bluuebunny/crossref_metadata_2025 huggingface dataset:
Rhinoviruses
Authors: Arden Katherine E , Mackay Ian M
Published: April 2013

Human rhinovirus (HRV) infections cause 70% of virus‐related wheezing exacerbations and cold and flu‐like disease. They are associated with otitis media, sinusitis and pneumonia. Annually, the health and socioeconomic impact of HRV infections costs billions of dollars. Since 1987, 100 officially recognised HRV serotypes have resided in two genetically distinct species, HRV‐A and HRV‐B. Their genome sequences were deduced in 2009. Recently a new species, HRV‐C was recognised, containing 60 genotypes, of which only two have been isolated in primary tissue. Little is known about HRV‐Cs. The HRVs reside within the genusEnterovirus, familyPicornaviridae. What drives the development and maintenance of so many distinct viruses is unknown. What role recombination plays in generating this diversity and whether there are species‐specific circulation patterns and clinical outcomes remains unclear. In short, much remains uncertain about the HRVs but the current key features and clinical outcomes from HRV infection are presented.

Key Concepts:

The nonenveloped HRVs have a small RNA genome of approximately 7000 base pairs.

A third, new species of HRV, HRV‐C was described in 2007; all species reside within the genusEnterovirus, familyPicornaviridae.

HRV prevalence peaks twice per year.

HRVs cause cold and flu‐like symptoms and trigger asthma and chronic obstructive pulmonary disease exacerbations.

HRVs are associated with diseases such as otitis media, sinusitis and pneumonia.

HRV infections are associated with considerable direct and indirect healthcare expenditure annually.
Viral Classification and Nomenclature
Authors: Fauquet Claude M , Martelli Giovanni P
Published: April 2013

As any classification is essentially an arbitrary human invention, it is imperative to have a unique source of classification also for viruses. The International Committee on Taxonomy of Viruses (ICTV), a committee of the Virology Division of the International Union of Microbiological Societies, has been in charge of this task since 1966 and has already published nine Reports updating the status of viral taxonomy. Contrary to other biological entities (vertebrates, invertebrates, plants, fungi and bacteria), viruses are not classified according to a Linnean latinised binomial system but, like these, they are arranged into species, genera, subfamilies, families and orders, whose names are written in italics with an initial capital letter. The last ICTV report (2011) lists 6 orders, 94 families, 22 subfamilies, 395 genera and 2480 recognised species. Species are the building blocks of the taxonomic construction. Although species identification is based on discriminating traits, their allocation into higher taxa takes into account common characters of increasingly hierarchical significance.

Key Concepts:

Taxonomy is an arbitrary organisation of biological entities to facilitate scientific studies and to identify common traits within similar taxonomic levels.

Classification and nomenclature are the two facets of taxonomy.

Classification is the arrangement of biological entities into taxonomic categories (taxa) on the basis of similarities and/or relationships (phylogeny).

Nomenclature is the assignment of names to taxa, according to international rules.

Virus classification is a rapidly evolving science particularly with the input of viral genome sequencing.

Viruses are not named according to a Linnean latinised binomial system and instead are named with international English‐based names and
de novo
international taxonomic names.

The ICTV is entrusted with the task of classifying and naming virus taxa.
Chlamydiae
Authors: Everett Karin DE
Published: April 2013

Chlamydiae
are bacterial species with a developmental cycle requiring replication in eukaryotic cells. They infect the cells of mammals, birds, marsupials, fish, reptiles, amphibians, insects and protozoa. The most famous species,

Chlamydia trachomatis

, causes sexually transmitted disease in humans. Analysis of available genome sequences for these bacterial species has shown that their common ancestor lived over a billion years ago. Because of their diversity,
Chlamydiae
are often recognised and grouped by using rDNA PCR methods. All
Chlamydiae
have 16S or 23S ribosomal
ribonucleic acid
(rRNA) sequences that are at least 80% identical to the rRNA of the
Chlamydiaceae
family.
Chlamydiae
are also characterised by four unique phenotypic traits: they have an electron dense infectious form (0.2 
μ
m), they have a morphologically and physiologically distinct replicative form (approximately 1.0 
μ
m), the outer membrane has lipopolysaccharide and is structurally dependent on disulfide‐crosslinked cysteine‐rich proteins, and in host cells Chlamydiae generally are located within membrane‐bound inclusions.

Key Concepts:

Chlamydia
was long believed to be a simple and mysterious disease.

Today we know it is a tiny intracellular bacterium so unique that it is classified at the highest level: phylum
Chlamydiae
.

Chlamydiae
probably includes thousands of species.

So far (since 1980) 25 chlamydial species have been described in some detail.

These species are found in animals, amoebae, insects and a worm living on the bottom of the ocean.

The complete genomes of 12 chlamydial species have been DNA sequenced.

Genome sequencing reveals that
Chlamydiae
existed a billion years ago.

The common ancestor of all
Chlamydiae
was directly related to the ancestors of plants and animals and other bacteria.

All genome‐sequenced
Chlamydiae
have 493 genes in common – approximately one quarter to one half of each genome.

