bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractFirst 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

Abstract

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

Abstract

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

AbstractEnvironmental 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

Abstract

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

AbstractThe 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

Abstract

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

AbstractScavenger 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

Abstract

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

AbstractHypophosphatasia (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

Abstract

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.