
Authors: Tibben Aad , Bijlsma Emilia
Published: December 2009

Predictive or presymptomatic genetic testing enables individuals at risk for a hereditary late‐onset disease to learn about their genetic status before symptoms have appeared. The predictive testing protocol for Huntington disease (HD) safeguards the interests of test candidates and has served as a model for other diseases. Most people seen for genetic counselling regarding HD are the asymptomatic children of an affected parent. Predictive testing provides the opportunity to get relief from the anguish of being at risk, to have prenatal tests or preimplantation genetic testing, to have children free from the disorder and to make informed plans for the future regarding marriage, education, professional career and finances. The common experience has been that tested individuals found relief from their prior psychological distress and that they benefited psychologically from testing. Having children proved to be an additional stress factor for partners.

Key concepts:

Predictive testing provides the opportunity to get relief from uncertainty and prepare better for the future.

Preimplantation genetic testing enables couples to have a pregnancy without the burden of termination after an unfavourable prenatal test result.

At 55 years of age and being not symptomatic, there is still a 25% empirical chance of being a carrier of the Huntington's gene.

The Huntington disease CAG repeat length accounts for roughly 50–77% of the variation in the age of onset.

Predictive testing requires informed consent by the individual at risk and the provision of psychological support.

Predictive testing for adult‐onset disorders without treatment options should not be offered to children and adolescents.

Exclusion testing is an important option for an individual at 25% risk because the genetic status of his at‐risk parent does not need to be revealed.

Counselling test candidates at 25% risk to get Huntington disease requires a family system approach.

The predictive test candidate's beliefs about causation and emotional, social and cultural issues may affect the perception of the information that is given in genetic counselling.
Public Understanding of Genetics: The Deficit Model
Authors: Marks Nicola J
Published: December 2009

Genetics is relevant to many aspects of our lives. According to the deficit model of public understanding, any misgivings people have about genetics and its applications stem from a lack of understanding of basic scientific principles. Consequently, education in genetics should lead to improved literacy and therefore support for this area. However, a number of studies show that education campaigns do not automatically lead to increased public support. Instead, it has been argued that understanding is a complex and dynamic process whereby people make sense of information in many different ways, which depend on prior knowledge and on their social and cultural locations. Therefore, members of the public should not be seen as
deficient
in understanding. Rather, it is argued that they have sophisticated understandings which should be acknowledged, and processes of
engagement
between science and public are put forward.

Key concepts:

According to the deficit model, lack of public understanding of genetics leads to an inability to fully participate in social life and potentially lack of support for new technologies. This can be remedied by education.

According to critical approaches to public understanding, ‘understanding’ is a complex process that involves social and cultural factors; the focus is on ‘knowledges in context’.

Public engagement, where people with different kinds of knowledge and opinions are consulted instead of merely educated, may help improve science–society relations.
Plant Virus Movement and the Impact ofRNASilencing
Authors: Heinlein Manfred
Published: December 2009

Plant virus‐encoded movement proteins support the spread of viral genomes through plasmodesmata and thus represent keys to the molecular mechanisms underlying macromolecular trafficking and intercellular communication. AlthoughTobacco mosaic virusemploys a movement mechanism involving the endoplasmic reticulum (ER)/actin network and microtubules, other viruses interact with membranes of the secretory or endocytic pathways. In addition to replication and targeting of plasmodesmata, efficient virus movement depends on the ability of the virus to interact with theribonucleic acid(RNA) silencing machinery. Viruses generally encode proteins that suppress silencing and, thus, enhance replication and systemic movement. However, new findings suggest that viruses may also be able to subvert the host silencing machinery to manipulate gene expression in cells to be invaded. Thus, successful virus movement relies on orchestrated interactions of virus‐encoded proteins with the cellular transport and RNA silencing immune systems of the plant.

Key concepts

Viruses and other macromolecules are transported through plasmodesmata.

Virus movement requires virus‐encoded proteins and interacting host factors.

Viruses use different strategies of movement.

Viruses interfere with RNA silencing in complex ways.
Drug Discovery in Apoptosis
Authors: O'Brien Tom , Dixit Vishva M
Published: December 2009

Regulation of cell death (apoptosis) is a crucial process that has to be precisely modulated during normal cell growth, and inappropriate regulation of this process has been implicated in a large number of ailments ranging from cancer to neurodegenerative diseases. Given that apoptosis can be either induced (e.g. following tissue injury or ischaemia) or attenuated (e.g. in cancer), there are a large number of potential intervention strategies that can be taken. To date, there are no approved therapeutics whose primary mode of action involves modulation of a critical component of the apoptotic pathway. However, there is an increasing number of therapeutics that are actively being tested in clinical trials, some of which are likely to become approved therapeutics.

