bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex: Advantage
Authors: Neiman Maurine , Jokela Jukka 
Published: September 2010

Abstract

One of the most important unanswered questions in evolutionary biology is why sexual reproduction is so common. In theory, sex is so costly that individuals that reproduce sexually should be at a major disadvantage relative to asexually reproducing competitors. This leads to the expectation that sex should lose in competition with asexual reproduction and thus be rare in nature, which is in striking contrast to its widespread occurrence. It is this profound disconnect between theory and reality that has motivated decades of research into potential advantages of sexual reproduction. While much progress has come from these efforts, why sex predominates is still unclear. It is likely that part of the answer is linked to an advantage of sex under pressure from coevolving parasites. Other important processes may be more efficient clearance of deleterious mutations and other costs associated with asexuality that are not direct consequences of the lack of recombination.

Key Concepts:

The fundamental difference between sexual and asexual reproduction is that sex produces offspring that have both unique combinations of alleles and different combinations of alleles than their parents and their siblings.

In theory, sex should be rare because it breaks up allele combinations that have proven to work well together and because sexual females waste resources on son production.

The predominance of sex in nature indicates that production of genetically distinct offspring must also generate profound benefits.

Comparing the geographic distribution of sexual and asexual populations can provide insights into the advantages and disadvantages of sex.

The most direct and powerful way to study sex is to compare coexisting sexual and asexual females that are phylogenetically close relatives and ecologically very similar with the exception of their reproductive mode.

Likely direct benefits of sex include evasion of biological enemies and clearance of harmful mutations.

The transition to asexuality may lower the fitness of asexual phenotypes and thus the cost of sex, in which case the maintenance of sex is easier to explain.
Species Concepts
Authors: Ghiselin Michael T 
Published: September 2010

Abstract

A species concept is roughly equivalent to a species definition. Considered in the abstract, the species is a class, or kind, of which particular species are concrete instances. So a species definition is a definition of species in general and not of a particular species. The biological species concept treats species as sexual populations, which are reproductively isolated from one another. The recognition species concept is a variant of the biological species concept that emphasises mate recognition of conspecifics. The evolutionary species concept stresses the point that species are historical lineages as well as populations. The various cladistic species concepts treat parts of biological species as species. Phenetic and morphological species concepts treat species not as populations or lineages but as classes or kinds of organisms that are similar to one another. Preference for one or the other concept often reflects differences among scientists as to what they consider important.

Key Concepts:

Species are fundamental units in evolution, classification and biodiversity.

Species are the products of the process of speciation.

Species concepts and definitions tell us what is meant by the term ‘species’ in the abstract.

The species, in the abstract, forms a level in the Linnaean hierarchy used in formal classification (taxonomy). Like the genus and the family, it is a taxonomic category.

The groups that are called species are instances of the species category. They are taxa.

Populations and lineages are wholes composed of organisms, not kinds of organisms.

Species concepts may be difficult to apply to particular cases, in part because species speciate and get transformed.
Vestibular System Disorders
Authors: Fetter Michael 
Published: September 2010

AbstractThe vestibular system provides vital sensory information for the control of balance and posture. Vestibular end organs on each side sense linear and angular acceleration in three‐dimensional space: the saccule and the utricle (linear motion), and the anterior, posterior and lateral semicircular canals (angular motion) and transduce this information to electrochemical signals. The central nervous system integrates this information from the vestibular system with visual and proprioceptive information to a best possible estimate of the actual movement of the head and body to stabilise gaze during head motion by means of the vestibulo‐ocular reflex (VOR) and to control balance by modulation of muscle tone through the vestibulocollic and vestibulospinal reflexes. Disorders of the vestibular system, either peripheral or central, often give rise to the sensory illusion of rotation, vertigo, disequilibrium or imbalance, common symptoms in clinical practice.Key Concepts:The role of the vestibular sensory organs is to transduce the forces associated with head acceleration and gravity into a biological signal.The control centres in the brain use this signal to develop a subjective awareness of head position and head movement in relation to the environment and to produce motor reflexes for equilibrium.The two main motor reflexes are the vestibule‐spinal reflex (responsible for the stability of the body) and the vestibule‐ocular reflex (responsible for stabilising gaze in space).Pathological dysfunction in the sensory organs or in the central pathways of the motor reflexes lead to the sensation of vertigo.History together with a careful clinical neuro‐otological examination are the keys for most vestibular disorders and much more important than recordings of eye movements or brain imaging techniques.Benign positional vertigo is the single most common cause of vertigo that can easily be diagnosed clinically and effectively treated by specific deliberation manoeuvres.Vestibular migraine, a since recently much underestimated disorder, should be suspected when frequent attacks of fully reversible vertigo occur with or without headaches and can be treated successfully with classical migraine medication both for the acute attack as well as prophylactic treatment.
Acid–Base Balance Disorders
Authors: Hawfield Amret T , DuBose Thomas D 
Published: September 2010

