bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of the Hox Gene Cluster
Authors: Ferrier David EK
Published: April 2013

The Hox genes are a family of developmental control genes containing a homeobox motif, and tend to be organised in distinctive clustered arrays in animals. Organisation within the cluster can relate to how the genes function. Whilst much has been discovered about the Hox gene cluster in traditional model systems of developmental biology, increasing amounts of data from a wider variety of species are illuminating more about the nature of the Hox cluster deep in animal ancestry, as well as revealing the evolutionary flexibility and derivations along present‐day lineages. The consensus view of the Hox cluster is that it patterns the anterior–posterior axis of bilaterally symmetrical (bilaterian) animals and exhibits the phenomenon of colinearity. There is, however, much evolutionary change within this system. This diversity in the Hox system is linked to the evolution of animal diversity and informs our understanding of the pre‐bilaterian origins of the Hox genes themselves.

Key Concepts:

Spatial colinearity is the phenomenon whereby the order of the expression domains of the Hox genes along the anterior–posterior axis of the embryo corresponds with the order of the genes along the chromosome.

Temporal colinearity is a further form of colinearity in which the Hox genes in some taxa are activated progressively, with the earliest time at which a gene is activated matching its position within the Hox cluster.

Anterior–posterior patterning by the Hox genes is distinct from the initial determination of the anterior–posterior axis and instead involves the specification of different developmental fates within the anterior–posterior axis of an embryo. This is one of the major roles of the Hox genes within the bilaterians, but the Hox genes do have further roles in development subsequent to this anterior–posterior patterning function.

A range of Hox gene organisation has evolved across different lineages, forming organised, disorganised, split and atomised Hox clusters, such that the Hox genes of some species are not actually organised into a Hox gene cluster.
Eye Movements
Authors: Mackay Devin D , Prasad Sashank
Published: April 2013

Eye movements are produced by six extraocular muscles for each eye, which are controlled by the third, fourth and sixth cranial nerves, their nuclei, and specialized populations of neurons in the medulla, pons, midbrain, cerebellum and cerebral hemispheres. Together, these neurons allow the eyes to move quickly together to an object of interest (saccades), follow a moving target (pursuit), maintain ocular alignment (conjugate gaze), and converge on a close target (vergence). Vestibular inputs allow vision to remain fixed on an object despite head movement, whereas their suppression helps the eyes and head follow a moving object together. A lesion in the pathways subserving eye movements leads to characteristic abnormalities that can often be localised upon careful clinical examination. Understanding the anatomy of these pathways and common diseases that affect them facilitates accurate diagnosis and appropriate treatment.

Key Concepts:

The third, fourth, and sixth cranial nerves are the final common pathway for all eye movements.

Binocular diplopia (that resolves with either eye covered) is the cardinal clinical symptom of misalignment of the eyes.

Saccades are fast conjugate eye movements that direct the eyes to a point of interest and originate with signals in the cortex.

Pursuits are slower conjugate eye movements that allow the eyes to follow a moving point of interest.

Abnormalities of conjugate horizontal eye movements may localise to the pons, where saccadic eye movements are controlled by neurons of the paramedian pontine reticular formation (PPRF) and maintained by neurons of the nucleus prepositus hypoglossus.

Abnormalities of conjugate vertical eye movements may localise to the midbrain, where saccadic eye movements are controlled by neurons of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and maintained by neurons of the interstitial nucleus of Cajal (inC).

Head and eye movements are coordinated by information from the semicircular canals and otolith organs and their specialized connections with the ocular motor nuclei.

The medial longitudinal fasciculus (MLF) is a highly myelinated fibre tract connecting the abducens nuclei and contralateral oculomotor nuclei, serving to facilitate rapid coordinated horizontal eye movements and maintain conjugate gaze.

Nystagmus (back and forth oscillations of the eyes) primarily results from abnormalities of the slow eye movement systems and gaze‐holding mechanisms.
Diabetic Neuropathies
Authors: Said Gérard
Published: April 2013

Diabetes is the most common cause of peripheral neuropathy in the world. Both type 1 (insulin‐dependent) and type 2 diabetes are commonly complicated by peripheral nerve disorders. Two main types of neuropathy are observed: the most common is a nerve fibre length dependent, distal symmetrical sensory polyneuropathy with little motor involvement but frequent, and potentially life threatening, autonomic dysfunction. Alteration of temperature and pain sensations in the feet is an early manifestation of diabetic polyneuropathy. The second pattern is a focal neuropathy which more commonly complicates or reveal type 2 diabetes. Poor diabetic control increases the risk of neuropathy with subsequent neuropathic pains and trophic changes in the feet, which can be prevented by patient's education.

Key Concepts:

Length‐dependent diabetic polyneuropathy is the most common neuropathy in the world.

Neuropathic pains are the most common symptoms of diabetic neuropathy.

Charcot joints and plantar ulcers are favored by loss of pain sensation.

Autonomic dysfunction is commonly associated with small fibre diabetic neuropathy.

The prevalence of diabetic polyneuropathy increases with duration and poor diabetic control.

