The function of ?-synuclein, a soluble protein abundant in the brain and concentrated at presynaptic terminals, is still undefined. Yet, ?-synuclein overexpression and the expression of its A30P mutant are associated with familial Parkinson's disease. Working in cell-free conditions, in two cell lines as well as in ...
PubMed Central
The fibrillization of ?-synuclein (?-syn) is a key event in the pathogenesis of ?-synucleinopathies. Mutant ?-syn (A53T, A30P, or E46K), each linked to familial Parkinson's disease, has altered aggregation properties, fibril morphologies, and fibrillization kinetics. Besides ?-syn, Lewy bodies also contain several ...
PubMed
Mutations in the N-terminus of the gene encoding ?-synuclein (?-syn) are linked to autosomal dominantly inherited Parkinson's disease (PD). The vast majority of PD patients develop neuropsychiatric symptoms preceding motor impairments. During this premotor stage, synucleinopathy is first detectable in the olfactory bulb (OB) and brain stem nuclei; however its impact on interconnected brain regions ...
Lewy bodies composed of aggregates of ?-synuclein (?S) in the brain are the main histopathological features of Lewy body diseases (LBD) such as Parkinson's disease and dementia with Lewy bodies. Mutations such as E46K, A30P and A53T in the ?S gene cause autosomal dominant LBD in a number of kindreds. Although these mutations accelerate ...
The major component of neural inclusions that are the pathological hallmark of Parkinson's disease are amyloid fibrils of the protein ?-synuclein (aS). Here we investigated if the disease-related mutation A30P not only modulates the kinetics of aS aggregation, but also alters the structure of amyloid fibrils. For this aim we optimized ...
We identified three S. cerevisiae lipid elongase null mutants (elo1?, elo2?, and elo3?) that enhance the toxicity of alpha-synuclein (?-syn). These elongases function in the endoplasmic reticulum (ER) to catalyze the elongation of medium chain fatty acids to very long chain fatty acids, which is a component of sphingolipids. Without ?-syn expression, the various elo ...
Familial Parkinson disease (PD) due to the A30P mutation in the SNCA gene encoding alpha-synuclein is clinically associated with PD symptoms. In this first pathoanatomical study of the brain of an A30P mutation carrier, we observed neuronal loss in the substantia nigra, locus coeruleus, and dorsal motor vagal nucleus, as well as widespread occurrence of alpha-synuclein immunopositive Lewy bodies, ...
Tests of available reduced-virulence auxotrophic mutants of S. typhi showed the aspartate mutant to be ppc, deficient of phosphoenolpyruvate carboxylase; a PAB mutant to be affected at the locus mutated in S. typhimurium mutants pab-501 and pab-503 and mu...
National Technical Information Service (NTIS)
Aggregation of alpha-synuclein (alpha-SYN) plays a key role in Parkinson's disease. We have previously shown that aggregation of alpha-SYN in vitro is accelerated by addition of FK506 binding proteins (FKBP) and that this effect can be counteracted by FK506, a specific inhibitor of these enzymes. In this paper, we investigated in detail the effect of FKBP12 on early aggregation and on fibril ...
Morphogenetic mutants of the colonial green alga, Volvox carteri f. nagariensis, were induced by chemical mutagenesis. The 68 independent mutants are classified into 12 readily identifiable phenotypes affecting various stages of asexual development. Nine of the mutants are temperature sensitive with normal ...
Parkinson's disease (PD) is characterized by the polymerization of wild-type (WT) or mutant alpha-synuclein (AS) into aggregates and fibrils, which are observed as Lewy bodies (LBs) and Lewy neurites (LNs) in PD patients. However, inability to demonstrate aggregation in many cell culture systems is a major drawback for effective in vitro modeling of AS aggregation. Utilizing ...
The ?-synuclein has been implicated in the pathophysiology of Parkinson's disease (PD), because mutations in the alpha-synuclein gene cause autosomal-dominant hereditary PD and fibrillary aggregates of alpha-synuclein are the major component of Lewy bodies. Since presynaptic accumulation of ?-synuclein aggregates may trigger synaptic dysfunction and degeneration, we have analyzed alterations in ...
Although the structures of the wild type (WT) and mutants (A53T, A30P, E46K) of ?-synuclein (?-syn) proteins related to Parkinson's disease have been studied extensively using both experimental and theoretical tools, the relationships between the structural properties and thermodynamic preferences at a molecular ...
