bluuebunny/crossref_metadata_2025 huggingface dataset:
Transitions and Relaxations
Authors: Myasnikova Liubov P.
Published: November 2010

The transitions and relaxation processes in polymers are considered. The recent progress and approaches toward both a phenomenological description and a theoretical understanding of its combined kinetic‐thermodynamic character are outlined. The article discusses some specificity of melting polymers, the nature of glass transition, and the secondary transitions and pays attention to a study of relaxation processes in surface nanolayers.
Weathering of Polymeric Materials
Authors: Searle Norma D. , McGreer Matthew , Zielnik Allen
Published: November 2010

The useful service life of polymeric materials depends on their ability to resist the effects of critical weather factors responsible for the deterioration of either or both the appearance and physical properties necessary in their applications. The effects of weather result from complex interactions of the environmental elements, primarily solar radiation, heat/cold, moisture, oxygen, and pollutants, with the materials. By far, the most destructive environmental factor is the ultraviolet (UV) portion of terrestrial solar radiation absorbed by a material because it is capable of breaking some of the chemical bonds and thus initiating the degradation reactions. Because photodegradation is wavelength specific, close simulation of the spectral power distribution (SPD)of the natural source by the radiation source used for laboratory accelerated weathering is essential for simulating the natural weathering processes. The presence of short wavelengths below the solar UV cut‐on, the absence of long wavelength UV and short wavelength visible radiation, and relative intensities that do not simulate those of solar radiation can produce differences in degradation mechanisms, types of failure, and weatherability rankings of products compared with natural weathering. Sample temperatures and type and amount of moisture have a significant influence on the rate of degradation through their effects on the secondary reactions following bond breakage. Unrealistic levels of all stress factors have to be used with caution to obtain good correlation of degradation processes between accelerated and natural weathering. Because acceleration of weathering by increase in the critical stress factors differs for each material and formulation, the acceleration factor must be determined experimentally for each product. The effects of critical weather factors on polymeric materials and the various types of outdoor and laboratory‐accelerated weathering tests and their test parameters are described. The critical weather factors in natural and artificial weathering are compared and potential methodologies for predicting long‐term performance of polymeric materials are reviewed.
Oligodendrocytes
Authors: Szuchet Sara , Domowicz Miriam S , Hudson Lynn D
Published: November 2010

Oligodendrocytes – a type of central nervous system glial cell – have diverse origins and are morphologically and phenotypically heterogeneous. They present two phenotypes: myelinating and nonmyelinating that derive from a common precursor pool. In the spinal cord, oligodendrocyte precursors and motor neurons arise from the same niche. In the embryonic forebrain, ganglionic eminences harbour sites that generate GABAergic neurons and oligodendrocyte precursors destined to populate the telencephalon. A strict spatio‐temporal expression of transcription factors and signalling molecules ensures the orderly appearance of precursors, their migration and differentiation. The two oligodendrocyte phenotypes are functionally interlocked with neurons. Myelinating oligodendrocytes associate with axons and organise them into segments surrounded by the multilayer membrane, myelin, separated by bare regions – nodes of Ranvier – that express voltage‐gated sodium channels, players in the generation of action potentials. Myelin contributes to axonal architecture. Nonmyelinating oligodendrocytes adhere to neuronal somata, but their code of communication is still unknown. In multiple sclerosis myelin is destroyed, oligodendrocytes die and axons degenerate. This overall knowledge constitutes a scaffold upon which further advancements are built.

Key Concepts:

Oligodendrocytes – one of the neural cell types from the central nervous system that have diverse origins and are morphologically and phenotypically hetererogeneous.

Oligodendrocytes provide support to axons that is independent of their role in the assembly and maintenance of myelin.

Oligodendrocytes are vulnerable cells because the making and sustaining of myelin come at a great metabolic cost.

Myelin is an intricate membrane organelle unique to vertebrate organisms.

Myelin is a multilayer membrane not only essential for fast nerve conduction, but is also a critical determinant of axonal architecture.

The advent of myelin marked an evolutionary leap because it allowed for the development of large organisms, but their existence is irrevocably tied to it.

The interaction between an oligodendrocyte and an axon is one of the most complex cell‐to‐cell communications.

Transcription factors act in a cell context–specific mode and regulate the determination of cellular fate.

Genetic and epigenetic factors exert strict supervision on nervous system development.

Diseases of oligodendrocytes or myelin can be classified as demyelinating or dysmyelinating.
Hepatitis Delta Virus
Authors: Taylor John M
Published: November 2010

Several viruses are important causes of acute and chronic infections of the human liver.

Hepatitis delta virus

(HDV) is a most unusual agent that is found only in association with

Hepatitis B virus

(HBV). HBV is a helper virus for HDV and provides the envelope proteins needed for the assembly of new HDV particles. Otherwise the replication of the HDV RNA (
ribonucleic acid
) genome is independent of HBV. HDV encodes only one protein, the delta antigen, a small basic RNA‐binding protein, which is essential for genome replication. In the animal world, HDV is unique to infections of humans. However, HDV shows some intriguing similarities to plant viroids, which have RNA genomes even smaller than HDV, and encode no known proteins and have no helper viruses.

