bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccination of Humans
Authors: Rappuoli Rino , Chiarot Emiliano 
Published: April 2013

Abstract

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

Abstract

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

Abstract

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

AbstractHoxgenes 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

Abstract

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

Abstract

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

Abstract

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.
Erythrocytes
Authors: Migliaccio Anna Rita F , Whitsett Carolyn 
Published: April 2013

Abstract

The erythrocyte is a highly specialized cell present in the blood designed for the transport of oxygen from the lungs to the body tissues and for the removal and transport of carbon dioxide from the tissues to the lungs. In primates, erythrocytes also clear the blood of complement‐bearing immune complexes and pathogens and exert anti‐inflammatory functions. The blood of an average adult contains approximately 25 million millions of erythrocytes. Maintaining this number of cells constant over time is a major challenge and requires production of as many as 210 billions of new erythrocytes per day (i.e. 24 millions per second). This production is tightly regulated by microenvironmental cues (growth factors) and by proteins present inside the cells (transcription factors). This regulation ensures that erythrocyte production is appropriately increased in response to sudden blood loss.

Key Concepts:

Erythrocytes are blood cells responsible for oxygen delivery to all the tissues of the body.

Erythrocytes are produced by hematopoietic stem cells present in the bone marrow.

Before birth, erythrocytes are derived from stem cell populations present in the yolk sac of the embryo and in the liver of the fetus.

Erythropoietin, a cytokine produced by the kidney, is primarily responsible for the regulation of erythrocyte production.

The bone marrow also contains several cytokines, which positively or negatively regulate erythrocyte production.

Erythrocytes exert their function by expressing on their surface and in their cytoplasm a number of erythroid‐specific proteins.

A series of DNA‐binding proteins (the erythroid transcription factors) assure that erythrocytes express adequate amounts of functional proteins.

The erythrocyte membrane is plastic and resistant to shear stress allowing the cells to pass through the microvasculature to deliver oxygen. The oxygen delivery function of the erythrocyte is performed by haemoglobin, a cytoplasmic protein whose structure is suited for oxygen transport/exchange.

The flexibility/deformability of the erythrocyte membrane is assured by a network between the proteins embedded in its lipid bilayer and the cell cytoskeleton.

Blood group antigens are epitopes present on the tertiary (glycosyl residues) or primary (amino‐acid sequence) structure of proteins present on the erythrocyte membrane.
Superantigens
Authors: Langley Ries J , Renno Toufic 
Published: April 2013

AbstractSuperantigens (SAgs) are microbial products that have the ability to promote massive activation of immune cells, leading to the release of inflammatory mediators that can ultimately result in hypotension, shock, organ failure and death. They achieve this by simultaneously binding and activating major histocompatibility complex class II molecules on antigen‐presenting cells and T‐cell receptors on T lymphocytes bearing susceptible Vβ regions. Why SAgs function in this manner is still not fully understood although it is thought that the resulting Th1 response may divert the immune system from effective microbial clearance and/or result in the cytokine‐mediated suppression and deletion of activated T cells. Many bacterial and viral species have adapted unrelated SAgs and this article will highlight some of the features of this diverse group of molecules, from the ways in which they interact with the host to the association of various SAgs with acute and chronic diseases.Key Concepts:Superantigens are toxins produced by many pathogenic bacteria and viruses.Superantigens are defined as molecules that bind to the major histocompatibility complex (MHC) class II and active T cells bearing a particular T‐cell receptor beta chain variable (Vβ) domain.Superantigens are implicated in inducing autoimmunity through the activation of autoreactive T cells that express particular Vβ elements.Superantigens are responsible for staphylococcal and streptococcal toxic shock.The superantigens ofStaphylococcus aureusare responsible for staphylococcal food poisoning.The endogenous superantigen of the mouse mammary tumour virus (MMTV) causes deletion of T cells bearing a particular Vβ element, amplification of infected B cells and transmission of virus to the offspring.
Bacterial Chemotaxis
Authors: Eisenbach Michael 
Published: April 2013

Abstract

Bacteria can move by a variety of means, the most common one by rotating their flagella. This movement is often directed towards favourable chemicals (chemoattractants) or away from unfavourable chemicals (chemorepellents), a process termed chemotaxis. This modulation of swimming direction is the outcome of controlled changes in the direction of flagellar rotation. Therefore, mechanistically, the essence of bacterial chemotaxis is to control the direction of flagellar rotation. This control is done by a sophisticated signal transduction system, involving a small protein, CheY, which shuttles back and forth between the receptor complexes clustered at the pole of the cell and the flagellar motor complexes around the cell. These interactions are modulated by phosphorylation and acetylation. The excitatory signalling process involves amplification. The adaptation signalling involves methylation of the receptors. Even though bacterial chemotaxis is considered the best understood signalling system at the molecular level, many major questions are still waiting to be resolved.

