bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ion Channels and Human Disorders
Authors: Raja Rayan Dipa L , Hanna Michael G 
Published: October 2010

AbstractThe human channelopathies are a rapidly expanding group of primarily genetic conditions. They are characterised by dysfunction of membrane‐bound glycoproteins (ion channels). Several neurological and general medical disorders have been shown to be due to underlying ion channel dysfunction and genetic analysis is now often routine clinical practice. These disorders exhibit extensive phenotypic and genetic heterogeneity with many distinct diseases caused by dysfunction of the same channel by differing mechanisms. Our understanding of the mechanisms behind these diseases continues to extend as more mutations are identified and functional analysis is performed. In the future this will lead to the identification of better targeted treatments for these diseases.Key Concepts:Ion channels are transmembrane glycoproteins important in intra‐ and intercellular processes.Channelopathies are commonly due to mutations in functionally important regions of either pore‐forming or auxillary channel subunits.Mutations often cause disease by altering channel gating, voltage dependence and channel assembly.Channelopathies may manifest with intermittent symptoms which may completely recover or have a secondary progression.Channleopathies, like myotonia congenita, have extensive phenotypic variability even within a single pedigree.Genetic heterogeneity occurs in many channelopathies like the episodic ataxias and periodic paralyses.In the calcium channel,CACNA1A, different mutations cause distinct central nervous diseases.Mutations in a number of channel genes can increase the predisposition to epilepsy.
Epilepsy: Genetics
Authors: Everett Kate V 
Published: October 2010

Abstract

At least 40% of all epilepsies have a genetic basis. Some forms of epilepsy have a simple Mendelian mode of inheritance, but these are very rare. The more common forms have a complex genetic background potentially involving several genes. Traditional methodologies for finding disease genes have been relatively successful for Mendelian forms of epilepsy. Although these approaches have been less successful for the common, complex epilepsies, it has still been possible to identify some disease‐associated genes. Most of the genes involved in epilepsy encode ion channel subunits making epilepsy an example of a ‘channelopathy’. The introduction of next generation genetic technologies has increased hope of identifying the specific genetic variants which contribute to individual susceptibility to common and Mendelian epilepsy; and with this comes hope of new
deoxyribonucleic acid
(DNA)‐based diagnostic techniques and the development of more specific therapies.

Key Concepts:

A large proportion of epilepsies have a genetic basis.

The majority of genetic epilepsies demonstrate a complex mode of inheritance.

Complex inheritance indicates that disease is caused by a combination of genetic changes potentially combined with nongenetic factors.

Mode of inheritance can vary between families.

Epilepsy is primarily a channelopathy; a disease caused by dysfunction of ion channels.

Some genetic changes directly cause disease whereas others alter disease susceptibility.

Genetic changes in the same gene can result in different epilepsies.

New genetic technologies will facilitate the identification of genetic changes causing both Mendelian and complex epilepsy.
DNARepair: Disorders
Authors: Lehmann Alan R , O'Driscoll Mark 
Published: October 2010

AbstractDeoxyribonucleic acid(DNA) inside cells is being damaged continually. Cells have evolved a series of complex mechanisms to repair all types of damage. Deficiencies in these repair pathways can result in several different genetic disorders. In many cases these are associated with a greatly elevated incidence of specific cancers. Other disorders do not show increased cancer susceptibility, but instead they present with neurological abnormalities or immune defects. Features of premature ageing also often result. These disorders indicate that DNA repair and damage response processes protect us from cancer and are important for the maintenance of a healthy condition.Key Concepts:DNA is damaged continually from both endogenous and exogenous sources.Cells have evolved many different ways for repairing different types of damage.Genetic defects in these pathways result in different disorders.Defective DNA repair often results in an increased mutation frequency and consequent elevated incidence of cancer. Many of the DNA repair disorders are highly cancer‐prone.The central nervous system appears to be particularly sensitive to DNA breaks. Several disorders caused by defective break repair are associated with neurological abnormalities including mental retardation, ataxia and microcephaly.Development of immunological diversity uses some of the enzymes required to repair double‐strand breaks. Disorders caused by defects in this process are associated with immune deficiencies.
Gastric Cancer
Authors: Becker Karl‐Friedrich , Keller Gisela 
Published: October 2010