Key Concepts:

HDV uses HBV as a helper virus to achieve assembly of new virus particles.

HDV has a small single‐stranded circular RNA genome.

During genome replication there arises the antigenome, an exact complement of the genome.

The HDV genome and antigenome are transcribed by redirection of a host RNA polymerase that normally acts on DNA templates.

Antigenomic HDV RNA sequences encode one small basic protein that is essential for genome replication

Site‐specific RNA‐editing on antigenomic RNA leads to the translation of a large delta antigen species, one that supports assembly via HBV envelope proteins.

The HDV RNA genome and its mode of replication show intriguing similarities to the plant viroid RNAs.
Innate Immune Mechanisms: Nonself Recognition
Authors: Quah Ben JC , Parish Christopher R
Published: November 2010

The initial defence of the body against pathogens relies on the innate immune system. The innate immune system recognises unique molecular patterns expressed by pathogens, referred to as pathogen‐associated molecular patterns (PAMPs), through receptors known as pattern recognition molecules (PRMs). PRMs are a diverse range of cell‐bound and soluble proteins that sense extracellular and intracellular pathogens and induce a number of responses to help aid in their destruction including phagocytosis through opsonisation, cytokine production and activation of complement. In addition to pathogen sensing, host cells express proteins, the complement regulatory proteins, that protect them from attack by the alternative pathway of complement activation, whereas foreign organisms lack these protective proteins and are, therefore, susceptible to complement attack.

Key Concepts:

The innate immune system recognises pathogen‐associated molecular patterns (PAMPs) that are unique to pathogens.

Cells of the innate immune system express a large range of pattern recognition molecules (PRM) that bind to PAMPs.

Host cells express complement regulatory proteins that protect them from attack by innate mechanisms.
Origin of Life
Authors: Brack André
Published: November 2010

Primitive life – defined as a chemical system capable of transfering its molecular information via self‐replication and also capable of evolving – probably originated about 4 billion years ago from the processing of organic molecules by liquid water. Organic matter might have been formed in the primitive atmosphere from methane or carbon dioxide but also in submarine hydrothermal vents. A large fraction of prebiotic organic material might have been brought by meteoritic and cometary dust grains decelerated by the atmosphere. Strategies to understand the origin of life include the reconstitution in the laboratory of an artificial life capable of self‐reproduction and evolution, the search for fossil traces of life in Archeaen sediments and the search for another example of natural life beyond the Earth, on Mars, Europa, Titan, Enceladus and exoplanets.

Key Concepts:

Life emerged about 4 billion years ago with organic molecules capable of self‐reproduction and of evolving in liquid water.

A large fraction of the prebiotic organic material came from space.

The reconstruction of life in a test tube lacks a simple synthesis of RNA.

The very early fossil traces of life have been erased.

The oldest accepted fossil traces of life are 3.45 billion years old.

Mars harboured large oceans in the past and was therefore hospitable to life.

Life may be present within the Europa's ocean.

Organic chemistry is universal. Life may therefore arise on appropriate extrasolar planets.
Mitochondria Protein Import: Methods
Authors: Stojanovski Diana , Ryan Michael T
Published: November 2010

Mitochondria are prominent and essential organelles within eukaryotic cells. The majority of proteins residing within mitochondria are nuclear‐encoded and consequently synthesised as precursor proteins on cytosolic ribosomes. These precursors must be imported across one or both of the mitochondrial membranes to reach their final destination where they can acquire their functional state. Currently we have knowledge of at least four different pathways that govern the import and sorting of nuclear‐encoded mitochondrial precursors. The elucidation and characterisation of these pathways has been greatly facilitated by the

in vitro

mitochondrial import assay. The

in vitro

assay is the main biochemical approach for analysing protein import into mitochondria and is performed by incubating a radiolabelled precursor protein with isolated mitochondria.

Key Concepts:

Most mitochondrial proteins are encoded by nuclear DNA and need to be imported into the organelle following translation.

Different pathways exist for the import of proteins into the various mitochondrial subcompartments.

In vitro
translated precursors can be imported into energised isolated mitochondria.

The final residence of the imported precursor can be analysed using various treatments.

In vitro
import reactions can be accompanied with monitoring the assembly of the precursor into complexes.
History of Developmental Biology
Authors: Horder Tim
Published: November 2010

Developmental biology – or ‘embryology’ – is a subject with a long and distinguished, but uneven, history. It is remarkable for the list of leading scientists and philosophers who have contributed to it from antiquity up to the present era. Because embryos are typically minute and inaccessible direct study and understanding has been slow and relatively recent: before the mid‐nineteenth century theories of reproduction and the origin of living forms were largely speculative. Since then embryology has varied greatly in its importance within mainline biological thinking. At one time it provided key evidence for evolution; later for early theories of genetics. Recently, and even now it can be argued, biologists are divided and unclear about how best to demarcate the subject because it overlaps with many other biological themes as diverse as reproduction, malformation, aging and cancer. Today it tends to be approached through the techniques of molecular biology and molecular genetics, and has acquired renewed interest in the context of fertility enhancement, stem cells and genetic engineering.

