bluuebunny/crossref_metadata_2025 huggingface dataset:
Lysosomal Storage Disorders: Gene Therapy
Authors: Cabrera‐Salazar Mario A , Barranger John A
Published: September 2006

History, therapeutic alternatives and different approaches to gene transfer in lysosomal storage diseases are important for the understanding of this group of inborn errors of metabolism. Recent advances have proved that gene therapy will soon be a part of standard medical practice.
Neurological Diseases: Gene Therapy
Authors: Lowenstein PR , Castro MG
Published: September 2006

Gene therapy is the use of nucleic acids as drugs. This type of genetic pharmacology can be used to treat either inherited (e.g. Huntington disease) or mainly sporadic (e.g. Parkinson disease) neurological diseases.
Diabetes Mellitus: Gene Therapy
Authors: Welsh Nils
Published: September 2006

Gene therapy in diabetes mellitus is the transfer of DNA to somatic cells in order to understand, treat or prevent the disease.
Antisense and Ribozymes
Authors: Scanlon Kevin , Kashani‐Sabet Mohammed
Published: September 2006

Antisense–ribozyme technology has evolved from being a tool in molecular biology to being used as a therapeutic agent in human disease. There is enormous potential in antisense and ribozyme therapy, but significant pitfalls and obstacles have yet to be overcome.
Chromatin in the Cell Nucleus: Higher‐order Organization
Authors: Cremer Thomas , Cremer Christoph G
Published: September 2006

The cell nucleus contains chromosome territories (CTs) and an interchromatin compartment (IC). The CT–IC model provides a framework for the functional nuclear architecture with a set of testable predictions. In particular, it predicts a topological level of gene regulation based on a cell‐type‐specific 3D architecture of higher‐order chromatin domains.
Synchronous and Asynchronous Replication
Authors: Selig Sara
Published: September 2006

Replication of nuclear DNA in animal cells is carried out according to a temporal program that is conserved from one cell division to the next. The order of replication of genomic regions can be determined by various methods. In most genomic regions both allelic copies replicate synchronously, with the exception of the X chromosomes in female mammals, regions containing imprinted genes or genes with one randomly inactivated allele.
Chromosome Preparation
Authors: Blennow Elisabeth
Published: September 2006

Standard chromosome preparations can be obtained from various tissues containing dividing cells.
Fluorescence Microscopy
Authors: Tanke Hans J
Published: September 2006

Fluorescence microscopy is applied to visualize gene and gene transcripts as stained
in situ
by methods such as fluorescence
in situ
hybridization. Instrumentation includes the use of cameras and interferometers for recording multicolor microscopic images, and confocallaser scanning microscopes for optical sectioning and subsequent reconstruction of three‐dimensional images of (living) cells.
Digital Image Analysis
Authors: Eils Roland , Conrad Christian
Published: September 2006

The comparative genome hybridization allows the measurement of copy‐number changes on a genome wide level. This method is useful for finding gene amplification and deletions.
Flow‐sorted Chromosomes
Authors: Carter Nigel P
Published: September 2006

Using flow sorting, metaphase chromosomes can be separated into purified fractions that can be used for constructing chromosome‐specific DNA libraries, chromosome painting probes and can be used as targets for PCR‐based gene mapping and sequencing.
Chromosome
Authors: Speicher Michael R
Published: September 2006

A chromosome is a linear DNA molecule, which carries the hereditary information, that is, the genes. A number of proteins pack the DNA string in several higher orders of folding. The morphology of chromosomes is characterized by length, arm ratio, appendages and banding pattern and is usually characteristic for a species.
Chromosome Structures: Visualization
Authors: Gilchrist Susan , Bickmore Wendy A
Published: September 2006

Chromosomes are the functional units of inheritance. Only by visualizing these complex and dynamic macromolecular entities can we begin to understand the implications of their structure and organization for the living cell.
Heterochromatin: Constitutive
Authors: Larizza Lidia , Doneda Luisa
Published: September 2006

Heterochromatin consists of a variety of nontranscribed tandemly repeated and interspersed repetitive deoxyribonucleic acid DNA sequences. The major classes of tandemly repeated DNA are: satellite DNA, composed of very long arrays mainly found in and around centromeres; minisatellite DNA, composed of moderately sized arrays located at or close to telomeres; and microsatellites, defined by short arrays and dispersed throughout the human genome. long interspersed nuclear elements and short interspersed nuclear elements are the two major classes of interspersed repeats, also referred to as transposon‐derived repeats. Rare fragile sites involve large expansions of microsatellites or minisatellites.
Telomere
Authors: Martin Christa Lese , Ledbetter David H
Published: September 2006

Telomeres, the ‘caps’ at the ends of human chromosomes, consist of specialized DNA and protein complexes that help to protect chromosomes from degradation. Other unique characteristics of telomeric DNA include the sequence homology shared between subtelomeric DNA regions, a high gene density and an increased frequency of chromosomal imbalances.
Epigenetic Factors and Chromosome Organization
Authors: Bourc'his Déborah , Viegas‐Péquignot Evani
Published: September 2006

