bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polymerase Chain Reaction (PCR): Specialised Applications
Authors: Frohman Michael A 
Published: September 2014

AbstractThe polymerase chain reaction (PCR) is a technique that rapidly amplifies selected subsets ofdeoxyribonucleic acid (DNA)orcomplementary DNA (cDNA)from initially complex biological mixtures. The efficiency of amplification or sequence of the amplified material can then be examined for many purposes, including genotyping or the characterisation of new genes, gene expression patterns, mutations or polymorphisms. Quantitative‐PCR (QT‐PCR) has become practical and popular over the past decade with the generation of libraries of individual primer sets and arrayed sets of primers by commercial entities. QT‐PCR machines can assay up to 384 samples at once, permitting the complete analysis of expression of families of genes, such as signalling kinases or cytokines, in a single experiment. Rapid amplification of cDNA ends‐PCR has also become popular to identify microRNAs (ribonucleic acid). PCR is highly useful in structural biology to rapidly modify the boundaries of protein domains intended for crystallisation and in genomics for high‐throughput sequencing.Key Concepts:PCR can be conducted on vanishingly small amounts of material.PCR can be used for rapid genotyping or sequencing.PCR is useful for quantitative analysis of gene expression of entire gene families or signalling networks in arrayed assays.PCR is frequently the method of choice for genetic engineering involving mutations, truncations or extensions of existing genes.PCR is a preferred method for high‐thoughput library screens.
Hot Deserts
Authors: Ezcurra Exequiel , Mellink Eric , Martínez‐Berdeja Alejandra 
Published: September 2014

AbstractHot deserts occur in two global belts north and south of the equator, at latitudes where calm air and a stable atmosphere dominate. Desert rainfall occurs in the form of highly unpredictable pulses followed by long periods of drought, and many plants and animals are finely adapted to these cycles of abundance and scarcity. Water‐storing succulents and short‐lived ephemeral plants are some of the most common life forms in these highly variable and strongly pulsating environments. In spite of their apparent barrenness, the hot deserts of the world harbour unique and rare biotas with impressive biological adaptations. As a result of evolution in isolation from each other, the world's deserts have high levels of endemism and harbour rare and unique life forms, a fact that makes them ecologically fragile and highly vulnerable to biological extinction.Key Concepts:Large deserts occur in the mid‐latitudes of the world, north and south of the equator, where the atmosphere is highly stable and calm air dominates.Smaller rain shadow deserts often develop in the leeward side of mountain ranges, which capture moisture before it reaches the downwind side.Coastal fog deserts, such as Atacama or the Namib, owe their aridity to cold ocean currents, and their moisture oscillates with oceanic ‘El Niño’ cycles.A panoply of morphological and physiological adaptations have evolved in desert environments, which allow plants and animals to survive the harsh desert conditions.Some plants store water in fleshy tissues, others develop extremely long roots to tap water in the deep soil aquifer, while others simply die as the drought sets‐in and survive long periods in the form of seed.Animals may migrate into areas where rain has fallen, and have a complex set of morphological and physiological traits that allows them to regulate their temperature without losing water.The harsh conditions of deserts have promoted the evolution of a complex set of positive relations among desert organisms, such as ‘nurse’ plants, and elaborate pollination and seed dispersal interactions.
Species Problem – A Philosophical Analysis
Authors: Richards Richard A 
Published: September 2014