Focal neuropathies are more common in type 2 diabetic patient.
Cerebral Palsy
Authors: Feather Danielle N , Ferguson Tanya S
Published: April 2013

Cerebral palsy is a nonprogressive movement disorder that causes permanent motor disabilities. It occurs in 3:1000 live births in the United States annually. Although it is considered a motor disorder, the symptoms of cerebral palsy are due to brain damage that occurs eitherin utero, during birth or within the first 2 years of life. Birth asphyxia was thought to be the primary cause of cerebral palsy; however, birth complications, including asphyxia, account for less than 10% of all known cases. The aetiology of the remaining 90% of cerebral palsy cases is unknown, suggesting that an undetected or undiagnosedin uteroevent is the primary cause. Many maternal risk factors have been identified, including multiple births, toxin exposure and high blood pressure. Fetal stroke and inflammation due to maternal infection may also play a role. There is no cure, only management of symptoms. Treatment includes various therapies as well as pharmaceuticals to decrease symptoms. Surgery may also be an option. Current research is investigating both the cause of and treatments for cerebral palsy with some recent promising results.

Key Concepts:

Cerebral palsy is a nonprogressive movement disorder.

It is identified by a typical pattern of brain injury to the motor regions of the brain, often before birth.

The different types of cerebral palsy are named after their location and symptoms.

The cause of cerebral palsy is unknown; however, many risk factors have been identified.

Treatment involves symptom management.

Research is currently focused on early detection, a potential cure and better symptoms management.
Exosome Complex
Authors: Chlebowski Aleksander , Dziembowski Andrzej
Published: April 2013

A living cell consists in a dynamic equilibrium of many opposing processes. Steady‐state levels of all
ribonucleic acid
(RNA) and protein molecules result from a specific balance between constant production and ongoing decay. RNA degradation is thus of paramount importance for the cell's wellbeing. A major player in this process is the exosome complex. It is a multisubunit entity endowed with
ribonuclease
activities. It is highly conserved in evolution, found in all
Eukaryota
and most
Archaea
;
Eubacteria
lack the exosome but they do have a very similar enzyme. The eukaryotic exosome has endo‐ and exoribonuclease activity and it engages a plethora of substrates in numerous pathways of RNA decay, RNA processing and RNA surveillance. Substrate specificity is conferred by a wide range of cofactors, some of them multisubunit complexes with interaction networks of their own.

Key Concepts:

The exosome core is a conserved protein complex.

Exosomes of
Archaea
and
Eukaryota
have different enzymatic activities.

Catalytic activity in eukaryotic exosomes comes from noncore subunits.

Catalytic subunits are organised differently in yeast, plants and mammals.

The exosome participates in RNA decay, processing and surveillance.

Many cofactors are responsible for recruiting substrates to the exosome.
Bacteriophages: Structure
Authors: Cuervo Ana , Carrascosa José L
Published: April 2013

Bacterial viruses, or bacteriophages, are ubiquitous organisms spanning very different ecological niches. Although genome comparison fails to show extensive relationship among bacteriophages, recent structural studies reveal a high degree of similarities. Most bacteriophages present an icosahedral proteinaceous head, which contains the nucleic acid, either
deoxyribonucleic acid (DNA)
or
ribonucleic acid (RNA)
. Exceptions to this rule are few cases where a lipid envelope forms part of the head, and those other cases where the head presents a filamentous geometry. The way bacteriophages infect the host cell is the basis of a main difference among them: one group (Caudovirales) has a specialised structure (the tail) that is responsible for the recognition of the host cell and the viral genome delivery, whereas those bacteriophages without tail present a variety of infecting strategies. In this study we will deal with the main common characteristics of bacteriophage heads and tails supporting their common evolutionary origin.

Key Concepts:

Bacteriophages share extended structural and functional similarities.

Bacteriophages are excellent examples of optimisation of genetic information to carry out complex functions.

Most bacteriophages enclose their nucleic acid in a protein container (built by multiple copies of one (or a few) proteins), and in a few cases they may include lipid envelopes.

The most conserved geometry in bacteriophage heads is icosahedral.

Double stranded DNA icosahedral bacteriophages follow a common assembly pathway.

The Caudovirales group (bacteriophages with icosahedral heads, dsDNA and a tail) are the most abundant virus type.

The packaging of dsDNA inside Caudovirales requires energy conversion (ATP hydrolysis) into mechanical translocation, and it is carried out by a dedicated viral machinery.

The maturation of icosahedral proheads into viral heads involves drastic reorganisations of the capsid components leading to more stable particles.

The tail of Caudovirales is a sophisticated machinery involved in cell recognition and nucleic acids delivery.

There are three main architectural designs of bacteriophage tails, each one adapting to different host interaction strategies.
Ethical Use of Placebo in Research and Practice
Authors: Zhang Hongliang
Published: April 2013

A placebo means a therapy or medical intervention that is used for its nonspecific psychophysiological effects, but is without actual effects on the condition being treated. The placebo effect denotes effects due to the meaning of an intervention. The placebo effect has the potential to augment the efficacy of all active medical treatments and procedures. The placebo effect and placebo constitute a convergence point for the social, psychological and physiological aspects of illness and health. The use of placebo has long been controversial, and the ethics of placebos have been debated frequently in history. In recent years, accumulating ethical concern has arisen from the common use of placebo in randomised controlled trials, which may render its participants without early and optimal treatment. This review presents an overview of placebo‐associated ethical questions and offers considerations that are of relevance to medical and research practise.

