bluuebunny/crossref_metadata_2025_split huggingface dataset:
Axon Guidance
Authors: Piper Michael J , Keynes Roger J , Cook Geoffrey MW 
Published: April 2013

AbstractAxon guidance is the means whereby axon processes growing from differentiating nerve cells are guided to their targets during embryonic development. The growing axon tip, the growth cone, is essential to this process, being capable of locomotion and responding to molecular cues in its cellular environment. A knowledge of the interaction of actin microfilaments and tubulin microtubules of the growth cone cytoskeleton is necessary to understand the dynamic properties of the growth cone. External guidance cues may be attractive or repulsive, and have been shown to fall into diverse molecular families. The signalling pathways that they trigger in the growth cone are being elucidated. Defects in axon guidance may underlie various abnormalities of nervous system development in humans.Key Concepts:The growth cone is both a motile and sensory apparatus for axon guidance.The growth cone cytoskeleton is divided into three regions that mediate distinct aspects of actin–tubulin dynamics.Regulation of actin assembly and disassembly is important for growth cone locomotion.Microtubules provide structural support and are responsible for transport of organelles and molecules to and from the growth cone.Dynamic microtubules are considered to play an instructive role in growth cone turning.There are two classes of growth cone guidance cue in the cellular environment; attractive/permissive or inhibitory/repulsive. Both classes include members that can act over short distances and members that can act over long distances.A diverse group of molecular families that mediate guidance has been identified, including members of the immunoglobulin superfamily, cadherins, netrins, Slits, semaphorins and Eph/ephrins.Growth cone responses to external cues are mediated by molecular signals such as mitogen‐activated protein kinases (MAPK), calcium ions, cyclic nucleotides and the Rho subfamily of small GTPases, which affect cytoskeletal dynamics.
Immune Responses at Mucosal Surfaces
Authors: Herbrand Heike , Pabst Oliver 
Published: April 2013

AbstractThe mucosal surfaces of the gastrointestinal or respiratory tracts form vast interfaces of the host organism with the environment and constitute major entry ports for pathogens. Strategies to defend mucosal surfaces have developed early in evolution and in mammals engage the innate as well as the adaptive arms of the immune system. This article depicts aspects of anatomy, development and function of the mucosa‐associated lymphoid tissues (MALT) with a focus on the intestinal immune system. The intestinal epithelium is continuously exposed to large amounts of foreign antigens. Thus, one of the key challenges of the intestinal immune system is to tolerate harmless food derived antigen and to keep peace with the commensal microbiota populating the gut tube, while efficiently combating pathogens and their toxins.Key Concepts:Innate and adaptive immunity synergise to protect mucosal surfaces.Adaptive immune responses at mucosal sites are initiated in Mucosa associated lymphoid tissues (MALT), such as the gut‐associated lymphoid tissue (GALT), the bronchus‐associated lymphoid tissue (BALT) and the nasal‐associated lymphoid tissue (NALT).The intestinal immune system is continuously challenged by innocuous antigen derived from food and the commensal microbiota.Interaction of the host with the commensal microbiota is required for the full maturation of the intestinal immune system whereas in turn the intestinal immune system restricts the growth and controls the composition of our commensal microbiota.Secretory IgA (SIgA) is the predominant Immunoglobulin at mucosal surfaces.Dysbiosis of the commensal microflora promotes diseases such as inflammatory bowel disease (IBD), diabetes and obesity and enhances the susceptibility to infection with enteropathogenic bacteria.Failure to induce oral tolerance towards food derived antigens manifests in allergy or coeliac disease.
Fc Receptors
Authors: Jacobino Shamir , Slomp Anne , Boross Peter , Leusen Jeanette HW 
Published: April 2013

Abstract

Receptors for the Fc region of immunoglobulins (Igs) play a central role during an immune response as they link humoral responses to cellular activities. The majority of these leucocyte Fc receptors exist as heterooligomeric complexes with unique ligand‐binding α chains and promiscuous accessory subunits involved in intracellular signal transduction. In humans, five major Fc receptor classes are known, FcγR for IgG, FcαR for IgA, FcɛR for IgE, FcμR for IgM and FcδR for IgD. Integration of both activating and inhibitory signals occurs on Ig‐Fc engagement of Fc receptors. Given their vital role in maintaining balanced immunity, dysregulation of Fc receptor function may lead to inflammatory or autoimmune disease. As such, much effort is focussed on identifying which single nucleotide polymorphisms and copy number variations in Fc receptor genes are linked with disease and understanding of how these affect therapeutic options.

