bluuebunny/crossref_metadata_2025 huggingface dataset:
Autoimmune Disease: Animal Models
Authors: Williams Richard
Published: October 2010

Animal models are used for the study of a number of human autoimmune diseases, including multiple sclerosis, diabetes, rheumatoid arthritis and systemic lupus erythematosis. Induced, spontaneous and genetically manipulated animal models can be described in terms of their parallels to human disease and as tools for the development of potential therapies. Studies in animal models have led to a number of important discoveries which have increased our understanding of the pathogenesis of autoimmune disease, including the roles played by regulatory T cells and TH17 cells. In addition, important therapeutic advances have emerged as a result of studies of immune intervention in animal models of autoimmunity. For example, Tumour necrosis factor (TNF) blocking drugs, which are widely used for the treatment of rheumatoid arthritis, were developed following pre‐clinical testing in animal models.

Key Concepts:

Animal models may be either spontaneously occurring or induced as a result of genetic manipulation or immunisation with a self‐antigen.

No animal model completely mimics human disease.

Animal models can be used to test novel therapeutic concepts and to understand mechanisms of drug action.

The use of transgenic and knockout strains facilitates the identification of key genes that contribute to disease susceptibility.
Anthocyanins
Authors: Andersen Øyvind M , Jordheim Monica
Published: October 2010

The anthocyanins, which belong to the flavonoid group provide the majority of red to blue colour shades and patterns of flowers, fruits and leaves of angiosperm plants. They are produced, often temporary, during the course of a shoot's growth, but they can also be promoted experimentally, for instance in green leaves by subjecting plants to mineral imbalances. About 650 anthocyanins have been identified. Each anthocyanin consists of an aglycone (anthocyanidin) and one or more glycosyl moieties. Each anthocyanidin may occur on different equilibrium forms, which are influenced by various factors including pH. The anthocyanins are integrated into the plant's strategies for survival by attracting or repelling pollinators and seed dispersers, serving protective roles as shields against abiotic stresses like UV (ultraviolet)–B radiation, visible light, temperature variation, etc., and active defensive roles against pathogens, insects and herbivores. The past two decades have witnessed increased interests in anthocyanins above all because of their potential health‐promoting properties, their use as natural food colorants, as well as their appearance in cultivars and plant mutants with new colours and shapes.

Key Concepts:

Anthocyanins provide the majority of red to blue colours of plants.

Anthocyanins in plants attract or repel pollinators and seed dispersers, and serve protective and defensive roles.

Anthocyanin colours are significantly influenced by structure, copigmentation and external factors like pH.

Anthocyanin stability is significantly influenced by structure and external factors like pH.

Anthocyanins have been approved for use in foods, in Europe with the label E163.

Anthocyanins are regarded as potentially important nutraceuticals.

Genetic engineering applied to anthocyanins has been used to modify flower colours and patterns bringing new varieties to the horticultural marked.
Evolution of Photosynthesis
Authors: Allen John F , Vermaas Wim FJ
Published: October 2010

Photosynthesis is the conversion of radiant energy, as light, into stored chemical energy. The central process is a light‐driven separation of electrical charge across a biological membrane. Photochemical reaction centres carry out this process, and their three‐dimensional protein structures now indicate that all modern reaction centres are homologous. Reaction centres with light‐harvesting complexes comprise photosynthetic units, two of which are required for the oxygenic photosynthesis that now dominates biological energy flow in the biosphere. The evolutionary origin of oxygenic photosynthesis in cyanobacteria had a profound effect on the chemistry of the Earth's atmosphere, on geology and on biology, paving the way for the evolution of complex, multicellular life. Eukaryotic plants and algae maintain the descendents of cyanobacteria as specialised, subcellular, cytoplasmic organelles called chloroplasts. The genes that remain in chloroplasts may be retained to be subject to regulatory control by the photosynthetic electron transport chain.

Key Concepts:

Photochemical reaction centres trap absorbed light energy as transmembrane charge separation.

This vectorial electron transfer forms part of an electron transport chain, and drives vectorial proton translocation, establishing a proton motive force.

The proton motive may also be produced by nonphotosynthetic electron transfer and perhaps, originally, by geothermal convection in the first living cells. Photosynthesis may have originated as a light‐driven supplement to vectorial metabolism.