Chlamydial phenotypes today display the observable effects of these genes.
Chlorinated Hydrocarbon Metabolism
Authors: Reineke Walter , Mandt Christian , Kaschabek Stefan R , Pieper Dietmar H
Published: April 2013

The widespread global distribution of chlorinated hydrocarbons, their high lipophilicity and their recalcitrance have contributed to their importance as environmental toxicants. Their metabolism under oxic and anoxic conditions mediated by prokaryotic and eukaryotic cells is discussed. Various aerobic bacteria are able to use chlorinated hydrocarbons as the sole source of carbon and energy and some anaerobic bacteria can use some of these as an artificial electron acceptor in reductive dechlorination. Liver enzymes are responsible for the formation of hydrophilic metabolites ready for excretion which often lead to highly reactive and potentially toxic intermediates. Whereas fungi, especially ligninolytic ones, usually only exhibit ‘side activities’ for chlorinated hydrocarbons. The capabilities of bacteria had led to the development of various bioremediation processes. Both, successes and failures within these processes are known. Therefore, current research aims at a better understanding of global community interactions.

Key Concepts:

Chlorinated hydrocarbons have been produced by the chemical industry since nearly a decade in large amounts, but they can also be observed as natural compounds, sometimes exceeding the industrially produced amounts.

Even though toxicological properties have pushed the chlorochemistry into the focus of considerable debate and governmental regulatory action, chlorinated hydrocarbons remain essential for certain applications.

The aerobic metabolism of chlorinated hydrocarbons by bacteria has been studied in detail and an immense amount of information is available on pathways, enzymes and genes involved in the mineralisation of chloroaromatics.

The anaerobic degradation of chlorinated hydrocarbons is due to the capablity of anaerobic bacteria to use them in anaerobic respiration, which results in dechlorination.

Dehalococcoides
organisms are the most versatile reductive dehalogenators as being capable to dehalogenate chlorinated dioxins, biphenyls, benzenes and vinyl chloride, among others.

Microbial activities have been widespread used for bioremediation purposes through natural attenuation, biostimulation and bioaugmentation.

The poor understanding of the functioning of the complex microbial activities
in situ
made bioremediation efforts quite unreliable.

The rapid development of molecular techniques in recent years allows immense insights into the processes
in situ
, but also on the overall physiology of biocatalysts.
Fetal–Maternal Immunological Relationships
Authors: Chaouat Gérard
Published: April 2013

Despite inheriting half of its genetic material from its father, the fetoplacental unit is not rejected by the maternal immune system because of a unique immunological relationship with the mother. Despite maternal immune recognition of the conceptus as evidenced by alloantibodies, unlike for conventional allografts, the immune response is spared, cytotoxic effectors being downregulated or suppressed, whereas several cytokinic responses, including inflammatory ones, are used or even provoked for their preimplantation or later on ‘immunotrophic’ effects. This unique relationship is partly due to the peculiar antigen expression in the placenta, culminating in humans with the sole expression of human leucocyte antigen C (HLA‐C) and monomorphic HLA‐G on invading cytotrophoblasts and also many immunoregulatory pathways, with special emphasis presently put on regulatory T cells. Moreover, uterine natural killer (uNK) cells are a distinct, specialised NK subset, endowed with immunoregulatory and angiogenic properties, necessary for local (spiral) arteries development. Consequences for abortion eclampsia are discussed, as well as antibody‐induced fetal haemolytic disease.

Key Concepts:

The fetus is usually seen as an allograft in mother's womb, which should be rejected by the maternal immune system.

Pregnancy induces systemic modifications in the maternal immune system but these do not really account for fetal survival.

Recognition of the ‘foreign’ nature of the fetus is good and even sometimes required for successful pregnancy.

Placenta acts as a barrier between the fetus and maternal cells.

Uterine natural killer cells are not endowed with the same properties as the ones found in peripheral blood.

One of the keys to fetal survival is the peculiar expression of MHC antigens in the placenta, including in human the expression of a nonpolymorphic antigen, HLA‐G, in membrane bound and soluble forms both endowed with immunoregulatory properties.

Uterine natural killer cells control local uterine angiogenesis.

The placenta bathes in/secretes immunotregulatory materials.

Regulatory T cells mitigate the effects of allorecognition by maternal immune system in placental mammals.

Allopregnancy is a Th2 phenomenon.

In variance with MHC antigens, red blood cells antigens can induce maternal antibodies which can cross the placenta, and destroyin uterofetal red blood cells.
Quinone Cofactors
Authors: Lang Albert , Klinman Judith P
Published: April 2013

Quinone cofactors are used by several classes of enzymes, which catalyse the oxidation of biogenic amines and alcohols, to help catalyse these reactions. Before 1990 only one cofactor, the peptide‐derived pyrroloquinoline quinone had been identified. During 1990–2001, however, four new quinone prosthetic groups derived from naturally occurring amino acids were discovered. The first protein‐derived, nondissociable cofactor identified was 2,4,5‐trihydroxyphenylalanine quinone, designated topaquinone (TPQ) in copperamine oxidases. The discovery of TPQ led to the identification of a series of new quinone cofactors, including lysine tyrosylquinone (LTQ) in lysyl oxidase, cysteine tryptophylquinone (CTQ) inquinohaemoprotein amine dehydrogenaseand tryptophan tryptophylquinone (TTQ) in bacterialmethylamine dehydrogenase. These cofactors contribute electrophillic capabilities (and stabilise free radical intermediates) that naturally occurring, unmodified amino acid side chains are unable to provide.