Key Concepts:

Fc receptors link the humoral and cellular arms of the immune system.

Cellular activities may be triggered by Fc receptor α chains independent of FcR γ chains.

Fc receptor ITAM and ITIM motifs transmit opposite signals to control leucocyte activation.

Inside‐out regulation of Fc receptors influences their affinity for immunoglobulin ligands.

Fc receptor genetic variations are linked with inflammation, autoimmunity and cancer.
Cytokines
Authors: Wilson Heather M , Barker Robert N 
Published: April 2013

Abstract

Cytokines are small secreted ‘messenger proteins’ that allow communication between cells. They contribute to a chemical signalling language that controls many processes in multicellular organisms, including haematopoiesis, chemoattraction, tissue repair, embryogenesis and virtually all aspects of immunity and inflammation. Cytokine functions are mediated by their binding to specific receptors to initiate intracellular signalling cascades that increase or decrease expression of transcription factors and genes regulating, for example, secretion of effector molecules (including other cytokines), cell proliferation and expression of membrane receptors. They play an important role in many pathologies, and indeed measurement of cytokine profiles in patients can provide a useful indicator of disease. Owing to their multiple functions in disease, therapeutic interference with cytokines, cytokine receptors or their signal transduction pathways offers new treatment options for a range of disorders.

Key Concepts:

Cytokines can be extremely potent, acting at picomolar or femtomolar concentrations.

Cytokines are not produced constitutively but are expressed on stimulation of cells, usually acting in an autocrine or paracrine fashion.

Individual cytokines can have many functions and can act synergistically or antagonistically.

Chemokines are a family of cytokines that are not only principally involved in chemoattraction but also participate in cell activation and angiogenesis.

Different cytokine receptors can share similar subunit structures, which divide them into families.

Most cytokine receptors are heterodimers, but some can be homodimers or heterotrimers.

Cytokines exert their effects by activating specific intracellular signalling pathways.

By sharing receptor subunits and signal transducing molecules, many cytokines are known to play redundant and pleiotropic roles.

Excessive cytokine production or activity can lead to several pathologies, and cytokine modifiers are proving to be a therapeutically effective approach in modifying such diseases.

Cytokine synthesis and activity is regulated by many mechanisms including signalling inhibitors, epigenetic modifications and cleavage of precursors.
Idiotype Network
Authors: Behn Ulrich 
Published: April 2013

AbstractB‐lymphocytes have receptors, antibodies, with highly specific binding sites which bind to complementary structures. Receptors of a given cell have exactly one specific set of binding sites, the idiotype. Complementary structures can be found not only on antigen but also on antibodies of different idiotype or on T‐cell receptors. Thus a network of idiotypically interacting immune cells is formed, the idiotype network. The network influences the shaping of the B‐ and T‐cell repertoirs and may be relevant in the control of autoreactive clones. The therapeutic use of monoclonal antibodies against autoimmune diseases, cancer (in particular lymphoma) and a few other diseases relies on idiotypic interactions and is of rapidly growing importance. This strongly motivates further research to understand the systemic consequences of immunomanipulation.Key Concepts:An idiotope is a site on a B‐cell receptor that can bind to complementary structures; also on T‐cell receptors such sites exist.The collection of idiotopes on one receptor is called idiotype; all receptors of a given cell have the same specific idiotype.A huge diversity of idiotypes is generated by random somatic rearrangements of genes.B‐cells of a given idiotype are stimulated to proliferate if its receptors are cross‐linked by complementary structures; unstimulated cells die.Structures that bind to idiotopes can be found on antigen, not only on B or T cells of anti‐idiotype, but also on other cells or signalling molecules.Immune cells, functionally connected by idiotypic interactions, form the idiotype network which influences the shaping of the B‐ and T‐cell repertoir and may be relevant in the control of autoreactive clones.Therapeutic strategies using monoclonal antibodies rely on idiotypic interactions.New technologies make extensive studies of the repertoir of immune receptors feasable, which are necessary to better understand the network properties and systemic consequences of immunomanipulation.In many different fields the network paradigm has proved successful in describing complex systems, the recent progress in theoretical understanding should inspire further research on idiotype networks.
Avian Influenza Viruses
Authors: Neumann Gabriele , Kawaoka Yoshihiro 
Published: April 2013