Key Concepts

Caspases are implicated as potential therapeutic targets in a large number of clinically relevant indications.

Small molecule caspase inhibitors can be identified, but developing these into therapeutic drugs has proven to be very challenging.

There are many liabilities associated with caspase inhibitors, such as the warhead (reversible or irreversible), the apparent near absolute requirement for a P1 aspartic acid and selectivity.

So far, only one of the four caspase inhibitors that have entered clinical trials is still being actively developed, the remaining three have been discontinued for a variety of reasons.

Novel approaches to drug discovery can be taken; for example, utilizing a novel allosteric site that many caspases appear to contain.

There are a number of additional targets in the apoptotic pathway that are therapeutically relevant.
Molecular Genetics of Spermatogenic Disturbances
Authors: Krausz Csilla
Published: December 2009

A large proportion of male infertility is predicted to be related to genetic factors. These factors may act directly at the testicular level or through the endocrine regulation of the testis. A number of new causative mutations have been identified in hypogonadotrophic hypogonadism allowing a genetic diagnosis in approximately 30–40% of cases. However, search for causative mutations in Y‐chromosome, autosomal and X‐linked genes with predicted spermatogenic function have been substantially unsuccessful with some rare exceptions. Up to now, only Y‐chromosome rearrangements such as AZoospermia Factor (AZF) deletions and gr/gr deletion have been confirmed as molecular genetic causes of primitive testicular failure.

Key concepts:

Spermatogenic failure can be caused by genetic factors acting at the pre‐testicular or directly at the testicular level.

Mutation in genes involved in the hormonal regulation of the testis (pre‐testicular level) is associated with hypogonadotrophic hypogonadism.

Genetic factors involved in primitive testicular failure can be divided in chromosomal abnormalities and monogenic mutations.

Microdeletions in specific regions of the long arm of the Y‐chromosome (AZFregions) represent the most frequent molecular genetic cause of primitive testicular failure. The diagnosis ofAZFdeletions is clinically relevant since it provides the aethiology of infertility, has a prognostic value for testicular sperm retrieval and the deletion will be obligatory transmitted to the male offspring. gr/gr deletion of theAZFcregion is the only significant risk factor for impaired sperm production identified to date.

Search for X‐linked and autosomal gene mutations/polymorphisms has been largely unsuccessful.

Given the polygenic nature of male infertility a major advancement will likely be achieved from future studies based on whole genome analyses in large study populations.
Trigeminal Neuralgia
Authors: Prasad Sashank , Galetta Steven L
Published: December 2009

Trigeminal neuralgia (TN) is characterized by paroxysmal excruciating unilateral facial pain. Knowledge of the proper diagnosis and management of trigeminal neuralgia is essential to successfully treat these patients. There are several clinical features that are typical of TN, but there may be red flags that should suggest alternative diagnoses. There is convincing evidence that TN develops from focal demyelination at the trigeminal root entry zone with subsequent ephaptic transmission (crosstalk) between axons. Vascular compression of the nerve root causes the demyelination in most patients. Medical management of this condition, with anticonvulsants and other drugs, aims to dampen the abnormal electrical signals and thereby ameliorate the symptoms. Refractory cases may require surgical intervention, such as microvascular decompression of the trigeminal root. Gamma knife therapy is emerging as an alternative treatment for patients with medically refractive TN, particularly the elderly patient with co‐morbid conditions.

Key concepts:

Trigeminal neuralgia (TN) may be an extremely disabling illness, characterized by a severe, electric, lancinating pain on one side of the face.

Most cases of TN are due to demyelination of trigeminal nerve sensory fibres within the proximal nerve root, caused by compression by an overlying blood vessel.

TN can also occur in disease of central demyelination (such as multiple sclerosis).

Patients with new‐onset trigeminal neuralgia should typically undergo an MRI to exclude a tumour, demyelination, stroke or other lesion. MR angiography may help identify vessels compressing the trigeminal nerve.

Most patients with TH will require daily prophylactic treatment, most commonly with an antiepileptic drug (such as carbamazepine, gabapentin or oxcarbamazepine).

Microvascular decompression is a very effective surgical procedure for the treatment of TN. Other procedures include radiofrequency thermocoagulation, retrogasserian glycerol injection and trigeminal ganglion balloon compression.

Stereotactic gamma knife radiosurgery is emerging as an effective alternative, particularly for elderly patients or those with co‐morbid conditions.