Abstract

Gastric carcinoma is a malignant epithelial tumour of the stomach mucosa. Its aetiology is multifactorial. Gastric cancer can be divided into two variants, each of which accounts for half of the cases. Intestinal‐type carcinomas, the predominant type of tumour in high‐risk areas, have a glandular pattern and are usually accompanied by papillary formation or solid components. By contrast, the so‐called diffuse‐type tumours include signet‐ring cell carcinomas and anaplastic adenocarcinomas whose small and fairly uniform cells spread individually. Genetic alterations in multiple oncogenes, tumour suppressor genes and deoxyribonucleic acid repair genes have been identified. Germline mutations in the cell adhesion molecule
E‐CADHERIN
are the molecular genetic cause for a hereditary diffuse‐type gastric cancer syndrome. As exemplified by a novel successful targeted therapy against overexpressed

HER2

, a greater understanding of the biology of gastric cancer may improve treatment selection and overall outcome of individual patients.

Key Concepts:

Gastric cancer is among the most frequent causes of cancer death in the world.

Genetic alterations for the two subtypes of gastric cancer, intestinal and diffuse type, are different.

The declining incidence of gastric cancer is mainly due to the decline of the intestinal type.

Infection with
Helicobacter pylori
is the strongest singular risk factor for cancers of the stomach.

Germline mutations in the E‐cadherin gene are associated with a hereditary gastric cancer syndrome.

A novel targeted therapy against overexpressed HER2 has shown clinical benefit.
Population Stratification, Adjustment for
Authors: Gao Xiaoyi , Edwards Todd L 
Published: October 2010

Abstract
Population stratification is a major concern in genetic association studies. Failure to control it effectively can lead to excess false‐positive results and failure to detect true associations. Many methods have been designed to adjust for population stratification, which mainly belong to the following categories: (1) genomic control, (2) structured association, (3) principal component or multidimensional scaling adjustment, (4) stratification score method and (5) other approaches. No method is likely to be superior in all situations. Care needs to be taken to ensure that the assumptions of the method are met and that the method is used for its intended purpose.
Pathogenetic Mechanisms in Alagille Syndrome
Authors: Guha Shaunta , Walls Dermot , Redmond Eileen M , Cahill Paul A 
Published: October 2010

Abstract

Alagille syndrome (AGS), also known as arteriohepatic dysplasia, is an autosomal dominant disorder characterised by a paucity of interlobular bile ducts and chronic cholestasis, cardiac and vascular dysfunction, skeletal and ocular abnormalities and a characteristic facial appearance. Most cases of AGS in patients harbour mutations in either the

JAGGED‐1

(

JAG1

) or
Notch2
receptor (
NOTCH2
) gene. The

JAG1

gene encodes a ligand for the Notch receptor. The Notch signalling network controls mammalian cell fate during embryonic development and also dictates several cell phenotypes in adult cells. The majority of
JAG1
mutations seen in AGS patients are null alleles, suggesting
JAG1
haploinsufficiency as a primary cause of this disorder.

Key Concepts:

Alagille syndrome is an autosomal dominant disorder with variable expression.

Alagille syndrome and associated abnormalities include those of the liver, heart, eye, skeleton and kidneys and characteristic facial features. Mild‐to‐moderate mental retardation also may be present.

Alagille syndrome is most often caused by a mutation, or defect, in the
JAGGED1
(JAG1) or
NOTCH2
receptor gene.

Alagille syndrome has been mapped to the 20p12‐jagged‐1 locus, JAG1, which encodes a ligand critical to the
NOTCH
gene–signalling cascade that is important in fetal development.

Notch signalling has been found to regulate formation of three‐dimensional intrahepatic biliary architecture in murine models and vascular cell phenotype during development.

A minority (6–7%) of patients have complete deletion of JAG1, and approximately 15–50% of mutations are spontaneous.