Key Concepts:

In bacteria, chemotaxis is the motile response to stimuli and it serves as a means of cell–environment and cell‐to‐cell communication.

Bacteria sense stimulant gradients (chemoattractants and chemorepellents) temporally rather than spatially.

The chemotaxis‐specific receptors are clustered at the bacterial poles. This clustering is essential for signalling and amplification.

Bacteria swim by rotating their flagella. The direction of rotation determines the swimming mode. Therefore, the essence of bacterial chemotaxis is to control the direction of flagellar rotation.

The direction of flagellar rotation is modulated by the signalling molecule, CheY, according to changes in receptor occupancy.

CheY function is modulated by phosphorylation at both the excitatory and adaptation signalling phases. The latter also involves receptor carboxy methylation.

Phosphorylated CheY binds to the switch at the base of the flagellar motor and, thereby, changes the direction of rotation.
Adhesive Specificity and the Evolution of Multicellularity
Authors: Vleminckx Kris 
Published: April 2013

Abstract

Most of the cells in a multicellular organism are connected to each other and/or attached to a substrate. Physically this is mediated by adhesion molecules exposed on the cell surface and attached to the cell membrane either by covalent linkage to the lipid bilayer or by a membrane‐spanning region. The establishment of cell–cell interactions is a key aspect in the origin of multicellular life forms and the acquisition of tissue and organ organisation in metazoa. Adhesion is mediated by specific adhesion molecules belonging to the immunoglobulin superfamily, the cadherins, the integrins, the lectins and the proteoglycans. Adhesive associations by these molecules are organising forces in the embryo, controlling morphogenesis, tissue formation and organogenesis. In the adult, cell adhesion helps to control tissue homoeostasis, the organisation of the stem cell niche and the functioning of the immune system.

Key Concepts:

Multicellularity requires cell–cell adhesion molecules.

Cell adhesion molecules interact structurally and/or functionally with the cytoskeleton of the cell.

Cell adhesion molecules integrate extracellular and intracellular cues with intracellular signalling.

Cell adhesion molecules are more than molecular glue; they can act as signalling receptors inducing changes in the cytoskeleton and in gene expression.

Expression of cell adhesion molecules is under tight developmental control.

Changes in cell adhesion are a driving force for morphogenesis, tissue formation and organogenesis.

In the adult cell adhesion helps to maintain the stem cell niche and controls homeostasis.

Cell adhesion is essential for the functioning of the immune system.

Aberrant regulation of cell adhesion is involved in several human diseases.
Shikimate Pathway and Aromatic Amino Acid Biosynthesis
Authors: Tzin Vered , Galili Gad , Aharoni Asaph 
Published: April 2013

Abstract

The shikimate pathway consists of seven enzymatic reactions whose end product chorismate is the precursor for the synthesis of the aromatic amino acids Phe, Tyr and Trp. In fungi and plants, chorismate is a precursor for many specialised metabolites (i.e. secondary metabolites) that play an important role in the plant's interaction with its environment. The shikimate pathway and aromatic amino acid biosynthesis have been extensively studied in a variety of microorganisms, fungi and plants. Furthermore, the dual involvement of the shikimate and aromatic amino acid biosynthesis pathways in central and specialised metabolism still raises major questions regarding the genes and enzymes involved, and their control, their evolutionary origins and coordinated regulation with genes of associated pathways in response to altered environmental conditions and diverse developmental programs.

Key Concepts:

The shikimate pathway is the only known pathway for biosynthesis of chorismate and the aromatic amino acids Phe, Tyr and Trp.

The shikimate pathway is a bridge between central metabolism and specialised metabolism.

The shikimate pathway occurs in various groups of microorganisms, plants and parasites, whereas it does not occur in animals.

The pathway enzymes are being targeted for antimicrobial drug and herbicide design.

Shikimic acid is an essential metabolite that may balance the metabolic status of the pathway.

Chorismate is a branch point metabolite for aromatic amino acids and phenolic compounds.

This is an ancient eukaryotic pathway which has been subject to diverse evolutionary processes.

Several enzymes from these pathways are allosterically regulated by their end products: Phe, Tyr or Trp.

The shikimate pathway and aromatic amino acids, and the specialised metabolites derived from them, simultaneously respond to rhythmic changes.