Key Concepts:

A placebo means a therapy or medical intervention that is used for its nonspecific psychophysiological effects, but is without actual effects on the condition being treated.

The placebo effect is genuine psychobiological events attributed to the overall therapeutic context.

Ethics is a branch of philosophy that involves systematising, defending and recommending concepts of right and wrong conduct.

A randomized controlled trial is a study in which people are allocated at random to receive one of several clinical interventions.

Evidence‐based medicine is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients.
Genetically Modified Food: Ethical Issues
Authors: Thompson Paul B
Published: April 2013

The use of recombinant DNA technology to transform agricultural plants and animals has been the subject of ethical controversy for the last quarter century. The argument favouring these technologies hinges on their role in lowering costs of farm production, as well as potential benefits to farmers. Arguments against cite a long litany of problems. Environmental and food safety risk debates touch upon both the nature and likelihood of potential hazards, and also the overall philosophy that should guide the assessment and management of these risks. In addition, critics of the technology have argued that risk assessments have neglected two categories of hazard entirely: impact on animals and socio‐economic impacts, especially on organic and smallholder farms. The latter issue makes the use of genetic engineering into a key episode in a more comprehensive debate over the future of agricultural production. In addition, ethical debates have taken up the extension of intellectual property rights to genes and their impact on the use, production and control of seeds. Labelling and consumer choice has also been debated. Finally, some authors have extended arguments over the possible unnatural character of genetic engineering from their more conventional medical setting to the domain of food.

Key Concepts:

Environmental and food safety hazards associated with genetically modified foods are not unique to the process of transformation that utilises recombinant DNA techniques.

Risk assessment and policy decision making for genetically modified foods has generally excluded socio‐economic impacts and effects on small farmers from consideration.

Concern over unequal distribution of power often lurks just beneath the surface of criticisms that have been levied against genetically engineered foods.
Hsp90 Chaperones
Authors: Zierer Bettina K , Buchner Johannes
Published: April 2013

Heat shock protein 90 (Hsp90) is an abundant molecular chaperone especially important in the cytosol of eukaryotic cells. Its function is coupled to large conformational rearrangements within the dimer coupled to nucleotide binding. Hsp90 assists a large set of so‐called ‘client’ proteins to stay folded or to achieve an active conformation. These client proteins include among others protein kinases and many transcription factors such as steroid hormone receptors. The function of the Hsp90 chaperone machinery itself is highly regulated on several levels. A large set of cochaperones as well as post‐translational modifications help to fine‐tune the conformational cycle. Inhibition of the low intrinsicadenosine triphosphatase(ATPase) activity of Hsp90 leads to destabilisation of its clients resulting in their degradation. As many of the clients are oncogenes, inhibition of Hsp90 is an important target in cancer therapy.

Key Concepts:

Hsp90 is an essential molecular chaperone in eukaryotes.

Hsp90 function is coupled to nucleotide‐induced conformational changes.

Hsp90 stabilises the active state of a large set of clients.

Hsp90 function can be regulated via cochaperones or post‐translational modifications.

Inhibition of Hsp90 is an anticancer strategy.
Sex Assignment in Disorders of Sex Development
Authors: Lucas‐Herald Angela K , Faisal Ahmed S
Published: April 2013

Disorders of sex development (DSD) are relatively rare conditions with diverse pathophysiology, which usually present in the newborn or adolescent periods. These conditions are very heterogeneous and can present in a variety of different ways, most commonly with ambiguous genitalia noticed in the newborn period or delayed puberty in adolescents. The impact of these disorders on the lives of these patients and their families should not be underestimated. These clinical situations can often be difficult to manage, particularly in those cases where the sex of rearing is uncertain. The needs of each individual patient presenting with DSD conditions must be fully considered, along with the needs of their families and where appropriate, cultural practices. The multidisciplinary team should be involved from early in the diagnosis and ethical principles must be considered at all stages of management of the condition.

Key Concepts:

Disorders of sex development usually present in the newborn or adolescent periods.

There are three broad groups of DSD: sex chromosome DSD; 46,XY DSD and 46,XX DSD.

Where there is uncertainty about the sex of a patient, sex assignment should be delayed until appropriate investigations have been carried out.

A multidisciplinary team should be involved from an early stage.

The psychosocial implications of a diagnosis of DSD must be considered for the family and the patient.
Obesity and Appetite Hormones in Humans: an Overview
Authors: Caylak Emrah
Published: April 2013

Obesity is one of the most important public health problems in the world. It is a medical condition with a chronic imbalance between energy intake and energy expenditure. The prevalence of overweight and obesity in adults and children are rapidly rising, and several factors contributing the increased risk of developing obesity are inactivity, overeating, age, give up smoking, ethnicity, secondary obesity and inherited predisposition or genetic defects.

