bluuebunny/crossref_metadata_2025_split huggingface dataset:
RNA
Viruses: Control, Mutagenesis and Extinction
Authors: Lázaro Ester 
Published: April 2013

Abstract

Ribonucleic acid (RNA)
viruses form populations with a high degree of genetic diversity, which facilitates adaptation to most changes in the environmental conditions. Therapeutic treatments are a type of change in the selective pressures to which RNA viruses also try to adapt. The selection of drug‐resistant mutants and escape mutants able to evade the immune response of the host are clear examples of the capacity of RNA viruses to maintain their infectivity in the presence of inhibitors. Therefore, it is increasingly evident that to find successful control measures for RNA viruses it is necessary to take into account the adaptive potential of these pathogens. Combination therapies and multiepitopic vaccines are antiviral strategies that have demonstrated their effectiveness. Another promising approach, referred to as lethal mutagenesis, exploits the high error rates of RNA viruses to push them above an error threshold incompatible with viability.

Key Concepts:

RNA viruses cause diseases that can be very difficult to treat.

RNA viruses replicate their genomes with a very high error rate, giving rise to populations that contain a large genetic diversity.

RNA viruses possess a great adaptive capacity that permits them to rapidly generate drug‐resistant mutants, as well as antibody or cytotoxic T lymphocyte escape mutants.

The development of strategies for the control of RNA viruses must take into account their adaptive potential.

One of the most successful strategies to control RNA viruses is the use of combination therapies.

Lethal mutagenesis is a new antiviral therapy, which consists in the artificial increase of the virus error rate above a limit that is incompatible with viability.
Clinical Chemistry in Paediatrics
Authors: Jones Patricia M 
Published: April 2013

Abstract

Clinical chemistry in the arena of paediatrics often involves some special concerns which are not commonly encountered in laboratories that perform testing on primarily adult populations. Being aware of these potential problems and the major differences between the two types of laboratories is important. A laboratory with an adult clientele will occasionally encounter specimens from paediatric patients and being conscious of possible issues allows the laboratory to respond correctly when they arise. The purpose of this article is to discuss basic day to day operational issues facing a chemistry laboratory in a paediatric setting, including several topics related to sample volume concerns and their effect on work flow. The article then describes the most noticeable differences in test menu and testing practices found between paediatric and adult institutions.

Key Concepts:

Paediatric patients have limited blood volume which restricts the sample volumes which are available for testing.

Test results from paediatric patients must be interpreted using age‐ and gender‐related reference intervals.

Testing for Inborn Errors of Metabolism is commonly performed in‐house in paediatric laboratories.

Sweat chloride testing is a common test in a paediatric laboratory and is still used to diagnose Cystic Fibrosis.
Molecular Genetics of Myeloproliferative Disorders
Authors: Finnegan Kathleen 
Published: April 2013

Abstract

The myeloproliferative neoplasms (MPNs) are a group of clonal stem cell disorders characterised by increased proliferation of one or more cell lines. The 2008 World Health Organization classification of the four major MPNs includes chronic myeloid leukaemia, polycythaemia vera, primary myelofibrosis and essential thrombocythemia. In recent years, the research and utilisation of molecular markers have been paving the way for a better understanding of the MPNs for pathophysiology, classification, prognosis and treatment. With the introduction of the BCR/ABL fusion 1 gene and the JAK 2 mutation involving the tyrosine kinase pathways, it is now used in evaluating patients for diagnosis, prognosis and enhancing current practices. More and more molecular markers (MPL, TET2, LNK, CBL, IDH1 and IDH2) are being identified with the hope of having a better understanding for clinical assessment and management of these neoplasms. The importance for patient care is about understanding the role of these molecular mutations in the MPNs and what the future is for prognosis and treatment of patients diagnosed with these disorders.

Key Concepts:

The myeloproliferative neoplasms are clonal stem cell disorders due to unregulated cell production.

The MPNs have increased tyrosine kinase involvement with an increase of cell proliferation and a loss of apoptosis.