The term epigenetics was introduced by C. H. Waddington in 1956 to describe all the interactions between genes and their environment that lead to phenotypic expression. Today it is used to define heritable modifications in gene expression that are not based on changes in nucleotide sequence. In mammalian chromosomes, the commonly reported epigenetic markers are cytosine methylation, histone methylation, histone acetylation, histone methylation and noncoding ribonucleic acid and chromosome association.
Microdeletions and Microduplications: Mechanism
Authors: Morrow Bernice E
Published: September 2006

Microdeletions and microduplications in the genome are caused by chromosome misalignment between blocks of region‐specific low copy repeats and result in genomic disorders.
Gene Distribution on Human Chromosomes
Authors: Bernardi Giorgio , Saccone Salvatore
Published: September 2006

The distribution of genes in the human genome is strikingly nonuniform. Gene density is very high in GC‐rich isochores and very low in GC‐poor isochores (isochores are long DNA regions characterized by a fairly homogeneous GC level). Since GC‐rich and GC‐poor isochores can be localized on human chromosomes, this ‘chromosomal compositional mapping’ provides information on the distribution of genes on chromosomes.
X and Y Chromosomes: Homologous Regions
Authors: El‐Mogharbel Nisrine , Graves Jennifer AM
Published: September 2006

The human X and Y chromosomes have quite different DNA and gene contents, and seem to be completely cytologically nonhomologous. However, they share many homologous regions, the relics of a process of gradual evolution from a homologous autosomal pair into the differentiated pair they are today.
Chromosome Y: General and Special Features
Authors: Tyler‐Smith Chris
Published: September 2006

The Y chromosome has a key role in human sex determination and carries the male sex‐determining gene,
SRY
. Its other unique features can be understood as a consequence of this function.
Chromosome 3
Authors: Naylor Susan L , Garcia Dawn K
Published: September 2006

Human chromosome 3 is the third largest chromosome, containing ∼7% of the genetic material in the genome. This metacentric chromosome contains the most common fragile site as well as clusters of olfactory receptor and chemokine receptor genes.
Chromosome 4
Authors: Altherr Michael R
Published: September 2006

Human chromosome 4 is a submetacentric chromosome that contains approximately 6.5% of the human genome.
Chromosome 7
Authors: Scherer Stephen W
Published: September 2006

Human chromosome 7 is a submetacentric chromosome containing 5.3% of the genome. It is characterized by T‐cell receptor and homeobox A gene clusters and contains several imprinted genes.
Chromosome 9
Authors: Slaugenhaupt Susan A , Ozelius Laurie J
Published: September 2006

Human chromosome 9 is a submetacentric chromosome that accounts for 4% of the human genome. It contains an unusually extensive pericentromeric heterochromatic region and gene clusters encoding, among other proteins, the α‐interpherons and olfactory receptors.
Chromosome 12
Authors: Montgomery Kate , Kucherlapati Raju
Published: September 2006

Human chromosome 12 is a submetacentric chromosome that contains 4.5% of the genetic material in the genome. It is characterized by gene clusters including those encoding homeobox C, type II keratins and proline‐rich proteins.
Chromosome 14
Authors: Kamnasaran Deepak , Cox Diane W
Published: September 2006

Human chromosome 14 is an acrocentric chromosome, rich in satellites on the short arm, which contains some 3.4% of the genetic material in the genome. It is characterized by several gene clusters including rRNA, T‐cell receptor, and immunoglobulin heavy chain genes, plus several regions containing imprinted genes.
Chromosome 17
Authors: Wadelius Claes
Published: September 2006

Human chromosome 17 is a submetacentric chromosome containing 2.6% of the genetic material in the genome. It has a greater number of genes than expected for its size, a G+C content above average and a large number of CpG islands. It is characterized by several gene clusters including those encoding homeobox B, olfactory receptors, type I keratins and SnRNAs.
Histones
Authors: Doenecke Detlef , Albig Werner
Published: September 2006

Histones, the major protein constituents of the eukaryotic chromosomes, are small proteins that are enriched in basic amino acids and highly conserved in evolution. They are classified either on the basis of their content of basic amino acids as very lysine rich (H1), moderately lysine rich (H2A and H2B) and arginine rich (H3 and H4), or in respect to their position in the nucleosome as linker or core histones.
Apolipoprotein Gene Structure and Function
Authors: Uelmen Huey Patricia , Chan Lawrence
Published: September 2006

Apolipoproteins are the protein components of lipoproteins, the lipid–protein complexes responsible for transporting lipids in the blood. They may have additional specialized functions that are encoded by their genes.
Microsatellites
Authors: Epplen Jörg T , Böhringer Stefan
Published: September 2006

Microsatellites are short, tandemly arranged repetitive
deoxyribonucleic acid
(
DNA
) elements scattered throughout most genomes. The basic unit lengths of microsatellites (or simple
DNA
sequence repeats) comprise up to six nucleotides and these motifs are perfectly reiterated from five to more than 100 times.
Methylation‐mediated Transcriptional Silencing in Tumorigenesis
Authors: Horan Martin P
Published: September 2006

