bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unravelling the Mystery of Sudden Cardiac Death Through Genetic Approaches
Authors: Koo Seok Hwee , Ku Chee Seng , Chui Paul , Lee Edmund Jon Deoon 
Published: April 2013

AbstractThe sudden unexplained death syndrome is a tragic and distressing event, which may arise due to an underlying fatal cardiac arrhythmia, which may be associated with a defective ion channel. These electrical abnormalities of the heart do not present with gross structural changes, rendering it a challenging task to the forensic pathologist in ascertaining the cause of death during autopsies. The attempts to identify genetic variations in the key ion channels known to cause arrhythmias have only been able to reveal the presence of putative mutations in a small percentage of the cases. It is thus imperative to look beyond the discovery of single‐nucleotide polymorphisms to other forms of genetic variations (such as copy number variations and structural rearrangements), as well as alternative mechanisms that may underlie the molecular pathogenesis of arrhythmias and electrocardiographic abnormalities causing sudden death. Additionally, the various technological platforms for genetic analysis are also described in this article.Key Concepts:Sudden unexplained death syndrome is an important clinical problem.Sudden death may be the result of a fatal cardiac arrhythmia.Arrhythmias are associated with genetic mutations in ion channel genes.Genetic mutations often exhibit incomplete penetrance.Genetic mutations may have functional impact on the ion channel.Single‐nucleotide polymorphisms only account for a fraction of the cases.Copy number variations and chromosomal aberrations may play a role in sudden death pathology.The role of alternative mechanisms such as epigenetics in arrhythmias/sudden death remains to be ascertained.The technology for identifying genetic variations is advancing rapidly.Genome‐wide sequencing is expected to become increasingly feasible.
Genetics of Atrial Fibrillation
Authors: Koo Seok Hwee , Ku Chee Seng , Chen Lin Yee , Lee Edmund Jon Deoon 
Published: April 2013

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia with poor prognosis, reaching epidemic proportions in the ageing population. The condition affects more than five million people worldwide and is a significant clinical problem. Of particular interest is a subset of younger patients (<60 years of age) who develop AF in the absence of known risk factors (such as advancing age, hypertension, structural heart disease and congestive heart failure), a condition classified as lone AF. Genetic variations in ion channel genes only account for a small percentage of the cases. Genome‐wide association studies (GWAS) look beyond the targeted genes and are capable of identifying novel mutations and genes, and biological pathways for AF. This review summarises the candidate gene and GWAS on AF, and discusses the application of exome sequencing approach in revisiting familial AF, as well as the potential clinical applications of the genetic data in the management of AF. A better understanding of the molecular mechanism of AF will aid the cardiologist in strategising the optimal therapeutic regimen for the patient.

Key Concepts:

Atrial fibrillation is an important clinical problem.

Atrial fibrillation is associated with genetic mutations in ion channel genes.

Genetic mutations often exhibit incomplete penetrance.

Genetic mutations may have functional impact on the ion channel.

Single‐nucleotide polymorphisms in ion channel genes only account for a small percentage of the cases.

The technology for identifying genetic variations is advancing rapidly.

Next‐generation sequencing is expected to become increasingly feasible.

The genetic data garnered from candidate gene and genome‐wide association studies have important clinical implications in management and treatment strategies of atrial fibrillation.
Sexual Selection and Female Competition
Authors: Bro‐Jørgensen Jakob 
Published: April 2013

Abstract

Sexual selection studies have traditionally focused on reproductive competition as a typical male characteristic, and regarded females as largely passive. However, empirical evidence now shows female competition to be widespread in nature. Sometimes the same conventional logic can be used to explain competitiveness in males and females: that the sex in surplus in the mating pool has to compete for the other sex as a limited resource. Still, female competition often does not follow this pattern. This is partly related to the fact that whereas the obvious target of male competition is usually access to mates, in females, competition for mating opportunities is often intertwined with competition for breeding resources. Rather than assuming a rigid dichotomous view of sex roles focusing on which sex is more competitive, the topic may be more rewardingly approached by identifying how ecology affects costs and benefits of competitiveness in the two sexes separately.