The BCR/ABL fusion gene1 plays a critical role in the pathogenesis of chronic myeloid leukaemia.

The BCR/ABL fusion gene is the reciprocal translocation between the chromosomes 9 and 22.

The MPNs that do not present with the BCR/ABL mutation are referred to the BCR/ABL negative neoplasms.

Tyrosine kinase activation involves signal transduction in the proliferative pathways.

JAK kinase is involved in myeloid cell proliferation and differentiation.

JaK2 mutation results in a ‘gain of function’ for the signalling molecule of the tyrosine kinase pathway.

Jak2 is present in most patients with PV, ET and PMF.

MPL, LNK, TET2, CBL, ASX‐L1,IDH1/IDH2, EZH2, DNMT3 and IKZF1 are currently known mutations in BCR/ABL negative MPNs.
Genetic Epidemiology of Smoking Behaviour and Nicotine Dependence
Authors: Korhonen Tellervo , Kaprio Jaakko 
Published: April 2013

AbstractThe public health significance of sustained smoking is overwhelming. The genetic epidemiology and architecture of smoking behaviour and nicotine dependence have been studied for several decades. Twin, family and adoption studies show consistent evidence for genetic effects on many aspects of smoking behaviour and nicotine dependence. Gene–environment interactions have been detected, such as parental monitoring moderating genetic vulnerability for smoking initiation. Molecular genetic analyses have only recently identified few genes consistently associated with amount smoked and nicotine dependence, whereas large genome‐wide association studies have identified only a handful of genes associated with nicotine dependence. The nicotinic receptor alpha 5 gene (CHRNA5) variant associated with nicotine dependence in genetic association studies is functional. Further studies with more sophisticated phenotypes, larger sample sizes and better measures of the environment are needed.Key Concepts:Smoking behaviour and nicotine dependence aggregate in families.Genetic liability underlies this familial aggregation.The heritability of smoking behaviour is moderate, but varies between populations.The genetic architecture of nicotine dependence is poorly known.Large genome‐wide association studies have identified only a handful of genes associated with nicotine dependence.The nicotinic receptor alpha 5 gene variant associated with nicotine dependence in genetic association studies is functional.This functional variant affects nicotine intake in animal models.Gene–environment interactions have been detected for smoking behaviours, such as parental monitoring moderating genetic vulnerability in youth.
Animal Personality
Authors: Réale Denis , Dingemanse Niels J 
Published: April 2013

AbstractPersonality represents individual behavioural differences that are consistent over time and across situations. In humans and many taxa of nonhuman animals, individuals differ in the way they react to novel and challenging situations, and these differences affect resource acquisition, social interactions, survival and reproduction. Researchers in fields like psychology, behaviour genetics or behavioural ecology have developed different methods to study and measure personality differences, each method being characterised by its own advantages and limitations. The results associated with each method provide different colours to the concept of personality. The main goal of students of animal personality is to understand why individuals differ in their behavioural responses to identical stimuli, and why they often show sets of correlated behaviour traits. Several adaptive theoretical hypotheses offer promising explanations for the maintenance of personality differences in wild populations, although empirical confirmation of their predictions is still needed.Key Concepts:Personality represents individual behavioural differences that are consistent over time and across situations.The concept ‘individual consistency’ only makes sense with the population as a referent.Individual differences define the evolutionary potential of a population.Individual differences within a population, differences between populations and potentially between species, are all expressions of genetic/environmental differences at different levels of organisation.Rating, coding and experimental manipulation, are the three approaches to study personality in animals: each approach has advantages and limitations.Individual behavioural differences are key to understanding many ecological processes and patterns.We distinguish five evolutionary mechanisms that can explain the maintenance of personality differences in wild populations: trade‐offs between life history traits; spatial‐temporal heterogeneity; frequency‐dependent selection; antagonistic selection; correlational selection.
Ecological Monitoring
Authors: Yoccoz Nigel Gilles 
Published: April 2013

