Spontaneous forward mutation versus reversion frequencies for maize Adh1 in pollen

Reliable quantitative data on spontaneous, specific gene mutation frequencies in higher plants and animals are few. Detergents include low natural frequencies and difficulty in obtaining in excess of 10(6) scorable organisms or gametophytes. The alcohol dehydrogenase-1 gene (Adh1 gene; ADH enzyme EC 1.1.1.1.), as expressed in pollen grains, is among the exceptionably suitable; much is known about the maize ADHs, Adh1 function is totally dispensible in an aerobic environment and maize pollen is a trinucleate gametophyte which expresses much of its haploid genome, including Adh1. In particular, there have been two recent methodological advances. First, I am able to cytochemically stain pollen, before or after in vitro germination, for the presence of above 5% normal ADH activity. And second, ADH1- pollen grains survive allyl alcohol (C=C-C-OH) vapour concentrations which kill ADH1+ grains; this selection scheme was developed for yeast by Megnet. My genetic resolution is approximately one mutant (Adh1+-->ADH-) per 10(7) chemically selected, viable gametophytes, and one (phenotypic) revertant (Adh1--->ADH+) per 10(8) unselected gatetophytes. In this note, I compare spontaneous forward mutant frequency with previously published revertant frequencies for one naturally occurring and six ethyl methanesulphonate-induced Adhl-deficient (Adh1-) alleles.     

A recurrent mutation in PALB2 in Finnish cancer families

BRCA1, BRCA2 and other known susceptibility genes account for less than half of the detectable hereditary predisposition to breast cancer. Other relevant genes therefore remain to be discovered. Recently a new BRCA2-binding protein, PALB2, was identified. The BRCA2-PALB2 interaction is crucial for certain key BRCA2 DNA damage response functions as well as its tumour suppression activity. Here we show, by screening for PALB2 mutations in Finland that a frameshift mutation, c.1592delT, is present at significantly elevated frequency in familial breast cancer cases compared with ancestry-matched population controls. The truncated PALB2 protein caused by this mutation retained little BRCA2-binding capacity and was deficient in homologous recombination and crosslink repair. Further screening of c.1592delT in unselected breast cancer individuals revealed a roughly fourfold enrichment of this mutation in patients compared with controls. Most of the mutation-positive unselected cases had a familial pattern of disease development. In addition, one multigenerational prostate cancer family that segregated the c.1592delT truncation allele was observed. These results indicate that PALB2 is a breast cancer susceptibility gene that, in a suitably mutant form, may also contribute to familial prostate cancer development.     

The scid mutation in mice causes a general defect in DNA repair

Mice homozygous for the scid mutation on chromosome 16 have a severe combined immune deficiency as a result of their inability to correctly rearrange their immunoglobulin and T-cell receptor genes. In scid mice, when precursors for B and T lymphocytes reach the stage of development requiring expression of these surface receptors, a defective recombinase system aberrantly cuts and rejoins the receptor gene segments greatly reducing the efficiency of producing functional receptors. As a result, most scid mice have no detectable B or T lymphocytes. We have demonstrated that the scid defect is not specific to lymphocyte development. Myeloid cells and fibroblasts from scid mice show a marked increase in sensitivity to ionizing radiation, indicating that the scid mutation leads to an inability to repair DNA damage induced by ionizing radiation as well as interfering with rearrangement of the immunoglobulin and T-cell receptor genes.     

A mutation in the conserved helix termination peptide of keratin 5 in hereditary skin blistering.

In the hereditary blistering condition epidermolysis bullosa simplex, the skin blisters on trauma following rupture of epidermal basal cells. Clinical variations range from severely incapacitating, especially in early childhood, to mild forms that may not even present clinically. Dowling-Meara epidermolysis bullosa simplex is characterized by clusters of epidermal blisters and keratin clumping in the cytoplasm; recent reports describe potentially causal mutations in keratin 14 (refs 2, 3). Here we describe a 'complementary' mutation at the other end of the other keratin expressed by these cells (K5, coexpressed with K14), a change from a Glu to a Gly in the helix termination peptide, detected by altered antibody binding and confirmed by sequencing using the polymerase chain reaction. The two conserved helix boundary peptides are predicted to be essential for filament assembly, and the requirement for two complementary (type I and type II) keratins is absolute. Epidermolysis bullosa simplex diseases demonstrate the function of the keratin cytoskeleton in resisting compaction stresses which otherwise lead to cell lysis.     