The regulation of appetite involves highly complex peripheral and central systems that are processed in the brain. The appetite hormones (hypothalamic orexigenic neuropeptides) play critical roles in the control of food intake and obesity. Understanding the pharmacology and physiology of appetite regulation and investigation of the role of appetite hormones in the regulation of food intake in humans will allow us to find potential therapeutic targets for the treatment of obesity.

Key Concepts:

Obesity is a medical condition, with excessed body weight in the form of fat, resulted from the failure of energy homoeostasis.

Many factors cause obesity including inactivity, overeating, higher age, drugs, diseases, ethnicity and inherited predisposition to obesity or specific genetic defects.

Obesity is most prevalent in worldwide, WHO predicted that they would rise up to 2.3 billion overweight and 700 million obese in 2015.

Obesity predisposes some chronic diseases as type 2 diabetes, cardiovascular diseases and various cancers or shortens life duration and increases mortality rates.

Neural and humoral signals regulate appetite in brain. The appetite hormones control food intake and energy expenditure, whereas a chronic imbalance in those hormones causes obesity.
Ghrelin Appetite Hormone in Health and Disease
Authors: Caylak Emrah
Published: April 2013

Ghrelin is a 28‐amino‐acid appetite hormone and has numerous physiological roles in appetite modulation, glucose and lipid metabolisms, gastrointestinal, cardiovascular, reproductive, pulmonary and bone systems or immune modulation and cell proliferation. Recent studies implicate ghrelin in the pathogenesis of many diseases, including obesity, Prader–Willi syndrome, cachexia, Anorexia nervosa, cardiovascular diseases, reproductive disorders, diabetes and inflammatory bowel disease. Understanding the pharmacology and physiology of ghrelin agonists and antagonists and investigation of the role of appetite hormones in the regulation of food intake in humans will allow us to find potential therapeutic managements for the treatment of many of those diseases.

Key Concepts:

Ghrelin, a 28 amino‐acid peptide hormone that was discovered as an endogenous ligand for the growth hormone secretagogue‐receptor (GHS‐R), has two circulating forms: acylated and desacyl. The acylated form is essential for ghrelin's biological activity through GHS‐R. It is produced primarily in the stomach, hypothalamus, pituitary, intestine, kidney, heart, lung, gonads and placenta.

Ghrelin is peripheral circulating appetite hormone, acts as a physiological hunger signal. Its secretion and blood levels rise during fasting and fall after eating. It stimulates appetite and increases food intake via secretion of GH. Repeated administration of ghrelin results in decreased energy expenditure; thus, increasing body fat and weight.

Ghrelin have major biological functions in glucose and lipid metabolism and main physiological systems such as gastrointestinal, cardiovascular, reproductive, pulmonary, bone and immune.

Ghrelin appears to be involved in the pathophysiological mechanisms of several human disorders, including obesity, Prader–Willi syndrome, cachexia, Anorexia nervosa, cardiovascular diseases, reproductive disorders, diabetes and inflammatory bowel disease.
Anorexigenic Peptides in Health and Disease
Authors: Caylak Emrah
Published: April 2013

The regulation of satiety and body weight involves highly complex multiple interactions between the gastrointestinal tract, adipose tissue and central nervous system. Several neuropeptides released by hypothalamic neurons including corticotropin‐releasing factor, α‐melanocyte stimulating hormone, corticotropin, brain‐derived neurotrophic factor, cocaine‐ and amphetamine‐regulated transcript, neuropeptides B, neuropeptides W and nesfatin‐1; and gastrointestinal hormones including obestatin, pancreatic polypeptide, amylin, cholecystokinin, peptide YY, oxyntomodulin, glucagon‐like peptide‐1 are reviewed in this article, emphasising both their effects on regulating satiety, and their physiological roles in many systems.

The dysfunctions of anorexigenic peptides in those processes will result metabolic disorders such as obesity and type 2 diabetes. The purpose of this review is also to consider the important roles of anorexigenic peptides including nesfatin‐1, obestatin, amylin and glucagon‐like peptide‐1 in obesity‐related pathophysiological conditions.

Key Concepts:

Satiety is the satisfied feeling of being full after eating. It refers to the inhibition of eating following a meal.

Neuropeptides released by hypothalamic neurons play a major role in the regulation of feeding such as CRF, melanocortins, BDNF, CART, neuropeptides B, neuropeptides W and nesfatin‐1.

Anorexigenic peptides released by gastrointestinal tract play a major role in the inhibition of food intake such as obestatin, pancreatic polypeptide, amylin, CCK, peptide YY, OXM and GLP‐1.

Obesity is the major contributor to cardiovascular disease, metabolic disorders (type 1 or 2 diabetes) and various cancers.

Obesity predisposes humans some chronic diseases as type 2 diabetes, cardiovascular diseases, and cancers or it shortens life duration and increases mortality rates.

