bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical Basis and Regulatory Framework for Microtrade: Combining Volunteerism with International Trade towards Poverty Elimination
Authors: Lee Yong-Shik
Published: December 2009

Poverty remains a serious global issue, and nearly half of the world's populations are still living below the poverty line. International trade has been a vehicle for successful economic development for some developing economies in East Asia, including South Korea, Taiwan, Hong Kong, Singapore, and more recently, China. With the success of their trade-based economic development policies and the export-driven development strategy, all of these countries escaped from poverty.Can other developing countries duplicate this success and also bring their populations out of poverty? Some factors, including political stability, organized government support, educated workforce, availability of foreign markets, and financial resources such as foreign loans, have been considered essential for the success of this export-driven economic development strategy. These factors are not present in many developing countries, particularly least-developed countries (LDCs), thus making it difficult for them to pursue successful trade-based development policies to break the circle of poverty.The author suggests "microtrade," defined as international trade of small quantities of locally-produced products (LPPs) produced on a small scale, as an alternative way to provide those living in LDCs with income sufficient to reduce or eliminate poverty. Microtrade, unlike the export-driven development policies undertaken at a national level, is not based on the development of large-scale export industries, which cannot be initiated by many LDCs. This article provides a discussion of the theoretical basis of microtrade and its regulatory framework from the perspective of international trade law.
Time-resolved imaging of fluorescent inclusions in optically turbid medium — phantom study
Authors: Kacprzak M. , Liebert A. , Sawosz P. , Żołek N. , Milej D. , Maniewski R.
Published: December 2009

We present results of application of a time-resolved optical system for imaging of fluorescence excited in an inclusion containing indocyanine green (ICG), and located in optically turbid medium. The developed imaging system enabled simultaneous acquisition of fluorescence and diffusive reflectance. Eight independent time-resolved measurement channels based on time-correlated single photon counting technique were applied. In four of these channels, used for the fluorescence detection, sets of filters were applied in order to block the excitation light. Fast optomechanical switches allowed us to illuminate sequentially nine different spots on the surface of the studied object and finally 4×4 pixels maps at excitation and emission wavelengths were obtained. A liquid phantom used in this study consists of the fish tank filed with a solution ofmilk and water with black ink added to obtain optical properties in the range of the optical properties typical for the living tissue. A gel ball of a diameter of 5 mm with precisely controlled concentration of ICG was immersed in the liquid. The measurements were performed for inclusion located at different depths and for various ICG concentrations in the gel ball and in the surrounding liquid. The recorded distributions of times of arrival (DTA) of fluorescence photons and times of flight (DTOF) of diffusely reflected photons were analyzed by calculation of their statistical moments. We observed specific changes in moments of the measured DTAs as a function of depth of immersion of the fluorescent inclusion in the medium. We noted also that the changes of moments depend significantly on concentration of the dye in the fluorescence inclusion as well as in the surrounding liquid.
Corneal Topography Six Years After Photorefractive Keratectomy for Myopia and Myopic Astigmatism
Authors: Serrao Sebastiano , Lombardo Giuseppe , Lombardo Marco , Palombi Marino , Roberts Cynthia J.
Published: December 2009

Purpose:

To analyze the 6-year response of corneal topography to photorefractive keratectomy (PRK) for myopia and myopic astigmatism.

Methods:

Twenty patients (40 eyes) who had PRK using the Technolas Keracor 217C excimer laser platform were followed up to 6 years after surgery. The eyes were subdivided into three groups according to the preoperative spherical equivalent refraction and astigmatism component. Corneal topographic maps were obtained with a Placido disk topographer (Keratron Scout). The pre- and postoperative topographical data were imported into custom software, which computed the average composite corneal map and average difference map for each study group to quantify the anterior corneal changes following laser ablation. The software defined three concentric zones of the surface topography, allowing characterization of the regional corneal response following surgery.

Results:

At 6 years, no changes in the surface topographic configuration of the central cornea were assessed following spherical myopic ablations in comparison with 1 year postoperatively. A slight peripheral flattening of approximately 0.60 diopters (D) (
P
<.001) was measured following the higher myopic ablations at 6 years compared with 1 year postoperatively. Minimal changes, of approximately 0.30 D (
P
<.001), in the anterior central cornea were observed following astigmatic correction during follow-up.

Conclusions:

Photorefractive keratectomy for the correction of myopia provides stable corneal topography, with no clinically significant changes in the curvature profile at 6 years after surgery. [
J Refract Surg
. 2009;25:451–458.]
Matrix Architecture Dictates Three-Dimensional Migration Modes of Human Macrophages: Differential Involvement of Proteases and Podosome-Like Structures
Authors: Van Goethem Emeline , Poincloux Renaud , Gauffre Fabienne , Maridonneau-Parini Isabelle , Le Cabec Véronique
Published: December 2009

