bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunological Memory
Authors: Zanetti Maurizio
Published: April 2013

Immunological memory is a distinct characteristic of the immune system and it relates to its ability to remember antigens on pathogens, tumour cells, tissue of the immunological self, and cells and tissues derived from other individuals of the species and mount an immunological response of greater magnitude and with faster kinetics upon re‐encounter of the same antigens. This property provides an advantage in the course of protective responses against pathogens and tumour cells, but represents a threat in the case of allogeneic cell or tissue transplant. During the past decade considerable progress has been made in the elucidation of the multiple cellular and molecular mechanisms regulating the induction and maintenance of immunological memory. Although our understanding remains imperfect, the current cumulative information allows one to recognise operational patterns and identify those principles that will aid in the design of better vaccines and better understanding the role of immune system in protection against disease.

Key Concepts:

Immunological memory represents an important aspect of the immune response in mammals.

Immunological memory exists for both B lymphocytes (antibody producing cells) and for T cells.

Memory responses by the immune system occur according to only partially understood operational principles.

Memory responses form the basis for the effectiveness of vaccines against pathogens and cancer cells.

Memory responses protect the individual and the species against the threat of pathogens and cancer cells.
Neonatal Immunity
Authors: Tregoning John S
Published: April 2013

Both our innate and adaptive immune responses are reduced in function at birth. This leads to an increased risk of infection coinciding with a period of maximum exposure to new pathogens, caused by the move from the sterile environment of the womb to the infectious environment of the world. However, not every new antigen seen is dangerous to the newborn, and a balance is required to ensure an appropriate immune response and avoid inflammatory responses to benign antigens. To supplement the period of immune immaturity, the mother transfers passive protection, principally antibody, to the child. Vaccines can be used in early life, but the reduced function of the neonatal immune response reduces the efficacy of vaccines, which are otherwise effective in adults, necessitating research on infant‐specific formulations.

Key Concepts:

The neonate immune system is reduced in capacity and can be described as hyporesponsive.

The immune system develops in a programmed series of cell maturation events.

Moving from the controlled, sterile environment of the womb to the outside world has a critical impact on the newborn's immune system.

Reduced pattern recognition by neonatal antigen‐presenting cells leads to the observed hyporesponsive phenotype.

The mother provides some immune protection to the child, especially via antibodies in breast milk.
Infertility: Immunological Aspects
Authors: Francavilla Felice , Barbonetti Arcangelo
Published: April 2013

Naturally occurring antisperm‐antibodies (ASA) exert an impairment to fertility, which is related to the extent of sperm autoimmunisation. It determines the degree of the interfering effect on sperm penetration through the cervical mucus independently from the antigenic specificity of ASA. Whether or to what extent an ASA‐interfering effect occurs, in each individual patient, downwards from the impairment of cervical mucus penetration is still hard to establish. The main reasons are the inability of current diagnostic tests to determine the antigenic specificity of ASA and to quantify the antibody density on the sperm surface, the main determinants of the ASA‐impairment at level of sperm/oocyte interaction. The current empirical treatment strategy (intrauterine insemination as first line‐treatment) would give way to a more rational one, with the development of tests detecting ASA directed against defined fertilisation‐related antigens.

Key Concepts:

Immunological infertility refers to couple infertility due to antisperm‐antibodies (ASA) occurring in the male or female partner.

Antisperm‐antibodies (ASA) exert an impairment to fertility, which is related to the extent of sperm‐immunisation.

The impairment of sperm penetration through the cervical mucus represents the primary mechanism of ASA interference with fertility.

An ASA interference at the level of gamete interaction can occur or not, depending on the relevance of the specific antigens, targeted by natural ASA in each individual patient, to the fertilisation process.
Baculoviruses
Authors: Guarino Linda
Published: April 2013

Baculoviruses are large, complex
deoxyribonucleic acid
(DNA) viruses that infect arthropods. The viruses are highly pathogenic and a few members have been successfully exploited as biological control agents for agricultural and forestry pests. With the exception of a virus pathogenic to silk moths (

Bombyx mori

nucleopolyhedrovirus (NPV)), most baculovirus research is geared towards increasing virulence. The type species of baculoviruses,

Autographa californica

NPV, is widely used as a eukaryotic expression system for the production of vaccines and other proteins of medical and biological importance. Baculoviruses are also good model systems for the study of apoptosis, DNA replication, transcription, pathogenesis, membrane fusion and virus infectivity.

Key Concepts:

Baculoviruses are rod‐shaped, enveloped viruses of 30–60 nm in diameter and 250–300 nm in length.

Baculoviruses infect insects of the orders Lepidoptera, Diptera and Hymenoptera.

Baculoviruses have been genetically engineered to be highly efficient eukaryotic expression systems.

Baculoviruses are unusual in making two different infectious forms: occluded virus for spreading infection from insect to insect and budded virus for spreading of viral infection within an infected insect.

Baculoviruses have circular‐double stranded genomes, ranging from 80 to 180 kb.

Baculoviruses use actin filaments for intracellular transport.

Baculovirus DNA is infectious.