Key Concepts:

Historically, developmental biology has at times been central to biological thinking: for example as key evidence for change and succession in body forms during evolution.

The historical theme of whether, in part, ‘ontogeny recapitulates phylogeny’ remains an open question to this day.

Investigative embryology created some of the most elegant and decisive experimental designs in the history of biology.

Developmental biology remains the repository of some of the greatest remaining challenges within biology: for example how to account for the complexity and dynamic properties of living systems.

The concepts of allometry and heterochrony have their origins in the study of embryos.

Developmental biology remains a crucial challenge to the currently dominant explanation of biological systems in terms of molecular genetics: it demonstrates the equal importance of frequently overlooked ‘epigenetic’ considerations in accounting for biological form.

IVF, the stem cells concept and the potential of regenerative medicine have their theoretical base in the standard concepts derived from developmental biology
DNA
: Mechanical Breakage
Authors: Quail Michael Andrew
Published: November 2010

In order to fragment
deoxyribonucleic acid
(DNA) in a random manner, a variety of methods involving the mechanical breakage of DNA have been employed. These include sonication, needle shear, nebulisation, point‐sink shearing and passage through a French pressure cell. The new sequencing technologies utilise smaller fragments than those traditionally generated by mechanical breakage. As a result a number of higher throughput and more powerful technologies for random shearing of DNA have been developed including focused acoustic shearing (Covaris Inc) and high power sonication devices (e.g. Sonicman and Bioruptor). These are able to efficiently fragment DNA down to 100 bp and options for multiplexed sample processing are available.

This article describes each of these approaches in turn giving the theory behind and the utility of each and giving practical tips where appropriate.

Key Concepts:

Shearing DNA using mechanical breakage produce random fragments.

Shearing DNA by utilising enzymatic action generates bias and produces a set of nonrandom fragments.

Several genomic analysis procedures, especially sequencing, require the shearing of DNA to a set of random DNA fragments.

Heat generated during physical shearing can cause A–T rich regions of DNA to permanently dissociate.

Randomly sheared DNA needs ‘repairing’, typically by incubation with Klenow or T4 polymerase in the presence of dNTPs, in order to make their termini available for ligation.
Evolutionary Game Theory
Authors: Broom Mark , Cannings Chris
Published: November 2010

In the natural world, there is a constant struggle between individuals to survive and reproduce; for example, prey compete against their predators and conspecifics compete for resources such as food and territory. The outcomes of these conflicts depend on the strategies adopted by individuals and impact on reproductive success. The theory of evolutionary games, or evolutionary conflicts, addresses the issues of what strategies prevail and coexistence within these competitions under natural selection. The original models were based on competitions between identical conspecifics, although they now cover a huge range of complex behavioural scenarios such as the adoption of elaborate behaviours or costly physical ornaments by male animals seeking mates or the formation of dominance hierarchies among social groups.

Key Concepts:

Strategies are the possible behaviours open to an individual within a game.

Knowing the behaviour of each individual determines the rewards (payoffs) to all individuals in the game.

An evolutionarily stable strategy (ESS) is a strategy that, if played by almost all, resists invasion by any other strategy and so persists through time.

It is possible to have a single ESS, more than one ESS or no ESSs for a given game.

There is the potential for larger payoffs than under an ESS if individuals could co‐operate, but such strategies do not resist invasion and so are unstable.

While there may be more than one ESS, there are important restrictions on which can coexist for simple two‐player conflicts. More complex restrictions apply for multiplayer conflicts, and some of the simpler restrictions of the two‐player conflicts may not apply.

A population composed of individuals playing different strategies is subject to change following evolutionary dynamics, for example, replicator dynamics.

The rest points of evolutionary dynamics are not always the same as the ESSs of a conflict and care must be taken in any specific analysis.

If populations are subject to only small changes in strategy through mutation, change can be modelled by adaptive dynamics.
m
RNA
: Intranuclear Transport
Authors: Politz Joan C Ritland , Pederson Thoru
Published: November 2010

Most genes are transcribed in the nuclear interior and the messenger ribonucleic acid (mRNA) must then move from its transcription site to the nuclear pores to be transported to the cytoplasm for translation. mRNAs interact with multiple proteins both during and after transcription, some of which help to determine their export competency. High‐resolution, live cell tracking studies show that when released from the transcription site, messenger ribonucleoprotein (mRNP) complexes move out into the nucleoplasm in all directions by simple diffusion. The mRNPs sometimes move discontinuously depending on obstacles they encounter and may be corralled in certain regions for a time, but overall, the nascent mRNPs rapidly distribute throughout the entire channel‐like interchromatin space. Export‐competent mRNPs then randomly encounter a nuclear pore and are captured for export to the cytoplasm.

Key Concepts:

mRNPs released from the transcription site move through the nucleoplasm primarily by diffusion.

Diffusing mRNPs can be corralled by encounters with obstacles such as chromatin.

Export‐competent mRNPs randomly encounter nuclear pores and are transported to the cytoplasm.