Abstract

Avian influenza viruses comprise all recognised antigenic subtypes within the genus
Influenza A
of the
Orthomyxoviridae
family. They are found prominently in waterfowl, shorebirds and terrestrial birds and are sporadically transmitted to mammalian species. The consequences of such transmissions range from a subclinical infection to a mild infectious and/or lethal respiratory disease, as witnessed with highly pathogenic avian H5N1 viruses, which occasionally infect humans (resulting in cases of fatality rates >50%). Further, avian influenza viruses may cause pandemics by transmitting directly to humans (e.g. possibly the 1918 pandemic) or by reassorting with human and/or other (e.g. swine) influenza viruses (1957, 1968 and 2009 pandemics). Avian influenza viruses thus play a critical role in the ecology of influenza A viruses, and in the generation of novel variants that may cause severe infections or pandemic outbreaks in humans.

Key Concepts:

Influenza A viruses of all known haemagglutinin (HA) and neuraminidase (NA) subtypes are found in aquatic birds.

Avian influenza viruses can be classified as low pathogenic avian influenza (LPAI) or highly pathogenic avian influenza (HPAI), based on their pathogenicity in chickens.

All mammalian influenza A viruses originate from avian influenza viruses.

Avian influenza viruses play a critical role in the generation of pandemic influenza viruses through direct transmission to humans or reassortment with human and/or swine influenza viruses.

Host species‐specific amino acids exist that distinguish avian and mammalian influenza viruses.

Host species‐specific amino acids may affect critical functions in the viral life cycle such as receptor recognition and replicative ability; adaptive changes at such key amino acid positions may be critical for avian influenza viruses to cause pandemics in humans.
Caliciviruses
Authors: Neill John D 
Published: April 2013

Abstract

The
Caliciviridae
is a family of small, nonenveloped viruses containing a single‐stranded, plus‐sense genomic
ribonucleic acid
(RNA) that is polyadenylated at its 3′‐end. Most, but not all, caliciviruses have distinctive cup‐shaped depressions (L.
calix
, cup) on their surface, giving them their characteristic ‘Star of David’ appearance by negative‐stain electron microscopy. The calicivirus nonstructural proteins are encoded in the 5′‐end of the genomic RNA and the structural proteins in the 3′‐end. The structural proteins are translated primarily from an abundant subgenomic RNA that is transcribed from the genomic RNA. The identity of several of the nonstructural proteins was made based on amino acid sequence similarities with other virus families. The caliciviruses encode a single capsid protein that forms the outer shell of the virus particle. These viruses have a large and diverse host range and cause diseases of both human and veterinary importance.

Key Concepts:

Caliciviruses constitute a unique family of viruses.

Caliciviruses have significant genetic diversity.

Calicivirusesare important agents of disease in both man and animals.
DNAHelicases
Authors: Bianco Piero R 
Published: April 2013

AbstractDeoxyribonucleic acid (DNA)andribonucleic acid (RNA)helicases are organised into six SuperFamilies (SF) of enzymes using sequence alignments, biochemical data and available crystal structures. DNA helicases, members of which are found in each of the SF, are an essential group of motor proteins that unwind DNA duplexes into their component single strands in a process that is coupled to the hydrolysis of nucleoside 5′‐triphosphates (NTPs). These enzymes share common biochemical properties that include the binding of single‐ and double‐stranded DNA, NTP binding and hydrolysis, and NTP hydrolysis‐coupled, polar unwinding of duplex DNA. DNA helicases participate in every aspect of DNA metabolism due to the requirement for transient separation of small regions of the duplex genome into its component strands so that replication, recombination and repair can occur.Key Concepts:DNA helicases unwind duplex DNA in catalytic fashion.DNA helicases translocate unidirectionally in polar fashion.Helicases hydrolyse nucleoside triphosphates.DNA helicases are critical to all aspects of DNA metabolism.There are two broad classes of DNA helicases: hexameric and nonhexameric.
Newcastle Disease Virus
Authors: Miller Patti J , Afonso Claudio L 
Published: April 2013