Baculoviruses use host RNA polymerase for synthesis of early genes and encode a viral RNA polymerase for transcription of late genes.

Baculovirus infection spreads through the tracheal system.

Baculoviruses have been successfully used to control insect pests.
Cytomegaloviruses
Authors: Chatterjee Archana , Livingston Robyn , Harrison Christopher J
Published: April 2013

The cytomegaloviruses are a common, ancient group of viruses that are widely distributed in the animal kingdom. They have a complex biology with a highly restricted host range. These viruses spread easily in the human population, causing mostly asymptomatic infection. This large reservoir of latent infection however, is a significant threat to high‐risk patients including immunocompromised hosts and the fetus in nonimmune pregnant mothers. Although a limited number of antiviral agents for treatment and prophylaxis in selected patient groups, as well as other adjunctive therapies have become available over the past few decades, newer, less toxic medications and a safe and effective vaccine remain in the research realm. Other areas still to be investigated include identification of the site of viral latency, characterisation of the targets of acute infection, determination of the exact role of virus and host immune response in disease and latency.

Key Concepts:

The cytomegaloviruses (CMVs) belong to the family of deoxyribonucleic acid (DNA) viruses known asHerpesviridae.

CMVs have complex biology and are widely distributed in nature, yet each animal species has its own CMV.

The prevalence of human CMV infection varies with age, geographic location, cultural and socioeconomic status, race or ethnicity and child‐rearing practices.

In most cases, human CMV infection in normal hosts is asymptomatic, but it can cause a mononucleosis syndrome similar to that fromEpstein–Barr Virus(EBv) infection.

The greatest risk from CMV is in immunocompromised patients and infants born to nonimmune mothers who develop primary infection during their pregnancy.

CMV has been one of the most important opportunistic infections in patients with AIDS.

Antiviral agents used to treat severe CMV disease include ganciclovir, valganciclovir, foscarnet, cidofovir and fomivirsen.

Passive immunoprophylaxis with CMV hyperimmunoglobulin (CMVIG) in post‐transplant patients, premature newborns at risk for postnatal infection and pregnant women is controversial.

Blood/organ donor screening, ‘leucocyte‐reduction’ in donated blood, handwashing and other hygienic measures can reduce the spread of CMV.

Newer therapeutic agents and a vaccine are under development.
Developmental Biology: Mathematical Modelling of Development
Authors: Maini Philip K , Baker Ruth E
Published: April 2013

Understanding how structures (e.g. hair, teeth, feathers, limbs and pigmentation patterns) arise from the initially unstructured fertilised egg is one of the key challenges in developmental biology. Mathematical models enable us to investigate how certain biochemical and/or biophysical processes interact to produce pattern and form. They provide a unifying theme for spatio‐temporal patterning across a vast range of biological applications by suggesting a set of underlying principles for pattern formation. Such models suggest that patterns and structures must have certain properties and these predictions motivate experiments. The results of such experiments help refine models and lead to more precise predictions. In this way, modelling, combined with experiment, can be a powerful investigative tool in helping unravel the complexity of morphogenesis (the formation of structure) in biology.

Key Concepts:

Patterning arises due to short‐range activation, long‐range inhibition.

Mathematical models suggest constraints on development.

Instabilities emerge from stabilising processes.

Pattern properties can be mechanism‐independent.

It is the integration of biochemical and biophysical processes that lead to structure formation.
Regeneration of Muscle
Authors: Grounds Miranda D
Published: April 2013

Muscle regeneration is the process by which damaged skeletal, smooth or cardiac muscle undergoes biological repair and formation of new muscle in response to death (necrosis) of muscle cells. The success of the regenerative process depends upon the extent of the initial damage and many intrinsic and environmental factors. Key cellular events required for regeneration include inflammation, revascularisation and innervation, in addition to myogenesis where new muscle is formed. In mammals, new muscle formation is generally excellent for skeletal muscle but poor for cardiac muscle; however a greater capacity for regeneration of cardiac muscle is seen in fish and some anurans. These aspects of regeneration are discussed with respect to myogenic stem cells, molecular regulation, ageing and implications for human therapies, with a strong focus on skeletal muscle. Other situations of muscle damage and restoration that do not involve necrosis (e.g. sarcomere disruption and atrophy) are here not considered as regeneration.

Key Concepts:

Necrosis is required for muscle regeneration.

Inflammation is essential to remove necrotic tissue and initiate myogenesis.

New blood vessel formation is required after major injury of muscles.

Skeletal muscle has an excellent capacity for regeneration. The major source of myogenic precursor (stem) cells is still considered to be the satellite cell, although other cells lying outside the myofibre may contribute to myogenesis.

The source of the myogenic precursor cells (myoblasts) varies between conventional tissue regeneration and epimorphic regeneration (where mature cells dedifferentiate).

The microenvironment, including the extracellular matrix, affects all aspects of regeneration, for example, the muscle precursors and their capacity for new muscle formation (and fibrosis impairs myogenesis).

Reinnervation is essential for functional recovery of skeletal muscle.

Excellent myogenesis can occur in geriatric muscle, although systemic factors essential for regeneration, for example, inflammation and innervation, may be suboptimal.

