bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Responses at Mucosal Surfaces
Authors: Herbrand Heike , Pabst Oliver
Published: April 2013

The 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

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

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

B‐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

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

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

Deoxyribonucleic 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

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

Autonomous 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

Mast 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

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.
Actin and Actin Filaments
Authors: Tondeleir Davina , Vandekerckhove Joël , Ampe Christophe
Published: April 2013

Actin is an evolutionary conserved molecule that self assembles into long polymers. These filaments form the building block of the actin cytoskeleton. This system is one of the main engines enabling cell motility processes. In muscle cells stable actin filaments participate in contraction. In nonmuscle cells, however, the filaments are more dynamic and polymerisation of actin generates the force for the formation of cellular protrusions required for cell migration. Various actin‐binding proteins orchestrate this dynamic turnover of actin filaments and thereby contribute to the different migration modes possible for nonmuscle cells. Next to its role in the cytoplasm actin also resides in the nucleus where it may regulate transcription in multiple ways. Because of its complexity, impaired regulation of the actin cytoskeleton disturbs cell function and deregulations of the actin machinery are associated with an increasing number of diseases such as myopathies and cancer.

Key Concepts:

Actins are conserved proteins with important functions during development and in adult life.

Actin self‐assembles into structurally and kinetically polarised filaments.

Numerous actin‐binding proteins regulate (dis)assembly and organise filaments in higher order structures.

Dynamic actin polymerisation drives multiple types of nonmuscle cell migration via formation of specific subcellular structures.

Actin cytoskeletal diseases are caused by mutations in actins or via disturbed regulation of the cytoskeleton.

In addition to its cytoplasmic function in cell motility processes, actin has a nuclear role in transcription.
Cell Junctions
Authors: Wegener Joachim
Published: April 2013

For any multicellular organism to function, it is a prerequisite that its individual cells interact with each other. These interactions are realised by cell‐to‐cell junctions that provide mechanical stability, information exchange or occlusion of extracellular diffusion pathways between neighbouring cells. The latter is an unconditional prerequisite for the formation of interfaces within the organism or between organism and environment. In order to provide these different physiological functions the corresponding cell junctions have their individual molecular architecture but share some common construction principles. For all of them transmembrane proteins are required that interact with corresponding structures on the surface of the opposing cell to form either mechanically stable interconnections, tight diffusion barriers, aqueous channels or well‐defined nanometre gaps for the fast diffusion of signal molecules. In most cases these transmembrane proteins interact with intracellular adapter proteins or the cytoskeleton, which is critical for their correct functionality.

Key Concepts:

More than 200 different cell types act together in the tissues and organs of the human body.

Cellular cooperation in multicellular organisms is based on various cellular interactions and cell junctions.

From a functional viewpoint cell junctions can be grouped into: (1) occluding junctions, (2) mechanical junctions and (3) communicating junctions.

Barrier‐forming epithelial and endothelial cells, which build up interfacial tissues between two fluid compartments, express tight junctions that occlude the diffusion pathway between adjacent cells.

Tight junctions are mainly composed of different transmembrane proteins (
occludin
, members of the claudin family, etc.) that use their extracellular domains to interact with the corresponding protein domains on the adjacent cell surface to block the intercellular cleft.

Mechanical stability of epithelial cell layers is based on adherens junctions and desmosomes that both provide a stable mechanical linkage between the intracellular cytoskeletons of adjacent cells.

Exchange of signalling molecules or metabolites smaller than 1000 g mol
−1
is provided by gap junctions (electrical synapses) who form aqueous channels between neighbouring cells.

Plant cells show a special kind of communicating junctions, the plasmodesmata.

Electrical communication between two neurons or a neuron and muscle cells is provided by chemical synapses, which relay electrochemical signals by a pulse of neurotransmitters.
Immunology: Comparative Immunology of Mammals
Authors: Ellis Shirley A
Published: April 2013

The mammalian immune system comprises a complex, coordinated and finely controlled series of interactions involving cells and molecules which has evolved to protect the host against disease. Mammals consist of a highly diverse group of animals in which the immune system has been subjected to a variety of selective pressures. This is reflected in differences in the organisation and function of their immune systems, and is seen especially in those gene families characterised by complexity and polymorphism, such as those encoding immunoglobulins (Ig), T‐cell receptors (TCR), major histocompatibility complex (MHC) molecules and natural killer (NK) cell receptors. The evolution of these components in a range of mammalian groups and species will be the main focus of this article.