Photochemical reaction centres today come in two broad types, I and II. These differ in their mode of electron transport, but the three‐dimensional structure of their proteins indicates a common origin.

Type I and type II reaction centres originated by gene duplication and subsequently diverged to give the reaction centres found today in different lineages of anoxygenic, photosynthetic bacteria, each with a single type of reaction centre.

Type I and type II reaction centres came together again, in the first cyanobacterium, as photosystem I and photosystem II, two mutually interdependent photosynthetic units connected in series.

Photosystem I and photosystem II together generate a sufficiently large electrical potential difference to permit photo‐oxidation of water and photo‐reduction of NADP+, with a consequent liberation of molecular oxygen.

Oxygenic photosynthesis was acquired by eukaryotic cells through endosymbiosis with cyanobacteria.

The overwhelming majority of cyanobacterial genes were either lost or relocated to the plant cell nucleus.

Control of gene expression by photosynthetic electron transport may be an absolute and continuing requirement that justifies the maintenance of the small, quasi‐autonomous, chloroplast genetic system.
Labelling of Cells Engaged in
DNA
Synthesis: Autoradiography and BrdU Staining
Authors: Madsen Peder
Published: October 2010

The cell cycle is divided in four phases: G1 phase, S phase (DNA‐synthesis), G2 phase (together termed interphase) and M phase (mitosis). Cells that have ceased proliferation enter a state of quiescence called G0. M phase is itself composed of two tightly coupled processes: mitosis, in which the cell's chromosomes are divided between the two daughter cells, and cytokinesis, in which the cell's cytoplasm divides in half forming distinct new cells. It is often necessary to evaluate the proportion of DNA‐replicating nuclei (S‐phase cells) in a given population of cells. Classical methods for detection of cells in the S phase use incorporation of modified nucleosides, followed by direct visualisation of the DNA ‐replicating cells.

Key Concepts:

Identification of actively DNA‐replicating nuclei by incorporation of bromodeoxyuridine and detection by immunofluorescence using bromodeoxyuridine specific antibodies or by incorporation of [
3
H]thymidine and visualisation by autoradiography.

Labelling of S‐phase cells by bromodeoxyuridine or [
3
H]thymidine is a direct method to asses the proliferative index of tissue cell cultures.

Cell cycle studies using the number of S‐phase cells as index for cell proliferation are conveniently conducted by incorporation of bromodeoxyuridine or [
3
H]thymidine into nuclei engaged in DNA synthesis.

Bromodeoxyuridine and [
3
H]thymidine are both incorporated into DNA by eukaryotic DNA polymerases and are therefore valuable tools in studies of hyperproliferative cells as well as normal cells, thereby aiding to the understanding of the transition of normal cells to cancer cells.
Histocultures and Their Use
Authors: Hoffman Robert M
Published: October 2010

Histocultures are three‐dimensional tissues that are put into growth medium either with a collagen gel support or simply free floating. Histocultures maintain their

in vivo

‐like phenotype in contrast to monolayer cultures. Histocultures have many uses, including culture and sensitivity testing of patient tumour to choose optimal individualised treatment. Clinical trials have demonstrated the clinical utility of the histoculture drug response assay (HDRA) to determine effective treatment for multiple types of cancer. The histoculture of skin to study hair growth and screen drugs that enhance or inhibit hair growth has enabled the discovery of hair follicle‐targeting cancer liposomes to deliver genes and other molecules to the hair follicles. The histoculture of lymphoid organs has been developed to study antibody production and effects of viruses on immune cells. Stem cell growth and differentiation are now being studied in histoculture.

Key Concepts:

Histocultures are the culture of intact tissues containing multiple cell types.

Histocultures retain their
in vivo
phenotype in contrast to monolayer cultures.

Histocultured tumour tissue contains cancer cells and stromal elements interacting with each other in their native structure.

Histocultured tumours can be tested for drug sensitivity to design effective individualised therapy for each patient.

Histocultured lymphoid tissue can enable the study of antibody production and virus infection
in vitro
.

Histocultured skin enables hair growth
in vitro
.