Tissue infiltration of macrophages, although critical for innate immunity, is also involved in pathologies, such as chronic inflammation and cancer. In vivo, macrophages migrate mostly in a constrained three-dimensional (3D) environment. However, in vitro studies, mainly focused on two dimensions, do not provide meaningful clues about the mechanisms involved in 3D macrophage migration. In contrast, tumor cell 3D migration is well documented. It comprises a protease-independent and Rho kinase (ROCK)-dependent amoeboid migration mode and a protease-dependent and ROCK-independent mesenchymal migration mode. In this study, we examined the influence of extracellular matrix (composition, architecture, and stiffness) on 3D migration of human macrophages derived from blood monocytes (MDMs). We show that: 1) MDMs use either the amoeboid migration mode in fibrillar collagen I or the mesenchymal migration mode in Matrigel and gelled collagen I, whereas HT1080 tumor cells only perform mesenchymal migration; 2) when MDMs use the mesenchymal migratory mode, they form 3D collagenolytic structures at the tips of cell protrusions that share several markers with podosomes as described in two dimensions; 3) in contrast to tumor cells, matrix metalloproteinase inhibitors do not impair protease-dependent macrophage 3D migration, suggesting the involvement of other proteolytic systems; and 4) MDMs infiltrating matrices of similar composition but with variable stiffness adapt their migration mode primarily to the matrix architecture. In conclusion, although it is admitted that leukocytes 3D migration is restricted to the amoeboid mode, we show that human macrophages also perform the mesenchymal mode but in a distinct manner than tumor cells, and they naturally adapt their migration mode to the environmental constraints.
Signaling Role for Lysophosphatidylcholine Acyltransferase 3 in Receptor-Regulated Arachidonic Acid Reacylation Reactions in Human Monocytes
Authors: Pérez-Chacón Gema , Astudillo Alma M. , Ruipérez Violeta , Balboa María A. , Balsinde Jesús
Published: December 2009

Cellular availability of free arachidonic acid (AA) is an important step in the production of pro- and anti-inflammatory eicosanoids. Control of free AA levels in cells is carried out by the action of phospholipase A2s and lysophospholipid acyltransferases, which are responsible for the reactions of deacylation and incorporation of AA from and into the sn-2 position of phospholipids, respectively. In this work, we have examined the pathways for AA incorporation into phospholipids in human monocytes stimulated by zymosan. Our data show that stimulated cells exhibit an enhanced incorporation of AA into phospholipids that is not secondary to an increased availability of lysophospholipid acceptors due to phospholipase A2 activation but rather reflects the receptor-regulated nature of the AA reacylation pathway. In vitro activity measurements indicate that the receptor-sensitive step of the AA reacylation pathway is the acyltransferase using lysophosphatidylcholine (lysoPC) as acceptor, and inhibition of the enzyme lysoPC acyltransferase 3 by specific small interfering RNA results in inhibition of the stimulated incorporation of AA into phospholipids. Collectively, these results define lysoPC acyltransferase 3 as a novel-signal–regulated enzyme that is centrally implicated in limiting free AA levels in activated cells.
Heat Shock Transcription Factor 1 Inhibits Expression of IL-6 through Activating Transcription Factor 3
Authors: Takii Ryosuke , Inouye Sachiye , Fujimoto Mitsuaki , Nakamura Tamami , Shinkawa Toyohide , Prakasam Ramachandran , Tan Ke , Hayashida Naoki , Ichikawa Hitoshi , Hai Tsonwin , Nakai Akira
Published: December 2009

The febrile response is a complex physiological reaction to disease, including a cytokine-mediated increase in body temperature and the activation of inflammatory systems. Fever has beneficial roles in terms of disease prognosis, partly by suppressing the expression of inflammatory cytokines. However, the molecular mechanisms underlining the fever-mediated suppression of inflammatory gene expression have not been clarified. In this study, we showed that heat shock suppresses LPS-induced expression of IL-6, a major pyrogenic cytokine, in mouse embryonic fibroblasts and macrophages. Heat shock transcription factor 1 (HSF1) activated by heat shock induced the expression of activating transcription factor (ATF) 3, a negative regulator of IL-6, and ATF3 was necessary for heat-mediated suppression of IL-6, indicating a fever-mediated feedback loop consisting of HSF1 and ATF3. A comprehensive analysis of inflammatory gene expression revealed that heat pretreatment suppresses LPS-induced expression of most genes (86%), in part (67%) via ATF3. When HSF1-null and ATF3-null mice were injected with LPS, they expressed much higher levels of IL-6 than wild-type mice, resulting in an exaggerated febrile response. These results demonstrate a novel inhibitory pathway for inflammatory cytokines.
The history of the Faculty of Theology at the University of Pretoria: A Dutch Reformed perspective 1938�2008
Authors: Van der Merwe Johan M. , Vos Cas J.A.
Published: December 2009

In 1938 the Faculty of Theology Section B was established at the University of Pretoria, which could be likened to a small fountain. As the fountain flowed through the decades of history, it grew and became a river that made a huge impact on the university, the Church and society. The aim of this article, coinciding with the centenary of the University of Pretoria, is to focus on the positive contribution of the Faculty of Theology towards university, church and society. Like any river it went through different stages. There were times of peace and tranquillity, but also times of raging rapids. At certain stages of growth and development both lecturers and students made a huge impact, playing leading roles in Church and society, clearly voicing the call of the Church. The voice of the Faculty was not always welcome and was at times met by strong reaction, which was possibly one of the reasons for the murder of Prof. J.A. Heyns. In 2000 a new era dawned when the stream that became a river was joined by streams of different denominations. This made the river even stronger, with much more impact. This article tells the story of the origin, growth and struggle of the Dutch Reformed Church at the Faculty of Theology at the University of Pretoria from 1938 to 2008.
T
Lymphocytes: Helpers
Authors: Kawachi Izumi , Kondo Takayuki
Published: December 2009