Key Concepts:

Larger mating skew in males than females often leads to stronger sexual selection on male competitive (and attractive) traits.

A switch from a male‐biased to a female‐biased operational sex ratio may often, but not always, explain reversal of competitive roles.

Female competition is widespread in species with otherwise conventional sex roles.

Female may compete for mates to increase conception probability, to secure the best providers, or to prevent others from reproducing and thereby reduce future resource competition.

Access to resources is more likely to be the ultimate cause of competitive traits in females compared to males.
Clinical Chemistry in Pregnancy
Authors: Taylor Anthony H , Melford Sarah E , Konje Justin C 
Published: April 2013

AbstractDuring pregnancy, a woman undergoes a multitude of normal physiochemical changes that are specific to pregnancy and with increasing frequency, challenged with pregnancy‐related conditions. Additionally, there are a number of problems affecting the unborn fetus that, in turn, affect normal maternal biochemistry, endocrinology and physiology. Furthermore, normal biochemical, hormonal and clinically relevant measurements for the nonpregnant state often no longer apply to the pregnant woman. This makes clinical laboratory measurement difficult and normal clinical diagnosis using nonpregnant values potentially dangerous, with inappropriate treatment (when it is not required) and no treatment (when it is required) being offered. Problems within early pregnancy, for example, spontaneous and recurrent miscarriage, thus become very complicated to predict or treat. Therefore, reexamining what clinical chemical tests are available and what is just emerging from the experimental laboratory (and thus becoming available in the standard clinical laboratory), should inform the unwary clinician.Key Concepts:‘Normal’ pregnancy biochemical marker (Biomarker) concentrations fluctuate throughout pregnancy.No single maternal biomarker can be used to predict gestational disease.Both the concentrations of urinary, serum, plasma, salivary and amniotic fluid biomarkers and the timing of clinical sampling are critical in disease diagnosis.Many new biomarkers are emerging, which may help aid the prediction/diagnosis of pregnancy‐related conditions.
Endocannabinoid System
Authors: Di Marzo Vincenzo 
Published: April 2013

Abstract

The endocannabinoid system (ECS) is defined as the signalling system composed of: (1) the two G‐protein‐coupled receptors known as cannabinoid receptors of type‐1 and ‐2 (CB
1
and CB
2
); (2) the two most studied endogenous agonists of such receptors, the endocannabinoids anandamide (
N
‐arachidonoyl‐ethanolamine) and 2‐AG (2‐arachidonoyl‐glycerol); (3) enzymes and other proteins regulating the tissue levels of endocannabinoids; and (4) enzymes and other proteins that, together with endocannabinoids, regulate the activity of cannabinoid receptors. A key role of the ECS is emerging in the control not only of central and peripheral nervous system functions, but also of most aspects of mammalian physiology, including energy intake, processing and storage, the immune response, reproduction and cell fate. The ECS is also subject to dysregulation, and this seems to contribute to the symptoms and progress of several diseases. Hence, the possibility of developing new therapies starting from our increasing knowledge of the ECS is discussed.

Key Concepts:

Endocannabinoids are local mediators with autocrine or paracrine function.

Endocannabinoids are usually produced

de novo

and ‘on demand’ following elevation of intracellular Ca
2+
concentrations.

Endocannabinoids often act in the central nervous system as ‘retrograde neuromodulators’, that is, they are released from post‐synaptic neurons and act at cannabinoid CB
1
receptors on pre‐synaptic axon terminals.

Endocannabinoids possess immune‐modulatory functions and usually inhibit cytokine release from immune cells and regulate the migration of the latter.

Endocannabinoids are key regulators of food intake, gastrointestinal function, energy storage in the adipose tissue and energy processing by the liver and the skeletal muscle.

Endocannabinoids are deeply involved in pain processing at peripheral, spinal and
supra
‐spinal sites.

Endocannabinoids regulate both male and female reproduction.

Endocannabinoid can differentially affect cell fate in healthy and cancer cells by regulating differentiation, proliferation and apoptosis.

Endocannabinoids, and anandamide in particular, also directly interact with non‐CB
1
, non‐CB
2
receptors, the most studied of which is the transient receptor potential vanilloid type‐1 (TRPV1) channel.