AbstractEcological monitoring aims at inferring causes of ecosystem changes, by measuring ecosystem state variables in space and time. This is required for management, when different actions are possible and their consequences need to be assessed and compared, and for science, which aims at establishing the causes of observed patterns. The success of an ecological monitoring programme will heavily depend on having well‐articulated questions and objectives, formulated using a simple conceptual model. Future challenges lie in integrating monitoring programmes through questions and models that include both global and local scales, and adding the human dimension in order to achieve social‐ecological monitoring.Key Concepts:Many ecological monitoring programmes have been inefficient and passive.Ecological monitoring should start with simple model(s) and questions.The model(s) and questions should be frequently confronted with data, and changed if necessary.Developments in statistics and other fields are crucial for accurate estimation of state variables.Long‐term ecological research (LTER) sites are examples of successful monitoring, with major results.More work is needed to integrate monitoring programmes in order to achieve local and global objectives.Social and economic aspects, such as ecosystem services, need to be added to monitoring programmes.
Genetics of Congenital Tooth Agenesis
Authors: Vieira Alexandre R 
Published: April 2013

AbstractTooth agenesis is the most common congenital anomaly in humans. It has variable expression and most severe forms segregate in families, which allowed for the application of strategies for gene identification. A subset of those cases is caused by mutations inPAX9,MSX1,AXIN2,EDA,EDAR,EDARADD, andWNT10A. However, the vast majority of cases of tooth agenesis is less severe and may be the result of hypomorphic genetic variations in multiple genes. Of particular interest is the association of tooth agenesis with other conditions such as cleft lip and palate and cancer. Individuals born with oral clefts have a much higher chance to have tooth agenesis outside the cleft area. Cases of tooth agenesis caused by mutations inAXIN2can also develop colorectal cancer. These types of cases suggest the understanding of the aetiology of developmental disruptions of dental development can also impact other relevant fields of medicine.Key Concepts:Oligodontia (agenesis of six or more teeth excluding third molars) is not common in the population (0.3%).Hypodontia (agenesis of less than six teeth excluding third molars) can be as common as 11% in the population.Mutations in genes such asPAX9,MSX1, andAXIN2explain just a small percentage of oligodontia cases segregating in an autosomal dominant fashion.Mutations in genes such asWNT10Aexplain just a small percentage of hypodontia cases segregating in an autosomal dominant fashion.X‐linked inheritance of isolated oligodontia can be caused by mutations in ectodermal dysplasia genes.Tooth agenesis is four times more common in individuals born with oral clefts, as well as in their relatives.Individuals with oligodontia caused by mutations inAXIN2are at higher risk for colorectal cancer.
Molecular Genetics of Congenital Adrenal Hyperplasia
Authors: Parajes Silvia , Krone Nils 
Published: April 2013

Abstract

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders causing an impairment of cortisol biosynthesis. The phenotypic expression of different CAH forms depends on the underlying enzymatic defect. Steroid 21‐hydroxylase (CYP21A2) and 11β‐hydroxylase (CYP11B1) deficiencies only affect adrenal steroidogenesis, whereas 17α‐hydroxylase (CYP17A1) and 3β‐hydroxysteroid dehydrogenase type 2 (HSD3B2) also impair gonadal steroid biosynthesis. P450 oxidoreductase deficiency (PORD) manifests with apparent combined CYP17A1–CYP21A2 deficiency. In contrast to other CAH forms, PORD also causes skeletal malformations and genital ambiguity in both sexes. Three additional enzymatic defects have been traditionally classified as CAH. Steroidogenic acute regulatory protein (StAR) deficiency results in congenital lipoid adrenal hyperplasia (CLAH), and has the unique feature of adrenal and gonadal lipid accumulation. P450 side‐chain cleavage (CYP11A1) deficiency resembles the CLAH phenotype, but patients have normal‐sized or absent adrenals. Aldosterone synthase (CYP11B2) deficiency manifests with isolated aldosterone deficiency and normal cortisol synthesis.