Abstract

Newcastle disease virus (NDV), a member of the
Avulavirus
genus in the
Paramyxoviridae
family, has a
ribonucleic acid
(RNA) genome that is negative sense, nonsegmented and single‐stranded. The genome codes for six structural proteins: nucleocapsid, phosphoprotein (P), matrix, fusion, hemagglutinin–neuraminidase and the RNA‐directed RNA polymerase, in addition to the nonstructural V protein that is produced by a frame shift in the P coding region. Virulent forms of NDV (vNDV) contain multiple basic amino acids in the fusion cleavage site along with a phenylalanine (F) at position 117, are found worldwide and are endemic in some countries. Infections of poultry species with vNDV lead to trade restrictions. Although all NDV strains are of one serotype, their genomes evolve over time, becoming more diverse. Strains of NDV have been used as viral vectors to formulate vaccines for other infectious diseases and experimentally to treat human cancers. The virus causes conjunctivitis in humans.

Key Concepts:

Virulent NDV (vNDV) is the aetiological agent of one of the most prevalent and virulent avian diseases in the world, and causes millions of birds to die, and significantly affects the poultry industries of many countries in Africa, Asia and South America.

Lentogenic NDV (loNDV) is widely distributed in wild birds where it does not cause significant disease or clinical signs.

Isolates of NDV are genetically diverse with at least two classes of viruses, each divided into 10 genotypes.

Depending on the virulence of the NDV isolate and the immune status of the host, Newcastle disease produces a large range of clinical signs.

The fusion protein cleavage site is a key determinant of virulence and a key element utilised for modern diagnostics and classification.

Because all NDV isolates are of a single serotype vaccines prepared with any NDV isolate should protect against disease from any other NDV infection.

Neutralising antibodies to the Fusion (F) and hemagglutinin–neuraminidase (HN) proteins of NDV are known to be important in preventing morbidity and morality from Newcastle disease.

Even vaccinated birds with high antibody titre to NDV will become infected when exposed to virulent NDV and these vaccinated birds will shed virulent NDV in oral secretion and fecal matter.

The genome of NDV has been used as a vaccine vector to carry foreign genes of other organisms for use in both animals and humans.
Autonomous Cell Fate Specification: Overview
Authors: Byrum Christine A , Wijesena Naveen M , Wikramanayake Athula H 
Published: April 2013

AbstractAutonomous cell fate specification is a form of embryonic specification in which a developing cell is able to differentiate (become a cell carrying out a specialised function) without receiving external signals. This property is enabled by cytoplasmic determinants (cytoplasmic regulatory factors necessary for specification) that are deposited in different regions of the ovum during oogenesis. These cytoplasmic determinants are partitioned into individual cells during embryonic cleavage, and thus endow these cells with the ability to form specific cell types. If an autonomously specified cell is removed from the embryo during early development and cultured in isolation, that cell will produce the descendants that it would have normally produced in the undisturbed embryo. Frequently, the embryo from which the cell was removed lacks the structures normally made by the missing cell. Autonomous cell fate specification is often used during patterning of invertebrate embryos such as ctenophores, annelids, molluscs, echinoderms and tunicates.Key Concepts:The cytoplasm of animal eggs is heterogeneous in composition due to the asymmetric deposition of key regulatory factors termed cytoplasmic determinants.In general, cytoplasmic determinants are asymmetrically distributed along the primordial axis of the ovum termed the animal–vegetal axis.Most cytoplasmic determinants are maternal (produced under the control of the mother's genome) ribonucleic acids (RNAs).Cytoplasmic determinants provide the necessary information for specifying embryonic cell fates.When inheritance of cytoplasmic determinants by a cell is sufficient for that cell to undergo its final differentiation, it is said to undergo autonomous cell fate specification.Autonomous cell fate specification is mostly seen in invertebrate embryos, but no embryo depends exclusively on this method of cell fate specification.
Mast Cells
Authors: Oboki Keisuke , Hagiyama Man , Inoue Takao , Ito Akihiko 
Published: April 2013