Abstract

Abnormalities in maintaining the pH of the blood in a range that is incompatible with sustaining metabolic processes are known as acid–base balance disorders. Here, we define normal acid–base balance and describe the four basic acid–base balance disorders including metabolic acidosis, metabolic alkalosis, respiratory acidosis and respiratory alkalosis that occur. We suggest a diagnostic approach in defining the disorders and a differential diagnosis to their causes. Routine management of these disorders is also discussed.

Key Concepts:

Normal Physiologic function depends on the maintenance of a systemic arterial pH between 7.35 and 7.45.

The coordination of renal and respiratory regulatory mechanisms is responsible for maintaining physiologic pH.

The use of simple equations can differentiate between different acid–base disorders.

The causes of metabolic acidosis can be divided among those that lead to a high anion gap and those that present with a normal anion gap.

An approach to differentiating the causes of metabolic alkalosis is based on assessing volume status.

Respiratory acidosis develops in the setting of hypoventilation.

Respiratory alkalosis occurs when carbon dioxide output in the lungs exceeds its metabolic production in the tissues.

The ultimate treatment of acid–base disorders is focused on identifying and managing their underlying cause.
History of Oral Contraceptives
Authors: Djerassi Carl 
Published: September 2010

AbstractProgesterone is the naturally occurring female sex hormone acting as nature's contraceptive by preventing women from conceiving during pregnancy. Since it is not orally active, progesterone cannot practically be used as an oral contraceptive. It required the efforts of organic chemists to synthesise steroids that mimic the biological activity of the natural hormone and that are effective by oral administration. The article concludes with the prognosis that the future prospects for developing fundamentally new contraceptives are dim, primarily because the priorities of the international pharmaceutical industry have shifted to diseases of the increasingly geriatric segments of the population of affluent countries.Key Concepts:The natural female sex hormone progesterone – nature's contraceptive – is not orally active.New synthetic steroids had to be developed, which retained the biological activity of progesterone, but would be orally active.The lead compound, norethindrone, was synthesised in 1951 and all but one of the subsequent steroid oral contraceptives are based on that chemical template.Research in new approaches to contraception has declined dramatically as the pharmaceutical industry has shifted its attention to diseases of the geriatric segment of the population.The prediction is made that the ultimate direction of birth control in the affluent, geriatric countries will consist of cryopreservation of ‘young’ gametes (particularly relevant for females), followed by sterilisation, and recourse to IVF for reproduction, thus completing the divorce of sex from reproduction.
Splicing of
Pre
‐
m
RNA
Authors: Lu Yu‐Shiou , Tarn Woan‐Yuh 
Published: September 2010

Abstract

Eukaryotic messenger
ribonucleic acids
(mRNAs) are initially transcribed as intron‐containing precursor mRNAs (pre‐mRNAs). Removal of introns from each pre‐mRNA by splicing occurs concurrently with ligation of the two flanking exons to generate a mature mRNA. Pre‐mRNA splicing is catalysed by the spliceosome, a large ribonucleoprotein complex containing five small nuclear RNAs and numerous protein factors. In higher eukaryotes, alternative splicing provides a mechanism to generate multiple mRNA isoforms from a single gene. Alternative splicing not only increases proteome diversity but also regulates the level of gene expression posttranscriptionally. Moreover, alternative splicing has a substantial impact on regulation of many physiological processes such as cell differentiation and development. Defects in pre‐mRNA splicing underlie a considerable number of genetic diseases and cancers.