Deoxyribonucleic acid (DNA) methylation is a process that inhibits the expression of genes through mechanisms that interfere with transcriptional initiation. Transcriptional silencing occurs when the 5′ flanking DNA region becomes heavily methylated, thereby interfering with the binding capacity of transcription factors. The effect of DNA hypermethylation is to reduce the expression potential of a gene.
Human Developmental Molecular Genetics
Authors: Wilson David Ian , Hanley Neil Anthony
Published: September 2006

Following the sequencing of the human genome, it is an ambitious but realistic goal to understand the genome‐wide molecular regulation of normal human development, both during the embryonic (<56 days post conception (dpc)) and fetal periods (>56 dpc). The use of human pluripotent embryonic cells as far‐sighted transplantation and regeneration strategies to treat human disease is an aspect of this topic.
Multiple Significance Testing in Genetic Epidemiology
Authors: Krawczak Michael
Published: September 2006

The simultaneous testing of multiple hypotheses in one and the same study tends to inflate the overall probability of obtaining one or more false positive results. Several methods have been devised to control this study‐wise global false positive rate through the adjustment of the test‐specific significance threshold applied to
p
‐values. The necessity of adjusting the significance levels in genetic analyses of complex human traits has, however, been a matter of scientific debate.
Microarrays in Disease Diagnosis and Prognosis
Authors: Stratowa Christian , Abseher Roger
Published: September 2006

Progress in microarray technologies will soon lead to their application in clinical practice. These high‐throughput technologies are expected to have a major impact on molecular pathology, initially in tumor classification and tumor staging.
Microarrays in Toxicological Research
Authors: Pennie William D
Published: September 2006

Toxicologists are increasingly applying oligonucleotide and complementary DNA microarrays in an attempt to understand adverse chemical reactions that occur during gene transcription. When applied in concert with the more established approaches of biochemical toxicology, pathology and so on, the appropriate use of these microarrays is improving our fundamental knowledge of mechanisms of toxicity and will have profound impact on safety assessment processes in the discovery and development of new pharmaceuticals.
Microarrays: Use in Mutation Detection
Authors: Syvänen Ann‐Christine
Published: September 2006

Microarrays are used in assay formats that allow parallel analyses of tens, hundreds or thousands of biomolecules in very small reaction volumes. One of the many application areas of the microarray format is to genotype or detect disease‐causing or disease‐predisposing mutations in the human genome for diagnostics, carrier identification and pharmacogenetic profiling.
Handedness, Left/Right: Genetics
Authors: Jones Gregory V , Martin Maryanne
Published: September 2006

A notable characteristic of the human species is that a majority of its population tends to favor the use of the right hand rather than the left, while a minority tends to favor the use of the left hand rather than the right. It has been often proposed that this pattern of behavior, although subject to modulation by social and other factors, represents a manifestation of underlying genetic variation.
Hereditary Nonpolyposis Colorectal Cancer
Authors: Frayling Ian
Published: September 2006

An inherited cancer predisposition syndrome characterized clinically by a propensity to colorectal, endometrial and other tumors, and molecularly by germline mutations in DNA mismatch repair genes.
DNA Coiling and Unwinding
Authors: Hugodot Yannick , Duguet Michel
Published: September 2006

The double‐helical structure of DNA and its higher orders of coiling are tightly controlled by two classes of enzyme, helicases and topoisomerases. These are part of large protein complexes that control the main DNA transactions within the cell. In humans, defects in these enzymes may result in various diseases.
Circadian Rhythm Genetics
Authors: van der Horst Gijsbertus TJ , Chaves Inês
Published: September 2006

Circadian clocks drive cyclic changes in behavior, physiology and metabolism, have a periodicity of about 24 h, and are entrained to the earthly day–night cycle by light. The circadian oscillator is composed of an autoregulatory feedback loop of clock genes that positively and negatively affect their own transcription levels and each other's.
Cre–
lox
‐Inducible Gene Targeting
Authors: Sauer Brian
Published: September 2006

Cre is a site‐specific DNA recombinase that is useful for either targeted excision or activation of a desired gene in the genome in a temporally and spatially controlled manner. Cre‐based recombination strategies also permit the design of precise chromosome translocations, deletions and duplications, which facilitate the genetic manipulation of the eukaryotic genome.
Yeast Two‐hybrid System and Related Methodology
Authors: Finley Russell L Jr
Published: September 2006

The identification and detailed characterization of the binary interactions between gene products in a cell is an essential step toward understanding the functions of genes and how they control cellular systems. Two‐hybrid assays have become powerful tools for this purpose.
RNA‐binding Proteins: Regulation of mRNA Splicing, Export and Decay
Authors: Gudikote Jayanthi P , Wilkinson Miles F
Published: September 2006

Mammalian messenger ribonucleic acid (mRNA)‐binding proteins regulate gene expression at several steps including pre‐mRNA processing, nucleocytoplasmic export and degradation.
Noncoding RNAs: A Regulatory Role?
Authors: Mattick John Stanley
Published: September 2006

Around 97–98% of the transcriptional output of the human genome is noncoding RNA, which is derived from noncoding RNA genes and from introns in protein‐coding genes. These RNAs may form a higher‐order regulatory network that integrates complex suites of gene activity during differentiation and development.
Histone Acetylation: Long‐range Patterns in the Genome
Authors: Bresnick Emery H , Im Hogune , Johnson Kirby D
Published: September 2006