Histocultured stem cells cancer differentiates
in vitro
.
Cold Spring Harbor Laboratory
Authors: Witkowski Jan A
Published: October 2010

The Biological Laboratory was established at Cold Spring Harbor, New York, USA, in 1890 as a summer school for teachers of biology. It began a transition to becoming a research institute in 1898, and in 1904, the Carnegie Institution of Washington created the Station for Experimental Evolution. A third institute, the Eugenics Records Office (ERO), was established in 1910. The ERO was closed in 1940, and the two remaining institutes amalgamated to create the Cold Spring Harbor Laboratory of Quantitative Biology in 1963. Genetics was and remains the central theme of the Laboratory's research, focusing on cancer, but current areas of research also include quantitative biology, neurobiology and plant genetics. The Laboratory is also the leading centre for meetings and courses in experimental biology; over 8500 scientists attend the over 50 meetings and 25 courses held annually. The Laboratory's DNA Learning Center provides education in molecular genetics for high school students, whereas the Watson School of Biological Sciences, founded in 1998, grants the PhD degree.

Key Concepts:

Cold Spring Harbor Laboratory is a world‐renowned institute for research on topics of biological and biomedical importance.

The Laboratory plays a key role in professional education through its meetings, courses and book publishing.

The Watson School of Biological Science offers graduate training leading to the PhD degree.

The DNA Learning Center provides teaching in molecular genetics for high school students.
Ion Channels and Human Disorders
Authors: Raja Rayan Dipa L , Hanna Michael G
Published: October 2010

The 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

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

Deoxyribonucleic 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

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

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

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

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

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

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

Cultural 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

Microsatellites 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

Annual 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

The 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

Researchers 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.
Patient repositioning reproducibility of joint space width measurements on hand radiographs
Authors: Neumann Gesa , dePablo Paola , Finckh Axel , Chibnik Lori B. , Wolfe Fred , Duryea Jeffrey
Published: October 2010

Objective

Computer‐based methods to measure radiographic joint space width (JSW) have the potential to improve the longitudinal assessment of rheumatoid arthritis (RA). The purpose of this report was to measure the long‐term patient repositioning reproducibility of software‐measured radiographic JSW.

Methods

Patients underwent baseline and followup hand radiography examinations with a followup time of ≤3 years. To eliminate any JSW change due to real disease progression, the evaluation was performed on “unaffected” joints, defined as having JSW and erosion Sharp scores of 0 at both baseline and followup. The root mean square SD (RMSSD) and coefficient of variation (CV) were used as the reproducibility metrics.

Results

The RMSSD was 0.14 mm (CV 10.5%) for all joints, 0.18 mm (CV 10.9%) for the metacarpophalangeal (MCP) joints, and 0.08 mm (CV 8.3%) for the proximal interphalangeal (PIP) joints. The distribution of JSW change was asymmetric, suggesting that narrowing due to RA progression occurred for several joints. A second analysis was performed, excluding joints where the loss of JSW was greater than 3 SDs. For this analysis, the RMSSD was 0.10 mm (CV 7.5%) for all joints, 0.12 mm (CV 7.3%) for the MCP joints, and 0.07 mm (CV 7.1%) for the PIP joints.

Conclusion

Repositioning reproducibility is very good but is likely to be a dominating factor compared to reader and software reproducibility. Additionally, further evidence is given that a software method is able to detect changes in some joints for which the Sharp score is insensitive.
Industrial Development of Cubic Texture in High‐Purity Aluminium: Discussion of the Research and Development Method
Authors: Boutin F. R.
Published: October 2010

The development of cubic texture in high purity aluminium in the seventies is used to demonstrate that reducing the overall duration of experimentation makes research more successful.
Impedance Measurements as a Simple Tool to Control the Quality of Conjugated Polymers Designed for Photovoltaic Applications
Authors: Troshin Pavel A. , Susarova Diana K. , Moskvin Yury L. , Kuznetsov Ilya E. , Ponomarenko Sergei A. , Myshkovskaya Ekaterina N. , Zakharcheva Ksenya A. , Balakai Alexander A. , Babenko Sergei D. , Razumov Vladimir F.
Published: October 2010