Mammalian heart muscle has a very poor capacity for regeneration and severe damage (e.g. heart attack) results in fibrosis and impaired function.

In contrast, the hearts of vertebrates such as salamanders and zebrafish can regenerate; the new heart muscle is derived from the dedifferentiation and proliferation of mature cardiomyocytes. It is hoped that an understanding of mechanisms involved in these situations will present opportunities to induce regeneration of damaged human cardiac muscle.
Biomedical Strategies for Axonal Regeneration
Authors: Saxena Tarun , Gilbert Ryan J , Pai Balakrishna S , Bellamkonda Ravi V
Published: April 2013

Deficits of the nervous system can be classified into two categories: ‘biochemical’, where replacement of a neurotransmitter like dopamine to a large measure corrects most Parkinsonian motor symptoms, and ‘networking’ deficits, where the connections between two sets of neurons or neurons and muscles are interrupted due to trauma or tumour resection. The underlying theme of all nervous system deficits is the loss of neuronal function. Consequently, the response of the body to an injury or lesion can be classified as being either pro‐regenerative or antiregenerative. Therefore, the goal of all therapies to treat nervous system disorders, ranging from Alzheimer disease to traumatic brain injury, is to foster pro‐regenerative repair mechanisms in nervous tissue. In an attempt to repair such deficits, various biomedical strategies that seek to promote axonal regeneration and plasticity, are being investigated.

Key Concepts:

A key difference between the CNS and the PNS is their differential abilities to repair traumatic damage. The PNS has an inherent capability to repair small injuries; the CNS has little or no ability to repair itself.

Schwann cells provide an organised matrix facilitating functional regeneration and repair in the PNS.

The gold standard in PNS repair using artificial nerve guidance channels is to match or exceed the performance of an autograft.

The glial scar in the CNS presents a highly inhibitory and disorganised terrain to regenerating neurites.

CNS and PNS repair strategies in the future must include multiple therapies acting synergistically.
SRY, Sex Determination and Gonadal Differentiation
Authors: Koopman Peter , Wilhelm Dagmar
Published: April 2013

The commitment to develop into a male or female embryo is dependent on whether testes or ovaries develop from the primordial gonads. This decision is in turn controlled by the function of a gene,SRY, found on the Y chromosome in mammals. The proper expression and function ofSRYin supporting cell precursors induces a cascade of gene expression that causes these cells to differentiate into Sertoli cells. Subsequently, Sertoli cells orchestrate the development of all other cell types resulting in the formation of testes, which produce hormones required for other aspects of male development. In the absence ofSRY, or ifSRYfunction is impaired, the supporting cells differentiate into granulosa cells, ovaries form and the embryo develops as a female.

Key Concepts:

Sex determination in mammals depends on the presence or absence of the Y‐chromosome geneSRY.

SRYinduces a program of gene expression in the sexually ambiguous primordial gonads of the embryo to induce differentiation of Sertoli cells.

Once Sertoli cells form, they influence other bipotential cell lineages to differentiate into cell types appropriate for a testis.

WhenSRYis absent or dysfunctional, a default genetic program instead causes granulosa cell differentiation and ovary development.

Mutations in genes involved in the testis and ovarian differentiation programs can cause human disorders of sex development.
Drosophila
Eye Development and Photoreceptor Specification
Authors: Şahin H Bahar , Çelik Arzu
Published: April 2013

The compound eye of the fruitfly

Drosophila melanogaster

is composed of 800 unit eyes called ommatidia, which are composed of eight neural photoreceptor cells and 12 supporting cells. All these cells are generated from an epithelial sheet called the eye imaginal disc through sequential specification and differentiation achieved by the spatially and temporally restricted expression of transcription factors and signalling pathways. Many of these factors and signals and their mode of action have been identified in recent years. Here, the authors give a brief overview of the molecular pathways that play major roles in photoreceptor specification and their terminal differentiation. Thus, the fly eye has provided important data to current understanding of developmental signalling processes and the specification of neural cell types, their patterning and structure and thus represents one of the most powerful genetic model systems for studying nervous system development.

Key Concepts:

The
Drosophila
eye is a highly preferred model system to dissect molecular interactions and developmental mechanisms of the nervous system.

It consists of ∼800 units called ommatidia; each has eight neural (photoreceptors) and 12 non‐neural (cone, pigment and bristle) cells.

The
Drosophila
eye emerges during late larval and pupal stage, from a monolayer epithelium called the eye‐antenna imaginal disc.

The morphogenetic furrow is a wave of differentiation sweeping across the eye imaginal disc from posterior to anterior initiating sequential differentiation at each line of cells it passes.

The morphogenetic furrow is initiated and pushed by a Hedgehog signal; this short‐range signal induces a long‐range Dpp signal to induce neurogenesis via Atonal, while the Dpp signal is suppressed by a Wingless signal secreted from the anterior margin of the eye imaginal disc.

Once the Morphogenetic Furrow passes a point in the eye imaginal disc, it creates a cluster of proneural cells resembling rosettes; a single cell out of this cluster is selected to become the the founder cell, R8. The rest of the photoreceptor cells are specified with the help of R8, using a network of molecular interactions.