Modification of core histones by acetylation establishes a chromatin environment permissive for gene expression. Complex patterns of acetylation spanning many kilobases have been identified at certain loci. However, little is known about the regulation and functional consequences of these broad domains of acetylation.
Tooth Morphogenesis and Patterning: Molecular Genetics
Authors: Tucker Abigail Saffron
Published: September 2006

Teeth develop by a series of epithelial–mesenchymal interactions that govern not only where the tooth will form within the developing jaw, but also what type of tooth will develop.
Absolute Pitch: Genetics
Authors: Gregersen Peter K
Published: September 2006

Absolute pitch is a cognitive trait characterized by the ability to identify or name the pitch of a note or ambient sound without the use of a reference pitch.
Complement System and
Fc
Receptors: Genetics
Authors: Roos Anja , Trouw Leendert A , Ioan‐Facsinay Andreea , Daha Mohamed R , Verbeek J Sjef
Published: September 2006

The complement system is a key component of the innate immune system that is involved in eliminating unwanted self and nonself material via cellular and humoral mechanisms. Complement receptors and Fc receptors, expressed on effector cells, have a synergistic role in antibody‐mediated immune modulation and antigen clearance.
Hamartomatous Polyposis Syndromes: Peutz–Jeghers Syndrome and Familial Juvenile Polyposis
Authors: Tomlinson Ian PM
Published: September 2006

The hamartomatous polyposes are rare syndromes but provide fascinating insights into both the different mechanisms by which cancer can develop and the precursor lesions involved.
DNA Repair: Disorders
Authors: Lehmann Alan R
Published: September 2006

Deoxyribonucleic acid 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, many of them cancer‐prone.
Variable Drug Response: Genetic Evaluation
Authors: Stumpf Michael PH , Goldstein David B
Published: September 2006

Pharmacogenetics is the study of genetic variation in response to drugs. Although there is some evidence that drug response genotypes cluster in ethnic groups, this effect is less important than individual variation.
DNA Structure
Authors: Bowater Richard P
Published: September 2006

Deoxyribonucleic acid (DNA) is a polymer of nucleotides. In the cell, DNA usually adopts a double‐stranded helical form, with complementary base‐pairing holding the two strands together. The most stable conformation is called B‐form DNA, although other structures can occur under specific conditions.
Malignant Hyperthermia
Authors: McCarthy Tommie V
Published: September 2006

Malignant hyperthermia is a potentially fatal pharmacogenetic disorder triggered by certain types of anesthetic agents. The skeletal muscle ryanodine receptor gene is the major causative gene for the disorder and for the related myopathy, central core disease.
Protein Misfolding and Degradation in Genetic Disease
Authors: Bross Peter , Andresen Brage S , Corydon Thomas J , Gregersen Niels
Published: September 2006

Molecular disease mechanisms in genetic deficiencie often center on missense mutations and amino‐acid deletions and insertions which affect the folding process, and/or the stability of the folded structure, of proteins.
Friedreich Ataxia
Authors: Koenig Michel
Published: September 2006

Friedreich ataxia is the most common cause of inherited ataxia in Caucasian populations. It affects the spinal cord and the heart, is of autosomal recessive inheritance and is due to the partial deficiency of a mitochondrial protein, frataxin, thought to be involved in the biogenesis of iron–sulfur clusters. The major mutation is a trinucleotide repeat expansion in intron 1 of the frataxin gene, which causes reduced synthesis of the corresponding transcript.
Tay–Sachs Disease
Authors: Mahuran Don J
Published: September 2006

Tay–Sachs disease was first described in the late nineteenth century. Not only has it served as a model for other lysosomal storage diseases but, as its disease mechanisms have been elucidated, other biological processes have been identified and characterized. Interestingly, mouse models of the disease do not produce a phenotype until very late in life, demonstrating that data from mice cannot always be extrapolated to humans.
Nuclear Receptors and Disease
Authors: Love James Daniel
Published: September 2006

Nuclear receptors are ligand‐modulated transcription factors that act in the nucleus to regulate target gene transcription through interaction with cofactor proteins. Owing to their roles in many diverse cellular processes, nuclear receptors are important therapeutic targets and aberrant receptor action results in significant human disease.
Oxidative Phosphorylation (OXPHOS) System: Nuclear Genes and Genetic Disease
Authors: Smeitink Jan AM , Nijtmans Leo , van den Heuvel Lambert
Published: September 2006

The underlying mutations in nuclear genes that directly affect the mitochondrial oxidative phosphorylation system are now known. Advances in this area have profited from progress in various genome projects.
Blood Groups: Molecular Genetic Basis
Authors: Avent Neil D
Published: September 2006

Human blood groups are of clinical significance in transfusion medicine and blood group incompatible pregnancy. Blood groups are due to polymorphic structures on human red cells, may arise from carbohydrates or proteins and include most species of proteins found in red cell membranes including transporters, adhesion molecules, structural proteins, complement control proteins, receptors and membrane‐bound enzymes.
Skin Pigmentation: Genetics
Authors: Rees Jonathan L
Published: September 2006