Key Concepts:

Quinone cofactors are a class of cofactors used by many enzymes to catalyse the oxidation of amines and alcohols.

Five quinone cofactors have been characterised: PQQ, TPQ, LTQ, TTQ and CTQ.

PQQ is a peptide‐derived cofactor that involves the expression of six genes located within an operon.

TPQ is derived from a precursor tyrosine and requires only Cu2+and O2for biogenesis.

LTQ is formed by the cross‐linking of a tyrosine residue and a lysine residue, also requiring only Cu2+and O2.

TTQ is formed by the cross‐linking of two tryprophan resides, with MauG completing biogenesis.

CTQ, the most recently discovered quinone cofactor, is formed by the cross‐linking of a cysteine reside and a tryptophan residue.
Enzymes: The Active Site
Authors: Ghanem Eman , Raushel Frank M
Published: April 2013

Enzymes are highly efficient and specific catalysts. They catalyse biochemical reactions with substantial rate enhancement compared to the uncatalysed reactions. The rate enhancement and specificity of enzymes are derived from a network of general acid/base catalysts, nucleophiles and noncovalent interactions in the active site, the part of the enzyme where cataylsis takes place. In catalysis, binding of the substrate and the transition state in the active site is of critical importance. Enzymes catalyse reactions by preferentially binding the transition state and, therefore, lowering the activation energy of the reaction. Enzymes bind their substrates via a network of weak, noncovalent intermolecular interactions such as hydrogen bonding, hydrophobic and electrostatic interactions. Enzymes utilise several mechanisms to accelerate a reaction such as acid/base catalysis, covalent catalysis and metal ion catalysis. Owing to their integral role in all biochemical pathways, enzymes are an attractive target for drug design and development.

Key Concepts:

Enzymes are biocatalysts that are involved in all forms of biochemical transformations.

Nearly all enzymes are proteins.

Enzymes catalyse reactions with a remarkable rate enhancement due primarily to lowering the energy of the transition state.

The active site is a cavity in the enzyme structure where catalysis occurs.

Amino acid residues in the active site provide the required framework for catalysis.
Vertebrate Embryo: Patterning the Neural Crest Lineage
Authors: Nitzan Erez , Kalcheim Chaya
Published: April 2013

Neural crest (NC) cells form as epithelial progenitors during the process of neurulation, then undergo an epithelio‐mesenchymal transition and become motile. As mesenchymal cells, they migrate through stereotypical pathways, reach their homing sites and differentiate into a large variety of derivatives that are specific and variable along the embryonic axis. These include neurons and glia of the sensory and autonomic nervous system, pigment cells, chromaffin cells of the adrenal gland and mesectoderm in the head region. Given that a few initial progenitors expand and diversify so substantially, the NC provides an excellent model to investigate fundamental questions in Developmental Biology, that is, defining the state of commitment of the different precursors throughout ontogeny, unravelling the nature of cellular interactions among adjacent crest cells and between crest progenitors and their environment, and elucidating the molecular basis of lineage segregation, cell migration and terminal differentiation.

Key Concepts:

NC progenitors are multipotent at the population level and become differentially restricted during ontogeny.

Lineage segregation in the trunk is likely to begin before NC emigration from the neural tube.

Epithelio‐mesenchymal transition of NC progenitors is orchestrated by a network of secreted factors (BMP/noggin and Wnt1) acting in concert with adhesion molecules, RhoGTPases, extracellular matrix components and cell intrinsic determinants.

NC cells migrate stereotypically to their homing sites and migration seems to be largely channelled by interactions between inhibitory environmental signals and NC cells expressing their cognate receptors.

Contact inhibition mediated by noncanonical Wnt signalling contributes to the directionality of NC migration.

Specification and subsequent differentiation of NC progenitors into the various phenotypes are regulated by reiterative signals (i.e. BMPs, Wnts) that induce lineage‐specific codes of transcription factors.

In spite of undergoing early fate restrictions
in vivo
, some NC cells, even following differentiation, retain significant plasticity as evidenced by
in vitro
analysis.
Potexviruses and Carlaviruses – Short Filamentous Viruses
Authors: Martelli Giovanni P , Rubino Luisa
Published: April 2013

Potexviruses and carlaviruses are plant‐infecting viruses belonging to the family
Aphaflexiviridae
and
Betaflexiviridae
, respectively. Both have slightly flexuous filamentous particles measuring 470–580×13 nm (potexviruses), and 610–700×12–15 nm (carlaviruses). Virions contain 94–95% protein and 5–6% positive sense, single‐stranded
ribonucleic acid
c
. 5800–7000 nucleotides (nt) (potexviruses) and 7900–9000 nt (carlaviruses) in size. Both virus types have a genome with a similar structural organisation, comprising five (potexviruses) or six (carlaviruses) open reading frames, three of which, known as the ‘triple gene block’, encode polypeptides that facilitate virus movement within the host. Natural hosts of both virus types are herbaceous (weeds, ornamentals, vegetables) rather than woody plants. Many potexviruses are agents of severe diseases, whereas a high percentage of carlaviruses induces symptomless infections. Transmission of potexviruses in nature is, by and large, by mechanical contact, whereas carlaviruses are transmitted primarily by aphids with a nonpersistent modality.