Understanding the physiological and pathological roles of anorexigenic peptides in health and disease in humans will allow us to find potential therapeutic targets for the treatment of many disorders.
First Messengers
Authors: Kodis Erin J , Smindak Richard J , Kefauver Jennifer M , Heffner Danielle L , Aschenbach Krista L , Brennan Elliot R , Chan Kelvin , Gamage Kanchana K , Lambeth Philip S , Lawler Jessica R , Sikora Arthur K , Vercruysse Nicholas R , Deppmann Christopher D
Published: April 2013

First messengers are broadly defined as any extracellular factor that elicits a response within a cell. As such, first messengers are incredibly diverse, ranging from environmental factors, such as light or heat, to small molecules and peptides, up through large multivalent proteins. Although there are thousands of first messengers, there are relatively few classes of receptors that can receive these signals and elicit a response within the cell. These receptor classes are ion channels, intracellular receptors, G‐protein coupled receptors and single‐pass transmembrane receptors. Although some individual first messengers are well characterised, this article attempts to create a more cumulative reference of the first messengers most common to vertebrates.

Key Concepts:

All species use a form of cellular communication known as signal transduction to respond to first messengers in their external environment.

The diversity of molecules and stimuli that act as first messengers is vast.

The variety of receptors classes that detect these molecules is surprisingly limited considering the wide variety of ligands utilised.

Organisms use first messengers to receive information from the outside world as well as conduits for communication between cells.
Parental Responsibility for the Health of Children with Chronic Disease: Moral Evaluation in Paediatrics
Authors: Freitag Daniela
Published: April 2013

Chronic disorders in children, particularly in newborns, challenge parents in many ways. For decades newborn screening has been applied in several European countries. It offers the chance to detect inborn chronic disorders, mainly metabolic ones, at an early stage. Medical knowledge about the (chronic) disorder, stringent therapeutic care and medical treatment are interrelated with parental responsibility. First of all, mothers and fathers act as accountable in defining when and how genetic knowledge about the disorder should be passed on in the family. Second, an empirical study on cystic fibrosis has demonstrated that acting as responsible medical caretaker is central to the parents’ identity construction. Additionally, in the case of inherited chronic disorders, parents evaluate responsible decision making in future reproductive choices and take into consideration their offspring's future decision making at reproductive age.

Key Concepts:

Responsibility of information management is one key element in parental coping with early newborn‐screening diagnosis.

For parents with children suffering from inherited chronic disorders, it is important to prove that they act as responsible medical carer(s) not only to themselves but also to others.

Detection of inheritable chronic disorders raises questions of parental responsibility in deciding on future reproductive choices.

Reproductive decisions are also influenced whether there already have been children in the family before a CF child has been diagnosed.

Parents of children with inherited chronic disorders are very clear about the essential medical knowledge that has been helpful for them.

Parents accountable decision making is influenced by the relationship with one's own child, a partner and other family members.
Ethical and Social Issues of the Spanish Model on Organ Donation and Transplantation
Authors: Domínguez‐Gil Beatriz , Escudero Dolores , Matesanz Rafael
Published: April 2013

A recent call to pursuit self‐sufficiency in transplantation based on the World Health Organization (WHO) Guiding Principles is confronted with an extreme disparity in transplantation rates between countries, mainly due to differences in deceased donation activities. Spain occupies a privileged worldwide position, with deceased donation rates maintained at 33–35 donors per million population (pmp) and transplantation rates close to 90 procedures pmp. Respectful with current international ethical standards on organ donation and transplantation, the Spanish Model is described in detail, with an ethical and social analysis of some of its key components: the appointment of intensive care doctors as professionals in direct charge of the realisation of the deceased donation process (donor transplant coordinators) and the way public support and trust in the donation system is gained.

Key Concepts:

Organ shortage remains the main challenge for the full development of transplantation therapies. It is the root cause of unacceptable practices, such as organ trafficking and transplant tourism.

WHO has recently called governments to be accountable in the pursuit for self‐sufficiency in transplantation, by decreasing the burden of diseases treatable through transplantation and increasing organ availability, while respecting current international ethical standards in the field.

The Spanish Model on organ donation and transplantation has become a reference in the response to that call, with deceased donation rates of 33–35 donors pmp, and a privilege position in terms of its transplantation activity.

The Spanish Model consists of a set of organisational measures that facilitate the identification of potential donors and their effective conversion into actual donors, implemented on an appropriate legal, health‐care, political and technical background.

Intensive care physicians play a key role in the deceased donation process. Their appointment as donor transplant coordinators, a key aspect of the Spanish approach, is respectful with the principles of autonomy, beneficence, nonmaleficence and justice.

Public support and trust in the donation system in Spain is not the result of direct promotional campaigns, but of a continuous and active collaboration with the mass media.

Professional training and education is critical for the effective realisation of the deceased donation process in general terms and for consent to organ donation in particular.
Environmental Ethics: An Overview
Authors: Attfield Robin
Published: April 2013

Environmental ethics is the study of normative issues and principles relating to human interactions with the natural environment. It comprises an increasingly significant field of applied ethics, crucial for the guidance of individuals, corporations and governments in shaping the principles affecting their lifestyles, their actions and their policies across the entire range of environmental issues. Debates include theories of normative ethics and of meta‐ethics, and the adequacy of individualist, holist and ecofeminist stances. It is characteristically concerned with the good of future generations and of nonhuman species as well as that of contemporary human beings. Its scope includes the interpretation and application of the precautionary principle and of policies of sustainable development, grounds and policies for biodiversity preservation, and the nature and basis of obligations to assist adaptation to global warming, and to mitigate the anthropogenic greenhouse gas emissions widely recognised to constitute one of its principal sources.