Helper T lymphocytes are major histocompatibility complex (MHC) class II restricted CD4+ T cells which can be divided into several subsets of cytokine releasing patterns: T‐helper 1 (T
H
1), T‐helper 2 (T
H
2), T‐helper 17 (T
H
‐17) and T‐follicular helper (T
FH
). Following are several transcription factors especially expressed, or function differently, in each of the clonal progeny to define separable effector T‐helper cell lineages. Helper T cells orchestrate antibody production and cellular immune responses. T
H
1 cells activate infected macrophages for the destruction of intracellular pathogens. T
H
2 and T
FH
cells provide help to B cells for antibody production, which is a response aimed mainly at extracellular pathogens. T
H
‐17 cells enhance neutrophil response for extracellular pathogens. Each T
H
subset plays a distinct role in host defence and autoimmunity.

Key concepts

Helper T lymphocytes are MHC class II restricted CD4+ T cells which can be divided into several subsets of cytokine releasing patterns: T‐helper 1 (T
H
1), T‐helper 2 (T
H
2), T‐helper 17 (T
H
‐17) and T‐follicular helper (T
FH
).

IFNγ, IL‐4 and IL‐17 are the representative cytokines of T
H
1, T
H
2 and T
H
‐17 cells, respectively, and are often used as subtype markers.

T
H
1 cells play an important role in cellular immune functions such as delayed‐type hypersensitivity or in the defence against intracellular organisms.

T
H
2 cells enhance antibody production from B cells.

T
H
‐17 cells are potent inducers of tissue inflammation in autoimmune diseases and confer protection against extracellular bacterial and fungal pathogens.

T
FH
cells regulate the step‐wise development of antigen‐specific B‐cell immunity in B‐cell follicles of lymphoid tissues.
Nucleotide Synthesis
De Novo
Authors: Traut Thomas
Published: December 2009

Nucleosides are composed of a heterocyclic ring (defined as the base) that is attached to a ribose. Addition to a nucleoside of a phosphate, at carbon 5 of the ribose, produces a nucleotide. Nucleotides function as ubiquitous building blocks for the synthesis of all nucleic acids, and also function in enzymatic reactions as cofactors and as a source of energy. These central metabolic roles require their continued biosynthesis from readily available precursors, and this process is defined as

de novo

nucleotide synthesis. The synthesis of purines starts with ribose‐phosphate, to which are attached in a stepwise fashion the individual atoms of the heterocyclic base. Pyrimidine synthesis starts with the stepwise formation of the base, to which is then added the ribose‐phosphate. Bases and nucleosides may also be recycled in salvage pathways.

Key concepts:

Nucleotides are so essential to metabolism that genetic defects generally are lethal, and for humans only a few gene defects are observed, at a low frequency.

Many of the enzymatic reactions in the
de novo
biosynthesis of nucleotides are combined as two or more reactions catalysed by a single multidomain protein. This has made nucleotide biosynthesis more efficient.

For a few of the biosynthetic steps alternate enzymatic strategies have emerged between bacteria and vertebrates, and these present possible targets for drugs as selective antibiotics.
Ploidy Variation in Plants
Authors: Birchler James A
Published: December 2009

Evidence from genome sequences of many plant species indicate that all plants have had a cyclical history of doubling of chromosome numbers, followed by gene deletions back to a near diploid level. Recent cases of increases in genome copy number are generally considered to comprise ploidy variation. Ploidy variation involves changes in the number of whole sets of chromosomes. Aneuploid variation involves changes in the number of individual chromosomes. The two types of chromosomal changes have different consequences for gene expression patterns.

Key concepts:

An increase in whole genome chromosome sets is a recurring process in plant evolution followed by deletion of genes back to a near diploid level.

Recent genome doubling can consist of genomes from slightly diverged species and are referred to as allopolyploids.

Recent genome doubling within a species is referred to as autopolyploids.

Allopolyploids and autopolyploids have different genetic behaviours.

Cell size increases with the number of genomes present, as does gene expression in general.

Aneuploidy is the change in copy number of part of the genome.

Aneuploidy produces greater changes in gene expression than does ploidy variation.
Cardiac Arrhythmias
Authors: Kastor John A , Saba Magdi M
Published: December 2009

Cardiac arrhythmias are disturbances in the rhythm of the heart manifested by irregularity or by abnormally fast (tachycardias or tachyarrhythmias) or abnormally slow (bradycardias or bradyarrhymias) rates. Some produce no symptoms, whereas others can endanger the patient's life. Among the most benign are premature beats that interrupt the normal rhythm of the heart. Tachyarrhythmias include atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia, ventricular tachycardia and ventricular fibrillation. Bradycardias include heart (atrioventricular) block and sick sinus syndrome. Antiarrhythmic drugs, cardiac pacing, ablation and implantable defibrillators can control most arrhythmias that need treatment.