A point mutation in the A gamma-globin gene promoter in Greek hereditary persistence of fetal haemoglobin

Hereditary persistance of fetal haemoglobin (HPFH) is a benign condition characterized by the production in adulthood of more than 1% fetal haemoglobin (HbF, alpha 2 gamma 2) in the absence of erythropoietic stress. Several genetic types have been discerned based on the level of HbF produced, the relative contributions of the duplicated fetal (G gamma and A gamma) globin genes, and the presence or absence of deletions involving the beta and delta genes in cis to the mutation. Greek HPFH is a non-deletion variety in which heterozygotes produce 10-20% HbF, predominantly due to overproduction of the A gamma chain. We have cloned a 40-kilobase (kb) region of the beta-globin cluster from a Greek HPFH allele and report here that a point mutation (G----A) occurs 117 base pairs (bp) 5' to the cap site of the A gamma-globin gene, just upstream of the distal CCAAT sequence. The corresponding region of the G gamma-globin gene is normal. We discuss the implications of this finding for the developmental regulation of globin gene expression.     

Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA

Tandem-repetitive minisatellite regions in vertebrate DNA frequently show substantial allelic variation in the number of repeat units. This variation is thought to arise through processes such as unequal crossover or replication slippage. We show here that the spontaneous mutation rate to new length alleles at extremely variable human minisatellites is sufficiently high to be directly measurable in human pedigrees. The mutation rate at different loci increases with variability in accord with the neutral mutation/random drift hypothesis, and rises to 5% per gamete for the most unstable human minisatellite isolated. Mutations are sporadic, occur with similar frequencies in sperm and oocytes, and can involve the gain or loss of substantial numbers of repeat units, consistent with length changes arising primarily by unequal exchange at meiosis. Germline instability must therefore be taken into account when using hypervariable loci as genetic markers, particularly in pedigree analysis and parenthood testing.     

Genetic and structural analyses suggest that a novel SPG3A mutation causes severe phenotypes of hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP) (MIM# 182600, etc.) is a group of heterogeneous neurodegenerative disorders, characterized by lower limb spasticity, hy- perreflexia, progressive spastic gait abnormalities and an extensor-plantar response[1]. The genot…     

完美C-超图的一个充分条件

混合超图是含有两种超边的超图，一种称为D-超边，一种称为C-超边，它们的区别主要体现在着色要求上．在任一着色中，要求每一D-超边至少有两个点着不同的颜色，每一C-超边至少有两个点着相同的颜色．只含D-超边的超图称为D-超图，只含C-超边的超图称为C-超图．主要讨论了C-超图的完美性问题，给出了完美C-超图的一个充分条件．     

Abnormal gonad development in Kit W-2Bao mice caused by a Kit gene missense mutation

Kit ^W-2Bao mice are single-gene autosomal dominant mutation mice with a B6 background that were bred in our laboratory. Heterozygotes had morphological characteristics including albinism of the abdomen, extremities, and tail, whereas the homozygotes had albinism of the body, black eyes, and infertility. The homozygous mutants showed small, structurally abnormal gonads, and lacked germ cells. Heterozygous male mice lacked germ cells in some contorted seminiferous tubules. This mutation has been mapped at 43.8 cM from the centromere in chromosome 5 by linkage analysis and Kit has been identified as the candidate gene. After Kit full-length mRNA amplification, it was found that a G to T conversion at position 1228 in the ORF changed the 410th amino acid from V to F. This amino acid change could affect the protein’s secondary structure. Heterozygous mutant mice were intercrossed and homozygous mutant mice were bred and genotyped. We found that no primordial germ cells (PGCs) appeared in the urogenital ridge area at fetus day 11.5 in the homozygotes. The number of PGCs also significantly decreased in heterozygotes. At fetus day 15.5, the differentiation of the testis tubule structure was unclear; as well, they contained no spermatogonia. Female homozygotes contained no primordial follicles in the ovary. The numbers of PGCs and primordial follicles were significantly decreased in heterozygous mice. W ^?2Bao is the only mutated site in the extracellular 4th Ig-like domain and this mutant mouse model provides new material for the study of the mechanism of reproductive system development.     