Key Concepts:

Environmental ethics is a field of study, adjacent and comparable to business ethics and bioethics, and not itself a normative stance.

Stances in environmental ethics characteristically take into account future generations and nonhuman creatures as well as contemporary human interests.

Environmental ethics as a branch of philosophy arose in the 1970s through the work of Richard Routley, John Passmore, Arne Naess and Holmes Rolston.

Far from being unavoidable, anthropocentrism avoidably disregards the intrinsic value of nonhuman flourishing and the prevalence of moral concern for nonhuman suffering.

Despite their differences of emphasis, animal ethics and environmental ethics need not conflict, and need to be informed by each other.

Environmental ethicists can adhere to a range of meta‐ethical stances, but objectivism and cognitivism have clear advantages concerning the status of reasons for action.

Ecofeminists such as Val Plumwood and Marti Kheel have well argued against excessive rationalism in environmental ethics and for a greater role for the emotions.

Rival theories of the causes of ecological problems often undermine each other, but solving these problems may require a restructuring of the global economic system.

Policies of sustainable development, as presented in the Brundtland Report of 1987, seek to address these problems through combining development and sustainability.

The precautionary principle suggests that a global agreement is urgently needed to mitigate emissions of greenhouse gases such as carbon dioxide and methane.
Testing Athletes for Risk of Cardiac Disease
Authors: Brosnan Maria J , Prior David L
Published: April 2013

Although regular exercise offers a degree of protection from cardiovascular disease, there is a transient increase in the risk of sudden cardiac death (SCD) during athletic activity for both young competitive athletes (YCAs) and older leisure athletes. SCD in YCAs usually occurs as a result of inherited diseases of the heart's structure. These diseases usually cause no symptoms prior to SCD, so many sporting bodies are now recommending preparticipation screening (PPS) for all YCAs to identify and enforce restriction of sports participation in those most at risk of SCD. There is ongoing debate about the effectiveness and cost‐effectiveness of such a strategy. Premature coronary artery disease (CAD) is responsible for most cases of SCD in athletes over 35 years of age, but is not yet clear whether PPS programs in this population could also prevent SCD by detecting those most at risk.

Key Concepts:

Causes of sports related sudden cardiac death differ depending on the age of the athlete; CAD is most common in those over 35 years of age, and structural, usually genetic cardiac abnormalities more common in those under 35.

In older leisure athletes, the cardiovascular benefits of exercise outweigh the risks of sports related SCD.

Most of the diseases responsible for SCD in YCAs are detectable on ECG.

Athletic training causes alterations to the ECG and echocardiogram, which can lead to diagnostic dilemmas, particularly in black, adolescent or endurance athletes.

Imaging modalities such as cardiac MRI (CMR) can help differentiate physiological cardiac adaptations from pathological changes in athletes.

There is evidence that PPS with an ECG may reduce the incidence of SCD in YCAs.

SCD in older leisure athletes most often occurs as a result of plaque rupture in coronary arteries that were not previously critically narrowed.

Most tests for coronary artery ischaemia depend on the presence of flow limiting coronary lesions, thus are of limited use in the athletic population with silent CAD.

There is a paucity of evidence for the efficacy of PPS in older leisure athletes.
Pentraxins
Authors: Mold Carolyn , Sun Peter D , Du Clos Terry W
Published: April 2013

The pentraxin family of proteins is characterised by sequence and structural homology and calcium‐dependent ligand binding. The human pentraxins are C‐reactive protein (CRP) and serum amyloid P component (SAP), the former of which is a strong acute phase protein. The activities of CRP and SAP are mediated through the classical complement pathway and through activation of Fc receptors (FcRs). Pentraxins are pattern recognition molecules that play important roles in host defence and control of inflammation. Measurement of CRP in blood has been used to monitor inflammation and infection and more recently to predict cardiovascular disease. Recent studies suggest that each of the pentraxins plays a role in the regulation of inflammation and tissue fibrosis. Knockout and transgenic models suggest that these effects are due to interaction with FcRs on macrophages and dendritic cells. Ongoing laboratory studies and clinical trials suggest that pentraxins may have therapeutic benefits.

Key Concepts:

Pentraxins form a family of proteins based on structural homology and calcium‐dependent ligand binding.

Pentraxins are serum proteins that are important in host defence and regulation of the inflammatory response.

The functional activities of CRP and SAP are mediated by complement activation and by interaction with Fc receptors on leucocytes.

Structurally pentraxins are planar pentamers with five calcium‐dependent ligand‐binding sites on one face and a binding site for a single Fc receptor on the opposite face.

CRP and SAP are the two members of the pentraxin family found in most animals.