AbstractThe ‘species problem’ is that there are multiple ways to conceive species that divide up biodiversity in inconsistent ways. Monistic responses to the species problem seek a single universal species concept, no single concept seems adequate though. Pluralistic responses recognise multiple species concepts, based on differences across biodiversity, theoretical interests or the functioning of concepts. But if what counts as a species taxon depends on human interests it isn't clear that species concepts divide biodiversity into real units and ‘cut nature at its joints’ in a straightforward way. The reality of species also seems to depend on their metaphysical status: what basic kinds of things are they? Some argue that species are sets of organisms, based on real essences, clusters of properties or historical relations. Others argue that they are spatiotemporally restricted individuals analogous to organisms.Key Concepts:The species problem is the use of multiple inconsistent species concepts that divide biodiversity in different ways.Monism is the view that correctly understood, there is only one kind of species thing.Natural kinds are groupings that are independent of human conventions and preferences, and are studied by science.Pluralism is the view that there are two or more kinds of species things.Pragmatic pluralism is the view that organisms can be grouped into species on the basis of different research interests.Realism is the view that species taxa are real and independent of human conventions.The species‐as‐individuals thesis is that species are historical individuals with beginnings, endings, change over time and cohesion. Organisms are ‘parts’ of a species.The species‐as‐sets thesis is that species are sets of organisms, where set inclusion is determined by intrinsic or extrinsic properties. Organisms are ‘members’ of a species.
Ethics of Research: Protection of Human Subjects
Authors: Gifford Fred 
Published: September 2014

AbstractMedical research involving human subjects is invaluable for answering both scientific and clinical questions, notably those centred on making medical intervention as effective and safe as possible. But it raises a number of difficult moral issues: such experimentation can impose risk, questions arise about the adequacy of informed consent, and clinical research creates a tension between the roles of clinical therapist and research scientist. Many of these are encapsulated in the various regulations that exist – this article focuses on the guidelines for the United States – so part of what is required to be an ethical researcher is an understanding of these regulations, but it also requires ethical reasoning about such issues as informed consent, confidentiality, randomisation, placebos, vulnerable populations and special issues that arise in research across national boundaries.Key Concepts:A data and safety monitoring board (DSMB) is a committee set up for a given trial, independent from the researchers, which monitors (unblended) data as they accumulate, so as to make judgements about changes in the study including recommending early termination of the study.Informed consent is the fundamental (legal and ethical) requirement that a human subject give his or her voluntary and informed consent before being subject to research.An institutional review board (IRB) is a committee given the responsibility for approving or rejecting research protocols to be carried out within a given institution (such as a hospital or university).Randomized clinical trials (RCTs) are studies where participants are assigned by chance to receive one or another clinical intervention, thus controlling for the effect of other variables.Equipoise is the situation where there is no way to judge the difference between values of the different arms of a clinical trial, and it is often said that this must obtain to ensure the ethical acceptabilty of the trial.
Stored Human Bodily Material: Use in Research in the United Kingdom
Authors: Skene Loane 
Published: September 2014

Abstract

Human bodily material can be removed from a living person and stored and used in research if the person has been informed about the storage and use of the material in research, and consented. If the person is a child (under 18), or not competent to consent, a parent or other lawfully authorised person may consent. Similarly, a lawfully authorised representative may consent for an adult who is not competent to consent. People, or their nominated representatives, may authorise the use of bodies or bodily material after death, for research. Bodily material removed for diagnostic or treatment procedures, or kept for audit or forensic testing, may be used in research without consent if a recognised research ethics committee has approved the research and the material is provided in unidentifiable form.

Key Concepts:

Human bodily material from a living person may be used in research if the person consents to its use in research.

A parent or legally authorised representative may be able to consent if the person is a child and not able to do consent; and a legally authorised representative may be able to consent for an adult who is not competent to consent.

Consent does not need to be in writing but the person should be provided with written or verbal information about the proposed research before consenting.

A person or the person's nominated representative may consent to the use of the person's body or bodily material in research after the person's death.

If the bodily material was initially removed for a purpose other than research, such as a diagnostic test, treatment, an audit or a forensic test, it can be used in research if consent can be obtained later; or in limited circumstances without consent, if it is unidentifiable; a recognised research ethics committee (REC) has approved the project; and, in England, Wales and Northern Ireland, but not Scotland, a licence has been obtained from the Human Tissue Authority.