相对论等离子体自发集体辐射

根据极化云电场对裸荷电粒子的阻尼力作的负功，得出相对论等离子体自发集体辐射的功率。对于共振静电辐射的特例，静电辐射功率与朗道阻尼的功率数值相等。     

Spontaneous coherence in a cold exciton gas

If bosonic particles are cooled down below the temperature of quantum degeneracy, they can spontaneously form a coherent state in which individual matter waves synchronize and combine. Spontaneous coherence of matter waves forms the basis of a number of fundamental phenomena in physics, including superconductivity, superfluidity and Bose-Einstein condensation. Spontaneous coherence is the key characteristic of condensation in momentum space. Excitons--bound pairs of electrons and holes--form a model system to explore the quantum physics of cold bosons in solids. Cold exciton gases can be realized in a system of indirect excitons, which can cool down below the temperature of quantum degeneracy owing to their long lifetimes. Here we report measurements of spontaneous coherence in a gas of indirect excitons. We found that spontaneous coherence of excitons emerges in the region of the macroscopically ordered exciton state and in the region of vortices of linear polarization. The coherence length in these regions is much larger than in a classical gas, indicating a coherent state with a much narrower than classical exciton distribution in momentum space, characteristic of a condensate. A pattern of extended spontaneous coherence is correlated with a pattern of spontaneous polarization, revealing the properties of a multicomponent coherent state. We also observed phase singularities in the coherent exciton gas. All these phenomena emerge when the exciton gas is cooled below a few kelvin.     

Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice

Rheumatoid arthritis (RA), which afflicts about 1% of the world population, is a chronic systemic inflammatory disease of unknown aetiology that primarily affects the synovial membranes of multiple joints. Although CD4(+) T cells seem to be the prime mediators of RA, it remains unclear how arthritogenic CD4(+) T cells are generated and activated. Given that highly self-reactive T-cell clones are deleted during normal T-cell development in the thymus, abnormality in T-cell selection has been suspected as one cause of autoimmune disease. Here we show that a spontaneous point mutation of the gene encoding an SH2 domain of ZAP-70, a key signal transduction molecule in T cells, causes chronic autoimmune arthritis in mice that resembles human RA in many aspects. Altered signal transduction from T-cell antigen receptor through the aberrant ZAP-70 changes the thresholds of T cells to thymic selection, leading to the positive selection of otherwise negatively selected autoimmune T cells. Thymic production of arthritogenic T cells due to a genetically determined selection shift of the T-cell repertoire towards high self-reactivity might also be crucial to the development of disease in a subset of patients with RA.     

一类多目标Lipschitz规划的最优性充分条件

对Lipschitz函数定义了广义本性伪凸的概念，并对包含这类广义凸函数的多目标Lipschitz规划的弱有效解给出了充分条件。     

A lethal mutation in mice eliminates the slow calcium current in skeletal muscle cells

Contraction of a vertebrate skeletal muscle fibre is triggered by electrical depolarization of sarcolemmal infoldings termed transverse-tubules (t-tubules), which in turn causes the release of calcium from an internal store, the sarcoplasmic reticulum (SR). The mechanism that links t-tubular depolarization to SR calcium release remains poorly understood. In principle, this link might be provided by the prominent slow calcium current that has been described in skeletal muscle cells of adult frogs and rats. However, blocking this current does not abolish the depolarization-induced contractile responses of frog muscle, and the function of this slow calcium current is unknown. Here we describe measurements of calcium currents in developing skeletal muscle cells of normal rats and mice, and of mice with muscular dysgenesis, a mutation that causes excitation-contraction (E-C) coupling to fail. We find that a slow calcium current is present in skeletal muscle cells of normal animals but absent from skeletal muscle cells of mutant animals. The effect of the mutation is specific to the slow calcium current of skeletal muscle; a fast calcium current is present in developing skeletal muscle cells of both normal and mutant animals, and slow calcium currents are present in cardiac and sensory neurones of mutant animals. We believe this to be the first report of a mutation affecting calcium currents in a multicellular organism. The effects of the mutation raise important questions about the relationship between the slow calcium current and skeletal muscle E-C coupling.