Differences in skin pigmentation are principally due to variation in the amount and type of melanin produced in cutaneous melanocytes. In humans, a large number of Mendelian disorders of pigmentation, including albinism, are now understood at a genetic level. Only one locus, the melanocortin 1 receptor, has been so far identified to contribute to normal variation in skin and hair color, but it is clear that many other loci (yet to be determined) must also play a role.
Spontaneous Function Correction of Pathogenic Alleles in Inherited Diseases Resulting in Somatic Mosaicism
Authors: Waisfisz Quinten , Joenje Hans
Published: September 2006

Inherited mutations can cause disease, but in monogenic disease correction of just one pathogenic mutation can lead to somatic mosaicism and revert the phenotype, which may ameliorate symptoms. The diseases for which this ‘natural gene therapy’ has been described include Fanconi anemia and Wiskott–Aldrich syndrome, among others.
Hemoglobin Disorders: Gene Therapy
Authors: Persons Derek A , Nienhuis Arthur W
Published: September 2006

Progress in the development of effective globin lentiviral vectors holds promise of making gene therapy for hemoglobin disorders an attainable goal. Formulation of therapeutic strategies to obtain an adequate number of corrected cells in an individual will be a crucial element in achieving eventual success.
Cell Cycle Checkpoint Genes and Cancer
Authors: Funk Jens Oliver
Published: September 2006

Several genes have been identified that control different ‘checkpoints’ in the cell division cycle. Some of these may have clinical significance, in the diagnosis and possible treatment of some cancers.
Gene Amplification and Cancer
Authors: Uchida Kazuhiko
Published: September 2006

Several types of alterations in the deoxyribonucleic acid (DNA) of somatic cells can induce phenotypic changes that lead to cancer, and gene amplification is the most frequently observed type of genetic change associated with cancer. The mechanisms of gene amplification are not well understood, but better understanding of the role played by gene amplification in cancer may lead to new cancer biomarkers and improved prognostic and diagnostic indicators of cancer progression.
Caretakers and Gatekeepers
Authors: Russo Antonio , Migliavacca Manuela , Zanna Ines , Macaluso Marcella , Gebbia Nicola , Bazan Viviana
Published: September 2006

It has now been generally accepted that the genes responsible for familial cancer syndromes can be divided into two categories, known as caretakers and gatekeepers. Caretakers are genes that control the maintenance of the genetic information integrity in each cell while gatekeepers are those genes which directly regulate tumor growth, codifying for proteins which either stimulate or inhibit proliferation, differentiation or apoptosis.
Oncogenic Kinases in Cancer
Authors: Tsatsanis Christos , Zafiropoulos Alexandros , Spandidos Demetrios A
Published: September 2006

Oncogenesis involves the generation and transmission of signals that result in alterations of cell morphology, deregulation of the cell cycle and apoptosis. Transmembrane or cytoplasmic tyrosine and serine/threonine kinases participate both directly and indirectly in cell transformation and tumorigenesis.
Prostate Cancer
Authors: Vogel Walther , Maier Christiane , Paiss Thomas
Published: September 2006

Prostate cancer is a complex disease with an etiology attributed to both genetic and environmental factors. Hereditary prostate cancer is thought to be caused by multiple high‐risk genes following a complex or polygenic pattern. Low‐risk genes may be involved in a significant proportion of sporadic prostate cancers.
Testicular Cancer
Authors: Chaganti RSK
Published: September 2006

Adult testicular germ cell tumors, although rare and curable, are an excellent model system for the study of mechanisms of germ cell transformation, chemotherapy sensitivity and resistance of tumors and regulation of embryonal lineage differentiation.
DNA Helicase‐deficiency Disorders
Authors: Levitt Nicola C , Hickson Ian D
Published: September 2006

Bloom syndrome, Werner syndrome and Rothmund–Thomson syndrome are three human disorders that are associated with premature aging and a predisposition to the development of malignancy. Each of these disorders is caused by a defect in a member of the RecQ family of DNA helicases, enzymes that separate the complementary strands of double‐stranded DNA.
Translocation Breakpoints in Cancer
Authors: Oliveira Andre Mascarenhas , Fletcher Jonathan Alfred
Published: September 2006

Chromosomal translocations are structural abnormalities generated by double‐strand DNA breakages in two or more chromosomes, followed by reciprocal exchange of the segments between the chromosomes. In cancer cells, these translocations often juxtapose regulatory or coding sequences from two different genes, resulting in highly activated oncogenes that regulate proliferation, apoptosis and other aspects of the neoplastic phenotype. Many such translocation‐associated oncogenes have been described in human cancers.
Barrett Esophagus
Authors: Maley Carlo C , Reid Brian J
Published: September 2006

The evolution of neoplastic cell lineages in Barrett esophagus is dominated by mutation, natural selection and genetic drift. The esophageal environment and therapies select for clones with competitive advantages that undergo selective sweeps, driving other cell types to extinction and providing a mechanism for expansion of neutral mutations as hitchhikers on the sweep.
Chromosomal Instability (CIN) in Cancer
Authors: Schmutte Chris
Published: September 2006