A minority of mRNAs are transcribed at the nuclear periphery and it is possible that these exit the nucleus through the nearest nuclear pore.
Atherosclerosis: Pathogenesis, Genetics and Experimental Models
Authors: Homeister Jonathon W , Willis Monte S
Published: November 2010

Atherosclerosis is a disease of the arteries that results in heart disease and stroke – the most common causes of death in developed countries, and a growing burden in developing countries. Atherosclerosis results from injury to the artery endothelium caused by mechanical and environmental factors, and the resulting inflammatory response in the vessel wall. The location and morphology of the atherosclerotic lesions predict the nature of the resulting vascular disease. Some risk factors for the disease are well known and current therapies are largely directed at modifying them, but the tendency to develop atherosclerosis is determined largely by polygenetic factors that are poorly understood. Recent developments in genetic studies have been applied to atherosclerosis, and are beginning to rapidly reveal the genetic factors that modulate the pathogenesis of this disease.

Key Concepts:

Atherosclerosis is a common, costly and deadly vascular disease that affects peoples of developed countries, and increasingly burdens developing countries.

Atherosclerosis is an inflammatory disease of the arterial vascular wall.

The pathogenesis of atherosclerosis is complex, but is generally explained by the ‘response to injury’ hypothesis.

Atherosclerotic lesions have varied morphology, and clinical manifestations correlate with lesion type and location.

Both environmental and heritable risk factors modulate atherosclerosis development.

Candidate gene and linkage analysis studies have failed to identify previously unknown pathways in the pathogenesis of atherosclerosis.

Recent publication of the HapMap has made possible genome‐wide association studies aimed at probing the pathogenesis of atherosclerosis.

Recent genome‐wide association studies have reproducibly identified several loci involved in the pathogenesis of atherosclerosis, and most of the identified genes are newly implicated in the disease process.

APOE‐ or LDLR‐deficient mice are widely used models to study the pathogenesis of atherosclerosis.
Multiple Endocrine Neoplasia Type 2
Authors: Raue Friedhelm , Frank‐Raue Karin
Published: November 2010

Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant hereditary cancer syndrome caused by missense gain‐of‐function mutations of the

RET

proto‐oncogene on chromosome 10. It has a strong penetrance of medullary thyroid carcinoma (MTC) and can be associated with bilateral pheochromocytoma and primary hyperparathyroidism. The specific

RET

mutation may suggest a predilection towards a particular phenotype and clinical course, with strong genotype–phenotype correlations. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on classification of

RET

mutations into risk levels according to genotype–phenotype correlations. By earlier identification of patients with hereditary MTC, the presentation changed from clinical tumours to preclinical disease resulting in a high cure rate of affected patients with much better prognosis.

Key Concepts:

The hereditary cancer syndrome (MEN 2) is caused by germline activating mutations of the
RET
‐proto‐oncogene.

Hereditary medullary thyroid carcinoma (MTC) is the most common manifestation of multiple endocrine neoplasia type 2 (MEN 2) syndrome.

Genetic testing detects nearly 100% of mutation carriers.

Three different clinical variants of MEN 2 are known, MEN 2A, MEN 2B and FMTC.

Each variant of MEN 2 results from different
RET
gene mutations with a good genotype–phenotype correlation.

Recommendation for the timing of prophylactic thyroidectomy and extent of surgery are based on a classification into four risk levels utilising the genotype–phenotype correlation.

If prophylactic thyroidectomy is done at early ages cure rate will be 100% and improves significantly long‐term outcome and prognosis of these patients.

Pheochromocytomas usually present after MTC or concomitantly, rarely it can be the first manifestation of MEN 2A, lifelong annual biochemical screening is necessary in carriers at risk.
DNAHelicase‐deficiency Disorders
Authors: Sidorova Julia M , Monnat Raymond J
Published: November 2010

Deoxyribonucleic acid (DNA) helicasesuse energy derived from the hydrolysis of adenosine triphosphate (ATP) to separate the complementary strands of DNA. This article focuses on one family ofDNA helicases, the humanRECQ (recombination) helicasesand the syndromes that arise due to their deficiency. The five humanRECQ helicasesshare a common, conserved helicase domain and all five proteins appear to play important roles in cellular DNA metabolism. Loss‐of‐function mutations in three family members cause the human cancer predisposition syndromes Bloom syndrome (BS), Werner syndrome (WS) and Rothmund–Thomson syndrome (RTS). This article outlines clinical features of theRECQ helicase‐deficiency syndromes and the underlying genetics, biochemistry and function of the associated humanRECQ helicasegenes and proteins. We discuss how the loss of RECQ function may promote genetic instability and disease pathogenesis, and howRECQ helicasesmay serve as predictors of cancer risk and the response to therapy.

Key Concepts:

RECQ helicases are found in all Kingdoms of life.

RECQ helicases use the energy of ATP hydrolysis to unwind the strands of duplex DNA molecules.

RECQ helicases play important roles in many aspects of DNA metabolism including DNA replication and repair, recombination and telomere maintenance.

Loss of RECQ helicase function is associated with defects in DNA metabolism, genetic instability, reduced cell proliferation and cellular senescence or apoptosis.