Key Concepts:

Potexviruses and carlaviruses infect primarily herbaceous hosts after mechanical or vector‐driven transmission, respectively.

Particles of both genera are filamentous and slightly flexuous and accumulate in aggregates in the cytoplasm of parenchyma cells.

Demarcation of species within the genera takes into account molecular and biological criteria.

Both genera are characterised by the presence of the so‐called triple gene block that provides the support for virus movement in infected hosts.

Potexviruses and carlaviruses constitute models for virus replication, movement and encapsidation studies.

Control is based on preventive measures, such as sanitary selection, production of virus‐free seed lots and resistance through conventional breeding and genetic engineering.
Virus Diseases of Tropical Crops
Authors: Geering Andrew D W , Randles John W
Published: April 2013

Virus diseases are serious constraints to the productivity and profitability of a wide range of tropical crops. Identification of the causal viruses and understanding their epidemiology is the key to estimating the incidence and economic impact of the diseases they cause, and to devising virus management strategies. Epidemics result from interactions between virus, host plant, vector and environmental factors, and every epidemic can be considered to be a unique pathosystem in which each of the components contributes to the epidemic, and in which none are limiting. Pathogen diagnosis is the key to managing diseases, and we list 18 crops, their main virus/viroid diseases and pathosystem descriptors for each. Six types of pathosystem are described on the basis of the mode of spread, and the different management strategies applicable to each are discussed. The Ninth Report of the International Committee on Taxonomy of Viruses (2012) is an essential reference for virologists working with tropical crops.

Key Concepts:

Identification of viruses or viroids is the key to managing the diseases they cause.

Koch's rules are applied to establish causal associations between viruses/viroids and disease.

Viruses/viroids are identified by their biological, morphological and genetic properties using classical and molecular methods.

The universal database for viruses/viroids published by the International Committee on Taxonomy of Viruses is the resource for classification.

Rapid diagnostic methods rely on nucleotide sequence comparisons with publicly available data bases.

Epidemics are driven by virus, vector, host, environment, time and human activity.

Vector–virus interaction is the main determinant of the rate, range, timing and pattern of disease spread.

Viruses/viroids of tropical plants have unique pathosystems.

A full description of a pathosystem is required to sustainably manage virus epidemics.

Management of epidemics can be achieved by destabilising or down‐regulating one or more components of the relevant pathosystem.
Plant Virus Satellites
Authors: Xu Ping , Roossinck Marilyn J
Published: April 2013

Plant virus satellites are molecular parasites of plant viruses that rely on a helper virus for replication but do not supply any essential function to the helper virus. They can affect the accumulation of the helper virus and alter the host symptoms induced by the helper virus. They include satellite viruses, satellite ribonucleic acids (RNAs) and satellite deoxyribonucleic acids (DNAs). Size, genome structure and replication strategies vary greatly among plant virus satellites. Some plant virus satellites have been used as biocontrol reagents or as vectors to express exogenous genes. They have also been used as reporters for studying the evolutionary mechanisms of the helper virus.

Key Concept:

Plant virus satellites depend on a helper virus for replication, but they may use different host factors.

Plant virus satellites do not provide any essential function for the helper virus.

Plant virus satellites have varied effects on their helper viruses and hosts, including reduction in virus titer and exacerbation or attenuation of symptoms.

Some plant satellite RNAs use ribozymes to resolve multimers generated during replication.

Satellite DNAs are the symptom determinants in an increasing number of crop diseases caused by geminiviruses.
Bacteriophages with
ss
RNA
Authors: Olsthoorn René , van Duin Jan
Published: April 2013

The single‐stranded
ribonucleic acid
(ssRNA) phages are small icosahedral viruses which infect their host via F‐ or polar pili. The best‐characterised are those infecting

Escherichia coli

, a Gram‐negative bacterium found in the gut and faecal sewage. The ssRNA phages are members of the
Leviviridae
family, which includes the two genera
Levivirus
and
Allolevivirus
. The family presently comprises about 100 isolates including the well‐known MS2 and Qβ coliphages.Their genome size ranges from 3400 to 4300 nt and codes for four proteins. The genome of ssRNA phages adopts a unique structure that regulates translation of the four genes, confers RNase resistance in the bacterial cytoplasm, ensures recognition by replicase and facilitates encapsidation by capsid or coat proteins. The interaction between RNA and coat protein by virtue of its high specificity and strength is used in many molecular biological applications.

Key Concepts:

ssRNA phages are members of the
Leviviridae
family which comprises the genera
Levivirus
and
Allolevivirus.

ssRNA phages infect their hosts via pili.

The nonenveloped quasi‐icosahedral shell of the virion has a
T
=3 surface lattice.

RNA inside the virion is structured.

The genome encodes four types of proteins: maturation, coat, lysis and replicase.

Replication requires the use of host proteins.

Translation of the genes is regulated by RNA secondary structure.

Forced evolution experiments reveal constraints on RNA secondary structure.