During the development of the retina, the cellular cytoskeleton and cell–cell junctions are actively reorganised.

Although the outer photoreceptors (R1–R6) express dim light‐sensitive rhodopsin Rh1, the inner photoreceptors 7 express either UV‐sensitive rhodopsin Rh3 or rhodopsin Rh4, where the blue‐sensitive rhodopsin Rh5 is always accompanied with Rh6 in photoreceptor 8.

Sequential activation of different transcription factors leads to regional or stochastic determination of photoreceptor subtypes.
Lymphocytes: Recirculation
Authors: Jalkanen Sirpa , Salmi Marko
Published: April 2013

Successful immunosurveillance requires endless patrolling of lymphoid tissues by lymphocytes in search of foreign antigens. Lymphocytes enter the lymphoid tissues either through the blood vessel walls or via the afferent lymphatic vessels. To leave the circulation, bloodborne lymphocytes first tether to the endothelial lining of the vessels and start to roll. After an activation step they firmly adhere and transmigrate through the vessel wall. They then navigate through the tissue stroma following chemotactic and other guidance molecules, possibly encounter their cognate antigens and eventually return via the lymphatic vessels back into the blood to be dispersed to the other tissues of the body. In this tightly controlled process called lymphocyte recirculation, different adhesion molecules and activation signals on the two opposing cell types play a critical role. Dysregulated lymphocyte recirculation is involved in the pathogenesis of many inflammatory diseases and immunodeficiencies, and nowadays several drugs target this process.

Key Concepts:

Lymphocytes continuously recirculate between blood and lymphoid organs.

Majority of the lymphocytes enter the lymph nodes via specialised vessels called high endothelial venules (HEV).

The remaining lymphocytes (15–20%), together with dendritic cells and antigens, enter the lymph nodes via afferent lymphatics.

Lymphocytes leave the lymph nodes via efferent lymphatics.

Lymphocyte recirculation allows the lymphocytes to meet their cognate antigens and other leucocyte subsets to evoke an efficient immune response.

Lymphocytes interact with the vessel wall in a multistep fashion, using several leucocyte surface molecules, which recognise their counter receptors on endothelial cells.

The rolling and tethering of lymphocytes on the vessel wall is mediated by selectins.

Chemokines and their receptors are needed to activate leucocyte integrins.

Activated integrins mediate firm adhesion between lymphocytes and endothelium.

The transmigration of leucocytes into the tissues requires adhesion molecules, proteinases and repair mechanisms.
T Lymphocytes: Cytotoxic
Authors: Gotch Frances M
Published: April 2013

Cytotoxic T lymphocytes (CTLs) are T cells that have the ability to recognise and destroy other nucleated target cells that express ‘nonself’ or ‘foreign’ peptide (e.g. derived from viral proteins) in the context of major histocompatibility complex (MHC) class I or class II molecules on their surface. Most CTLs are MHC class I restricted CD8 T cells, but some CD4 T cells (besides their well‐known helper and regulatory functions) also have the capacity to recognise and kill infected cells. Cytotoxic T cells are of great importance in host defence against cytosolic pathogens in general.

Key Concepts:

Cytotoxic T‐cells (cytotoxic T lymphocytes, CTLs) are a subset of lymphocytes that participate in cellular immunity.

They originate from haematopoietic stem cells in the bone marrow but develop in the thymus.

Their main role is to combat intracellular infection.

They possess antigen‐specific receptors (T‐cell receptor, TCR) on their cell surface.

Most CTL are CD8+and recognise antigen‐derived peptides presented by MHC class I molecules on the surface of the infected cell.

A minority of CTL are CD4+and recognise peptides presented by MHC class II molecules.

In addition to destroying infected cells, CTL also play a role in antitumour and autoimmune responses.

They destroy infected cells by induction of apoptotic cell death in the target cell.

Apoptosis can be induced in the target cell using the granzyme/perforin, Fas/Fas ligand or tumour necrosis factor (TNF)/TNF receptor pathways.
Animal Models of Human Primary Immunodeficiency Diseases
Authors: Blundell Michael P , Kinnon Christine
Published: April 2013

Animals with immunodeficiencies provide useful model systems for the study of corresponding immunological disorders in man. There has been substantial progress made in the availability and numbers of animal models since the 1970s when naturally occurring models were the only source. Improved molecular biology techniques, embryonic stem (ES) cell technologies and the sequencing of whole animal genomes has not only increased the number of models but also has led to improved models, particularly in mice. The increased understanding of the immune system, immune disorders and the generation of novel therapies owes much to animal models of disease. Further work is now in generating larger animal models which in addition to expressing the immunological disorders have a more directly comparable physiology.

Key Concepts:

Animal models of human immunodeficiency have been useful in studying the immune system.

The phenotypes resulting from genetic defects in animals do not always mirror those seen in humans.

Technologies exist to knock‐out, knock‐in and knock‐down relevant genes as well as replace them with human loci in animal models to improve the comparability of the phenotype.

Murine models are the most commonly described and used animal models but technologies are being developed for larger animal models.