Deaths in people with Alagille syndrome are most often caused by liver failure, heart problems and blood vessel abnormalities.
Chromosome Instability (
CIN
), Aneuploidy and Cancer
Authors: Yuen Karen Wing Yee 
Published: October 2010

Abstract

Chromosome instability (CIN) describes an increased
rate
of chromosome missegregation in mitosis resulting in a failure to maintain the correct chromosomal complement (euploidy). The aberrant chromosomal
state
of a cell can be classified based on the changes in ploidy, gain or loss of whole chromosomes (aneuploidy) or gross chromosomal rearrangements (GCR), all of which are hallmarks of solid cancers. CIN can be caused by multiple mechanisms involved in chromosome segregation, including a weakened or overactivated mitotic spindle assembly checkpoint, sister chromatid cohesion defects, increased merotelic kinetochore‐microtubule attachments or the presence of extra centrosomes. CIN occurs early in cancer development, and is associated with poor prognosis. CIN has long been proposed to contribute to tumour progression. However, recent studies suggest that CIN can either promote or suppress tumour progression, depending on the contexts. Targeting characteristics specific to tumour cells, such as CIN, is an attractive therapeutic avenue.

Key Concepts:

Stable aneuploidy can occur without CIN (e.g. Down syndrome patients with trisomy chromosome 21), but aneuploidy observed in cancer is often caused by CIN.

CIN is a hallmark of solid cancers, occurring early in tumorigenesis, and is associated with poor prognosis.

CIN can arise from defects that affect different steps of chromosome segregation, including the spindle checkpoint, kinetochore‐microtubule attachments, sister chromatid cohesion, centrosome duplication and bipolar spindle assembly.

Mutations and misregulation of genes functioning at the spindle checkpoint, at the kinetochore, sister chromatid cohesion and centrosomes are associated with various cancer types.

Germline biallelic mutations in spindle checkpoint gene BUB1B are associated with mosaic variegated aneuploidy (MVA) and predispositions to various types of cancer, strongly supporting a causal link between CIN and cancer development. However, only low frequency of somatic mutations in spindle checkpoint components has been found in spontaneous cancers.

Either a weakened spindle checkpoint or a prolonged activated checkpoint can cause chromosome missegregation, presumably due to premature sister chromatid separation or increased frequency of uncorrected merotelic attachments, respectively.

Extra centrosomes usually cluster to form bipolar spindles, but they undergo a transient multipolar stage, increasing the frequency of merotelic attachments and lagging chromosomes.

Animal models with CIN can either promote or suppress cancers, depending on the genetic background and contexts.

Stable aneuploidy per se does not cause CIN, and is antiproliferative.

CIN can be exploited as a cancer‐specific target for selective killing of tumours.
Legius Syndrome and

SPRED

1
Authors: Brems Hilde , de Ravel Thomy , Legius Eric 
Published: October 2010

Abstract

Legius syndrome, initially reported as neurofibromatosis type 1‐like syndrome, is an autosomal dominant disorder caused by heterozygous inactivating

SPRED1

mutations. The disease is characterised by multiple café‐au‐lait spots (CALs), sometimes associated with axillary or inguinal freckling and macrocephaly as seen in neurofibromatosis type 1 (
NF1
). Other typical
NF1
associated features (Lisch nodules, bone abnormalities, neurofibromas, optic pathway gliomas and malignant peripheral nerve sheath tumours) are lacking. Some degree of learning disability and/or speech problems in infancy are frequently observed and are usually milder than in
NF1
.

The
SPRED1
protein is a negative regulator of the RAS (rat sarcoma viral oncogene homolog)‐MAPK (
mitogen‐activated protein kinase
) pathway. CALs in Legius syndrome result from bi‐allelic

SPRED1

inactivation in melanocytes.

SPRED1

loss‐of‐function results in overactivation of the RAS‐MAPK signalling pathway. This is similar to what is seen in a group of disorders caused by mutations in other genes coding for key proteins of the RAS‐MAPK pathway (referred as RASopathies).

Key Concepts:

Legius syndrome is an autosomal dominant disorder.

It is caused by heterozygous mutations in the
SPRED1
gene.