Phage particles can be used to display foreign epitopes.

RNA phages are used as indicator organisms for the presence of pathogens in drink and surface water.
Neural Crest: Origin, Migration and Differentiation
Authors: Kelsh Robert N , Erickson Carol A
Published: April 2013

The neural crest is a population of cells that emigrates from the dorsal neural tube during early embryogenesis and migrates extensively to give rise to a myriad of cell types. Patterns of migration are controlled largely by extracellular cues in the environment. Neural crest cells are initially multipotent. Cell fate specification – the selection of an individual cell fate from all the possibilities available to a multipotent progenitor – is likely to involve a series of steps, in which cells become progressively restricted to individual fates, a process that is likely to begin while still in the dorsal neural tube, but which then is usually completed during, or even after migration. Extracellular cues in the migratory and postmigratory environment act together with intrinsic transcription factors to ensure that specific fates are chosen. Together, these result in expression of one or more transcription factors that activate or cement a gene regulatory network that establishes and maintains expression of the differentiated phenotype.

Key Concepts:

The neural crest is an important tissue, as reflected in its nickname, ‘the fourth germ layer’.

Neural crest cells give rise to many different cell‐types.

Neural crest cells are induced at the boundary of the developing neural plate and prospective epidermis.

Neural crest induction depends on BMP signalling in the prospective epidermis and Wnt signalling from the underlying mesoderm.

These signals induce neural crest in two phases, specification of the neural plate border, and specification/maintenance of definitive neural crest.

Neural crest migration patterns are complex, and usually specific to the derivative fate adopted.

Neural crest migration is controlled by the environmental distribution of repellent and attractive/permissive signals, with cell‐type specific receptor expression in the neural crest cells determining their response.

While some or all neural crest cells are initially multipotent, specification of individual derivative fates likely results from progressive fate restriction.

Neural crest fate specification involves a combination of intracellular and extracellular factors.

Fate specification results from transcriptional activation of key genes encoding (a combination of) specific transcription factors.

These transcription factors activate and maintain the fate‐specific gene regulatory networks that characterise each cell‐type.
Neurogenesis in
Drosophila
Authors: Jarman Andrew
Published: April 2013

Neurogenesis is the process by which neurons are born during the development of an animal. The nervous system entails great cellular diversity and is the most complex of any organ system. A developing animal needs to harness sophisticated cellular and genetic mechanisms to ensure the orderly generation of large numbers of neurons in the right places and times, and in the right numbers. A long history of molecular genetic studies in the fruit fly,

Drosophila melanogaster

, has provided many insights into how this is achieved. Neurogenesis involves the initial patterning of the ectoderm, the formation of neural precursor cells from the ectoderm and the formation of neurons from these precursors through fixed lineages involving asymmetric cell division. Many of the concepts uncovered apply to neurogenesis in other animals. Indeed, many of the molecular mechanisms are highly conserved.

Key Concepts:

The fruit fly has relatively few neurons in its nervous system, making it tractable to detailed developmental analysis.

The arrangement of these neurons is, as far as is known, very precisely determined by the mechanisms controlling neurogenesis during development.

Neurons are the progeny of neural precursor cells that derive from the ectoderm.

The precursor cells are specified by the action of proneural transcription factors, which are opposed by Notch signalling in the process of lateral inhibition.

At their formation, the precursors are already specified to contribute specific neuronal progeny via fixed lineages of cell division.

For the PNS, neural precursor identity is endowed by proneural factors, their cofactors.

For the CNS, neuroblasts have unique identities according to their location, due to their inheriting different combinations of ectodermal patterning factors.

Within the fixed division lineages, cellular diversity arises through asymmetric cell division, which is driven largely by asymmetrically localised and inherited cell fate determinants.
Catalytic
RNA
Authors: Burke Cassandra R , Lupták Andrej
Published: April 2013

Ribonucleic acid
(RNA) molecules have diverse roles in biological systems. Although some code for proteins or act to translate codons to amino acids, others fold into specific shapes that endow them with the ability to catalyse specific chemical transformations. These catalytic RNAs, ribozymes, are responsible for protein synthesis,
transfer RNA
(tRNA) processing, self‐splicing of certain introns, self‐scission during rolling circle replication of some single‐stranded RNA viruses and cofactor‐dependent gene regulation in bacteria. Other ribozymes have been evolved

in vitro

to perform a wide variety of transformations. Two of these, tRNA aminoacylase and RNA polymerase ribozymes, are featured here because molecules with such capabilities are thought to have existed on early Earth, before proteins took over as the dominant biological catalysts. Most of the ribozymes have been shown to perform multiturnover catalysis and thus act as true enzymes, either in their natural, biological form or as engineered constructs.

Key Concepts:

RNA molecules can fold into specific conformations and accelerate chemical transformations, thus acting as catalytic biomacromolecules, ribozymes.

Ribozymes can accelerate chemical reactions by many orders of magnitude.

Many ribozymes are capable of multiturnover catalysis, acting as enzymes.

Protein synthesis templated by mRNA is catalysed by ribosomal RNA.

Most ribozymes are phosphoryl transferases.

In vitro
selected ribozymes have been shown to catalyse a wide variety of reactions.