Key Concepts:

Cardiac arrhythmias are disturbances in the rhythm of the heart in which the heart beats are irregular, too fast, or too slow.

Cardiac arrhythmias range in severity from asymptomatic to life‐threatening.

Most arrhythmias that require treatment can be controlled by antiarrhythmic drugs, cardiac pacing, ablation and implantable defibrillators.

Some arrhythmias can be treated with ablation in which the physician locates the source of the arrhythmia and, using electrode‐catheters, destroys it.

Premature beats are among the most common cardiac arrhythmias. Specific treatment is seldom required if the patient can be assured that they are benign, which is usually the case.

Atrial fibrillation is the most common sustained cardiac arrhythmia.

Atrial flutter is a rapid rhythm that is best treated with ablation.

In heart block, the electrical signals from the atria cannot reach the ventricles. Symptoms develop when the heart rate slows excessively. Treatment with pacemakers usually relieves the symptoms.

When patients have ventricular tachycardia, the rapid heart rate can produce syncope (fainting). This is a dangerous condition, and electrophysiological treatment is usually required.

Ventricular fibrillation is the arrhythmia that most frequently causes cardiac arrest.
Circular Dichroism: Studies of Proteins
Authors: Kelly Sharon M , Price Nicholas C
Published: December 2009

Circular dichroism (CD) is the differential absorption of the left‐ and right‐circularly polarized components of plane‐polarized electromagnetic radiation. It can provide structural and dynamic information about biological macromolecules, particularly proteins. The CD spectra in the far‐UV (typically 180–240 nm) can give reliable quantitative estimates of the proportions of secondary structural features (helix, sheet, turn, etc.) present in proteins. The spectra in the near‐UV (260–320 nm) can be used to explore the environments of aromatic amino acid side‐chains and hence to give a measure of tertiary structure. Although CD cannot provide the high‐resolution structural data available from X‐ray crystallography or nuclear magnetic resonance, its convenience and applicability under a wide variety of experimental conditions make it the technique of choice in many applications, including exploring protein–ligand interactions, conformational changes and protein folding.

Key concepts:

Circular dichroism (CD) refers to the difference in absorption of the two components (left‐ and right‐circularly polarized) of plane‐polarized radiation.

CD is observed when the absorbing molecule or group exhibits chirality (optical activity).

Protein structures are chiral and so give rise to CD signals.

CD can be used to explore protein structures under a wide range of experimental conditions.

The relatively small CD signals observed from proteins mean that care must be taken to gather reliable experimental data.

CD signals from proteins in the far‐UV and near‐UV can be used to explore their secondary and tertiary structures, respectively.

CD is an ideal technique to monitor conformational changes in proteins which occur on binding to other molecules.

CD can be used to assess the extents of protein unfolding (denaturation) and of refolding of denatured proteins.
Fatty Acid Oxidation Disorders
Authors: Polinati Padmini P , Eskelin Petra , Tyni Tiina
Published: December 2009

Mitochondrial fatty acid oxidation (FAO) is a major energy‐providing pathway under conditions of prolonged fasting, exercise or metabolic stress. A number of inherited disorders affecting this metabolic pathway have been known for almost two decades. Defects of mitochondrial FAO characteristically present with severe metabolic crises associated with low blood glucose (hypoglycaemia) during infancy and childhood and are also a relatively frequent cause of muscle diseases and cardiac muscle disease. The symptoms are typically episodic and often associated with mild viral infections or fasting. Therapeutic interventions are generally effective in preventing metabolic decompensation, which emphasizes the importance of early diagnosis. Diagnostic testing, determining optimal dietary regimens for each disorder and prenatal screening for these disorders may essentially alter an otherwise poor prognosis for many patients with FAO disorders.

Key Concepts:

Fatty acids can be oxidized by α‐oxidation in peroxisomes, by β‐oxidation in mitochondria and peroxisomes, and ω‐oxidation in the endoplasmic reticulum.

Mitochondrial FAO is a major energy‐providing pathway under conditions of prolonged fasting, exercise or metabolic stress.

A single β‐oxidation cycle consists of a series of four repeated enzymatic steps: dehydrogenation (oxidation), hydration, a second dehydrogenation and thiolytic cleavage of the carbon chain.

Mitochondrial FAO defects present with severe metabolic crises associated with nonketotic hypoglycaemia, fatty liver, muscle weakness and cardiomyopathy.

As a group, mitochondrial FAO defects are among the most common autosomal recessively inherited metabolic disorders.

The main objective of therapeutic intervention is to secure sufficient caloric intake during periods of metabolic stress and fasting, and prevent accumulation of β‐oxidation intermediates.