People do not legally ‘own’ bodily material removed from their body. They have no legal right to have the material returned to them; used only in a particular way or destroyed. However, under ethical guidelines, bodily material should not be used in research if people are known to object.
Philosophy of Biological Classification
Authors: Richards Richard A 
Published: September 2014

AbstractBiological classification is natural in that all cultures classify life, and humans acquire classifications as they learn the general terms in a language. This tendency is reflected in the Linnaean hierarchy that has dominated biological classification for the last several centuries. Even as this hierarchy has become entrenched though, there are enduring disputes about biological classification. First is metaphysical, the nature of biological categories. Are they natural kinds, historical kinds or historical individuals? Second are the theoretical bases and operational procedures. What should a biological classification represent, and how should it be constructed? Third are the nature and value of tree thinking, and the implications that has for the formal classificatory framework. If a classification is to represent the evolutionary tree in all its complexity, it is not clear that the Linnaean hierarchy and its nomenclature will be adequate.Key Concepts:The theoretical basis of a classification is what it represents.The formal structure of a classification involves the organisation of the categories.The operational procedures of a classification are the rules for generating the classification.An evolutionary tree is a branching diagram that represents at minimum the branching order of evolution.Nomenclature is the naming system for the categories in a classification.
Evolutionary History of the Proviruses
HERV
‐K 113 and
HERV
‐K 115
Authors: Garrison Keith E , Nixon Douglas F , Pillai Satish K , Jha Aashish R 
Published: September 2014

Abstract

Human endogenous retroviruses are found throughout the genome, and most insertions predate human divergence from other primates. A small number are unique to humans and unfixed in the human genome. Much scientific interest has centered on the human endogenous retroviruses (HERV)‐K113 and HERV‐K115 insertions. The evolutionary history of these two endogenous proviruses is complex, and the estimates of both of their insertion times have recently been revised. HERV‐K113 inserted into the genome sometime between 0.8 and 1.3 million years ago (Ma), while HERV‐K115 was inserted into the genome sometime between 1.1 and 1.9 Ma. Both insertions occurred during a time when

Homo erectus

is believed to have been the dominant hominin species.

Key Concepts:

HERV‐K113 and HERV‐K115 are members of the HML‐2 group of endogenous retroviruses and neither insertion is fixed in the modern human genome.

Despite their unfixed state, HERV‐K113 and HERV‐K115 are not recent insertions into the human genome.

HERV‐K113 inserted into the genome sometime between 0.8 and 1.3 Ma.

HERV‐K115 inserted into the genome sometime between 1.1 and 1.9 Ma.

Despite a possibly wide separation in their insertion times, HERV‐K113 and HERV‐K115 are highly similar in sequence.

Both insertions occurred during a time when
Homo erectus
is believed to have been the dominant hominin species.
Molecular Genetics of 21‐Hydroxylase Deficiency
Authors: Parajes Silvia , Krone Nils 
Published: September 2014

Abstract

Steroid 21‐hydroxylase deficiency (21OHD) accounts for approximately 95% of cases of congenital adrenal hyperplasia, one of the most common inherited metabolic disorders. It can be clinically classified into classic and nonclassic 21OHD. Classic 21OHD is associated with glucocorticoid deficiency and, in 46,XX patients, with disorder of sex development. Mineralocorticoid synthesis may also be significantly impaired in two‐thirds of patients, leading to life‐threatening salt‐wasting (SW) crises. Nonclassic 21OHD is milder and presents mainly with hyperandrogenism. 21OHD is caused by mutations in the
CYP21A2
gene. The vast majority of
CYP21A2
mutations are a result of unequal crossing overs and gene conversions with its highly homologous pseudogene,
CYP21A1P
. Molecular genetic analysis is challenging and requires the combination of different methods to detect gene deletions, chimeric genes, gene duplications and point mutations. An overall good genotype–phenotype correlation exists for the SW phenotype. Therefore, molecular diagnosis of 21OHD complements clinical diagnosis and allows for clinical and genetic counselling.

Key Concepts:

Steroid 21‐hydroxylase deficiency (21OHD) is an autosomal recessive disorder caused by mutations in the
CYP21A2
gene and represents the most common form of congenital adrenal hyperplasia.

A good genotype–phenotype correlation exists for the mineralocorticoid deficiency phenotype.

Although a trend exists, the severity of 46,XX disorder of sex development as well as of other hyperandrogenic signs and symptoms correlates less strongly with the
CYP21A2
genotype.