Animal models have been crucial in the development of novel therapies for immunodeficiencies.
Immunosuppressive Drugs
Authors: Braun Felix , Becker Thomas , Renders Lutz , Ringe Burckhardt
Published: April 2013

Immunosuppressive drugs are used for the prevention or treatment of rejection after transplantation of solid organs, tissues and cells, as well as therapy of autoimmune and a variety of other diseases. Primary goals of immunosuppression are: (1) to effectively control immune responses against foreign antigens and (2) to minimise any undesired drug side effects and toxicities. The development of numerous substances, together with the understanding of their molecular action has paved the way to meet these goals, and to individualise immunosuppression. The objective of this inventory is to give a systematic overview on immunosuppressive agents currently in use or under evaluation for transplantation, as a guide for scientific research and clinical practice.

Key Concepts:

Immunosuppressive drugs are required for prophylaxis and therapy of rejection in solid organ transplantation.

A broad spectrum of immunosuppressive drugs is available and new drugs are in the pipeline or under development.

Some immunosuppressive drugs are critical dose drugs with a narrow therapeutic index and require therapeutic drug monitoring.

Calcineurin inhibitors are commonly used as the basic immunosuppressives despite their nephrotoxic potential.

Immunosuppressive drug combinations with different mode of actions are helpful to lower single drug dosages and avoid drug‐related adverse effects as well as to use synergistic or additive immunosuppressive effects.

Many factors (e.g. age, gender, liver or renal dysfunction, genetic polymorphism, drug–drug interactions, etc.) can alter the pharmacokinetics of immunosuppressive drugs.

Withdrawal of immunosuppressive medication in solid organ transplantation can cause graft failure.
Xenotransplantation
Authors: Cooper David KC , Ekser Burcin , Ezzelarab Mohamed , Hara Hidetaka
Published: April 2013

The transplantation of organs and tissues across species is called xenotransplantation. The most likely source of animal organs and cells for transplantation into humans is the pig. Pigs, therefore, have been genetically engineered to provide their tissues with some protection against the human immune response. The classical ‘rejection’ of pig organs has largely been overcome, but thromboses (clots) occur in the small blood vessels of the graft. Pigs with human ‘antithrombotic’ genes are now becoming available and it is hoped will prevent this complication. Hearts from genetically engineered pigs have functioned in nonhuman primates for up to 8 months, and pig pancreatic islets (that produce insulin) have controlled diabetes in monkeys for longer than 1 year. The safety of xenotransplantation remains of some concern. Is there a risk of the transfer of a pig infectious microorganism into the community? Present evidence is that this potential risk is low. This potential, however, has legal and regulatory implications.

Key Concepts:

There is a critical shortage of organs from deceased humans for transplantation into patients with vital organ failure.

There are an estimated one and a half million people in the USA alone with Type 1 (juvenile) diabetes who might benefit by the transplantation of pancreatic islets (which secrete insulin).

Because of its anatomical and physiological similarities to humans, the pig is in many ways a suitable source of organs and cells for transplantation into patients.

Protection from the primate immune response can be achieved in pigs by genetic engineering, which largely consists of introducing into the pig one or more human ‘protective’ genes.

The major remaining problem appears to be a tendency for thromboses (clots) to form in the blood vessels of the pig organ graft, but it is hoped this will be resolved by the introduction of human ‘antithrombotic’ genes into the pig.

There is some concern that a pig infectious microorganism could be transferred to the human recipient of a pig organ and that this microorganism could be passed on to the recipient's contacts, but this risk is now considered to be low.

Clinical trials of pig organ and cell transplantation will need to be regulated by national regulatory agencies such as the FDA in the USA.
Muscle Contraction
Authors: Squire John M
Published: April 2013

Muscular contraction is one of the few biological processes that can be appreciated directly in our everyday lives. In the past few decades a detailed understanding of the underlying molecular processes that produce force and movement has been obtained. Striated muscles contain well organised repeating units called sarcomeres which each include overlapping arrays of filaments of the proteins myosin and actin. Myosin filaments have projections on their surfaces known as crossbridges. These are the myosin head parts of the myosin molecules which form the myosin filament. It is the myosin heads, which are enzymes (ATPases) which interact with actin filaments to produce force and movement. Actin filaments contain additional proteins troponin and tropomyosin which are involved in switching muscle activity on and off (muscle regulation).

Key Concepts:

Vertebrates have two types of striated muscle namely cardiac muscle, which drives our heart and skeletal muscles which move our skeleton.

Vertebrate skeletal muscles contain long thin fibres (multinucleate cells) about 20–100 μm in diameter and very long (mms to cms).

Muscle fibres are parallel arrays of long, thin myofibrils about 2–5 μm in diameter and sometimes as long as the fibres.

Cardiac muscle cells (myocytes) are much shorter than skeletal muscle fibres and link end‐to‐end to provide long lengths of muscle. They also contain myofibrils.

The basic repeating unit in all striated muscles is the sarcomere. In vertebrates this is about 2–2.5 μm long. A myofibril is a long string of sarcomeres.

The sarcomere comprises overlapping arrays of myosin and actin filaments.