Neonatal screening of FAO disorders has been initiated in several countries worldwide, improving the opportunities for early dietary therapies.
Toll‐like Receptors
Authors: Seya Tsukasa , Miyake Kensuke
Published: December 2009

Toll‐like receptors (TLRs) are mainly expressed on antigen‐presenting cells (APCs) and function as adjuvant receptors that modulate cellular immunity. Their pleiotropic functions depend on a variety of signals. Ten members of the TLR family in humans and 10∼20 TLRs in other vertebrates cope with microbial pattern molecules, that is, TLR agonists. In addition, a number of molecules negatively or positively regulate the TLR signal pathways. TLR agonists are capable of activating either of the two main TLR pathways driven by the adaptors, myeloid differentiation primary‐response gene 88 (MyD88) and TRIF (TIR‐containing adaptor‐inducing interferon‐β TIR‐containing adaptor molecule‐1, TICAM‐1), which confer differential maturation modes on myeloid (mDCs) and plasmacytoid dendritic cells (pDCs). Natural killer (NK), CD8 T, CD4 T and B cells are activated through matured dendritic cells. TLRs are therefore involved in not only inducing the acute phase of inflammatory responses but also raising the acquired immune responses including allergy, cancer and infectious immunity.

Key concepts

Innate immune system consists of TLRs, lectin receptors and complement receptors; they recognize foreign and host materials marked or labelled with their ligands.

TLR signal pathways activate transcription factors in affected cells and induce host‐defence agents, including antimicrobial peptides, chemical mediators, cytokines, chemokines and cell‐adhesion molecules.

Dendritic cells play a pivotal role in evoking acquired immunity by liberation of cytokines/chemokines and cell‐to‐cell contact.

There are four adaptors connecting with the TLR TIR domains. These adaptors also possess the TIR domain and directly bind their counterparts. Only myeloid differentiation primary‐response gene 88 (MyD88) and TICAM‐1 (TRIF) are signalling adaptors.

Land‐living vertebrates possess mammalian (M)‐type TLR family, a representative of which is human TLRs. Water‐living vertebrates possess the TLR20 family in addition to the M‐type TLR family.

Plasmacytoid DC is formerly called interferon‐producing cells (IPC).

Tumour necrosis factor receptor–associated factor (TRAF) family proteins act as E3 ubiquitin ligases and closely associated with molecules in the TLR pathways.
Genetics as Explanation: Limits to the Human Genome Project
Authors: Cohen Irun R , Atlan Henri , Efroni Sol
Published: December 2009

Living organisms are composed of cells and all living cells contain a genome, the organism's stock of
deoxyribonucleic acid
(DNA). The role of the genome has been likened to a program that encodes the organism's development and its subsequent response to the environment. This computer metaphor teaches that the organism – the hardware – is controlled by the software – the genome. Thus, the organism and its fate can be explained by genetics, the plans written into the sequence of genomic DNA; the Genome Project was devised to decipher this program. However, it is now clear that the genome does not directly program the organism; the computer program metaphor has misled us. The genome is only one class of vital information that serves the organism. Metaphorically, the genome can be likened to a vocabulary of words that can be deployed to make meaningful sentences, or to a toolbox for accomplishing specific tasks.

Key concepts:

The genome does not function as a master plan or computer program for controlling the organism; the genome is the organism's servant, not its master.

The genome is a reservoir of DNA sequence information and a vehicle for transmitting this information; the meaning of DNA emerges from the cellular processing of this raw information into proteins and other functional molecules.

DNA is only one class of vital information that serves the organism; the organism epigenetically uses, manipulates, regulates and, in the case of the immune system, creates genes.

The effects of a gene vary with the organism's environment; the interactions between genes and environment are not linear and, in most cases, not additive. Therefore, one cannot compute with certainty the relative contributions of genes and environment to an organism's observed features – its phenotype.

Metaphorically, we can think of the genome as akin to a list of words, a vocabulary, which can be used to build and express a meaningful language; like a vocabulary, a genome by itself has no functional meaning.

The genome is thus akin to a toolbox of DNA sequences that provide molecular tools as requested by the internal state of the organism and the state of the environment.

One's genes cannot explain one's being: an organism is the expression of a dynamic and ongoing interaction between the state of its environment and its internal state, which includes its past history and its toolbox of DNA sequences.
Microbial Diversity
Authors: Oren Aharon
Published: December 2009

Prokaryotic and eukaryotic microorganisms dominate life on Earth with respect to the numbers of individuals and biomass. Yet, the number of species of macroorganisms described as well as the estimated numbers of yet to be described species exceeds those of the microorganisms by an order of magnitude. Such numbers give an incomplete picture of the diversity in the microbial world. Only two modes of life are found in higher plants and animals: oxygenic photosynthesis and aerobic respiration. In the microbial world a great variety of processes occur, aerobic as well as anaerobic, phototrophic (oxygenic and anoxygenic), respiratory (with oxygen or other electron acceptors), fermentative and chemoautotrophic (using reduced inorganic compounds as energy sources). Also phylogenetically the microbial world is by far the most diverse. Most branches in the small ribosomal subunit
ribonucleic acid
(RNA)‐based phylogenetic tree contain only microorganisms, whereas higher plants and animals only form short lineages in the eukaryotic branch.

Key concepts

The microbial world encompasses most of the phylogenetic diversity on Earth, as all Bacteria, all Archaea and most lineages of the Eukarya are microorganisms.