The existence of ribozymes supports the RNA World hypothesis.
Spleen
Authors: Steiniger Birte
Published: April 2013

The spleen is a secondary lymphoid organ present in all vertebrates, which monitors the blood. It consists of sessile stroma cells (fibroblasts), migratory cells of the immune system and blood‐filled spaces and vessels. Splenic functions and microanatomy differ according to the species investigated. Certain functions such as immunological monitoring of bloodborne antigens, destruction of intravasal microorganisms and aged or abnormal blood cells, are more or less invariant. In rodents and humans the spleen is composed of two large compartments, the white pulp and the red pulp. The white pulp harbours dense accumulations of more or less migratory lymphocytes and antigen‐presenting cells, which crawl on a meshwork of specialised fibroblasts. The red pulp is composed of connective tissue cords containing arterioles and capillaries and of sinuses, which represent a spleen‐specific initial part of the venous circulation. The connective tissue of the red pulp cords is filled with blood and represents the only place where an open circulation occurs in the body. In addition, the cords harbour a dense population of specialised macrophages and some plasma cells. The article describes the microanatomical compartments of rat and human spleens, the course of B lymphocyte immune reactions in rodent spleens and the consequences of splenectomy in humans.

Key Concepts:

The spleen monitors the antigen composition of the blood.

The monitoring is predominantly carried out by lymphocytes recirculating through the spleen in the white pulp and by sessile macrophages in the red pulp cords.

Specialised fibroblasts recruit lymphocytes and macrophages to their compartments with the help of several mechanisms, such as secretion of chemokines or expression of certain adhesion molecules.

The splenic red pulp cords are the only location in the body with an open circulation. This means that blood flows in spaces not lined by any barrier‐forming cells such as endothelia.

The open circulation thus permits a direct contact between the blood and resident macrophages.

In rodents and humans the spleen contains a special type of B lymphocytes, the marginal zone cells. These cells recognise polysaccharide antigens and are easily activated to become antibody‐secreting plasma cells.

In humans, splenectomy leads to the loss of marginal zone‐type B cells in the blood and to a reduced resistance against bacteria with polysaccharide capsules. This is especially relevant in children.

The susceptibility to overwhelming post‐splenectomy infections in humans may be due to loss of the marginal zone and its special stromal cells in combination with loss of the large phagocyte compartment in the splenic red pulp.
Major Histocompatibility Complex: Interaction with Peptides
Authors: Liu Jun , Gao George F
Published: April 2013

T‐cell‐specific immunity functions in a major histocompatibility complex (MHC)‐dependent manner. MHC molecules present antigenic peptides on the surface of cells to be recognised by specific T‐cells. MHC class I and class II molecules possess highly similar structural features used to load peptides. Specifically, both contain peptide‐binding grooves formed by two α‐helices and eight β‐strands. In the peptide‐binding groove, specific amino acids compose pockets that accommodate the corresponding side chains of the anchor residues of the presented peptides. Peptide‐binding preferences exist among different alleles of both of MHC I and MHC II molecules, which are mainly dependent on amino acid polymorphisms in the peptide‐binding grooves of MHC chains. Aside from the common binding of peptides to MHC molecules, the currently determined structures of post‐translationally modified peptides to MHC molecules demonstrate that the modified groups have important roles in the peptide–MHC interaction. The illumination of the binding features of peptides to MHC molecules has aided our understanding of T‐cell‐specific immunity and the development of T‐cell epitope‐related vaccines.

Key Concepts:

MHC I and class II molecules fold into a highly similar conformations featuring a peptide‐binding groove to present T‐cell epitopes.

Peptide‐binding grooves of MHC I molecules are composed of two α‐helices and eight β‐strands formed by one heavy chain, while MHC II uses two domains from different chains to construct the peptide‐binding groove.

Peptides bind to MHC molecules through primary and secondary anchor residues protruding into the pockets in the peptide‐binding grooves.

Peptide preferences are dependent on the amino acids polymorphisms comprising the anchor pockets, which are related to the various alleles of MHC.

The conformations of peptides presented by MHC I molecules are length‐dependant.

The modified groups of post‐translationally modified peptides have important roles in the peptide–MHC interaction.

MHC is called HLA, human leucocyte antigen, in human; H‐2 in mice.
Vaccination of Humans
Authors: Rappuoli Rino , Chiarot Emiliano
Published: April 2013

In 1796 Edward Jenner inoculated a young boy with cowpox infected material from cows then demonstrated that he was protected against a subsequent challenge with the variola agent smallpox. This is universally accepted as the first step in the development of the modern vaccination technique. For almost one century, vaccination meant take infectious agents or part of them, inactivate them using heat or chemical treatments and inoculate these products into humans. Modern techniques, such as recombinant deoxyribonucleic acid (DNA), polysaccharide conjugation and, more recently, the genomic approach, have allowed not only to obtain safer vaccines, but also to develop new products against those agents for which a vaccine had not been yet developed. Vaccines have been one of the most effective means of combating deadly infectious diseases in the near past and they will also become an important tool to fight some plagues of our time, such as tumours, chronic and autoimmune diseases and allergies.

Key Concepts:

People who survive an infectious disease, generally, do not develop the same disease again.