Dysregulation of the ECS underlies several neurological, immune and metabolic disorders, and therapeutic strategies manipulating the ECS are being developed.
Protein Association with Membrane Rafts
Authors: Veit Michael , Thaa Bastian 
Published: April 2013

Abstract

Membrane rafts are very small and highly dynamic assemblies in cellular membranes enriched in cholesterol and sphingolipids. Some proteins can functionally associate with rafts: peripheral membrane proteins are incorporated into rafts depending on cues such as the presence of a glycosyl‐phosphatidylinositol (GPI) anchor or S‐acylation (palmitoylation); transmembrane proteins can partition into raft domains depending on specific features within their transmembrane domain. Raft association of membrane proteins was originally defined by their resistance to cold Triton X‐100 extraction, which is however insufficient as the sole criterion – more sophisticated methodology such as fluorescence resonance energy transfer (FRET) has to be employed to determine whether and how a given protein interacts with raft structures.

Key Concepts:

Membrane rafts are small, dynamic clusters within biological membranes enriched in cholesterol and sphingolipids.

Rafts can be coalesced and stabilised to fulfil a biological function, for example, signal transduction or virus budding.

Some proteins are capable of partitioning into raft domains.

Raft‐targeting features in proteins are glycosyl‐phosphatidylinositol (GPI) anchors, S‐acylation (palmitoylation) and structural motifs in the transmembrane domain.

Assessment of detergent‐resistant membranes (DRM), the original biochemical method to analyse raft association of a protein, is artefact‐prone and therefore not suitable to prove raft involvement in a biological process.

More sophisticated methodology such as fluorescence resonance energy transfer (FRET) is needed to decipher raft association of a protein.
Oxidative Protein Folding
Authors: Gennaris Alexandra , Collet Jean‐François 
Published: April 2013

Abstract

Oxidative protein folding is the process by which a protein recovers both its native structure and its native disulphide bonds. Disulphide bonds are vital for the correct folding of many secreted proteins, such as insulin, albumin, tissue plasminogen activator and antibodies. The formation of a disulphide bond between two cysteine residues is a rate‐limiting step of the folding process. Therefore, living cells contain proteins that catalyse this reaction (DsbA, protein disulphide isomerase (PDI), Mia40). Pathways that form disulphide bonds have now been unraveled in the bacterial periplasm, the endoplasmic reticulum and the mitochondrial intermembrane space. These pathways have in common to form a relay that channels the electrons released upon cysteine oxidation to a final electron acceptor.

Key Concepts:

Disulphide bond formation is required for the correct folding of many secreted proteins.

Disulphide bond formation is a catalysed process
in vivo
.

Pathways of disulphide bond formation are found both in prokaryotes and in eukaryotes.

Pathways of disulphide bond formation form a relay that channels the electrons away from the substrate protein to a final electron acceptor.

Pathways of disulphide bond formation involve a direct disulphide donor and a disulphide generator.

Formation of native disulphides in proteins with multiple cysteine residues involves a disulphide isomerase.

A disulphide formation pathway and a disulphide isomerisation pathway co‐exist in bacteria such as
Escherichia coli
.

Protein disulphide isomerase (PDI) catalyses both disulphide bond formation and disulphide bond isomerisation in the endoplasmic reticulum.
Molecular Genetics of Medulloblastoma
Authors: Nadi Mustafa , Rutka James 
Published: April 2013

Abstract

Medulloblastoma (MB), the most common malignant paediatric brain tumour, arises in the cerebellum. Recent high‐throughput technology that includes ribonucleic acid‐based expression analysis and deoxyribonucleic acid (DNA)‐based copy number analysis, as well as whole‐genome sequencing studies have unravelled the mysteries of this embryonic tumour from clinical, histological and molecular standpoints. Studies of hereditary syndromes associated with MB have led to an increased understanding of the genomics of this tumour. Signalling pathways and growth factors, which are crucial in normal cerebellum development, are also involved in MB formation. The molecular discoveries in the last decade have led to advances in two major areas: (1) The clinical and molecular subgrouping of patients and their stratification; and (2) research being performed to individualise treatments according to the genetics of the patient's tumour. The use of extensive cancer genetic databases will ensure that future discoveries in MB pathogenesis will be made.