Key Concepts:

The mammalian immune system has evolved to protect the host against disease.

The system is complex, involving specialised tissues, cells, soluble mediators and membrane‐bound molecules.

The mammalian adaptive immune response is characterised by extreme specificity in terms of antigen recognition.

This specificity is largely determined by genes encoding the major histocompatibility complex (MHC) molecules, immunoglobulins (Igs) and T‐cell receptors (TCRs).

Selection pressure by pathogens is believed to drive the generation of polymorphism in functional MHC genes.

MHC molecules present antigen to TCR and some additionally interact with NK cell receptors.

NK cells act as both effector and regulatory cells of the immune response.

Different mammalian groups and species have evolved a wide range of strategies to cope with rapidly changing pathogens, all aimed at protecting the host from disease.
Cell Cycle: Regulation by Cyclins
Authors: Truman Andrew W , Kitazono Ana A , Fitz Gerald Jonathan N , Kron Stephen J
Published: April 2013

The cell cycle is defined as the periodic occurrence of events that result in chromosome duplication (
deoxyribonucleic acid, DNA
replication in S phase) and separation (mitosis). This process is directly regulated by both external stimuli (such as nutrient availability) and internal stimuli (such as cell size and
DNA
integrity). These events are co‐ordinately driven by the
cyclin‐dependent kinases (CDKs)
. Although the expression of CDKs typically remains relatively constant, their activities are highly regulated by
CDK‐binding proteins
known as
Cyclins
.
Cyclins
are structurally related proteins whose levels fluctuate throughout the cell cycle. Cyclin levels in the cell are dynamically regulated through tight control over both their rate of synthesis and degradation via
ubiquitin
‐mediated proteolysis. These
CDK
activators also impart distinct substrate specificity to
CDKs
for the temporal regulation of cell division.

Key Concepts:

Cyclin levels oscillate throughout the cell cycle.

Cyclins bind to CDKs and regulate their kinase activity.

Cyclin‐CDK complexes direct the specificity of appropriate substrate interactions during the cell cycle.

Inappropriate regulation of cyclins can be both the cause and the result of oncogenesis.

As well as controlling normal cell cycle progression, cyclins function also in the exiting of the cell cycle (such as G0 in terminally differentiated cells and the onset of senescence caused by DNA damage).
Group Translocation –
PEP
:
PTS
Authors: Saier Milton H , Shlykov Maksim A
Published: April 2013

The phosphoenolpyruvate:carbohydrate phospho‐transferase system (PEP:PTS) is a prokaryotic enzyme/transport system that phosphorylates its extracellular carbohydrate substrates during transport, leading to intracellular accumulation of the sugar phosphate esters. Several phosphoryl transfer proteins play essential roles in sugar uptake, and they comprise a phosphoryl transfer chain using PEP as the phosphoryl donor, and the incoming sugar as the ultimate phosphoryl acceptor. This phosphoryl transfer chain is: PEP→EI→HPr→IIA→IIB+ IIC→sugar, where E=Enzyme and HPr=a small heat stable, histidine‐containing protein, and only the IIC constituent, the transport protein, is not phosphorylated. In mixtures of carbon sources, preferential growth on PTS substrates often occurs, as the phosphorylation state of PTS proteins coordinates the activities and synthesis of enzymes that initiate sugar metabolism. The mechanisms of regulation are different in representative Gram‐negative and Gram‐positive bacteria, but in both cases the PTS plays a central role. The PTS in

Escherichia coli

accomplishes this goal by regulating both cyclic adenosine monophosphate (AMP) synthesis and the uptake of sugar inducers of enzyme synthesis. It also plays a role in the coordination of nitrogen metabolism with carbon metabolism. In many bacteria, the PTS serves as a chemosensory system, directing movement of bacteria up concentration gradients of PTS sugars. In a few bacteria, the PTS functions in regulation but not in sugar uptake. Although this enzyme system has not been found in eukaryotes, it has been identified in archaea. The PTS is thus a multifunctional enzyme/transport/sensor/regulatory system that coordinates many activities in prokaryotic cells.

Key Concepts:

Biological membranes provide the fundamental barrier that separates the inside of a cell (the cytoplasm) from the extracellular space.

Embedded in these structures are proteins, many of which transport substances across the membrane.

The phosphotransferase system (PTS) serves as a complex transport system.

It consists of energy‐coupling enzymes (Enzymes I, HPr, IIA and IIB) as well as the PTS permeases (Enzymes IIC or IICs).