The phenotype consists of café‐au‐lait spots, sometimes with axillary or inguinal freckling and a variable degree of macrocephaly.

Learning disabilities and speech problems in infants are frequently reported.

SPRED1 is a negative regulator of the RAS‐MAPK pathway at the level of activation of RAF by RAS‐GTP.

Legius syndrome is a RASopathy (RAS‐MAPK syndrome).
Animals and Their Unicellular Ancestors
Authors: Paps Jordi , Ruiz‐Trillo Iñaki 
Published: October 2010

Abstract

Animals belong to the Opisthokonta, one of the major divisions of the eukaryotic Tree of Life. This supergroup also includes other well‐known groups such as fungi and choanoflagellates, in addition to some newly discovered unicellular taxa as the Ichthyosporea or the Filasterea. To unveil the origin of animal multicellularity, it is vital to understand the evolution of their single‐celled relatives, as they might hold key genetic clues that might help us understand how the unicellular ancestors of animals became animals. Our current knowledge of unicellular animal relatives, their specific phylogenetic relationships and the role they might play in future research is being improved, thanks to molecular data.

Key Concepts:

Animals are members of the opisthokonts.

The Opisthokonta clade includes animals, fungi and several unicellular lineages.

Choanoflagellates are the closest animal unicellular relatives.

Ichthyosporea and Filasterea lineages are most closely related to animals than to fungi.

The opisthokonts include several multicellular types.

The opisthokont is a key evolutionary window to understand the unicellular to multicellular transition.
Cultural Transmission and Evolution
Authors: Castro Laureano , Toro Miguel A 
Published: October 2010

AbstractCultural transmission in our species is a cumulative inheritance system that leads to a cultural evolution process with a great adaptive value. Our genes have promoted a social learning system very effective for the transmission of learned behaviours. The ability to accumulate knowledge based on an efficient transmission process is what distinguishes human culture from other kinds of social learning present in nonhuman primates. Human behaviour is a product of two different and interacting processes: genetic evolution and cultural evolution. Much variation in human behaviour cannot be understood without accounting for beliefs, values and other socially acquired determinants of behaviour. Thus, culture is crucial for understanding human behaviour and coevolves with biology. On the one hand, the psychobiological capacities guiding cultural processes are the product of evolution. On the other hand, culture modifies the environment in which we live and therefore determine future action of natural selection.Key Concepts:Human culture is a system of inheritance, in which people acquire skills, techniques, beliefs, values, norms, desires and so on, by imitation and teaching.Cultural transmission arises from genetically evolved psychological adaptations for acquiring cultural traits from other individuals by observation and inference.Cultural transmission differs from nonhuman primate social learning in that it is cumulative.Cumulative cultural transmission led to a cultural evolution process with a great adaptive value.Evolved psychobiological mechanisms guide the preference among different cultural variants.Culture created social environments, in which specific adaptations were selected for by natural selection.
Evolution of Microsatellites
Authors: Takezaki Naoko 
Published: October 2010

AbstractMicrosatellites are tandem repeats of short nucleotide sequence (1–6 bp) and abundant in the eukaryotic genome. Mutation rate is high (10−2–10−6per locus per generation), and there is large variation among species. Mutational changes of microsatellites are mostly repeat number change by one. However, there are some multistep changes, and the mutation rate shows a complex relationship with repeat length, repeat unit size and motif composition. Microsatellites are useful to study the evolutionary relationship among populations. Genetic distance, a measure of the extent of genetic differentiation between populations, calculated for human populations appears to increase approximately linearly with the time after population divergence. Interestingly, the total number of repeats of microsatellite loci in an individual's genome also appears to diverge with the time after population divergence. Variation of repeat number in microsatellite loci contributes the variation of genome size of an individual due to its abundance in the genome.Key Concepts:Microsatellites are tandem repeats of short nucleotide sequence (1 – 6 bp) and abundant in eukaryotic genome.The mutational changes of microsatellites are mostly increase or decrease of the repeat number by one.The repeat number change of microsatellite occurs through a mechanism called replication slippage.The mutational pattern of microsatellites roughly follows the stepwise mutation model.The equilibrium distribution of repeat number in miscrosatellites may be obtained by balance between replication slippage and disruption of repeats by point mutation as well as by balance between higher expansion rate over contraction rate for short repeats and higher contraction rate over expansion rate for longer repeats.The mutation rate of microsatellites varies with size and motif of repeat unit.The mutation rate and repeat length of microsatellites vary among species.Genetic distance of microsatellites increases proportionally with the time after human population divergence.The average difference of total repeat number of individuals between populations increases with time after population divergence.Contribution of the repeat number variation of microsatellites to genome size variation may be quite large.
Adaptive Divergence in Sunflowers
Authors: Strasburg Jared L 
Published: October 2010