Key Concepts:

Congenital adrenal hyperplasia (CAH) is one of the most common inherited metabolic disorders and comprises a group of autosomal recessive conditions.

Molecular genetic analysis of the
CYP21A2
gene is challenging due to a high rate of conversions and a multitude of possible complex rearrangements.

Common mutations in
CYP21A2
account for the majority of cases including gene deletions, chimeric genes, seven single point mutations, an eight base‐pair deletions and a cluster of point mutations.

CYP21A2
gene duplications have to be considered in carriers of the p.Gln318X mutation to provide the correct molecular genetic diagnosis.

Other forms of CAH are less often caused by common mutations, which are only found in specific populations.

The genotype correlates overall well with the adrenal phenotype in all CAH forms, CLAH, CYP11A1 and CYP11B2 deficiencies.

Although a trend exists, correlation between genotype and genital development is weaker, and it is particularly poor in CYP11A1 or 3β‐hydroxysteroid dehydrogenase type 2 deficiencies.

Mutations in
POR
and
CYP17A1
genes can be associated with clinically isolated 17,20‐lyase deficiency.

CYP11A1 deficiency and CLAH due to StAR deficiency can manifest with a phenotype resembling familial glucocorticoid deficiency.

Molecular genetic diagnosis is essential to provide the correct diagnosis and allow for appropriate clinical and genetic counselling.
Genetic and Epigenetic Heterogeneity in Cancer
Authors: Stevens Joshua B , Abdallah Batoul Y , Horne Steven D , Liu Guo , Bremer Steven W , Heng Henry H 
Published: April 2013

Abstract

Cancer is commonly viewed as a disease of the stepwise accumulation of gene mutations. However, genetic and epigenetic heterogeneity (GEH) is pervasive in cancer, playing a key role in promoting cancer progression. GEH occurs at three primary levels, the genome, gene and epigenetic levels and increases during the aging process and during stress. GEH at the genome level plays the largest role of the three in cancer evolution, as genome level change creates new cellular systems whereas genetic and epigenetic level change mainly modify the existing system. This system replacement achieved by genome level change is essential for cancer evolution. GEH challenges traditional molecular‐based cancer research that focuses on common gene mutations in linear models of progression. Clinically, GEH must be monitored in order to determine the evolutionary potential of a tumour. Increased knowledge about GEH will benefit basic research and cancer treatment.

Key Concepts:

Cancer progression is a typical process of somatic evolution of which system heterogeneity is a key component.

Genetic and epigenetic heterogeneity occurs at three levels: the genome level, the gene level and the epigenetic level. The three levels of genetic and epigenetic heterogeneity are highly interactive. Genome level heterogeneity can influence gene and epigenetic level heterogeneity and vice versa.

Genetic and epigenetic heterogeneity, especially at the genome level is the key driver of somatic evolution.

Genome level change results in macroevolution, which creates new systems, whereas gene and epigenetic level changes result in microevolution which modifies the existing system.

The heterogeneity within cancer can lead to the identification of multiple driver pathways, however, each identified pathway reduces the relative contributions of the others to the cancer phenotype within patient populations. This leads to limitations of clinical predictions that are based on individual genes or pathways.

Monitoring heterogeneity rather than specific pathways will lead to a better understanding of the evolutionary potential of a tumour and will aid in treatment and diagnosis.
Biodiversity and Ecosystem Function of Decomposition
Authors: Swan Christopher M , Kominoski John S 
Published: April 2013