The problem of batch‐to‐batch variation of electronic properties and purity of conjugated polymers used as electron donor and photon harvesting materials in organic solar cells is addressed. A simple method is developed for rapid analysis of electronic quality of polymer‐based materials. It is shown that appearance of impurities capable of charge trapping changes electrophysical properties of conjugated polymers. In particular, a clear correlation between the effective relaxation time τeff and relative photovoltaic performance (η/ηmax) is revealed for samples of poly(3‐hexylthiophene) intentionally polluted with a palladium catalyst. This dependence is also valid for all other investigated samples of conjugated polymers. Therefore, fast impedance measurements at three different frequencies allow one to draw conclusions about the purity of the analyzed polymer sample and even estimate its photovoltaic performance. The developed method might find extensive applications as a simple tool for product quality control in the laboratory and industrial‐scale production of conjugated polymers for electronic applications.
Asbestos is still with us: Repeat call for a universal ban
Authors: Ramazzini Collegium
Published: October 2010

All forms of asbestos are proven human carcinogens. All forms of asbestos cause malignant mesothelioma, lung, and laryngeal cancers, and may cause ovarian, gastrointestinal, and other cancers [Straif et al., 2009]. No exposure to asbestos is without risk. Asbestos cancer victims die painful lingering deaths. These deaths are almost entirely preventable.

When evidence of the carcinogenicity of all forms of asbestos became incontrovertible, concerned parties, including the Collegium Ramazzini, called for a universal ban on the mining, manufacture, and use of asbestos in all countries around the world [Collegium Ramazzini, 1999]. Asbestos is now banned in 52 countries [IBAS, 2010], and safer products have replaced many materials that once were made with asbestos. Nonetheless, a large number of countries still use, import, and export asbestos and asbestos‐containing products. And in many countries that have banned other forms of asbestos, the so‐called “controlled use” of chrysotile asbestos is exempted from the ban, an exemption that has no basis in medical science but rather reflects the political and economic influence of the asbestos mining and manufacturing industry.

All countries of the world have an obligation to their citizens to join in the international endeavor to ban all forms of asbestos. An international ban on asbestos is urgently needed. Am. J. Ind. Med. 54:168–173, 2011. © 2010 Wiley‐Liss, Inc.
Ascertainment of occupational histories in the working population: The occupational history calendar approach
Authors: Lilley R.C. , Cryer P.C. , Firth H.M. , Herbison G.P. , Feyer A‐M.
Published: October 2010

Background

Self‐reported occupational histories are an important means for collecting historical data in epidemiological studies. An occupational history calendar (OHC) has been developed for use alongside a national occupational hazard surveillance tool. This study presents the systematic development of the OHC and compares work histories collected via this calendar to those collected via a traditional questionnaire.

Methods

The paper describes the systematic development of an OHC for use in the general working population. A comparison of data quality and recall was undertaken in 51 participants where both tools were administered.

Results

The OHC enhanced job recall compared with the traditional questionnaire. Good agreement in the data captured by both tools was observed, with the exception of hazard exposures.

Conclusions

A calendar approach is suitable for collecting occupational histories from the general working population. Despite enhancing job recall the OHC approach has some shortcomings outweighing this advantage in large‐scale population surveillance. Am. J. Ind. Med. 54:21–31, 2011. © 2010 Wiley‐Liss, Inc.
Lung cancer and occupation: A new zealand cancer registry‐based case–control study
Authors: Corbin Marine , McLean David , Mannetje Andrea 't , Dryson Evan , Walls Chris , McKenzie Fiona , Maule Milena , Cheng Soo , Cunningham Chris , Kromhout Hans , Blair Aaron , Pearce Neil
Published: October 2010

Background

There are many proven and suspected occupational causes of lung cancer, which will become relatively more important over time, as smoking prevalence decreases.

Methods

We interviewed 457 cases aged 20–75 years notified to the New Zealand Cancer Registry during 2007–2008, and 792 population controls. We collected information on demographic details, potential confounders, and employment history. Associations were estimated using logistic regression adjusted for gender, age, ethnicity, smoking, and socio‐economic status.