Key Concepts:

In most eukaryotic pre‐mRNAs, the coding sequences (exons) are interrupted by stretches of noncoding sequences (introns).

The spliceosome uses a two‐step transesterification reaction to remove introns and join exons of pre‐mRNAs.

The snRNAs and spliceosomal protein Prp8 are implicated in the key catalytic steps of splicing.

Alternative splicing extends proteome diversity and regulates gene expression levels.

Alternative splicing is determined by interplays between
trans
‐acting factors and
cis
‐elements of pre‐mRNAs.

Alteration of
cis
‐elements and aberrant control of
trans
‐acting factors lead to diseases.
Brain: Neurodevelopmental Genetics
Authors: Baker Kate D , Skuse David H 
Published: September 2010

Abstract

Genes expressed during development regulate the emergent structure and function of the growing brain. Genetic mechanisms interact with environmental influences to predispose individuals to structural and functional brain disorders. The embryological sequence of nervous system development is relatively well understood. Longitudinal neuroimaging studies have highlighted that prolonged postnatal brain change is associated with acquisition of higher level cognitive skills such as language, memory and executive function. However, understanding of developmental neurobiology has not yet been extensively integrated with systems neuroscience, to identify key molecular and cellular mechanisms relevant to human cognition. Furthermore, little is known about genetic variants that constrain embryological and later brain development to influence neurological and cognitive outcomes in developmental disabilities and psychiatric disorders. Following the completion of the Human Genome Project, new technologies have enabled an extraordinary expansion in knowledge of genetic sequence variation, gene expression and epigenetics. Establishing convergence between developmental biology, systems neuroscience and genomics to understand the neurobiological bases for neurodevelopmental disorders remains an exciting challenge for the next decades.

Key Concepts:

Brain development involves differentiation of highly specialised cell types, in predictable temporal sequences, and their organisation into precise spatial systems.

Genetic variation interacts with environmental influences to predispose individuals to structural and functional brain disorders, by influencing developmental mechanisms.

Major events in early nervous system development include induction of the neural plate, neurogenesis, differentiation of neuronal and glial cell types, and migration of cells into their correct position.

Postnatal brain development, including maturation of white matter tracts and synaptic pruning in response to stimulation and behaviour, is also important, but the neurobiology is much less well understood.

Both early and later developmental processes may be disrupted by genetic mutations or influenced by sequence variation, but links from gene to brain to cognitive functions are complex and require investigation by convergent methods.

New methods of investigating genomic organisation and the structure and function of the living human brain are increasingly being integrated to elucidate molecular and cellular mechanisms of relevance to neurodevelopmental disorders.
Twin Methodology
Authors: Snieder Harold , Wang Xiaoling , MacGregor Alex J 
Published: September 2010

Abstract

The classic twin study is established as the ideal study design with which to investigate the relative importance of genetic and environmental factors to traits and diseases in human populations. Twin methodology is concerned with analysis techniques that have been developed to estimate and quantify the relative contribution of genes and environment to the disease or trait of interest. The current chapter gives an overview of the most important approaches. Both concordance measures and variance components approaches are discussed. The latter include analysis of variance (ANOVA), the DeFries–Fulker regression method and structural equation modelling (or path analysis). Structural equation models for twin data have recently been extended to incorporate and evaluate gene–environment interaction. Twin studies continue to play an important role in the postgenomic era, especially in the study of complex traits and diseases.

Key Concepts:

Most phenotypes show large individual differences (i.e. variance), the source of which may be genetic or environmental.

The classic twin study is the ideal study design to investigate the relative importance of genetic and environmental factors to traits and diseases in human populations.

Concordance measures express the similarity of twins for dichotomous traits such as the presence or absence of a disease.