Myosin filaments are made of myosin molecules which consist of a rod‐shaped region with two heads on.

The myosin heads projecting from the myosin filament surface can hydrolyse ATP (adenosine triphosphate; they are ATPase enzymes), a process which is accelerated when heads interact with actin to produce force and movement.

In striated muscles the interaction of myosin heads with actin is controlled by the proteins troponin and tropomyosin on the actin filaments.

It is calcium ions released by the sarcoplasmic reticulum around myofibrils in response to nervous stimulus that interact with troponin, move tropomyosin and allow the actin–myosin interaction to proceed.
Calcium Signalling and Regulation of Cell Function
Authors: Bootman Martin D , Rietdorf Katja , Hardy Holly , Dautova Yana , Corps Elaine , Pierro Cristina , Stapleton Eloise , Kang Esther , Proudfoot Diane
Published: April 2013

The calcium ion (Ca
2+
) is a versatile intracellular messenger. It provides dynamic regulation of vast array of cellular processes such as gene transcription, differentiation and contraction. Ca
2+
signals range from microsecond, nanoscopic events to intercellular waves lasting for many seconds. This diversity of Ca
2+
signals arises from the wide assortment of Ca
2+
transport and Ca
2+
buffering processes employed by cells. Additional diversity in Ca
2+
signalling stems from the ability of cells to utilise different sources of Ca
2+
. The cytosol is the principal Ca
2+
signalling compartment. When Ca
2+
ions enter the cytosol they interact with numerous Ca
2+
‐binding proteins, thereby leading to activation, or inhibition, of cellular processes. Specificity is achieved by regulating the spatial and kinetic properties of Ca
2+
signal. In this way, many concurrent Ca
2+
‐sensitive cellular processes can be discretely regulated. A number of pathologies have been related to the breakdown of cellular Ca
2+
homoeostasis or to aberrant Ca
2+
signalling.

Key Concepts:

Calcium is a critical intracellular signal that controls key cell fate decisions.

Calcium signals derive from multiple sources that are accessed by a diverse range of transport mechanisms.

The kinetics and spatial properties of calcium signals determine their impact on cellular activity.

Ca
2+
signals are tissue‐specific and are appropriate to regulate the physiological functions of individual cell types.
Antibody Engineering
Authors: Paul Sudhir , Planque Stephanie
Published: April 2013

The antigen‐binding site of antibodies is composed of the heavy and light chain variable domains (V domains). Therapeutic human antibodies specific for individual antigen can be obtained by inducing adaptive B cell development in transgenic animal or by test‐tube affinity maturation of cloned antibody V domain repertoires. The V domains are recloned as full‐length antibodies to improve their pharmacokinetic behaviour and incorporate effector functions residing in the constant domains. Assembly of the V domains into multivalent constructs improves the binding avidity. Linkage to enzymes, toxins or delivery proteins imparts novel functions to the constructs. Emerging engineering strategies include the development of antibodies with catalytic activity and antibodies that can target intracellular antigens.

Key Concepts:

Antibodies are highly adaptive structures. They are encoded by germline genes that have diversified over evolutionary time and then undergo further antigen‐driven adaptive development over the life time of an individual organism.

The antigen combining site is composed of the antibody light and heavy chain subunit variable domains. The constant domain contributes effector functions such complement activation and Fc receptor binding.

Monoclonal antibodies have emerged as a major class of biological drugs for various diseases. The efficacy and safety of monoclonal antibody drugs depend on their antigen recognition affinity, specificity andin vivopharmacokinetics.

Understanding the natural process underlying adaptive sequence diversification has permitted isolation of monoclonal antibodies meeting the criteria for therapeutic applications. Antibody display and cloning methods have enabled identification of individual antibodies with defined antigenic specificities from vast repertoires.

Improvement of antibody functions can be attained in the test tube by rational or random mutagenesis coupled with directed selection of the mutants.

Catalytic antibodies combining the specificity of the antigen‐binding site with the turnover capability of enzymatic sites have emerged as a viable second generation technology for novel antibody applications.
Autoimmune Disease: Diagnosis
Authors: Dey Ida Dzifa , Isenberg David A
Published: April 2013

The diagnosis of autoimmune diseases invariably requires the detection of autoantibodies, in association with suggestive clinical symptoms, which develop in relation to the involvement of specific or nonspecific organ systems. Many autoantibodies have well‐defined target antigens and can be detected with high analytical sensitivity. Autoantibodies act as biomarkers helping to diagnose disease subsets and monitor autoimmune diseases. The indirect immunoflorescence technique remains the hallmark of diagnosis, but is increasingly being replaced by enzyme immunoassays or multiplexed assays. Comprehensive methods of analysing multiple antibodies simultaneously using multiplex assays are being developed for routine use in the diagnosis, study of the specificity and pathophysiology of autoimmune diseases and the development of antigen specific therapies. Clinical proteomics offers the opportunity to identify new disease biomarkers to help in diagnosing and managing autoimmune diseases.

Key Concepts:

The diagnosis of autoimmune diseases depends on clinical suspicion and supportive immunological tests.

Test for autoantibodies only when there is a clinical suspicion of autoimmune disease as weakly positive ANAs may be present in the normal healthy population.