Heritable human RECQ helicase deficiencies are rare. Three distinct autosomal recessive RECQ helicase deficiency syndromes have been identified thus far.

RECQ helicase‐deficient individuals have an elevated risk of cancer together with additional developmental or acquired findings.

Acquired RECQ helicase deficiencies may be common in adult cancer, where loss‐of‐function may modify the response to therapy.
Neural Tube Defects: Genetics
Authors: O'Byrne Michelle R , Au Kit Sing , Northrup Hope
Published: November 2010

Neural tube defects (NTDs) are malformations of the brain and the spinal cord, resulting from lack of closure of the developing neural tube during embryological development. NTDs are complex birth disorders with a worldwide prevalence from 0.5 to 2.0 per 1000 births. The two most common types of NTD are anencephaly and spina bifida, which involve failure of neural tube closure in the cranial and in the back regions respectively. NTDs are hypothesised to be a result of genetic abnormalities and environmental factors; yet, the aetiology remains undetermined. Research studies over the past decade have indicated that maternal folate deficiency is an extremely important risk factor for an NTD birth, with maternal folate supplementation decreasing risk. However, the role that folate plays in NTD risk is not well defined.

Key Concepts:

Neural tube defects (NTDs) are congenital malformations of the brain and spinal cord.

The prevalence rates of NTDs vary worldwide.

NTDs are complex birth defects composed of both genetic and environmental components.

The underlying mechanism remains undetermined.

NTDs are classified by whether they are open or closed and by the location of the lesion.

Folic acid supplementation ameliorates NTD risk.

The majority of NTDs are sporadic and nonsyndromic.

To date, association studies in relatively small patient cohorts have been used in an attempt to find causative genes.

Future additional approaches will include Genome‐Wide Association Study (GWAS) and high‐throughput sequencing.
Genetics of X‐linked Mental Retardation
Authors: Lisik Małgorzata Zofia
Published: November 2010

X‐linked mental retardation (XLMR) refers to a group of inherited disorders characterised by varying degrees of mental retardation, caused by mutations in various genes present on the X‐chromosome. Historically, XLMR is divided into syndromic (MRXS) and nonsyndromic (MRX). At least 209 different XLMR disorders have been described including 143 forms of syndromic mental retardation. Fragile X syndrome is the most frequent syndrome and most studied XLMR syndrome. It is now possible to identify 42% of the genetic defects in XLMR families with obligate female carriers. Most of the mutated genes in XLMR are thought to influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in brain. Thus the diagnosis of mental retardation in a child has an enormous impact in most affected families. Genetic counselling is strongly recommended to family members.

Key Concepts:

X‐linked mental retardation (XLMR) is a very heterogeneous set of conditions responsible for a large proportion of inherited mental retardation.

XLMR can be divided into syndromic (MRXS) and nonsyndromic (MRX).

Genes involved in XLMR influence development, cell migration, formation and maintenance of neural networks and cell‐to‐cell communication in brain.

Mental retardation phenotype can emerge as the final common pathway of many different types of abnormal cellular processing.

Genetic counselling is an important part in general management in the case of mental retardation.
Sexual Selection: Its Possible Contribution to Recent Human Evolution
Authors: Richards Richard A
Published: November 2010

Darwin's appeal to sexual selection in hisDescent of Manwas motivated by the need to explain traits not obviously of survival value – sexually dimorphic and ornamental traits. After Darwin, there was little interest in sexual selection until the 1970s. Since then there has been much progress due to first, what we now know about sexual reproduction and human evolution in general; second, theoretical developments related to runaway processes, parental investment, mating systems and sexual conflicts and cooperation; third, new empirical data about actual mating preferences in humans and closely related species. Three issues have motivated the debates about sexual selection: the explanatory scope of sexual selection; the nature and existence of sexual selection; the relation between naturalsurvivalselection and sexual selection. One recent approach combines survival and sexual selection in the idea that many distinctively human capacities and behaviour are the products of sexual selection on fitness indicators.

Key Concepts:

The explanatory scopeof a theory or hypothesis is the range of phenomena it can potentially explain.

Human fitness indicatorsare those traits that are possible only in highly fit individuals, and are therefore indicative of high fitness.

Parental investmentis the amount of resources a parent devotes to the production and care of offspring, in development from the generation of gametes to birth, and to the feeding, education and support of offspring.

Sexual selectionis a result of the struggle to reproduce, and is to be distinguished from natural selection and the struggle to survive.

Surplus abilitiesin humans are those abilities not obviously explainable in terms of naturalsurvivalselection and advantages for survival, such as we see in advanced mathematics, poetry, dancing, music and more.
Rho
GTPase
Function in Cell Morphogenesis
Authors: Pedersen Esben , Brakebusch Cord
Published: November 2010

Cell morphogenesis is the development of a specific cell morphology, which includes the acquisition of cell shape, cell polarity, cell–cell and cell–ECM (extracellular matrix) contacts. Cell morphogenesis is dependent on the interaction of the cell with its environment and therefore not a cell autonomous process. Crucial for cell morphogenesis is the regulation of the
actin
cytoskeleton. Furthermore, regulation of gene expression and activation of different intracellular signalling pathways contribute to cell morphogenesis. Rho
guanosine triphosphatases
(GTPases) are master regulators of the
actin
cytoskeleton, which affects cell shape and the position of integrins and cadherins,
actin
cytoskeleton attached cell surface receptors. In addition, Rho GTPases regulate endocytosis, vesicle transport, secretion and gene expression. Not surprisingly, therefore, this family of molecules was found to be particularly important for cell morphogenesis.