Heritability is defined as the proportion of phenotypic variation that can be attributed to genetic variation.

Structural equation modelling is a standard tool in twin research and involves solving a series of simultaneous linear structural equations to estimate genetic and environmental parameters that best fit the observed twin variances and covariances.

Structural equation models for twin data have recently been extended to incorporate and evaluate gene–environment interaction.

Twin studies have often provided the first crucial proof of the importance of genes in the aetiology of a disease or trait, justifying further search for the underlying genes.
Sickle Cell Disease as a Multifactorial Condition
Authors: Verhovsek Madeleine M , Steinberg Martin H 
Published: September 2010

Abstract

The phenotype of sickle cell anaemia is heterogeneous. Although all patients have the identical sickle cell mutation, the type, severity and frequency of complications is variable. The products of epistatic modifying genes and the sickle haemoglobin gene, along with environmental influences, interact to determine the disease phenotype. Haemoglobin F concentration and distribution among erythrocytes is likely the most important genetic modulator of sickle cell disease severity. Several genetic loci are associated with haemoglobin F expression, including

BCL11A

in chromosome 2p, the

HBS1L

‐

MYB

locus on 6q23, the C‐T polymorphism 5′ to

HBG2

on chromosome 11p, and the olfactory receptor genes,

OR51B6

and

OR51B5

, also on 11p. α‐Thalassaemia is another modulator of sickle cell disease. There is evidence that genes associated with endothelial activation, inflammation, red blood cell hydration and hemostasis might all play a role in phenotypic diversity.

Key Concepts:

Sickle cell anaemia is a single‐gene disorder with heterogeneous clinical features.

The phenotype of sickle cell anaemia is affected by epistatic modifier genes.

Haemoglobin F is the best‐known genetic modifier of sickle cell anaemia.

Polymorphisms in three established quantitative trait loci modulate haemoglobin F.

Co‐inheritance of α‐thalassaemia is associated with reduced rates of haemolysis and vasculopathic complications, but increased incidence of viscosity‐vaso‐occlusive manifestations.

Candidate gene and genome‐wide association studies have identified genes that potentially affect sickle cell disease phenotype by modifying disease pathogenesis.
22q11 Deletion Syndrome: A Role for Tbx1 in Pharynx and Cardiovascular Development
Authors: Calmont Amelie , Scambler Peter 
Published: September 2010

Abstract

DiGeorge and velocardiofacial syndromes result from a chromosomal deletion involving proximal chromosome 22 and affected individuals commonly present with congenital heart defects, feeding problems, speech delay and learning problems. Psychiatric illness may present later in life. Mutation analysis and creation of mouse models which mimic the human disorder have identified that the

Tbx1

(T‐box 1) transcription factor is the major dosage‐sensitive gene in the deletion region and have allowed exploration of the underlying developmental pathways and signalling networks disrupted in these syndromes. Of particular importance in this regard are
Fgf
(fibroblast growth factor) and retinoic acid signalling.

Tbx1

is in genetic epistasis with loci encoding several transcription factors and signalling molecules, providing some rationale for the very variable clinical presentation. Gain‐of‐function, or duplications containing

Tbx1

, is also associated with heart defect.

Key Concepts:

The presence of a dominant phenotype secondary to gene hemizygosity is called haploinsufficiency.

Genetic epistasis is the phenomenon where the effects of one gene are modified by one or several other genes, which are called modifier genes.

Each pharyngeal arch surrounds an arch artery that connects the heart, by means of the aortic sac, to the dorsal aortae.

The neural crest is a pluripotent embryonic neuroectodermal cell population that migrates extensively and differentiates into diverse structures such as the face, neck, heart, adrenal gland, peripheral nervous system and skin.