Common pseudogene‐derived mutations account for the majority of 21OHD disease‐causing alleles; these include gene deletions, chimeric genes, seven single point mutations, an 8 base‐pair deletion and a cluster of three point mutations.

Molecular genetic analysis of the
CYP21A2
gene is challenging due to the high‐sequence homology with its pseudogene (
CYP21A1P
), the high rate of large rearrangements with different break points, and the presence of complex alleles carrying various mutations.

Some less common mutations are highly prevalent in specific populations due to founder effects. These should be considered in the genetic diagnosis of 21OHD when only screening for otherwise common
CYP21A2
mutations.

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

Molecular genetic diagnosis is essential to provide the correct diagnosis and allows for appropriate clinical and genetic counselling.
Cannabinoids and the Brain
Authors: Alexander Stephen PH 
Published: September 2014

Abstract

The cannabinoid system in the brain is targetted in the use and abuse of preparations from the
Cannabis
plant. This system is composed of synthetic enzymes for the endogenous lipid‐derived ligands, the cannabinoid receptors they activate and the enzymes which transform them. These endocannabinoids are amides, such as anandamide, or esters, such as 2‐arachidonoylglycerol, whose primary target in the central nervous system is the CB
1
cannabinoid receptor, a G protein‐coupled receptor expressed to unusually high levels. Δ
9
‐Tetrahydrocannabinol (THC) appears to be the sole psychoactive entity present in
Cannabis
plant, which elicits the characteristic responses in man and animals. The pharmacology and biochemistry of the endocannabinoid system has been thoroughly investigated since the identification of CB
1
cannabinoid receptors. As yet, however, the translation of this knowledge into a clinical setting has been of limited success.

Key Concepts:

Δ
9
‐Tetrahydrocannabinol appears to be the major psychoactive agent present in the
Cannabis
plant.

Δ
9
‐Tetrahydrocannabinol acts as a partial agonist at the CB
1
cannabinoid receptor.

CB
1
cannabinoid receptors appear to be the most densely expressed G protein‐coupled receptors in the brain.

CB
1
cannabinoid receptors couple functionally to an inhibition of transmitter release.

CB
2
cannabinoid receptors are primarily associated with the immune system, but may also be found in the CNS.

Endogenous cannabinoids, termed endocannabinoids, are fatty acid derivatives.

Endocannabinoids are not stored in vesicles, but rather are made on demand.

Endocannabinoid production is involved in two neurophysiological phenomena, termed depolarisation‐evoked suppression of excitation (DSE) and depolarisation‐evoked suppression of inhibition (DSI).

Endocannabinoids may also act at particular ligand‐gated ion channels (notably the TRPV1 vanilloid receptor) and nuclear hormone receptors (notably peroxisome proliferator‐activated receptors).
Genetics of Preterm Birth
Authors: Lengyel Candice , Muglia Louis J , Pavličev Mihaela 
Published: September 2014

Abstract

The control of normal birth timing in mammals and the fundamental signals that initiate preterm birth in humans are critical areas of scientific investigation. Preterm birth is the leading cause of infant mortality throughout the world, and the single greatest challenge in women's and children's health today. Despite the recognised importance of this area of investigation, relatively limited advances have been made. In part, this limited success in revealing mechanisms results from divergence in the endocrine physiology of pregnancy between species. To have an effect on these biological and medical gaps in knowledge, new genetic studies in humans and comparative genomic investigations across species have been undertaken. In this article, the authors summarise the current status of genetic and genomic approaches to elucidate the control of birth timing.

Key Concepts:

Genetic factors, primarily in the maternal genome, contribute to preterm birth risk.

The physiology of human pregnancy differs from other species except for other higher primates.

Humans have unique constraints for birth timing related to foetal size and/or metabolism.

Candidate gene association studies have not been generally informative.