Key Concepts:

There is more than one cell of origin for MB.

MBs are genetically and histologically heterogeneous.

MB growth is similar to the normal growth of the cerebellum but it is growth gone awry.

Signalling pathways play significant roles in cerebellar growth. Mutations in these pathways lead to tumour formation.

Growth factor and DNA repair pathway mutations may drive MB formation.

MB in adults is different from that in children.

Metastatic MB has specific genomics that are different from the primary tumour in the same patient.

The new molecular discoveries have important prognostication impact.

The next era is to individualise novel therapies against each patient's MB.
Role of Bioinformatics in Genome‐wide Association Studies
Authors: Gilbert‐Diamond Diane , Asselbergs Folkert W , Williams Scott M , Moore Jason H 
Published: April 2013

AbstractA central goal of human genetics is to identify genetic variants that are associated with disease. Better understanding the role of genetic and environmental factors in disease risk will likely improve diagnosis, prevention and treatment. It is now technically and economically feasible to conduct genome‐wide association studies (GWAS) with over a million single‐nucleotide polymorphisms (SNPs) distributed across the genome. Although GWAS have led to many discoveries, the genetic underpinnings of most common diseases remain largely unexplained. One likely explanation for this “missing hereditability” is that traditional GWAS approaches have focused on one SNP at a time and have failed to account for the complexity of many genotype–phenotype relationships that are characterised by substantial heterogeneity, and gene–gene and gene–environment interactions. Such underlying genetic complexity creates bioinformatics challenges related to modelling, attribute selection and biological interpretation that must be addressed in order to realise the full potential of GWAS. The benefits of meeting these bioinformatics challenges will also extend to whole‐genome and whole‐exome sequence analysis.Key Concepts:Genetic complexity is likely to underlie many common diseases.Bioinformatics tools will be necessary to uncover nonlinear genetic predictors of common diseases.Data mining and machine learning methods can increase power to discover nonlinear genetic predictors of common disease.Filter and wrapper algorithms are necessary to limit the number of attributes examined so modelling strategies are powerful and computationally practical.Prior biological knowledge can improve the analysis and interpretation of GWAS data.Powerful and intuitive software packages are necessary to enable collaboration between biologists, biostatisticians and bioinformaticists.
Genetics of Taste Perception
Authors: Bachmanov Alexander A , Boughter John D 
Published: April 2013

Abstract

There is considerable genetic variation in taste perception within and among species. Some taste perception phenotypes have simple monogenic inheritance, whereas others have complex genetic architecture. Recent advances with genomic resources have made genetics a powerful approach to identify taste‐related genes. Chromosomal mapping and positional cloning studies facilitated discovery of taste receptors. The genetic mapping and candidate gene association studies show that taste perception phenotypes are influenced by allelic variation of genes involved in both peripheral and central taste processing. Sequence variation of taste receptor genes explains some species differences in taste perception and sheds light on evolution of ingestive behaviour. Genetic variation in taste perception impacts human nutrition and health and may be useful as a biomarker of predisposition to some diseases. Identification of genes responsible for within‐ and between‐species variation in taste can provide tools to better control food choice and intake in humans and other animals.

Key Concepts:

Genes contribute to individual variation in perception of each of the five primary taste qualities: bitter, sweet, umami, salty and sour.

Genetic variation in taste perception involves polymorphisms of taste receptors, genes involved in peripheral taste transduction and central taste processing.