Low copy number repeat are 1–400 kb blocks of genomic sequence that are duplicated in one or more locations on a chromosome and can act as substrates for aberrant recombination events.
Tuberous Sclerosis Complex and the Mammalian Target of Rapamycin Pathways
Authors: Yu Jane 
Published: September 2010

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominant disease in which the
mammalian target of rapamycin complex 1
(
mTORC1
) is hyperactivated. Lymphangioleiomyomatosis (LAM) is the pulmonary manifestation of TSC which occurs primarily in women. The TSC proteins
tuberin
and
hamartin
regulate the small
guanosine triphophatase
(
GTPase
)
Rheb
(
Ras
homologue enriched in brain), a direct activator of
mTORC1
. Activation of
mTORC1
has been observed in TSC tumours and other human tumours, and
mTORC1
inhibitors have been tested for the treatment of TSC and for malignancies including renal cancer. In this article, we discuss diagnostic features, updated molecular basis, evidences of
mTORC1
activation, preclinical models and completed clinical trials of
mTORC1
inhibitors in TSC. We also review the evidence of
mTORC1
‐independent functions of the TSC proteins, and discuss future therapeutic perspectives combining
mTORC1
inhibitors with agents targeting other cellular pathways.

Key Concepts:

Tuberous sclerosis complex (TSC) is a hereditary disease characterised by the development of seizures, mental retardation, autism and hamartomas in multiple organs including the brain, retina, kidney, heart and skin.

Lymphangioleiomyomatosis (LAM) is the metastatic pulmonary manifestation of TSC occurring almost exclusively in women, in whom the lungs are infiltrated with abnormal smooth muscle‐like cells and there is degeneration of lung parenchyma.

Metastasis is the multistep process in which tumour cells at the primary site spread to distant tissues/organs to proliferate.

Loss of heterozygosity refers to the loss of a normal allele on a chromosome while the other allele has a genetic alteration or mutation.

Mammalian target of rapamycin (mTOR) refers to the
FRAP1
gene product, a serine/threonine protein kinase that controls ribosome biogenesis, protein translation, cell growth and metabolism.
LDL
Receptor and Its Role in Inherited Disease
Authors: Soutar Anne K 
Published: September 2010

Abstract

The low‐density lipoprotein (LDL) receptor mediates the specific uptake of LDL from the circulation and its intracellular degradation by a process known as the LDL receptor pathway. LDL receptor gene expression is regulated by intracellular sterol content, and is limited mainly to the liver

in vivo

. Mutations in

LDLR

, the gene encoding the LDL receptor, cause familial hypercholesterolaemia (FH), a dominantly inherited disease where accumulation of LDL in the circulation increases the risk of coronary heart disease. Defects in other genes, including

APOB

, encoding the ligand for the LDL receptor,

ARH

, encoding a protein required for its internalisation and
proprotein convertase subtilisin/kexin type 9
(

PCSK9

), encoding a protein that reduces LDL receptor protein levels, cause a similar disorder because the encoded proteins are involved in the LDL receptor pathway. FH can readily be treated with cholesterol‐lowering drugs to reduce cardiovascular risk effectively, and identification of the causal genetic defect allows unequivocal and early diagnosis.

Key Concepts:

The LDL receptor mediates specific uptake and intracellular degradation of serum LDL.

Inherited defects in the LDL receptor pathway cause familial hypercholesterolaemia (FH), characterised by increased serum LDL and increased risk of coronary heart disease.

Most FH patients have mutations in
LDLR
, but defects in other genes cause a similar disorder.

A recessive form of FH is caused by null mutations in ARH, a clathrin adaptor protein required for LDL receptor internalisation.

A dominant form of FH is caused by gain‐of‐function mutations in
PCSK9
, which encodes a protein that promotes degradation of LDL receptor protein.

Dominant loss‐of‐function mutations in
PCSK9
reduce serum cholesterol and risk of coronary heart disease.

One relatively common dominant mutation in
APOB
, encoding the ligand for the LDL receptor, causes familial defective apoB (FDB).

LDLR
transcription is regulated by sterol response element‐binding proteins (SREBP) in a complex mechanism involving several other proteins.

FH can readily be treated with cholesterol‐lowering drug therapy to abolish the increased risk of coronary disease, but is currently under‐diagnosed.

Identifying causal mutations in known patients and screening their relatives should identify more affected individuals.