The IIC components couple phosphoryl transfer from IIB∼P to sugar substrate phosphorylation.

The process of coupled sugar uptake with sugar phosphorylation, involving substrate modification, is called ‘group translocation’.

The PTS serves as a chemoreception system, directing the activity of the bacterial flagellum so that bacteria swim up concentration gradients of nutrient sugars.

The PTS is a complex multifaceted system, regulating the activities of many non‐PTS enzymes and transporters, thereby creating a hierarchical system of carbon sources.

PTS protein domains are incorporated into many transcription factors, enzymes and transporters, allowing it to regulate these determinants of prokaryotic cell physiology and pathology.

A comprehensive understanding of prokaryotic cell biology requires a detailed understanding of the PTS.
Sleep Disorders
Authors: Sinton Christopher M , McCarley Robert W
Published: April 2013

Sleep medicine is an increasingly important specialty as the adverse health consequences of disturbed sleep are recognised by patients and physicians, and the current classification of sleep disorders, as recognised by the American Academy of Sleep Medicine (AASM), is summarised. Two primary sleep disorders, narcolepsy with cataplexy and the disorders of arousal, a symptomatic cluster that includes sleepwalking, confusional arousal and sleep terrors, are reviewed in greater detail. Both disorders can be summarised as being caused by inappropriate switching between the states of vigilance, although they are very different in age of onset, severity and impact on health. In narcolepsy the boundary between sleep and wakefulness is uncontrolled but in the disorders of arousal the boundary between states of sleep is affected. These two disorders also have a genetic predisposition suggesting that advances in knowledge of the relevant mutations could eventually translate into better understanding of the possible mechanisms and hence lead to improved treatments.

Key Concepts:

The disorders of sleep are primary, for example as a result of pathology in the mechanisms of sleep and wakefulness, or secondary, for example resulting from a medical condition.

Apnoea, interruptions of breathing lasting longer than 10 s that result in arousal from sleep, is the principal presenting condition at sleep clinics.

Polysomnography is used to record physiological parameters such as respiration rate, heart rate and blood oxygen level simultaneously with data allowing the stage of sleep or wakefulness to be defined.

Basic research into the neurophysiology, molecular genetics and neurochemistry of sleep and wakefulness has been critical for understanding the causes of many sleep disorders.

The classification of sleep disorders is continuously evolving and being refined as new disorders are recognised in the clinic and neurophysiological and neurochemical pathologies are better understood.
Gnathostomulida (Unsegmented Marine Worms)
Authors: Sterrer Wolfgang
Published: April 2013

First described in 1956, Gnathostomulida is a phylum of microscopic, free‐living, unsegmented and hermaphroditic marine worms. Uniquely distinguished by a monociliated epidermis (that is, a body surface where each cell carries only one cilium) and possession of complex cuticular mouthparts consisting of paired jaws and an unpaired basal plate, they are most likely related to Rotifera, Acanthocephala and Micrognathozoa. There are two orders, Filospermoidea (with a pointed anterior devoid of compound sensory bristles; without a bursa copulatrix; and filiform sperm, with one flagellum) and Bursovaginoidea (with a rounded anterior with compound sensory bristles; with a bursa; and rounded or cone‐shaped sperm, aflagellate). Approximately 100 species have been recorded to date, of which many are with global or circumtropical distribution. Gnathostomulids may numerically dominate the invertebrate meiobenthos in detritus‐rich, sulfide‐rich and oxygen‐poor shallow sandy bottoms (0–25 m, rarely to 400 m) where they typically occur, seemingly feeding on microbes that they scrape off sand grains.

Key Concepts:

Gnathostomulida is a small phylum of microscopic, free‐living, unsegmented and hermaphroditic marine worms.

Gnathostomulids are unique among animals in having an entirely monociliated epidermis.

Gnathostomulids have complex cuticular mouthparts consisting of paired jaws and an unpaired basal plate.

Gnathostomulids are most likely related to Rotifera, Acanthocephala and Micrognathozoa, with which they can be united in the superphylum Gnathozoa.