AbstractAnnual sunflowers have been developed into a model system for the study of adaptation, hybridisation and speciation. Various species and populations have adapted to a wide range of extreme habitats, including salt marshes, sand dunes, desert floor and agricultural environments. In many cases, the process of adaptation has been facilitated by hybridisation between distinct species. Population genetic analyses of several species have revealed evidence of natural selection at loci potentially associated with adaptation to different environments, and genomic analyses indicate that the signature of adaptive divergence is found throughout the genomes of these species. In some cases, the genetic architecture of reproductive isolation and species differences may facilitate adaptive introgression and the formation of new hybrid species through adaptive ecological divergence.Key Concepts:Hybridisation has played an important role in adaptation in sunflowers, both through adaptive introgression and through the formation of adaptively divergent hybrid species.Evidence for adaptive divergence in sunflowers comes from a number of sources, including field experiments, genetic mapping of adaptive traits and DNA sequence analyses.The early morphological and ecological divergence of hybrid species can be experimentally replicated under environmental conditions similar to those encountered by the hybrid species in nature, providing strong evidence that it is adaptive.Data from a number of sunflower species support the hypothesis that adaptive divergence is associated with large population size.
The effect of short duration heart rate variability (HRV) biofeedback on cognitive performance during laboratory induced cognitive stress
Authors: Prinsloo Gabriell E. , Rauch H. G. Laurie , Lambert Michael I. , Muench Frederick , Noakes Timothy D. , Derman Wayne E. 
Published: October 2010

AbstractThe aim of this study was to examine the effect of 10 minutes of heart rate variability (HRV) biofeedback on cognitive performance and affect scores during induced stress. Eighteen healthy male volunteers (aged 23–41 years) exposed to work‐related stress, were randomised into an HRV biofeedback intervention (BIO) and a comparative intervention group (COM). Subjects completed a modified Stroop task, which included having to mentally count 18 white squares randomly presented between colour words, before and after a 10‐minute intervention. Subjects also completed questionnaires to rate their anxiety. BIO subjects improved their reaction times and consistency of responses, and made fewer mistakes in counting squares during the modified Stroop task. They also felt more relaxed, less anxious and less sleepy than the COM subjects. In conclusion our results suggest that short duration HRV biofeedback is associated with improved cognitive performance while concurrently aiding relaxation. Copyright © 2010 John Wiley & Sons, Ltd.
A comparison of presentation methods of video identification parades
Authors: Wilcock Rachel , Kneller Wendy 
Published: October 2010

AbstractResearchers have demonstrated that sequential lineup presentation reduces false identifications from perpetrator absent lineups. In England and Wales police identification parades are shown on video in a sequential manner. However, police sequential presentation varies from the strict sequential presentation advocated by researchers. In addition, after police have shown the sequential presentation they also have the option to show witnesses a matrix of the parade where witnesses can see all members of the parade simultaneously. The research reported investigated the effect of strict sequential presentation, police sequential presentation and police sequential presentation plus matrix on mock witnesses' performance on perpetrator present and absent video identification parades. Strict sequential presentation led to fewer correct identifications of the perpetrator than police sequential and police sequential plus matrix, with no difference in performance between either of the police conditions. For perpetrator absent lineups there was no effect of lineup presentation condition on lineup performance. Copyright © 2010 John Wiley & Sons, Ltd.