The morphological diversity in the microbial world is much smaller than that of the higher plants and animals.

With respect to numbers of individual microorganisms and biomass the microbial world is far more important than the world of macroorganisms, but the numbers of species of microorganisms described to date and the predicted numbers of yet undescribed species are about an order of magnitude lower than those of the macroorganisms.

Based on their modes of energy generation and the variety of organic and inorganic compounds used as energy source and/or nutrients, the microbial world and especially the world of the prokaryotes, has many more possibilities than are realized by macroscopic animals and plants.

Sequencing of microbial DNA isolated from natural environments (environmental genomics, metagenomics) has revealed the existence of a tremendous variety of yet uncultured microorganisms, showing that the true microbial diversity in nature is much higher than currently recognized on the basis of organisms studied in culture.
Phloem Long‐Distance Trafficking of Proteins and
RNAs
Authors: Wolf Shmuel
Published: December 2009

Phloem sap contains a wide range of macromolecules, including
ribonucleic acids
(RNAs) and proteins. Recent advances in genomic and proteomic technologies have enabled the identification of thousands of these macromolecules. However, technical limitations are still the main obstacle to the complete characterization of macromolecule profiles in the sieve tube.

Grafting experiments have established that numerous macromolecules are capable of moving long distances between tissues, providing the foundation for the hypothesis of an interorgan information superhighway in higher plants involving the phloem. This chapter presents the current knowledge on proteins and messenger RNA (mRNA) molecules present in the sieve tube. The challenge now is to characterize the biological role of trafficking macromolecules, such as their involvement in the signal‐transduction pathway(s) elicited by environmental cues and in orchestrating developmental processes at the whole‐plant level.

Key concepts

Phloem sap contains macromolecules such as proteins and RNAs.

Protein profiles in the sieve tube are tissue specific.

Phloem proteins act as long‐distance signalling molecules.

Plant viruses move long distance via the phloem.

Endogenous RNA molecules are capable of trafficking long distance via the phloem.

mRNA molecules may act as long‐distance signalling molecules.
Functional Imaging of Nervous Systems Using Voltage‐Sensitive Dyes
Authors: Salzberg Brian M
Published: December 2009

Voltage‐sensitive dyes are small molecules that bind to cell membranes and change their optical properties, absorption or fluorescence, in response to changes in membrane potential, the voltage across the membrane. These optical changes are extremely rapid and tend to be linear reporters of local electrical events. Thus, these ‘potentiometric probes’ behave as molecular voltmeters and can be used, with a high‐speed camera or other image dissector, for functional imaging of electrical activity including action potentials, synaptic potentials, and passive (electrotonic) signals. No physical contact with the object is required and spatial and temporal resolution is limited primarily by signal‐to‐noise considerations. Such millisecond time‐resolved functional imaging can be of single cells, of regions of cells or of nervous systems, of cardiac muscle or of any other electrically active tissue. In the nervous system, functional imaging of electrical activity can lead to an understanding of the spatio‐temporal relationships between neurons and of their functional connectivity.

Key Concepts:

In electrically excitable cells, the membrane potential can change extremely rapidly.

Some coloured molecules (dyes) change their optical properties in response to changes in the local electric field.

Changes in the optical properties of the molecules that stain‐cell membranes can be used to follow rapid changes in membrane potential.

A high‐speed camera, usually with a microscope, can be used together with these dyes to monitor the electrical activity at hundreds or even thousands of sites, virtually simultaneously.

Functional imaging of electrical activity can lead to an understanding of the spatio‐temporal relationships in nervous systems, and to the functional connectivity among neurons.
Coltiviruses and Seadornaviruses
Authors: Mohd Jaafar Fauziah , Mertens Peter , Attoui Houssam
Published: December 2009

Coltiviruses and seadornaviruses are members of family
Reoviridae
, which encompasses alongside genera

Coltivirus

and

Seadornavirus

13 other genera of viruses that can infect mammals, birds, aquatic animals, reptiles, insects, plants, fungi and protists. Coltiviruses are transmitted by hard ticks of the family
Ixodidae
, whereas seadornaviruses are mosquito‐borne. These viruses can infect humans, following the bite of adult‐infected female ticks or mosquitoes, causing febrile illnesses and are occasionally responsible for encephalitis. Coltiviruses are principally endemic in the northwestern parts of the USA and Canada and were also reported in European countries, including France and Germany. Antibodies to coltiviruses have also been identified from patients in the former Czechoslovakia and in South Korea. Seadornaviruses are principally endemic in the south east of Asia, although recent data showed that there has been an expansion of their distribution northwards, reaching the north‐western Chinese borders.

Key concepts:

Coltiviruses are transmitted by adult female tick (family
Ixodidae
) bite and have animal reservoirs.

Coltiviruses can infect humans causing febrile illnesses and can cause encephalitis in rare cases.

Seadornaviruses are transmitted by mosquitoes and no animal reservoir is known to date.

Seadornaviruses can infect animals and humans causing febrile illnesses and were reported to be responsible for cases of encephalitis.