New data emerging from non‐biased genome‐wide approaches have suggested new pathways for birth timing and preterm birth risk.
Molecular Genetics of Human Congenital Limb Malformations
Authors: Pickering Joseph , Towers Matthew 
Published: September 2014

Abstract

Congenital limb malformations are observed in approximately 1 in 500 people making them one of the most frequent birth defects. Increasing numbers of genes are being identified that when functionally perturbed result in human limb abnormalities. The functions of many of these genes have been investigated in the two main models of limb development – the chick and the mouse. Limb defects are often part of complex syndromes that affect other structures in the body. This reflects the multiple roles that many genes play during embryonic development. Recently, an emerging theme is that the disruption of
cis
‐regulatory enhancers controlling expression of important developmental genes can lead to limb‐specific birth defects. Future research focusing on how the human limb develops will increase our understanding of the molecular and genetic basis of congenital defects.

Key Concepts:

Chick and mouse embryology has contributed to our knowledge of limb development and the basis of human limb defects.

Many key patterning genes found in mouse and chick research cause human limb defects when mutated.

Limb defects are often part of complex syndromes.

Defects which affect only the limb are often caused by disruption of
cis
‐regulatory enhancers.

Future work on how the human limb develops will further our understanding of congenital defects.
Genetics of Neonatal Autoimmune and Autoinflammatory Diseases
Authors: Bachove Inessa , Chang Christopher 
Published: September 2014

Abstract

Genetic predisposition has been widely studied in autoimmune and autoinflammatory diseases and has been found to play a significant role in pathogenesis, although the environment, including dietary habits, chemicals and hygienic conditions have been postulated to influence expression of these diseases as well. The autoimmune diseases most prevalent in the newborn include neonatal lupus and neonatal antiphospholipid antibody syndrome. The diseases are characterised by maternal antibodies to SS‐A (Ro) and SS‐B (La). The genetics underlying these diseases have been found to involve both HLA and non‐HLA associations. The neonatal autoinflammatory diseases include the cryopyrin‐associated periodic syndromes (CAPS), of which familial cold autoinflammatory syndrome (FCAS), Muckle–Wells syndrome (MWS) and neonatal onset multisystem inflammatory diseases (NOMID) are the three distinct phenotypes resulting from mutations in the
CIAS
1 gene (
NLRP3
gene). The gene mutation in CAPS are gain‐of‐function mutation of the NLRP3 gene coding for cryopyrin, resulting in dysfunctional inflammasomes. A defect in the inflammasome leads to overproduction of interleukin‐1, resulting in inflammatory symptoms seen in CAPS. Understanding the genetics responsible for neonatal lupus, neonatal antiphospholipid antibody syndrome and CAPS may drive future research into an elucidation of complex pathophysiologic mechanisms of these diseases and perhaps ultimately lead to better treatment modalities.

Key Concepts:

Diseases that involve immune dysfunction in the neonate include neonatal autoimmune and autoinflammatory conditions, along with the more well‐defined immunodeficiency syndromes.

The genetics of neonatal autoimmunity and neonatal autoinflammatory syndromes are very different.

In addition to a genetic component, the pathogenesis of these two groups of diseases may also involve an epigenetic and environmental component.

The presence of a common genetic defect may result in different clinical phenotypes, as illustrated by the three CAPS syndromes.

Treatment of these diseases is dependent on an increased knowledge of the pathogenesis of these diseases.

Genetic counselling is an important component of the management of these diseases.
Sequencing Strategies and Tactics inDNAandRNAAnalysis
Authors: Azhikina Tatyana L. 
Published: September 2014

The primary structure of nucleic acids is a key not only to physical and chemical properties of the molecules but also to the biological (genetic) information therein, including structures of genes and proteins, the ways of gene regulation and cell response to different signals. Sequencing procedures are aimed at the determination of sequences of monomer units constituting linear biopolymer molecules, DNA or RNA residues in case of nucleic acids.This article reviews existing sequencing strategies: different approaches of random or systematic sequencing applicable to long and unique DNA fragments, including entire genomes; massive sequencing of relatively short fragments such as RNAs and complementary DNAs (cDNAs); and comparative sequencing of related DNA fragments originating from various individuals or different species.