Gnathostomulids typically occur interstitially in detritus‐ and sulfide‐rich but oxygen‐poor shallow sandy bottoms.
Post‐Permian Radiation
Authors: Twitchett Richard J , Foster William J
Published: April 2013

Events at the close of the Permian Period, led to the most severe mass extinction of the Phanerozoic. Sepkoski's ‘Palaeozoic Fauna’ suffered most; the surviving groups, more ‘modern’ in aspect, were those that would seed the post‐Permian radiation. This radiation has long been identified as a ‘delayed’ radiation, being apparently of longer duration than other post‐extinction radiations, although recent advances in radiometric dating have shortened the Early Triassic. Comparing rates of recovery between different groups or regions is not straightforward because the quality of the fossil record is rather poor during the Early Triassic. The analysis of trace fossils provides one approach to assessing ecological recovery in the absence of well‐preserved shells. Groups that radiated into vacant or largely vacated ecospace include the bivalves, which colonised deeper infaunal habitats; the Scleractinia which replaced the Palaeozoic reef‐building metazoans; and the reptiles that became top marine predators.

Key Concepts:

The Late Permian mass extinction event is the most severe extinction event known from the fossil record.

Late Permian global warming led to a reduction in ocean circulation, increased ocean stratification and expansion of low‐oxygen ‘dead zones’.

The Palaeozoic fauna is dominated by sessile, epifaunal filter‐feeders such as corals, crinoids and brachiopods, whereas the Modern fauna is dominated by motile, epifaunal and infaunal organisms such as bivalves, echinoids and gastropods.

The best‐preserved fossil remains usually require an absence of scavenging animals, rapid burial and rapid mineralisation.

The quality of the fossil record is not constant through time and is affected by a number of different sampling and preservational factors.

Trace fossils provide evidence of the activities of benthic organisms that may not be preserved as body fossils, and are the only records of the responses of these animals to past extinction events.
Extinction: K–Pg Mass Extinction
Authors: MacLeod Norman
Published: April 2013

The K–Pg mass extinction event occurred at the end of the Cretaceous System (K, for kreta or chalk, a common Cretaceous rock type) and the beginning of the Paleogene System (Pg). During the last million years of the Cretaceous, just prior to the K–Pg boundary, between 40% and 75% of marine invertebrate and terrestrial vertebrate species disappear from the fossil record. Included in this extinction are such well‐known groups as dinosaurs (but not birds), pterosaurs, mosasaurs, ammonites and many species of marine plankton. Although there is broad consensus that these extinctions were driven by climate/oceanographic change, the potential causes of these changes remain topics of controversy. What is known is that the Earth was subjected to a substantial fall in sea‐level (c. 100 m), widespread volcanism, and a large comet/meteor impact during the extinction interval.

Key Concepts:

Mass extinctions occur when atypically high numbers of organismal extinctions take place within geologically short intervals of time.

Stratigraphic successions are characterised by stacked intervals of net sediment accumulation and discontinuities that mark intervals of no sediment accumulation or active erosion.

Molecular phylogenetic data indicate that many groups originally thought to have radiated after the K–Pg extinction (e.g. mammals and birds) have deeper histories than is indicated by the fossil record and should be regarded as K–Pg survivors.

Sea‐level changes across the K–Pg boundary indicate that more complete records of the biotic change will be found in shallow marine environments rather than in terrestrial or deep‐marine settings.

Patterns of species extinction in complete K–Pg successions indicate that this event occurred over a prolonged interval (e.g. tens to hundreds of thousands of years) prior to the K–Pg boundary rather than suddenly and coincident with the K–Pg boundary.

Of the three main K–Pg extinction mechanisms – sea‐level change, volcanism, asteroid/comet impact – all affect the environment in remarkably similar ways.

Flood basalt volcanism is the only extinction mechanism that exhibits a consistent association with intervals of mass extinction.

The multiple‐cause model – in which a geologically unusual juxtaposition of sea‐level change, volcanism and asteroid/comet impact seems the most likely candidate for the cause of this extinction event.
Evolution of Development
Authors: Bickel Ryan D , Brisson Jennifer A
Published: April 2013

Research in the field of evolutionary developmental biology, or “evo‐devo”, addresses how genetic changes result in developmental changes, causing phenotypic differences between species over evolutionary time. Evo‐devo has its roots in comparative embryology of the late nineteenth and early twentieth centuries, but the fields of evolution and development diverged soon thereafter. Advances in developmental genetics in the 1970s and 1980s, combined with the discovery that distantly related organisms share key regulatory genes and processes, provided new avenues of research in evo‐devo. Today the strong interest in this field illustrates that evolutionary biologists increasingly wish to understand mechanistically how genotypic differences are translated into phenotypic diversity. Current studies compare developmental processes across many taxonomic scales, from between phyla to between closely related species. The combination of traditional developmental biology techniques and modern approaches such as genomics has made evo‐devo studies possible in a wide range of organisms.