Chromosomal instability is definied as an increased rate of gross chromosomal abnormalities combined with loss of heterozygosity and change in ploidy of genes structural CIN, and the inability of cells to maintain a diploid karyotype numerical CIN.
Retinitis Pigmentosa
Authors: Wang Qing , Chen Qiuyun
Published: September 2006

Retinitis pigmentosa is a heterogeneous group of retinal dystrophies that are characterized by photoreceptor cell degeneration, night blindness, a gradual loss of peripheral visual fields and eventual loss of central vision. Several genes responsible for the development of retinitis pigmentosa have now been identified and cloned, and these discoveries have defined the genetic pathways for pathogenesis of retinitis pigmentosa.
DiGeorge Syndrome and Velocardiofacial Syndrome (VCFS)
Authors: Scambler Peter
Published: September 2006

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. The creation of mouse models that mimic the human disorder has identified that the
Tbx1
transcription factor gene is the major dosage‐sensitive gene in the deletion region and has allowed exploration of the underlying developmental pathways disrupted in these syndromes.
Globin Genes: Polymorphic Variants and Mutations
Authors: Old John Michael
Published: September 2006

The globin genes encode the globin chains that make up hemoglobin (Hb). More than 1000 polymorphic variants of the globin genes have been characterized, consisting of single nucleotide substitutions through to complex gene rearrangements. Most globin gene mutations either alter the amino acid sequence of a globin chain, creating an abnormal hemoglobin such as Hb S, or cause a reduction in the synthesis of one or more normal globin chains (the thalassemia disorders). A few mutations cause both types of defect, while others are simple natural polymorphisms that are used as DNA markers.
Marfan Syndrome
Authors: Robinson Peter N
Published: September 2006

Marfan syndrome is a common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the eye, skeleton and cardiovascular system. Mutations in the gene for fibrillin‐1 (
FBN1
) can cause Marfan syndrome.
Gonadotropin Hormones: Disorders
Authors: Achermann John C , Jameson J Larry
Published: September 2006

Abnormalities in gonadotropin hormone release and function can arise from mutations in a variety of genes expressed throughout the hypothalamic–pituitary (gonadotrope)–gonadal axis. The identification and characterization of these naturally occurring mutations are providing important information about the reproductive axis in humans and may result in improved treatment and counseling for patients with infertility problems.
Mutation Rate: Sex Biases
Authors: Hurst Laurence D
Published: September 2006

At least in humans, more spontaneous point mutations occur in the male germ line than in the female germ line. One explanation for this is the greater number of germ‐cell divisions in males than in females.
Erythrocyte Membrane Disorders
Authors: Tse Willian T
Published: September 2006

Erythrocyte membrane disorders, such as hereditary spherocytosis and elliptocytosis, usually present with abnormal red cell shapes, hemolysis and anemia. Recent genomic research has shown that defects in proteins that constitute the erythrocyte membrane skeleton are often the causes of these disorders.
Hypertrophic Cardiomyopathy
Authors: Semsarian Christopher , Chung Man‐Wei
Published: September 2006

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder characterized by cardiac hypertrophy. Discovery of the genetic basis of HCM has had a major impact on understanding disease pathogenesis, diagnosis and clinical management. Future studies will further elucidate these areas and improve our understanding of cardiac biology and function.
Hair Loss: Genetics
Authors: Irvine Alan
Published: September 2006

Hair formation is a complex molecular process, and abnormal hair is a feature of many genetic disorders. There is increasing understanding of the molecular basis of several single‐gene disorders with hair loss, although the genetic basis for the commonest forms of hair loss is not well understood.
Lens Disorders
Authors: Francis Peter
Published: September 2006

The function of the crystalline lens of the eye is to focus light onto the retina. It has a unique structure, as lens cells are never shed but continually added throughout life. Cataract, or opacification, is by far the most common disorder affecting the lens.
DNA Damage Response
Authors: Khanna Kum Kum , Tibbetts Randal S
Published: September 2006

The deoxyribonucleic acid (DNA) damage response pathway is a surveillance network whereby lesions are eliminated from DNA. DNA damage response detects aberrant DNA and chromosomal structures and coordinates it in some manner with each of the other DNA transactions, including regulation of the cell cycle, DNA repair, replication and under some circumstances the triggering of programmed cell death. Many aspects of DNA damage signaling are highly conserved throughout evolution.
Endometrial Cancer
Authors: Ellenson Lora Hedrick
Published: September 2006

Endometrial cancer is the most common malignancy of the female genital tract in the United States. Molecular studies have led to key insights into the pathogenesis of endometrial carcinoma and have provided a genetic basis for the current broad classification of this common malignancy. The recent development of a mouse model will promote studies aimed at understanding the interaction of genetic alterations and hormones in the pathogenesis of endometrioid carcinoma.
Peroxisome Biogenesis Disorders
Authors: Fujiki Yukio
Published: September 2006

Peroxisome biogenesis disorders are progressive disorders characterized by loss of multiple peroxisomal metabolic functions. These diseases, consisting of 12 complementation groups, are inherited in an autosomal recessive manner and are caused by defects in peroxisome assembly.
Brain Tumors
Authors: Cummings Thomas J , McLendon Roger E , Bigner Darell D
Published: September 2006