Results

Among occupations of a priori interest, elevated odds ratios (ORs) were observed for sawmill, wood panel and related wood‐processing plant operators (OR 4.63; 95% CI 1.05–20.29), butchers (OR 8.77, 95% CI 1.06–72.55), rubber and plastics products machine operators (4.27; 1.16–15.66), heavy truck drivers (2.24; 1.19–4.21) and workers in petroleum, coal, chemical and associated product manufacturing (1.80; 1.11–2.90); non‐significantly elevated risks were also observed for loggers (4.67; 0.81–27.03), welders and flame‐cutters (2.50; 0.86–7.25), pressers (5.74; 0.96–34.42), and electric and electronic equipment assemblers (3.61; 0.96–13.57). Several occupations and industries not of a priori interest also showed increased risks, including nursing associate professionals (5.45; 2.29–12.99), enrolled nurses (7.95; 3.10–20.42), care givers (3.47; 1.40–8.59), plant and machine operators and assemblers (1.61; 1.20–2.16), stationary machine operators and assemblers (1.67; 1.22–2.28), food and related products processing machine operators (1.98; 1.23–3.19), laborers and related elementary service workers (1.45; 1.05–2.00), manufacturing (1.34; 1.02–1.77), car retailing (3.08; 1.36–6.94), and road freight transport (3.02; 1.45–6.27).

Conclusions

Certain occupations and industries have increased lung cancer risks in New Zealand, including wood workers, metal workers, meat workers, textile workers and drivers. Am. J. Ind. Med. 54:89–101, 2011. © 2010 Wiley‐Liss, Inc.
Interpreting borderline belpt results
Authors: Middleton D.C. , Mayer A.S. , Lewin M.D. , Mroz M.M. , Maier L.A.
Published: October 2010

Background

The beryllium lymphocyte proliferation test (BeLPT) identifies persons sensitized to beryllium (BeS) and thus at risk for chronic beryllium disease (CBD). BeLPT test results are abnormal (AB), borderline (BL), or normal (NL). This manuscript addresses the predictive value and interpretation of BL BeLPT results.

Methods

The various three‐result combinations that meet or exceed a nominal referral criteria of 1 AB + 1 BL are assessed with probability modeling and compared.

Results

At 2% prevalence, the three‐result combinations that meet or exceed this referral criteria and associated probabilities of BeS are: (a) 1 AB + 1 BL + 1 NL (72%); (b) 3 BL (91%); (c) 2 AB + 1 NL (95%); (d) 1 AB + 2 BL (99%); (e) 2 AB + 1 BL (100%); and (f) 3 AB (100%).

Conclusion

These results suggest that BL results are meaningful and that three BL results predict BeS across a broad range of population prevalences. An analysis of longitudinal BeLPT results and clinical findings from an actual surveillance program is warranted to confirm the model's predictions. Am. J. Ind. Med. 54:205–209, 2011. © 2010 Wiley‐Liss, Inc.
Airway response to chlorine inhalation (bleach) among cleaning workers with and without bronchial hyperresponsiveness
Authors: Sastre Joaquín , Madero Mauro F. , Fernández‐Nieto Mar , Sastre Beatriz , del Pozo Victoria , Potro Manuela García‐del , Quirce Santiago
Published: October 2010

Background

Symptoms of obstructive lung disease in domestic cleaning staff have been related to the use of bleach and other irritant cleaning products.

Material and Methods

Included in the study were thirteen cleaning employees with work‐related asthma‐like symptoms, three asthmatic controls and three atopic subjects without bronchial hyperresponsiveness (BHR) who had no exposure to cleaning products. The study protocol consisted of a methacholine test, sputum induction and fraction of exhaled nitric oxide measurement (FENO) both at baseline and 24 hr after a 1‐hr inhalation challenge with either placebo or bleach at a concentration of 0.4 ppm of chlorine.

Results

The inhalation of the placebo caused no bronchial reactions. Mean maximum fall in FEV1 during challenge testing with bleach was significantly higher than the values obtained during the placebo challenge. Inhalation challenge with bleach elicited two isolated late asthmatic reactions and one dual asthmatic reaction. Of all the patients who underwent challenge testing with bleach, only one had a ≥2‐fold decrease in methacholine PC20 24 hr after the challenge. No significant correlation was found between maximum fall in FEV1 and PC20 methacholine. Following challenge testing with bleach, no clinically significant changes in sputum cell counts or FENO were detected.

Conclusions

These results suggest that bleach inhalation at a concentration of 0.4 ppm—a concentration below 8‐hr permissible occupational exposure level—brings about a substantial decrease in FEV1 in subjects with and without BHR. Some subjects have a positive challenge response to bleach inhalation. Am. J. Ind. Med. 54:293–299, 2011. © 2010 Wiley‐Liss, Inc.