Key Concepts:

Rho GTPases are signal integrators.

Rho GTPases have overlapping functions.

Rho GTPases regulate cell shape by controlling remodelling of the actin cytoskeleton.

Cdc42 regulates different aspects of cell polarity in a cell type‐specific manner.

Rho GTPases regulate cell adhesion to the extracellular matrix and to other cells.
Climate Change Impacts: Insects
Authors: Stange Erik E , Ayres Matthew P
Published: November 2010

Climate exerts powerful effects on the distribution and abundance of the earth's insect species, and we should expect climate warming to generate changes for many insect populations and the ecosystems they inhabit. A substantial scientific literature provides a foundation for describing how insect species are responding to recent climatic trends on the basis of insect physiology, and predicting generalised species distributions and population dynamics for the future. Warmer temperatures generally lead to more rapid development and survival in insects in mid‐ to high latitudes, which can account for detectable and unambiguous shifts in a range of insect species over the past half century. Increased warmth also advances the onset of insect life cycles for the many species that use thermal cues to match the timing of life history events with the changing seasons. Owing to their relatively short life cycles, high reproductive capacity and high degree of mobility, insects’ physiological responses to warming temperatures can also generate particularly large and rapid effects on species population dynamics.

Key Concepts:

Warmer temperatures associated with climate changes will tend to influence (and frequently amplify) insect species’ population dynamics directly through effects on survival, generation time, fecundity and dispersal.

Individual insect species’ responses to climate change, however, will depend on their geographic range, trophic level and natural history.

Insect populations in mid‐ to high latitudes are expected to benefit most from climate change through more rapid development and increased survival. Much less is known about the effects of increased warming on tropical insect species.

Insect species’ mortality may decrease with warmer winter temperatures, thereby leading to poleward range expansions.

The physiological effects of climatic warming on insects species can also act indirectly through trophic interactions (i.e. host plants and natural enemies).

Insects feature prominently among the documented range expansions that illustrate biological responses to recent climate change.

Because insect species in general have relatively short life cycles, high reproductive capacity and high degree of mobility, the physiological responses to warming temperatures can produce large and rapid effects on species population dynamics.
Barcoding South American Birds
Authors: Lijtmaer Darío A , Tubaro Pablo L
Published: November 2010

DNA barcoding, a genetic‐based species identification system, has proven to be highly effective. The project to barcode all the birds of the world was one of the first campaigns to be launched and over 30% of the species have been already barcoded. The Neotropics are the most biodiverse region of the planet, including almost 4000 species of birds, and barcoding its avifauna is therefore vital for the project. Most of the progress within this region has been made in South America, including the first large‐scale barcode study of Neotropical vertebrates, which is being carried out in Argentina. This study has shown that barcoding is highly efficient in the southern Neotropics, allowing the recognition of more than 98% of bird species. Large‐scale barcoding surveys also allow flagging interesting species or groups of species worthy of deeper analysis, studying avian diversification and analysing continental patterns of evolution, biogeography and speciation.

Key Concepts:

DNA barcoding is a system for species identification that is based on the use of a short, standardised DNA fragment (COI in the case of animals).

The All Birds Barcoding Inititative (ABBI) is the campaign that aims to barcode all the birds of the world, and approximately 30% of the species have been already barcoded.

The Neotropical region is the most biodiverse of the Planet, including almost 4000 bird species, and barcoding its avifauna is therefore vital for the advancement of the ABBI.

Most of the progress in the Neotropics has been made in South America, where a large‐scale project to barcode the Birds of Argentina is being performed.

Barcoding has proven to be highly efficient for species recognition in the southern Neotropics, where more than 98% of bird species can be identified using COI.

Barcoding the Argentine avifauna also flagged many interesting species or groups of species worthy of further analysis, including approximately 5% of species in which at least two deeply diverging lineages were found.

The study of avian diversification patterns in the region using COI showed cases of allopatric, paraptric and sympatric divergences.

The comparison of the COI datasets between the southern Neotropics and the Nearctic suggests that species are slightly older in the former and supports the notion that phylogenetic structuring is more complex in the Neotropics.
Evolution of Immune Proteins in Insects
Authors: Bulmer Mark S
Published: November 2010

Insect immune proteins evolve more rapidly than nonimmune proteins. Based largely on genetic studies inDrosophilaspecies, this elevated rate appears to be due to adaptive evolution in only a small subset of immune proteins. The genetic signature of adaptive evolution is apparently a response by the host to interference or evasion of the immune system by pathogens, which are usually unknown. In contrast, many insect immune proteins appear to be constrained not to change because they interact with conserved molecular targets in a pathogen's cell wall or plasma membrane. Adaptive immune protein evolution may be attributable to a sustained arms race between host and pathogen or to rapid environmental change that exposes insects to new pathogen suites. Evidence of a correlation between the strength of selection and functional divergence in antimicrobial peptides provides confirmation that the inferred genetic signatures of adaptive evolution reflect a response to pathogen selective pressure.