Coltiviruses show an evolutionary relationship to the turreted mycoreoviruses, aquareoviruses and orthoreoviruses.

Seadornaviruses show an evolutionary relationship to the nonturreted rotaviruses.

Coltiviruses seem to represent a missing link between turreted and nonturreted members of family
Reoviridae.

Differential diagnostic serological and molecular assays for coltiviruses and seadornaviruses are available.

Structure of the viral particles of Banna virus shows striking similarities to that of the rotaviruses.
Death Receptor‐induced Necroptosis
Authors: Declercq Wim , Van Herreweghe Franky , Berghe Tom Vanden , Vandenabeele Peter
Published: December 2009

Recent studies on cellular

in vitro

models have made it clear that death receptor (DR)‐induced necrosis, also called necroptosis, is a programmed form of necrotic cell death. In contrast, accidental necrosis is mainly induced by physicochemical stress, such as heath or chemicals. Many DRs signal to apoptosis or necroptosis depending on whether caspases are active or not. The
kinase
activities of
receptor‐interacting protein 1
(
RIP1
) and
RIP3
have emerged as crucial regulators of DR‐induced necroptosis. The precise execution mechanisms during necroptosis are still poorly understood but involve different cellular compartments such as the mitochondria, the lysosomes and the cell membrane.

In vivo

, necroptosis occurs mainly in pathophysiological processes such as ischaemia‐reperfusion injury in heart, brain and kidneys, viral infection and pancreatitis, and is capable of killing tumour cells that have developed strategies to evade apoptosis. Thus, detailed knowledge of necroptotic signalling may be exploited in therapeutic strategies.

Key concepts:

Necrosis is characterized by swelling of the endoplasmic reticulum, mitochondria and cytoplasm, with subsequent rupture of the plasma membrane and lysis of the cells.

Death receptor‐induced necrosis, also called necroptosis, is a programmed form of necrotic cell death. This is in contrast to necrosis induced by physicochemical stress, such as heath or hydrogen peroxide.

The necrosis‐signalling complex, or necrosome, consists of a complex containing FADD, caspase‐8, RIP1 and RIP3.

Expression of RIP3 renders cells permissive to death receptor‐induced necroptosis.

RIP1 and RIP3 kinase activity is crucial for necroptotic signalling.

Apoptosis counteracts necrotic signalling by cleavage of RIP1 and RIP3.

Necroptosis forms a back‐up cell death mode in case caspases activity is prevented or inhibited.

In vivo
, necroptosis occurs mainly in pathophysiological processes such as ischaemia‐reperfusion injury in heart, brain and kidneys, viral infection and pancreatitis, and is capable of killing tumour cells that have developed strategies to evade apoptosis.
Caspases, Substrates and Sequential Activation
Authors: Walsh John G , Martin Seamus J
Published: December 2009

Superfluous, aged or damaged cells are eliminated from tissues via a controlled cell death process, called apoptosis. Apoptosis is coordinated by a group ofcysteine aspartic acid‐specific proteases(caspases) that become specifically activated within cells destined to die. Some of these proteases act as initiators, their role being to interface with signalling events and initiate the proteolytic cascade, whereas others act as executioner enzymes and carry out the internal dismantling of the cell that results in death. During the terminal phase of apoptosis the executioner caspases (caspases‐3 and ‐7) simultaneously cleave hundreds of protein substrates to terminate cell viability and produce the characteristic apoptotic phenotype. This large‐scale proteolysis also dismembers the cell into discrete fragments that are recognized and removed by scavenging phagocytes. Recent evidence also suggests that the actions of executioner caspases may disable molecules that are capable of initiating or exacerbating immune responses if released into the extracellular space.

Key Concepts:

Pro‐apoptotic stimuli lead to the activation of caspases.

Caspase activation takes the form of a cascade of sequential activation events.

Caspases mediate the structural changes characteristic of apoptotic cell death by processing key protein substrates.

Caspase‐dependent demolition of the apoptotic cell facilitates its safe removal by surveying phagocytes.
Structural Variation in Great Ape Genomes
Authors: Aerts Jan A , Tyler‐Smith Chris
Published: December 2009

Structural variation within and between Great Ape genomes affects more nucleotides than single‐base variation, yet its extent and phenotypic consequences are much less well understood. The most‐studied structural variants are copy number variations (CNVs) which can be generated by several different mechanisms including non‐allelic homologous recombination, non‐homologous end‐joining anddeoxyribonucleic acid(DNA) replication‐related fork stalling and template switching. CNVs are closely related to segmental duplications (SDs): SDs can stimulate the formation of CNVs and themselves started out as CNVs, but became fixed in a species. Structural variation can be neutral but has also influenced our phenotypic evolution, for example our susceptibility to disease and our ability to digest certain types of food. Our understanding of the extent of structural variation is increasing rapidly, but it will be much more difficult to understand its phenotypic consequences.

Key concepts

Structural variation includes balanced variants such as inversions and translocations, and unbalanced ones such as duplications and deletions (copy number variations or CNVs).

Structural variants can arise by several mechanisms, including nonallelic homologous recombination (NAHR), nonhomologous end‐joining (NHEJ) and DNA replication‐based fork stalling and template switching (FoSTeS).