Brain tumor genetics allow for improved classification and development of therapeutic options for certain primary brain tumors. Tumors with specific genetic alterations and molecular profiles are also associated with certain inherited familial cancer syndromes.
Methylated DNA‐binding Proteins
Authors: Ballestar Esteban , Esteller Manel
Published: September 2006

The information encoded by deoxyribonucleic acid methylation is interpreted by a family of proteins that share the methylated CpG‐binding domain. These proteins are associated with histone deacetylase and mediate gene silencing through the modification of chromatin.
DNA Methylation and Mutation
Authors: Pfeifer Gerd P
Published: September 2006

The human genome contains about 50 million 5‐methylcytosine bases, most of them occurring at the CpG dinucleotide sequence. Methylated CpG dinucleotides are the targets of several of the mutations, mostly transition mutations, found in human genetic diseases and cancer.
Mitochondrial DNA: Fate of the Paternal Mitochondrial Genome
Authors: Cummins Jim
Published: September 2006

Elimination of the paternal mitochondrial deoxyribonucleic acid among most eukaryotic organisms is achieved by a diverse array of species‐ and strain‐specific mechanisms that help to ensure homoplasmy (a single type of genome), probably to suppress the possibility of invasion of selfish genetic elements. This may reflect the outcome of hierarchical selection pressures on multiple genomes.
Telomerase: Structure and Function
Authors: Hansen Nathaniel J , Poole Joseph C , Andrews Lucy G , Tollefsbol Trygve O
Published: September 2006

Telomerase, the enzyme that completes DNA replication at the termini of eukaryotic chromosomes, is an important factor in chromosomal stability, cellular senescence and tumorigenesis.
DNA Replication Fidelity
Authors: Friedberg Errol C , Fischhaber Paula L
Published: September 2006

DNA polymerases are proteins that catalyse the polymerization of DNA. Fidelity in this process refers to the ability of the polymerase to avoid or to correct errors in the newly synthesized DNA strand.
Desmin‐related Myopathies
Authors: Goldfarb Lev G , Vicart Patrick , Goebel Hans H
Published: September 2006

Outstanding progress in elucidating the pathology of muscular disorders at light and electron microscopic levels has allowed the identification of proteins involved in pathological alterations. This, in turn, has led to discoveries of multiple genes and mutations associated with previously poorly understood conditions. An unexpected result is that phenotypically similar and pathogenetically related neuromuscular disorders are associated with mutations in one or the other of several interacting proteins.
Thyroid Cancer: Molecular Genetics
Authors: Ludgate Marian , Evans Carol
Published: September 2006

The thyroid comprises two specialized cell types, follicular thyrocytes and C cells. Papillary and follicular cancers are differentiated carcinomas of thyrocytes; medullary cancers arise from the C cells. A spectrum of thyroid‐specific and nonspecific gene mutations and rearrangements underlines the molecular mechanisms resulting in thyroid cancer.
Genomics, Pharmacogenetics and Proteomics: An Integration
Authors: Wilkins Martin R , Shiga Tsuyoshi , Hughes Robert , Town Margaret
Published: September 2006

Pharmacogenomics studies the influence of the genome on drug response, whereas proteomics is concerned with the range and type of proteins produced by an individual. These techniques may be used to improve drug discovery, identification and validation.
Preparation Artefacts in Proteomics: Technological Issues
Authors: Righetti Pier Giorgio , Hamdan Mahmoud
Published: September 2006

In addition to taking into account the more than 200 endogenously produced posttranslational modifications, a detailed analysis of proteins separated by two‐dimensional electrophoresis must consider other modifications that a protein can experience during the various steps of its separation.
Brain Trauma Leads to Enhanced Lung Inflammation and Injury: Evidence for Role of P4504Fs in Resolution
Authors: Kalsotra Auinash , Zhao Jing , Anakk Sayeepriyadarshini , Dash Pramod K , Strobel Henry W
Published: September 2006

Traumatic brain injury is known to cause several secondary effects, which lead to multiple organ dysfunction syndrome. An acute systemic inflammatory response seems to play an integral role in the development of such complications providing the potential for massive secondary injury. We show that a contusion injury to the rat brain causes large migration of inflammatory cells (especially macrophages and neutrophils) in the major airways and alveolar spaces at 24 h post-injury, which is associated with enhanced pulmonary leukotriene B4 (LTB4) production within the lung. However, by 2 weeks after injury, a temporal switch occurs and the resolution of inflammation is underway. We provide evidence that 5-lipoxygenase and Cytochrome P450 4Fs (CYP4Fs), the respective enzymes responsible for LTB4 synthesis and breakdown, play crucial roles in setting the cellular concentration of LTB4. Activation of LTB4 breakdown via induction of CYP4Fs, predominantly in the lung tissue, serves as an endogenous signal to ameliorate further secondary damage. In addition, we show that CYP4Fs are localized primarily in the airways and pulmonary endothelium. Given the fact that adherence to the microvascular endothelium is an initial step in neutrophil diapedesis, the temporally regulated LTB4 clearance in the endothelium presents a novel focus for treatment of pulmonary inflammation after injury.
Computational analysis of thermally stimulated currents in Bi12TiO20 single crystals
Authors: Aneva Z. , Nesheva D. , Vateva E.
Published: September 2006