Key Concepts:

A small set of immune proteins inDrosophilaevolve much more rapidly than other proteins.

Insect antiviral proteins of the RNA interference system are among the top 3% of rapidly evolving proteins inDrosophila.

There is surprisingly little evidence of adaptive evolution inDrosophilaantimicrobial peptides.

Many receptors and effectors of the insect immune system appear to be evolutionary constrained due to their interaction with conserved target molecules.

Pathogens target certain vulnerable immune proteins for suppression and positive selection in these proteins appears to reflect a counter response to this suppression.

The selective pressure imposed by pathogens appears to be greater for social than nonsocial insects.

Rapid changes in the types of pathogen that hosts encounter as well as long‐term co‐evolutionary arms races may drive adaptive immune protein evolution.

Positive selection appears to drive the functional divergence of antimicrobial peptides in termites and other animals.
Evolution of Notch Transmembrane Receptors
Authors: Gazave Eve , Renard Emmanuelle
Published: November 2010

Notchis the transmembrane receptor of a juxtacrine signalling pathway (Notch pathway) crucial for cell programming during animal development. The activeNotchpathway is an innovation of the metazoan lineage: several major components of this molecular network are absent from other eukaryotes. The transmembrane multidomain proteinNotchemerged through the assembly of both ancient and recent domains: some were probably already present in LUCA (Last Universal Common Ancestor) whereas others appeared during animal evolution. Data from a choanoflagellate genome suggest that the domain shuffling events which gave rise to the typical domain composition ofNotchprobably occurred before the emergence of animals. More genomic and functional experiments are needed to fully understand the evolution of theNotchreceptor and the interactions with its ligands.

Key Concepts:

Multicellularity emerged independently several times during Life History.

Intercellular communication mechanisms can be performed either through direct cytoplasmic exchanges or through interactions involving membrane components.

Juxtacrine signalling requires physical contact between the two cells involved.

About 20 signalling pathways are involved in cell signalling in the metazoan (animal) lineage; among them, 7 are known to play major roles during animal development.

EGF repeats are known to be commonly used domains for protein–protein interactions in Eukaryota.

ANK repeats are one of the most common protein–protein interaction motifs in living beings.

The domain shuffling mechanism is important in genome evolution.

Gene duplication events represent a powerful tool for molecular and functional innovations.

Notch is the receptor of a juxtacrine signalling pathway crucial for cell programming during animal development.
Evolution of Visual Performance‐associated Genes inDrosophila
Authors: Friedrich Markus
Published: November 2010

The leading model of insect vision, the fruitflyDrosophila melanogaster, is a representative of the higher Diptera (Brachycera), which excel by swift flight abilities, one of the fastest photoresponse mechanisms known and a unique form of neural superposition optics. Recent gene‐specific as well as comparative genomic investigations have begun to yield first insights into the genetic origins ofDrosophilavisual organisation and performance. These studies suggest discrete stages in the molecular evolution ofDrosophilavision culminating in changes that enhanced the speed and versatility of diurnal vision specifically during the early evolution of the higher Diptera. Comparative genomic analysis revealed that gene duplication played an unusually important role during this final stage ofDrosophilavision evolution. Select gene‐specific studies, however, also uncovered specificcis‐regulatory and coding region changes that were of key importance in the evolution theDrosophilaphototransduction and retinal organisation.

Key Concepts:

The shared deployment of the phototransduction protein machinery in the photoreceptors of highly diversified visual organs inDrosophila(the larval eyes, ocelli and the adult compound eye) may impose adaptive constraints.

In contrast to the detailed mechanistic understanding of irradiance and color vision inDrosophila, the ecological role and significance of these sophisticated visual capacities is still little known inDrosophilaand the related Diptera.

The complex retinal organisation ofDrosophilais representative of all members of the species‐rich higher Diptera suggesting strong functional or developmental constraints.

Phylogenetic evidence indicates a correlation of significant structural and molecular changes in the visual system ofDrosophilaand the higher Diptera the cause of which requires further comporative research.

Gene duplication played a critical role in the early visual evolution of the higher Diptera.

The evolution of theDrosophilavisual system is a paradigm example of the combined effects ofcis‐regulatory and coding sequence evolution.