CNV is closely linked to segmental duplication, but is not exactly the same. Segmental duplications can stimulate CNV formation by NAHR, and themselves arise from CNVs that have become fixed.

Segmental duplications did not appear uniformly during the evolution of the Great Ape species, but rather during a burst of activity around the time of the divergence of gorilla from the human/chimpanzee ancestor.

Duplicated genes play a critical role in the evolution of a genome as they act as ‘spare parts’ than can evolve to perform new or more specialized functions.

Effects of structural variation on gene expression can be identified but only a few examples of the consequences for species biology have been documented.

CCL3L1copy number varies within humans and has been reported to influence HIV susceptibility. It has been reported to differ in copy number between humans and chimpanzees as well, although other research shows no species difference, illustrating the technical complications associated with such analyses.

Humans have more copies of the amylase geneAMY1than chimpanzees and so are better able to digest starch, which forms a larger part of their diet.

Chimpanzees have deleted several inflammatory‐response genes (APOL1,APOL4,CARD18,IL1F7andIL1F8) and are thus likely to differ in this pathway, but the specific evolutionary force that has driven this change, if any, is unknown.
Antibiotics and the Evolution of Antibiotic Resistance
Authors: Martinez Jose L , Baquero Fernando
Published: December 2009

Antibiotics were introduced for human therapy few decades ago and their utilization has produced the rapid evolution of bacterial pathogens towards resistance. Before this recent and fast evolution, antibiotics and their resistance genes have evolved for millions of years in environmental microorganisms. Recent results suggest that, besides serving for inhibiting the growth of competitors, antibiotics might be signalling molecules in natural ecosystems and that some metabolic enzymes and signal‐trafficking efflux pumps might render a phenotype of resistance in the presence of high concentrations of antibiotics. Antibiotic resistance can be developed by mutation or by the acquisition of resistance determinants by means of horizontal gene transfer. Spread of resistance is achieved through the combination of different elements, from resistance genes to plasmids and bacterial clones. The release of high amounts of antibiotics and resistance genes in natural habitats is challenging the microbial populations present in these ecosystems.

Key concepts

Some antibiotics can be involved in intermicrobial communication at the low concentrations likely found in most natural ecosystems.

The origin, spread and diversification of mechanisms of antibiotic resistance is an excellent model for studying real‐time evolution.

The fact that a given gene confers resistance when transferred to a bacterial human pathogen does not necessarily mean that it plays the same functional role in its original host.

Exaptation is an evolutionary process by which a given determinant changes its function, without changing its structure, as the consequence of an environmental change.

Anthropogenic antibiotic pollution in the environment might modify the genetic structure of bacterial populations and communities.

Antibiotic resistance evolves frequently in a modular fashion, combining sequences, genes, genetic platforms and genetic vehicles.

The association of several antibiotic resistance genes in the same genetic vehicle favours their dissemination and persistence.

The spread of antibiotic resistance frequently occurs by the global dissemination of particularly transmissible bacterial resistant clones.

Antibiotic resistance is fixed in human or animal populations when the resistance genes enter into endemic clones.

Prediction of evolutionary trajectories should constitute the ultimate way to demonstrate the truth of hypothesis in evolutionary sciences.
Inhibitors of Initiation Phase of Bacterial Protein Synthesis
Authors: Marquez Viter , Sohmen Daniel , Wilson Daniel N
Published: December 2009

The initiation phase is the rate‐limiting step in protein synthesis where messenger
ribonucleic acid
(mRNA), initiator‐transfer RNA (tRNA) and ribosomal subunits are assembled together in the presence of specific initiation factors. This process is the target for a diverse subset of antibiotics that inhibit the initiation step in a variety of different ways. Dissecting the mechanism of action of these antibiotics has provided insight not only into their inhibitory action but also into the process of translation initiation itself. With the dramatic increase in resistance of bacterial strains to many clinically relevant antibiotics, the discovery of improved inhibitors is becoming more important. Because the known initiation inhibitors bind to distinct regions of the ribosome compared with clinically used antibiotics, revisiting the initiation inhibitors may open new avenues to the development of novel antimicrobial agents.

Key Concepts:

Initiation of protein synthesis in bacteria operates through a 30S pre‐initiation complex.

Aurintricarboxylic acid is a nonspecific compound that
in vitro
at least can prevent translation initiation by perturbing binding of mRNA to the small ribosomal subunit.

Kasugamycin binds within the path of the mRNA on the small subunit to prevent correct interaction between initiator tRNA and start codon to prevent translation initiation.

Binding of edeine to the small subunit induces base pair formation between G795 and C693 and prevents binding of initiator tRNA to the small subunit.

Pactamycin binds in the E‐site in the path of the mRNA and prevents the first translocation reaction in a tRNA‐dependent fashion.

Evernimicin binds to the large subunit and prevents IF2‐dependent formation of the 70S initiation complex.

The tetrapeptide GE81112 binds to the 30S subunit to inhibit 30S initiation complex formation.

Antibiotics that inhibit translation also induce ribosomal assembly defects.