Autoantibodies can be used in diagnosis, monitoring of disease flares and remission, sub‐setting disease, evaluating severity and prognosis.

The indirect immunoflorescence technique remains the hallmark of diagnosis, but is increasingly being replaced by enzyme immunoassays or multiplexed assays.

Multiplexed immunoassays support the identification of multiple autoantibodies from a single determination simultaneously without having to do follow up testing.

Multiplex assays are advantageous as a single test may be used for both screening and determining antibodies of clinical significance.

Clinical proteomics offers the opportunity to identify new disease biomarkers in body fluids, cells and tissues to help diagnose diseases.
Cell Cycle
Authors: Stein Gary S , Medina Ricardo , van Wijnen André J , Stein Janet L , Lian Jane B , Owen Thomas A
Published: April 2013

Competency for proliferation and cell cycle progression are governed by complex and interdependent processes that support DNA replication and mitotic division. Genetic and epigenetic controls are operative. The architectural organisation of the regulatory machinery for gene expression is compartmentalised in microenvironments of interphase nucleus and at gene loci on mitotic chromosomes. The cell cycle requires selective expression of genes that encode cell cycle regulatory proteins. A broad spectrum of signalling mechanisms integrate and amplify growth‐related regulatory cues that mediate fidelity of cell cycle control. There are unique requirements for cell cycle control to support the rapid proliferation that occurs during initial stages of embryogenesis and continued renewal of stem cell populations. The cell cycle regulatory mechanisms that are compromised in cancer cells provide insight into control of transformation and tumourigenesis as well as serve as targets for therapy.

Key Concepts:

Competency for proliferation and cell cycle progression requires selective expression of genes that encode cell cycle regulatory proteins.

Transcriptional and post‐transcriptional mechanisms mediate control of the cell cycle.

Genetic and epigenetic mechanisms support cell cycle progression.

The regulatory machinery for gene expression that supports cell cycle control is architecturally organised and assembled in nuclear microenvironments.

Unique mechanisms govern control of proliferation during early embryogenesis and for renewal of stem cell populations.

Regulatory parameters of cell cycle control that are compromised in cancer cells serve as a platform for tumour diagnosis and therapy.

Synchronisation of cell cycle progression supports identification of cell cycle regulatory parameters and mechanisms that are compromised in transformed and tumour cells.

Regulatory mechanisms that control the cell cycle in yeast have provided valuable insight into cell cycle control in mammalian cells.
Tunicate Embryos and Cell Specification
Authors: Satoh Noriyuki
Published: April 2013

Tunicates are marine invertebrate chordates and closest relatives of vertebrates. The most common tunicates are ascidians. The fertilised egg of ascidians develops quickly into a tadpole‐type larva. The larva is composed of approximately 2600 cells and has distinct organs including the nervous system, endoderm and mesenchyme in the trunk, and muscle and notochord in the tail. The larval surface is covered by an epidermis. This configuration represents a basic body plan of chordates. Every blastomere of early embryos up to the gastrula stage is distinguishable, and invariant lineage of embryonic cells is well documented. Cell fate restriction occurs relatively early in ascidian embryos. Maternal factors are responsible for differentiation of muscle, endoderm and epidermis, whereas the notochord and nervous system are specified by cellular interactions. Genes that are involved in the specification of embryonic cells have been identified. The tunicate is an emerging model for studies of embryonic cell specification.

Key Concepts:

In ascidians, invariant lineage of embryonic cells is completely described up to the gastrula stage.

Developmental fates of most embryonic cells are determined during the blastula formation.

Maternal factors are responsible for differentiation of muscle, endoderm and epidermis.

The notochord and nervous system are specified by cellular interactions.

Genes that are responsible for the specification of embryonic cells have been identified.

The tunicate is an emerging model for studies of embryonic cell specification.
Diversity of Life
Authors: Minelli Alessandro , Bonato Lucio
Published: April 2013

Diversity of life (also called biological diversity or biodiversity) is the variety of living systems. It may refer to extant organisms, but also to their diversity in the past. It is usually meant to encompass multiple levels of biological systems, from the gene level, through the level of populations and species, up to the communities of organisms and the ecosystems to which they belong. Habitat fragmentation and host specialisation are two of the major causes explaining the origin of the multiplication of living species in the course of evolutionary history. About 2 million species have been described to date and some 17 000–19 000 new entries are added every year to this list. The number of living species existing on Earth is unknown, current estimates favouring figures in the range of 8–12 millions.

Key Concepts:

There are three major ranks of biological diversity on Earth, at the gene, species and ecosystem level respectively.

Species diversity is fostered mainly by geographical isolation and by strict interspecific relationships such as parasitism, food specialisation and plant pollination by insects.

All animal phyla are represented in the sea and several phyla including echinoderms, ctenophores and brachiopods are exclusively marine, but only 15% of all living species described to date inhabit the sea.

Insects represent more than one half of the total species‐level biological diversity on Earth.

Key events in the history of life were the Cambrian ‘explosion’ and the invasion of land by plants (Middle Silurian), arthropods (Upper Silurian) and vertebrates (Upper Devonian).