Genetic variation in taste perception impacts human nutrition and health and could be used as a biomarker of predisposition to some diseases.
Stress‐induced Mutagenesis in Bacteria
Authors: Foster Patricia L 
Published: April 2013

AbstractBacteria spend their lives experiencing repeated rounds of feast and famine. In addition, they are buffeted by a variety of environmental insults such as fluctuations in temperature, pH, osmotic pressure, as well as exposure to DNA damaging agents and antibiotics. To cope with these changing conditions, bacteria have a variety of stress‐responses that result in profound but temporary cell‐wide changes in gene expression and protein activities. Keyed into these responses are a variety of ways in which the potential for genetic change is enhanced. Research has provided a number of examples of stress‐induced mutagenesis. Such transient mutator states may be important for adaptive evolution.Key Concepts:Bacteria respond to stress by inducing temporary cell‐wide changes in gene expression and protein activities. Some of these changes can increase the cell's potential for genetic change.Adaptive evolution can be accelerated when mutation rates are high, but persistent high mutation rates are also deleterious. Thus, transient increases in mutation rates are potentially of greater evolutionary advantage than permanent increases.Stress‐induced mutagenesis appears to be widespread among bacteria.There are many mechanisms that contribute to stress‐induced mutagenesis.
HTLV‐1
Authors: Bangham Charles RM 
Published: April 2013

AbstractHuman T lymphotropic virus Type 1 (HTLV‐1) was the first human retrovirus discovered. Like the related virus human immunodeficiency virus Type‐1 (HIV‐1), HTLV‐1 persists lifelong in the host. HIV‐1 causes disease in over 99% of untreated infected people, whereas HTLV‐1 causes disease in only 2–8%: either a fatal leukaemia or lymphoma, or a disabling chronic inflammatory disease of the nervous system that causes paralysis of the legs. There is no satisfactory treatment for the malignant or inflammatory diseases, and no vaccine. HTLV‐1 is thought to have existed in the human population for over 50 thousand years; it is widely but unevenly distributed in the tropics and in some subtropical areas. A highly dynamic equilibrium is established in each infected person between persistent HTLV‐1 replication and the host immune response. The increasing understanding of this equilibrium has led to discoveries and conclusions of wide significance for virology, immunology and persistent infections.Key Concepts:Viral load and risk of HTLV‐1‐associated diseases are determined by the efficiency of the host's cell‐mediated immune response.Immunological efficiency is determined by host genetic polymorphisms – chiefly HLA – and by targeting critical weak points in the pathogen's life cycle.An immunodominant antigen is not necessarily the antigen recognised by the protective host immune response.Attributes of T cells such as phenotype, frequency and function do not correlate with their efficiency in protecting against a pathogen in a persistent infection at equilibrium.Viruses that target mobile cells such as leukocytes can use the mobility of the host cell to spread within and between hosts: they do not need to release large numbers of cell‐free virus particles.Some viruses, such as HTLV‐1, can spread from one cell to another by an active, triggered process that involves formation of a specialised cell‐to‐cell contact called a virological synapse.
Polyomavirus Infections of Humans
Authors: Java Anuja , Cheng Xingxing , Brennan Daniel C 
Published: April 2013

Abstract

Research on polyomaviruses began in 1953 when Ludwik Gross isolated a filterable agent that induced tumours in newborn mice. This agent became the archetypal member of the
Polyomaviridae
family. In 1971, JC virus and BK virus were reported and named after the patients’ initials. More than 30 years passed before the Karolinska Institute virus and Washington University virus were identified from respiratory samples in paediatric patients. The Merkel cell polyomavirus was identified in 2008 for its association with the aggressive Merkel cell carcinoma skin cancer. Recently, polyomaviruses 6, 7, 9 and the trichodysplasia spinulosa‐associated polyomavirus have been discovered. Along with simian virus 40, which has been associated with human disease, there are now 10 polyomaviruses relevant to humans. The range of diseases associated with these human polyomaviruses shows that they are significant causes of human infections. The accumulated knowledge gained from the study of each individual virus helps to understand each in their particular niche.

Key Concepts:

Polyomaviruses are DNA viruses.

Polyomaviruses cause significant human infections, especially in the immunocompromised population.

Human infection most likely occurs during childhood.

Haemorrhagic cystitis and polyomavirus‐associated nephropathy are significant clinical entities caused by the BK virus in solid organ transplant recipients.

Progressive multifocal encephalopathy is a fatal demyelinating disease caused by the JC virus.

Merkel cell virus and SV40 are potential oncogenic agents.

Treatment is supportive and an effective antiviral agent has not been identified so far.