Critical analysis of several methods for determination of trap parameters using the rate equations of the thermally stimulated currents (TSCs) has been performed and equations for the precise determination of the energy depth of a single trap have been suggested for both slow and fast retrappings. In the slow retrapping regime four different temperature dependences of the capture cross section of the trap can be considered. The approach developed has been applied to determine the main parameters of traps in Bi12TiO20 single crystals from the TSC spectra taken in the temperature range of 77–300K. The thermal cleaning method has been applied to determine the number of the TSC bands in this temperature range and 15 traps have been resolved. Based on this result a multiple peak fitting has been performed, which ensured an excellent coincidence between the total experimental curve and the fitting one. An investigation of TSC above room temperature was also carried out, which has resolved four deep traps having TSC maxima at around 325, 350, 370, and 390K. A value of 0.92eV has been obtained for the depth of the “350K” trap.
Edge Thomson scattering on RFX-mod
Authors: Alfier A. , Pasqualotto R.
Published: September 2006

Electron temperature and density profiles of the RFX-mod experiment are characterized by edge gradients typically steeper than the flatter central region. The main Thomson scattering (TS) diagnostic which measures 84-point profiles along a diameter is mainly devoted to cover the core region. A second TS system has been developed to measure 12-point profiles in the external region 0.8<r∕a<1, with a spatial resolution of 1cm. It uses a single shot ruby laser. Input and collection optics share the same vacuum port and they are mounted on one optical bench, which allows offline aligning the system before connecting it to the vessel. The scattered signal is collected by a row of 12 fibers, while 4 fibers on the sides are used to check the alignment and measure the plasma light. The fibers, arranged in a 4×4 pattern, are fed into a four channel filter spectrometer and the spectrum is detected by a GaAs intensified charge-coupled device camera. The filters are arranged in a zigzag geometry, such that only one detector is needed.
Thomson scattering calibration with ultrabright supercontinuum light source
Authors: Pasqualotto R. , Alfier A.
Published: September 2006

The recently developed supercontinuum light source (SLS) finds a useful application in the calibration of a Thomson scattering (TS) diagnostic. When filter polychromators are used, the relative responsivity of the spectral channels is generally measured with a cw halogen light source from the dc output of the detectors, while the TS signal is measured from an ac output. In a TS system with optical delay lines, like in RFX-mod, a cw light source cannot discriminate differences between the relative responsivities of the positions that share the same polychromator but are connected to different delay lines: this can be achieved with a pulsed white light source instead. In addition a pulsed source with a time response similar to the TS signals would avoid any frequency response problem, because the same ac output of the detectors used for the TS signals could also be used for the calibration. An SLS produces a 5ns Gaussian pulse, with a wide and smooth spectrum that covers the range of 550–1600nm. The SLS provides a light source sufficiently bright to calibrate simultaneously all spectrometers. The experimental setup used for the calibration and obtained results are presented.
Fast gas injection as a diagnostic technique for particle confinement time measurements
Authors: Gray T. , Kaita R. , Majeski R. , Spaleta J. , Timberlake J.
Published: September 2006

The determination of the effective particle confinement time (τp*), i.e., the particle confinement time normalized to recycling coefficient, is difficult when its value is long compared to the discharge duration in magnetically confined plasmas. Recent experiments on the current drive experiment upgrade (CDX-U) spherical torus have successfully achieved a significant reduction in recycling with large-area liquid lithium plasma-facing surfaces. The low recycling walls result in an increase in particle pumping and make it possible to measure τp* in short duration plasmas. Measurements of τp* are made using a supersonic gas injector which is closely coupled to plasma. A fast gas pulse is emitted from the supersonic gas injector, after which the density decay is measured using a microwave interferometer. The design of the supersonic gas injector and its configuration on CDX-U will be presented. The results of this technique will be shown as applied to the study of the effects of a liquid lithium toroidal limiter and evaporative lithium coatings on overall plasma density and τp*.
Experimental estimation of the local energy balance of the potential-confining electrons in tandem-mirror plasmas
Authors: Numakura T. , Cho T. , Kohagura J. , Hirata M. , Minami R. , Miyata Y. , Tomii Y. , Miyake Y. , Kiminami S. , Shimizu K. , Morimoto N. , Itou M. , Imai T. , Miyoshi S. , Ogura K.
Published: September 2006

Our proposed “matrix-type” semiconductor detectors are applied for studying the local energy balance of bulk electrons in the tandem-mirror GAMMA 10. The matrix-type detector array consists of compactly produced six “rows” having different thicknesses of thin dead layers (SiO2) on its surface. Each row has seven channel units (“columns”) for measuring radiation profiles in the radial direction of plasmas. These various SiO2 layers are, thus, employed as “unbreakable ultrathin radiation-absorption filters” having various thicknesses to distinguish x rays from charge-exchange neutral particles and analyze the radial profiles of both plasma ion and electron temperatures simultaneously. The radial profiles of the energy confinement time and the thermal diffusivity obtained from the local energy balance analysis imply that the improvement of the plasma confinement is associated with the strong shear of radial electric fields due to a high plasma confining potentials.