AbstractDecomposition of organic matter derived from plants is an important ecosystem process in many environments, both aquatic and terrestrial. This process underlies soil formation and the liberalisation of energy to higher trophic levels. Since consumers do not influence the renewal rate of detritus, this donor‐controlled resource often serves to stabilise food web dynamics. How species loss influences decomposition rate involves different mechanisms than invoked for plant and consumer communities. In particular, loss of tree species in forests translates into loss of leaf litter species in the detrital pool. As there can exist high interspecific variation in leaf litter chemistry among tree species, how consumers (e.g. bacteria, fungi, invertebrates) respond to resource variability is often the focus of biodiversity–ecosystem function research in these ecosystems. Although competition and facilitation among microbial and invertebrate consumers might generate emergent effects of biodiversity on organic matter processing rates at the consumer level, the strong interactions between consumers and leaf litter species diversity comprise an important link as to how biodiversity in detritus‐based ecosystems influences decomposition.Key Concepts:Decomposition of senesced plant material is an important ecosystem process.Loss of tree species translates in the loss of resource diversity from the detrital pool.Interspecific variation in leaf litter quality drives nonadditive effects of biodiversity on decomposition via responses by microbial and invertebrate consumers.Composition and dominance, more so than species richnessper se, drive the strength of nonadditive effects.
Parasites as Prey
Authors: Goedknegt Anouk , Welsh Jennifer , Thieltges David W 
Published: April 2013

Abstract

Parasites are usually considered to use their hosts as a resource for energy. However, there is increasing awareness that parasites can also become a resource themselves and serve as prey for other organisms. Here we describe various types of predation in which parasites act as prey for other organisms: (1) predation of nonhosts on infected hosts (concomitant predation), (2) predation on free‐living parasite life cycle stages, (3) predation on ectoparasites in form of grooming or cleaning and (4) predation or hyperparasitism by other parasites. In many cases, these types of predation significantly reduce the numbers of parasites and thus affect parasite population dynamics. In contrast, predation on parasites is often beneficial for the hosts as they are released from parasite burden. Finally, when parasites act as prey they may contribute to the nonhost predator's diet, in some cases constituting a significant proportion of energy intake.

Key Concepts:

There is increasing awareness that parasites can become a resource themselves by serving as prey for other organisms.

Predation on parasites can have significant effects on parasite population dynamics, for example, by interfering with the transmission of infective stages.

For hosts, parasite predation may result in a reduced parasite burden, the so‐called dilution effect.

When nonhosts prey on parasites or infected prey, this may have an effect on their energy uptake by mediating the energetic value of their prey.

Future studies on the levels of predation on parasites in food webs will increase our understanding of disease dynamics as well as the topology and functioning of food webs.
Ecology of Deep Oceans: Hadal Trenches
Authors: Jamieson Alan J 
Published: April 2013

AbstractThe majority of the Earth is covered by ocean which itself averages greater than 3500 m deep. It is comprised mainly of the vast deep ocean plains, which span a depth range of 2000–6000 m. The maximum depth of the ocean however is nearly 11 000 m deep. These extremely deep areas are a result of tectonic plate convergence where an oceanic plate is subducted beneath a neighbouring continental plate. This subduction forms extraordinarily deep trenches which comprise what is known as the ‘hadal zone’. The hadal zone (6000–11 000 m) is therefore encompassed by clusters of disjunct and often extremely isolated deep trenches and troughs. The morphology of these habitats had provided a setting where environmental conditions (hydrostatic pressure and food supply) differ greatly from the majority of the deep‐sea and has resulted in high levels of species endemism at the greatest depths.Key Concepts:The deepest biozone in the oceans is the hadal zone (6000–11 000 m deep).The hadal zone is comprised mainly of deep trenches formed by tectonic convergence.The trench environment is characterised by high hydrostatic pressure, low temperatures, the absence of light and a limited food supply.Trench topography provides a unique setting with regard to food supply input because organic matter (food) is accumulated at the deepest trench axis.High levels of species endemism are observed in trenches as a result of their geographical isolation.Physiological adaptation to high pressure and low food supply is an essential prerequisite for survival in the trenches.Most metazoan taxa are represented in these deep trenches.Until recently, the technical challenges of studying the hadal zone were responsible for a dearth of information regarding the ecology at these depths.Research into the ecology of the hadal zone is in its infancy relative to shallower biozones.