Vaccination means to expose the body to biological material that mimics the infectious agents giving protection without suffering disease.

Vaccines are the most effective tool to combat deadly infectious agents.

Combination vaccines are used to reduce the number of shots, especially in children.

Killed/inactivated infectious agents or part of them were the only vaccines used for most of the twentieth century.

Polysaccharide conjugation, recombinant DNA techniques and, more recently, reverse vaccinology have led the development of new generation vaccines.

Therapeutic vaccines will be used to fight chronic infectious diseases, cancers, neurodegenerative diseases, allergies and autoimmune diseases.

New delivery systems and new adjuvants will be developed to increment vaccine‐induced immune response against many infectious agents.
Feline Leukaemia Virus
Authors: Jarrett Oswald , Neil James C
Published: April 2013

Feline leukaemia virus
(FeLV) is a gammaretrovirus that causes a variety of fatal diseases including leukaemia and lymphoma in its host, the domestic cat, and occasionally in large cat species. Many cats become persistently infected and develop disease after an incubation period of several years, during which virus can be transmitted to other cats. Disease is often associated with the generation of FeLV variants with increased pathogenic potential that can arise by mutation of envelope sequences, duplication of transcriptional enhancer elements or recombination with host proto‐oncogene sequences. FeLV can also produce variants by recombination with endogenous proviruses related to FeLV that are found in the domestic cat and its close relatives. The prevalence of FeLV infection has been reduced in many cat populations by isolation of infected carriers and more recently by vaccines that augment the natural ability of most cats to control infection.

Key Concepts:

The outcome of infection by FeLV depends on the infectious dose, age and immunocompetence of the host. Many cats achieve lifelong control, if not elimination of infection.

Cats that become persistently viraemic are at risk of a variety of FeLV‐related diseases after a latent period of up to several years.

The common infectious form, FeLV‐A can acquire altered entry receptor specificity by envelope gene mutation (to FeLV‐C) or recombination with endogenous FeLV‐related proviruses (to FeLV‐B).

FeLV envelope variants may induce fatal diseases of rapid onset including nonregenerative anaemia (FeLV‐C) or wasting and immunodeficiency (FeLV‐T).

The oncogenic potential of FeLV can evolve by duplication of transcriptional enhancer control elements in the long‐terminal repeat or by transduction of host proto‐oncogene sequences.

Although the immune parameters of vaccine protection remain unclear, FeLV demonstrates the feasibility of effective immunisation against the gamma retroviruses.

Commercial FeLV vaccines in recent or current use include inactivated FeLV, infected cell extracts, recombinant envelope protein and live recombinant poxvirus vaccines.
Influenza Viruses: Molecular Virology
Authors: Neumann Gabriele , Kawaoka Yoshihiro
Published: April 2013

Influenza viruses cause mild to potentially lethal respiratory disease. Influenza A viruses cause annual outbreaks of local scale and occasional outbreaks of global scale, as witnessed with the pandemic of 2009 that was caused by an influenza A viruses of the H1N1 subtype. Influenza B viruses also cause disease in humans, whereas influenza C viruses are not a recognised public health concern. Influenza A, B and C viruses share many similarities in their coding strategies and life cycles, but can also be distinguished by key differences. Here we summarise the molecular virology of influenza A, B and C viruses, that is the similarities and differences in coding strategies, the replication cycle and the functions of the viral proteins.

Key Concepts:

Influenza A, B and C viruses differ in their impact on human health.

Although influenza A, B and C viruses share many similarities, they differ in their coding strategies.

The basic functions of the viral proteins are now understood, but many questions remain about the interplay between the viral proteins, and the interplay between viral and cellular proteins.
Evolutionary Developmental Biology:HoxGene Evolution
Authors: Nolte Christof , Ahn Youngwook , Krumlauf Robb
Published: April 2013

Hoxgenes are the homologues of the homeobox‐containing genes in the homeotic complex (HOM‐C) of the fruit flyDrosophilaand encode transcription factors that play crucial roles in determining positional identity along the anterior–posterior body axis during animal development. Their expansion and duplication during metazoan evolution suggests that they have played a major role in generating animal diversity. In the protostomes,Hoxgenes are organised into a single cluster of genes that in some phyla has undergone gene loss and in others has become dispersed. On the contrary, cluster integrity is generally maintained in the deuterostomes, and during chordate evolution the single deuterostome cluster has undergone internal expansion as well as whole cluster duplications, generating animals with four or more clusters. Whereas these expansions and duplications are correlated with an increase in animal diversity, the main mechanisms driving metazoan evolution from aHoxperspective probably involve alterations incis‐regulatory sequences ofHoxgenes and, to a lesser extent, changes in their coding sequences.

Key Concepts:

The prototypeHoxgene potentially evolved from an ancestral NK homeobox gene very early in metazoan evolution.

Tandem and genome‐wide duplications generated the prototypical vertebrateHoxclusters.

Hoxgenes encode transcription factors that may have originally patterned bilaterian's evolving nervous system; however, as body organisation became more complicated and cells became more interdependent,Hoxgenes’ function may have co‐evolved with the function of other HB‐containing genes to jointly specify positional information in the derivatives of all three germ layers.