Human CRP is a strong acute phase reactant made in the liver in response to tissue injury or infection. CRP is often used to monitor inflammation or infection because of its rapid synthesis and clearance.

CRP has anti‐inflammatory activity mediated through Fcγ receptors in a number of mouse autoimmune models and in endotoxin shock.

SAP inhibits fibrocyte differentiation and prevents fibrosis in pulmonary and renal models.

Genetic polymorphisms in noncoding regions of the CRP gene determine baseline levels of CRP and are the risk factors for systemic lupus erythematosus, but not cardiovascular disease.
The Polymeric Immunoglobulin Receptor
Authors: Kaetzel Charlotte S
Published: April 2013

Secretory Immunoglobulin A (SIgA) antibodies represent the first line of antigen‐specific immune defence protecting the mucosal surfaces against environmental pathogens and antigens and maintaining homoeostasis with the commensal microbiota. The polymeric Ig receptor (pIgR) plays the dual role of transporting locally produced dimeric IgA across mucosal epithelia and serving as the precursor of the secretory component moiety of SIgA. The complex regulation of pIgR expression and transcytosis by host and microbial factors is finely tuned to optimise the role of SIgA in mucosal immunity. Recent discoveries highlight the dynamic cross‐talk between pIgR, SIgA and the commensal microbiota that populate our mucosal surfaces. Dysregulation of pIgR expression and/or function can result in profound consequences for the pathogenesis of infectious, inflammatory and neoplastic diseases. Future research into the function and regulation of pIgR and SIgA may offer new insights into the prevention and treatment of diseases that originate at mucosal surfaces.

Key Concepts:

Secretory IgA (SIgA) antibodies represent the first line of antigen‐specific immune defence at mucosal surfaces.

The polymeric immunoglobulin receptor (pIgR) transports dimeric IgA across mucosal epithelial cells and serves as the precursor for the secretory component of SIgA.

Transcription of the
PIGR
gene in mucosal epithelial cells is regulated by signalling pathways initiated by host cytokines and microbial factors, involving the cytoplasmic adapter protein, myeloid differentiation primary response protein 88 (MyD88).

SIgA mediates immune protection by immune exclusion, intracellular neutralisation of antigens and pathogens and excretion of IgA‐containing immune complexes by pIgR‐mediated epithelial transcytosis.

Cross‐talk between pIgR, SIgA and commensal bacteria regulates the composition of the gut microbiota and promotes intestinal homoeostasis.

Dysregulated expression or function of pIgR can contribute to the pathology of infectious, inflammatory and neoplastic diseases.
Scavenger Receptors: Structure, Function and Diversity
Authors: Stephen Sam L , Ponnambalam Sreenivasan
Published: April 2013

Scavenger receptors (SRs) form an increasingly important group of cell surface receptors that bind and internalise a variety of ligands. These membrane‐bound receptors were initially classified within this group on the basis of their ability to bind to modified low‐density lipoprotein (LDL) particles and as of date, at least 17 members of this family, organised into eight families, have been identified in nematodes, arthropods and higher organisms. Members of the SR family play key roles in many pathological conditions including pattern recognition in immune responses, pathogen infection and in the development and progression of atherosclerosis. The uptake of modified lipid particles by SRs in macrophages can lead to the formation of foam cells. Perturbation in the levels of some SRs can enhance or reduce the risk of cardiovascular disease. In this review, we describe the well‐characterised members of this group of proteins and discuss the functional and biological roles of these proteins in animal health and disease.

Key Concepts:

SR family contains membrane bound and soluble proteins.

SRs bind to a variety of ligands including lipoproteins, carbohydrates and proteoglycans.

SRs seem to play an important role in innate immunity against bacteria, with the lack of certain SRs leading to fatal susceptibility to infection.

The malarial parasite and viruses may also exploit SR function to infect cells.

SRs expressed in macrophages and endothelial cells bind to modified LDL particles to initiate atherosclerosis.

The binding of modified LDL to SRs result in signalling cascades inside the cells, which may result in apoptosis.

Knockdown of specific SRs or overexpression can reduce atherosclerosis incidence.

SRs may also be involved in tumour metastasis.
Somatic Mutations in Polycythaemia Vera and Other Philadelphia Chromosome Negative Myeloproliferative Neoplasms
Authors: Gondek Lukasz P , Spivak Jerry L
Published: April 2013

The just another kinase (JAK) family kinases function as the cognate tyrosine kinases for Type I/II cytokine receptors that lack intrinsic kinase domains. Perhaps the most important is JAK2, which is also a chaperone for the erythropoietin and thrombopoietin receptors as well as the kinase utilised alone or with other JAK kinases in the majority of cytokine receptors. JAK2 can be considered an oncogene because it is responsible for promoting cell proliferation and preventing apoptosis and its constitutive activation causes acute and chronic leukaemias and lymphomas. The most common JAK2‐activating mutation, V617F, is responsible for the clinical phenotype of polycythaemia vera and that of approximately 50% of cases of essential thrombocytosis and primary myelofibrosis. In recent studies of JAK2 inhibitors in primary myelofibrosis there was amelioration of clinical symptoms and a reduction in splenomegaly, supporting an important role of JAK2 in the myeloproliferative phenotype and identifying a new treatment for these disorders.