The history of biological diversity was punctuated by major critical events (mass extinctions) of which the most severe marks the end of the Palaeozoic era.

Recent descriptions of previously unknown species include a few cetaceans and other large animals as well as small animals representing completely new classes or phyla, such as Loricifera, Cicliophora and Micrognathozoa.

A sensible approach to estimating the number of existing species is to compare the number of described and undescribed species collected by prolonged sampling efforts in biologically rich and hitherto less investigated areas.

Global estimates of existing biodiversity range from 5 to 130 million species, a figure of 8–12 millions being currently favoured.
Phylogeny and Stratigraphy Comparison
Authors: Wagner Peter
Published: April 2013

Phylogenetic relationships among taxa can be estimated in a number of ways. Given known fossil records, phylogenetic estimates implicitly hypothesise the latest possible origination times of taxa. One can use these inferences as models to evaluate the quality of the fossil record. Originally, it was hoped that these metrics would obviate the need for probabilistic models. However, subsequent research shows that all these metrics are affected by the same factors affecting probabilistic models while also being highly sensitive to the accuracy of the model phylogeny. Alternatively, one can treat these inferences as hypotheses to be tested by stratigraphic distribution data. Given the sensitivity of phylogenetic inference to ideas about character evolution and levels of convergence, this offers a promising avenue for reducing untested assumptions yielding initial phylogenetic estimates.

Key Concepts:

Particular ideas about phylogenetic relationships have implications about both macroevolutionary models and preservation models.

There are several ways to describe gaps implied by inferred phylogenies, but all reflect factors other than simple preservation rate, especially the accuracy of the phylogeny.

Using stratigraphic data to test phylogenetic inferences as hypotheses might help assess the assumptions underlying phylogenetic inference.
Old World Monkeys
Authors: Frost Stephen R , Rosenberger Alfred L , Hartwig Walter C
Published: April 2013

Old World monkeys, or cercopithecoids, are a diverse and widespread group of primates found throughout Africa and Asia. They are characterised by their specialised molar teeth, quadrupedal running behaviour, often spending more time on the ground than other primates, as well as their often large and complex social groups. They survive in the widest range of habitats of any nonhuman primates, with some species restricted to humid tropical forests whereas others are found in mountains and deserts. There are two main groups: the cercopithecines, which have cheek‐pouches and include macaques, baboons, mangabeys, vervets and guenons; and the colobines, characterised by complex stomach anatomy that allows them to digest leaves and which include langurs, proboscis monkeys, doucs and snub‐nosed monkeys and colobus monkeys. Although they are termed ‘monkeys’ they are more closely related to apes and humans (hominoids) than they are to the monkeys of Central and South America.

Key Concepts:

As they are large, occur in large social groups, are often terrestrial and active during the day, Old World monkeys are some of the most thoroughly studied wild primates.

Groups of closely related females, called matrilines, usually form the core of Old World monkey social groups because females remain in the same group as their mothers, whereas males generally transfer to a new group when they become adults.

Old World monkeys are the most diverse group of primates in terms of environmental and geographic range, as well as number of species, but have achieved this diversity through relatively narrow morphological and behavioural adaptations that allow for ecological flexibility.

Compared to other primate groups, Old World monkeys are a recent adaptive radiation, which may in part explain their relative lack of anatomical diversity, and they seem to have replaced the apes as the predominant primates in Africa and Eurasia as climatic change made environments more open and seasonal.
Nematomorpha (Horsehair Worms)
Authors: Poinar George
Published: April 2013

The phylum Nematomorpha, the hairworms, occurs worldwide. All members are developmental parasites of aquatic or terrestrial invertebrates. One genus,
Nectonema
, is marine, whereas the remaining species occur in freshwater as free‐living stages or inside terrestrial hosts. Hairworms have two or more hosts in their life cycle. The first paratenic host is just a carrier to the second developmental host. In the developmental host, the hairworm grows to maturity and often kills the host upon emergence. There is no direct economic or medical importance of hairworms and while they can reach up to a foot in length, they are rarely seen. A few species may effect populations of herbivorous insects, but most are not important as biological control agents. Most freshwater hairworms are threatened from polluted waters, habitat displacement and reduced host populations. Many could be considered as candidates for the Red Data Book of rare and endangered species. Hairworms are a relict group that is not closely related to any other living phylum. The preparasitic larvae are quite different from the adults since they possess spines for entering the body cavity of paratenic hosts. Once inside the paratenic host, the larva is surrounded by host tissue and is known as an ‘encysted’ larva. It remains in the cyst until the paratenic host is ingested by a suitable developmental host. If the second host is not suitable for development, the hairworm larvae can encyst again in the new paratenic host.

Key Concepts:

Hairworms are becoming endangered in many areas of the world.

Hairworms have attracted the attention of behaviourists who study how these parasites control the movements of their hosts.

Hairworms have no direct economic or medical importance.

Hairworms have the ability to arrest development in nondevelopmental hosts.

Hairworms are an enigmatic group that are not closely related to any other invertebrates.

Hairworms are an ancient group, with fossils dating back to the Early Cretaceous.