The clustering ofHoxgenes appears to be necessary for animals that use signalling pathways during development. This supports the presence of global control mechanisms that regulate all or a subset of genes within the cluster.

Organisms in which cells are primarily determined in early embryogenesis and develop autonomously begin to loseHoxcluster integrity.

The major morphological diversity in vertebrate lineages does not appear to be causally related to changes in the number or complement of theHoxgenes. Therefore,Hoxinput into morphological diversity is likely to occur through alteredcis‐regulation and/or downstream targets ofHoxgenes.

As the genome sequence of more species becomes available, the molecular phylogenetics ofHoxcluster evolution will become clearer with an emphasis in understanding the evolution of the regulatory modules that partitionHoxexpression domains.
Evolutionary Developmental Biology: Developmental Bias and Constraint
Authors: Arthur Wallace
Published: April 2013

Developmental trajectories can be more readily altered in some ways than others by mutations in the genes that govern them. This is developmental bias. Both positive and negative biases are possible: these can be called, respectively, developmental drive and developmental constraint. These processes may have major effects on the direction of evolutionary change. Here, such effects are considered both in general and through looking at particular examples, including the evolution of centipedes and turtles. It is noted that developmental bias may be especially important in the origins of evolutionary novelties – such as the turtle ‘shell’. Developmental bias relates to the structure of variation in developmental pathways. When such variation is highly structured (high degree of bias) there are limits to the ‘evolvability’ of the creatures concerned. In contrast, cases of low bias mean that evolvability is correspondingly higher.

Key Concepts:

Developmental bias refers to situations in which some variant developmental trajectories are more probable than others.

It is likely that such bias is ubiquitous in nature but that its extent is highly variable.

Developmental bias may interact with natural selection to determine the direction of evolutionary change and/or the array of character states found.

Bias is best studied by the investigation of particular examples.

The evolution of centipede segment number and the origin of the turtle shell are used as examples herein.

Developmental bias is complementary to the concept of evolvability.

Although most discussion of bias, evolvability and related concepts has taken place in the era of evolutionary developmental biology (1980 to the present), earlier discussions of similar ideas (but using different terms) can be traced back to Charles Darwin and Alfred Russel Wallace.
Cleavage and Gastrulation in
Xenopus laevis
Embryos
Authors: Elinson Richard P
Published: April 2013

The

Xenopus laevis

egg contains an asymmetric distribution of
ribonucleic acids (RNAs)
, which are parceled out to different cells during cleavage. These RNAs initiate the formation of the germ layers, ectoderm, mesoderm and endoderm, as well as a set of dorsal axial structures, including the central nervous system. Cleavage is initially rapid and synchronous, but becomes slower and asynchronous at the midblastula transition, when the embryo's genes become active. The different cells signal among each other in a process known as induction, leading to more types of cells. The cells undergo rearrangements in a complicated set of coordinated movements during gastrulation. Signalling continues through gastrulation with a major centre, the Spemann organiser, responsible for generating the dorsal axial structures. These inductions and movements lead to the proper positioning of the forming tissues and organs, and the body plan of the embryo emerges.

Key Concepts:

The job of the fertilised egg is to generate the body plan.

The body plan of a vertebrate embryo consists of three tubes, known as germ layers, and a set of dorsal axial structures.

In
Xenopus
, RNAs localised in the egg initiate formation of both the germ layers and the dorsal axial structures.

The
Xenopus
egg rapidly divides into smaller cells to prepare for cell movements and organ formation.

A key signalling centre is established known as the Spemann organiser.

Signals from the Spemann organiser cause the formation of the dorsal axial structures including the central nervous system.

The complicated cell movements of gastrulation can be followed using fate maps.

Several types of cell movements are coordinated during gastrulation to bring about their final arrangement in the embryo.

The body plan emerges with the completion of gastrulation.
Rotaviruses
Authors: Palombo Enzo A , Bishop Ruth F
Published: April 2013

Rotaviruses are infectious agents, transmitted by the faecal–oral route. Distinguishing features include a genome consisting of 11 segments of double‐stranded ribonucleic acid (dsRNA), distinctive morphological appearance by electron microscopy and unique morphogenesis involving transient lipid‐enveloped particles. Primary rotavirus infections in the young of mammals and birds can cause severe diarrhoea after replication in the small intestine. Reinfections result in protective immune responses. Worldwide morbidity and mortality rates in children justify vaccination to protect against this disease. Two safe live oral rotavirus vaccines, based on either a single attenuated human rotavirus strain, or a pentavalent mixture of human–bovine rotavirus reassortants, are now licensed and in use in many countries. Both are immunogenic and highly efficacious in prevention of severe rotavirus diarrhoea in children in developed countries. Recent trials have demonstrated lower vaccine efficacy in children in Africa and Asia. WHO has recommended the universal use of both vaccines.

Key Concepts:

An estimated 4.6 million people, including 2.5 million children, die from diarrhoea every year particularly in developing countries.

Worldwide, rotavirus is the major cause of infectious diarrhoea, particularly among young children.

There have been major efforts to produce safe, effective and affordable rotavirus vaccines for worldwide use.

The recent licensing of two human rotavirus vaccines provides optimism for controlling rotavirus disease.