Key Concepts:

Evolutionary developmental biology is the study of how developmental differences result in phenotypic diversity.

Homologues of regulatory genes often have similar functions in even distantly related species.

Enhancer modularity allows regulatory genes to evolve new functions while maintaining previously established functions.

Studies between closely related species increase the power of detecting nucleotide changes that cause phenotypic differences.
Speciation: Introduction
Authors: Hvala John A , Wood Troy E
Published: April 2013

Speciation is the formation of two or more new species from one ancestral species. How new species form is a complex process and a fundamental biological question. Answering this question provides insights into patterns of biodiversity and informs conservation strategies. Research on the causes and patterns of speciation is heavily influenced by species concepts – how we define species. The biological species concept is perhaps the most influential, and it groups individuals into species on the basis of the ability to interbreed. Consequently, most research on the process of speciation is driven by the search for mechanisms that affect reproductive compatibility among closely related lineages. Once formed, a new species can maintain its identity by sharing advantageous genes among dispersed and reproductively compatible populations. Conversely, distinguishing traits can be maintained between species via isolating mechanisms. These contrasting mechanisms produce discrete clusters of phenotypic variation rather than a continuum of forms.

Key Concepts:

Speciation tends to form clusters of biodiversity rather than continuous gradients.

Species concepts heavily influence conclusions about how speciation occurs.

Choice of species concept depends on the goal of the research and the organisms being studied.

Species remain distinct from each other because of various isolating mechanisms, which prevent gene flow between species.

Isolating mechanisms have a genetic basis.

Hybridisation between species pairs often occurs in nature and can yield insights into the causes of speciation.

Hybridisation can lead to the fusion of two species into one, to reinforcement of reproductive barriers, or even to the formation of new ‘hybrid species’ that are ecologically distinct and genetically isolated from their parent species.
Sympatric Speciation
Authors: Veltsos Paris , Ritchie Michael G
Published: April 2013

Sympatric and parapatric speciation refer to the origin of biological species in the absence of complete geographic isolation between the diverging taxa. Until recently, most biologists believed that geographic isolation was almost universal in the development of species, i.e. most species originated in allopatry. However, new empirical and theoretical studies have shown that speciation may occur despite the diverging populations having adjacent or overlapping geographic ranges and despite on‐going gene flow. Attention in speciation studies has shifted to the mechanisms responsible for reducing gene flow, regardless of the extent of geographic range overlap.

Key Concepts:

The generation of new species has historically been classified according to geographic context, based on the overlap of different populations.

Geographic overlap is usually thought to influence gene flow between populations.

Of all possible cases, diversification in sympatry has been considered the most unlikely.

Theoretical models and examples from nature have shown sympatric speciation to be possible, but rare. A sympatric stage following allopatric divergence may be more common.

Divergence in the presence of gene flow may be common, especially if disruptive selection and/or assortative mating are strong.

A modern view of speciation focuses on processes that generate divergence, rather than a strict geographical classification.

Speciation is usually the result of complex interactions between different genetic, environmental and geographic processes, and must be understood in terms of this more complicated reality.
Homology in Character Evolution
Authors: Staton Joseph L
Published: April 2013

Homology forms the basis of organisation for comparative biology. Richard Owen's simple definition of homology as the ‘same organ in different animals under every variety of form and function’ takes on new meaning in light of Darwin's concept of descent with modification. The modern study of comparative biology and phylogenetics is grounded in the notion that organisms share a greater proportion of homologous (i.e. ‘derived’) characteristics the more recently they share a common ancestor. Instead of solely being the purview of anatomical study, homology of these characteristics can be applied at the level of molecular evolution, genomic organisation and modern evolutionary developmental biology (‘evo/devo’). Aspects of homology help us formulate hypotheses about the meaning of changes in homologous structures in the inference of evolution of organisms at all levels of biological organisation.

Key Concepts:

Homology was originally a measure of correspondence between anatomical structures.

Descent with modification explains homology as a result of shared ancestry that reflects modifications in characteristics within related lineages.

Comparative methods use changes in homologous characteristics to infer evolution within groups (phylogenetics).

Recent advances in molecular biology allow for the comparison of homologous characteristics at more diverse levels, including DNA sequences, genomic arrangements and developmental pathways.

Recent work highlights homologous characteristics at a fundamental or ancient level, termed ‘deep homology’.