Select mechanisms of theDrosophilaphotoresponse are likely to differ in insect species outside the higher Diptera complicating functional gene orthology inferrences and warranting further research in other models of insect vision.
The Chemistry ofNO‐ andHNO‐Producing Diazeniumdiolates
Authors: S. Evans Anthony , P. Toscano John
Published: November 2010

Although most diazeniumdiolates (R‐N(O)=NO−Na+) are stable as solid salts, current interest in their chemistry stems from their ability to produce nitric oxide (NO), nitroxyl (HNO), and/or a mixture of NO and HNO upon decomposition in aqueous solution. Following a discussion concerning the synthesis of diazeniumdiolates, this chapter focuses on how the substituent (R) and experimental conditions influence decomposition chemistry and NO/HNO production. Representative applications of NO‐ and HNO‐producing diazeniumdiolates are also provided.
Hydroxamic Acids: Biological Properties and Potential Uses as Therapeutic Agents
Authors: Mai Antonello
Published: November 2010

Hydroxamic acids take their biological properties from the ability to chelate metal ions which are important for a variety of biological processes, as well as for the catalytic activity of a number of metalloenzymes. In particular, the preference for chelation of iron and zinc ions by hydroxamates led to derivatives endowed with high potential as therapeutic agents. As iron chelators, most hydroxamates and retro‐hydroxamates (zileuton, atreleuton) are potent 5‐lipoxygenase inhibitors, useful for treatment of inflammatory diseases, asthma, and cancer, others (deferoxamine) can be used for the molecular control of iron homeostasis during transfusional iron overload, and for the treatment of acute ischemic stroke, thalassemia, and sickle cell anemia. Metal ion complexation by hydroxamates furnished also highly active antibacterial agents, through inhibition of two metal‐containing enzymes (peptide deformylase with iron, and UDP‐3‐O‐(R‐3‐hydroxymyristoyl)‐N‐acetylglucosamine deacetylase (LpxC) with zinc) crucial for bacterial growth and viability. The ability of hydroxamates to efficiently complex zinc ion makes them useful compounds for inhibiting matrix metalloproteinases (MMPs) and related enzymes (see for example prinomastat) responsible for cancer and arthritis diseases, and histone deacetylases (HDACs), a family of enzymes involved in gene silencing and loss of tumor suppressor functions (see for example vorinostat and romidepsin, recently approved by FDA for the treatment of cutaneous T‐cell lymphoma).
Preparation and Reactivity of Organomanganese Compounds
Authors: Cahiez Gérard , Gager Olivier
Published: November 2010

This chapter deals with the preparation of organomanganese reagents from organolithium or organomagnesium compounds (transmetallation) as well as from organic halides and manganese metal (oxidative addition). The influence of various parameters on the stability of organomanganese reagents is then discussed (nature of the reagent RMnX, R
2
Mn, R
3
MnLI or R
3
MnMgX; effect of ligands and solvents…). The second part of the chapter is devoted to the reactivity of these reagents and to their uses in organic synthesis. They are especially interesting for their chemoselectivity, as illustracted by the addition to aldehydes and ketones, the preparation of ketones by acylation or the copper‐catalyzed conjugate addition to enones, enals and enoates. Organomanganese reagents can also be used to perform various iron, palladium or nickel‐catalyzed cross‐coupling reactions. Manganese salts are efficient catalyst to achieve various homo‐ and heterocoupling reactions using Grignard reagents. They are also used to catalyze the addition of Grignard reagents to acetylenes, 1,3‐dienes and allenes. Finally, various radical cyclization reactions promoted by organomanganates are presented.
Hydroxychloroquine use associated with improvement in lipid profiles in rheumatoid arthritis patients
Authors: Morris Stephanie J. , Wasko Mary Chester M. , Antohe Jana L. , Sartorius Jennifer A. , Kirchner H. Lester , Dancea Sorina , Bili Androniki
Published: November 2010

Objective

Cardiovascular disease (CVD) is the leading cause of death in patients with rheumatoid arthritis (RA). Disease‐modifying therapies that improve risk factors for CVD, such as dyslipidemia, are desired. This study used an electronic health record to determine if hydroxychloroquine (HCQ) use was associated with an improvement in lipid levels in an inception RA cohort.

Methods

All adult individuals with the initial diagnosis of RA between January 1, 2001, and March 31, 2008, were identified (n = 1,539). Only patients with at least one lipid level post–RA diagnosis were included (n = 706). Information on demographics, medical history, body mass index (BMI), laboratory measures, and medications were collected at office visits. Potential risk and protective factors for dyslipidemia were controlled for in linear mixed‐effects regression models for low‐density lipoprotein (LDL), high‐density lipoprotein (HDL), total cholesterol, triglycerides, LDL/HDL, and total cholesterol/HDL.

Results

Patients were 69% women and 98% white, with a median age of 65 years and a median BMI of 29.8 kg/m2. In the adjusted regression models, HCQ use was associated with the following average differences in lipids: LDL decrease of 7.55 mg/dl (P < 0.001), HDL increase of 1.02 mg/dl (P = 0.20), total cholesterol decrease of 7.70 mg/dl (P = 0.002), triglycerides decrease of 10.91 mg/dl (P = 0.06), LDL/HDL decrease of 0.136 (P = 0.008), and total cholesterol/HDL decrease of 0.191 (P = 0.006), which were stable over time.

Conclusion

Use of HCQ in this RA cohort was independently associated with a significant decrease in LDL, total cholesterol, LDL/HDL, and total cholesterol/HDL. Considering these results, its safety profile, and low cost, HCQ remains a valuable initial or adjunct therapy in this patient population at high risk for CVD.