AbstractMast cell is a type of connective tissue cell but originates from the haematopoietic stem cell. Adult mouse mast cell‐committed progenitor, which is the common myeloid progenitor lineage, can be identified in bone marrow. Additionally, a unique progenitor having bipotent activity (e.g. basophil/mast cell progenitor) is found in the spleen, which is unique lymphoid organ having a function to sustain hematopoiesis. Mast cell‐lineage specification is coordinated by transcription factor GATA‐binding protein‐1 (GATA‐1), GATA‐2, PU.1 and CCAAT/enhancer‐binding protein‐α, and its maturation process is regulated by microphthalmia transcription factor. Mast cell progenitors distribute in various tissues through the blood stream by using known/unknown chemokines and integrins and located around blood vessels, peripheral nerves or lymphatic vessels. The most established function of mast cells is amplification of immunoglobulin E‐dependent hypersensitivity reaction. Mouse models have mainly been utilised to understand the mast cell biology and have given us many evidences especially in the developmental origin of mast cell. Although controversial results have emerged in the role of mast cells, recent advances in next generation mast cell‐deficient mice models will improve the knowledge about the roles of mast cell in various disease settings.Key Concepts:Adult mouse mast cell progenitors (MCPs), which differentiate through the stage of common myeloid progenitor, are able to detect by combination of specific cell surface markers.Adult mouse MCPs are identifiable in bone marrow. Bipotent basophil/mast cell progenitors (BMCPs) can be found in the spleen. The developmental and functional relationship of these cells remains to be determined.Mouse mast cells are classified into two types (mucosal and connective tissue type) by histological sites (e.g. mucosa or connective tissue). However, human mast cells are classified into two types by its protease expression pattern (e.g. tryptase+chymase−type and tryptase+chymase+type). Recently, nonclassical protease expression patterns have been found in human and mouse mast cells.Mast cell heterogeneity is determined by tissue microenvironments.Although KIT mutant mice have long been used for the study of mast cell function, some subsidiary effects are concerned because KIT mutant mice have several defects other than mast cells. Recently developed genetically engineered mast cell deficient mice may give us more convincing evidences of mast cell function in various diseases except for the established function of IgE‐mast cell in immediate hypersensitivity.
Tumours of the Immune System
Authors: Johnson Peter WM , Lim Sean H 
Published: April 2013

Abstract

Tumours of the immune system are malignant proliferations of haematopoietic cells, and are classified according to their cell of origin. Disorders of the myeloid lineage result in acute or chronic myeloid malignancy, whereas disorders of the lymphoid lineage result in Hodgkin lymphoma, non‐Hodgkin lymphoma (NHL) and multiple myeloma. These malignancies share many similarities in that acquired genetic changes are involved in their aetiology and are useful prognostic markers. The diagnosis of these conditions involves microscopic examination of peripheral blood or tumour biopsy and often, bone marrow examination. This is also supplemented by immunophenotyping and cytogenetic and molecular analysis. Treatment has previously been based on nonspecific cytotoxic agents and external beam irradiation but increasingly, targeted therapies such as the tyrosine kinase inhibitor, imatinib, and monoclonal antibodies are included in frontline therapy.

Key Concepts:

Tumours of the immune system are classified based on morphologic, cytochemical, immunophenotypic, and genetic features.

These malignancies exhibit a range of behaviour, with some developing extremely slowly over years, requiring minimal or no therapy, whereas others are among the most aggressive malignancies known and require treatment as emergencies.

Most types present most often in the elderly, but they occur throughout life and some are among the commonest childhood malignancies.

Cytogenetic and molecular abnormalities are invaluable in guiding the diagnosis and management route of some haematological malignancies.

General treatment options comprise radiotherapy, chemotherapy and targeted therapies, depending on the specific disease.

A proportion of these malignancies are curable with appropriate treatment, whereas others are susceptible to long term control which falls short of complete eradication, and may require multiple episodes of treatment.

This is a field in which research into mechanisms of pathogenesis and therapy is having a direct impact upon treatments and cures.