Key Concepts:

The Janus kinase family has a crucial role in hematopoietic and immune cell function.

JAK2 V617F‐activating mutation is the most frequent genetic alteration in polycythaemia vera, essential thrombocytosis and primary meylofibrosis.

JAK2 V617F has oncogenic properties and is responsible for uncontrolled cell proliferation, inhibition of apoptosis, genetic instability via induction of proto‐oncogenes, reactive oxygen species and promotion of mitotic recombination.

JAK2 exon 12 mutations are frequent in JAK2 V617‐negative polycythaemia vera patients.

JAK2 mutation alone cannot entirely explain the disease phenotype in the myeloproliferative disorders and genetic predisposition seems to play an important role in both the acquisition of these mutations and disease pathogenesis.

The role of JAK2 V617F mutation as a marker for disease prognosis is unresolved.

JAK2 inhibitors improve constitutional symptoms and reduce splenomegaly in primary myelofibrosis patients.
Molecular Genetics of Hypophosphatasia
Authors: Mornet Etienne
Published: April 2013

Hypophosphatasia (HPP) is a rare inherited disorder affecting bone and dental mineralisation. The disease is due to loss‐of‐function mutations in theALPLgene that encodes the tissue‐nonspecific alkaline phosphatase (TNSALP). Genetic aspects of HPP, and their molecular bases, are particularly exciting, due to the inheritance that may be recessive or dominant, the extremely variable clinical and allelic heterogeneity, and the puzzling and inconstant prenatal evolution. During the past 15 years, a great effort has been conducted by various groups to evaluate the effect of alkaline phosphatase liver type gene (ALPL) mutations and to decipher genotype–phenotype relationships. A very large part of the clinical heterogeneity is due to the great variety of missense mutations that allow variable enzymatic activity of TNSALP, as shown by site‐directed mutagenesis experiments. A residual part, that remains to be studied, could be due to modifier genes, epigenetic and environmental factors.

Key Concepts:

The high clinical variability observed in HPP for a large part result from the very high allelic variability of theALPLgene.

Missense mutations allow possible residual alkaline phosphatase activity, explaining moderate alleles responsible for mild phenotypes.

Alkaline phosphatase is an allosteric enzyme active in a dimeric form, and the formation of mutant/wild‐type dimers explains the dominant inheritance often observed in moderate hypophosphatasia.

Site‐directed mutagenesis experiments and 3D‐modelling show a good correlation of genotype and phenotype.

However, recent deciphering of bone mineralisation suggests that other genes, and perhaps environmental and/or epigenetic factors, could play a role in modulating the hypophosphatasia phenotype.
Molecular Genetics of Familial Cerebral Cavernous Malformations
Authors: Dru Alexander , Eales Justin , Martirosyan Nikolay L , Mushtaq Raza , Cavalcanti Daniel D , Kalani M Yashar S , Zabramski Joseph M , Spetzler Robert F , Preul Mark C
Published: April 2013

Cerebral cavernous malformations (CCMs) are vascular lesions that afflict the central nervous system. The prevalence of CCMs in the general population is 0.1–0.5%, and the disease may present as a sporadic or familial form. The familial form of the disease shows a strong predilection for the Hispanic–American ethnic group. Current research suggests that the familial form of CCMs arises due to mutations that occur in one or more of three genes:
CCM1
,
CCM2
and
CCM3
, which encode KRIT‐1 protein, malcavernin and programmed cell death 10, respectively. This article examines the known genetic insults to the CCM genes that may cause mutated, nonfunctioning protein products. Each has unique downstream intracellular effects that lead to CCM formation. Recommendations regarding genetic counselling for families with CCMs are presented.

Key Concepts:

Genetic Counselling, gross pathology and molecular genetics of CCM, differences in inheritance patterns between familial and sporadic CCM.

CCMs are mulberry‐like vascular defects characterized by enlarged, leaky capillaries within the central nervous system.

CCMs have a strong predilection for the Hispanic‐American ethnic group and may be present in patients as either a sporadic single lesion or an inherited multi‐lesion form.

The most common symptoms for CCM patients with supratentorial vascular lesions are recurrent headaches and seizures whereas infratentorial lesions result in focal neurological defects and ataxia.

The familial form of CCM disease is caused by mutations in one or more of the three genes:
CCM1
,
CCM2
and
CCM3
whose protein products are relevant to endothelial proliferation regulation, intracellular osmoregulation and endothelial migration, respectively.

K‐Rev interaction trapped 1, the protein product of
CCM1
, is mutated in 56% of the familial CCM patients thus preventing its association with malcavernin and RAP‐1A/ICAP1 α leading to abnormal vascular morphogenesis and dysregulation of sprouting angiogenesis

For the familial variant of CCMs, the strong genetic inheritance patterns suggest physicians should recommend patients for genetic screening for
CCM1
,
CCM2
and
CCM3
mutations, as well as for patients with solitary lesions and a family history of the disease.