NASA Astrophysics Data System (ADS)
Genetic suppression refers to the phenomenon in which the mutant phenotype is restored to normal without affecting the mutant allele itself. Enhancement refers to the phenomenon in which a mutant phenotype is made more extreme; both suppression and enhanc...
Proteosomal degradation of proteins is one of the major mechanisms of intracellular protein turnover. Failure of the proteosome to degrade misfolded protein is implicated in the accumulation of alpha-synuclein in Parkinson's disease (PD). Heme oxygenase-1 (HO-1), an enzyme that converts heme to free iron, carbon monoxide (CO) and biliverdin (bilirubin precursor) is expressed in response to various ...
A number of chlorate-resistant mutants of Azotobacter vinelandii affected in a general control of nitrogen metabolism were isolated. These mutants could not utilize dinitrogen, nitrate, or nitrite as a nitrogen source. The reason for this inability is that they were simultaneously deficient in nitrogenase and nitrate and nitrite ...
Dihydrofolate reductase mutants with amino acid replacements in the active center (Thr35-->Asp mutant, Arg57-->His mutant and the mutant with triple replacement Thr35-->Asp, Asn37-->Ser, Arg57-->His) were obtained by site-directed mutagenesis. The stabilization effect of trimethoprim and NADP.H on ...
One of the most well known characteristics for Parkinson's disease (PD) is a polymerization of wild-type or mutant alpha-synuclein into aggregates and fibrils, commonly observed as Lewy bodies and Lewy neuritis in PD patients. Although numerous studies on alpha-synuclein fibrillation have been reported, the molecular mechanisms of aggregation and fibrillation are not well ...
BackgroundIncreased reactive microglia are a histological characteristic of Parkinson's disease (PD) brains, positively correlating with levels of deposited ?-synuclein protein. This suggests that microglial-mediated inflammatory events may contribute to disease pathophysiology. Mutations in the gene coding for ?-synuclein lead to a familial form of PD. Based upon our prior findings that ...
... The purpose of this project is to search for mutations that affect breast cancer ... control MN-lO line, the mutant gene will be studied by genetic mapping ...
DTIC Science & Technology
A series of mutants has been isolated with alterations to protein 3A of the outer membrane. These mutations map at the previously described con locus as shown by cotransduction with pyrD. Most of them do not have detectable levels of protein 3A but are thought to have low levels of altered protein. These mutants have been detected by screening con ...
We evaluated the application of gas chromatography-mass spectrometry metabolic fingerprinting to classify forward genetic mutants with similar phenotypes. Mutations affecting distinct metabolic or signaling pathways can result in common phenotypic traits that are used to identify mutants in genetic screens. Measurement of a broad range ...
In Parkinson disease (PD) brain, a progressive loss of dopaminergic neurons leads to dopamine depletion in the striatum and reduced motor function. Lewy bodies, the characteristic neuropathological lesions found in the brain of PD patients, are composed mainly of ?-synuclein protein. Three point mutations in the ?-synuclein gene are associated with familial PD. In addition, genome-wide association ...
Because oligomers and aggregates of the protein ?-synuclein (?S) are implicated in the initiation and progression of Parkinson�s disease, investigation of various ?S aggregation pathways and intermediates aims to clarify the etiology of this common neurodegenerative disorder. Here, we report the formation of short, flexible, ?-sheet-rich fibrillar species by incubation of ?S in the presence of ...
A transgenic Sprague Dawley rat bearing the A30P and A53T ?-synuclein (?-syn) human mutations under the control of the tyrosine hydroxylase promoter was generated in order to get a better understanding of the role of the human ?-syn mutations on the neuropathological events involved in the progression of the Parkinson's disease (PD). This rat displayed olfactory deficits in the absence of motor ...
The linkage relationship of mutants involved in the synthesis of flagella was determined by PBSl transduction. Mutants that affect the structure of flagellin (hag) and temperature-sensitive mutants (flaTS) that produce flagella when grown at 37 C but not when grown at 46 C were examined. All of the ...
The goal of this project is to investigate the steps necessary to effect starch synthesis in developing endosperms of maize with the primary experimental probes being the mutants in which this process is disrupted. The authors have given considerable atte...
We have completed the initial genetic and phenotypic characterization of several classes of new mutants that affect CAB gene expression. The doc mutants (for dark overexpression of cab) are characterized by elevated levels of CAB gene expression in the da...
There are varieties of mutant house mouse (Mus musculus) in which the inner ears are affected (Deol, 1968). Among the mutants, ...
NASA Website
The possibility of the combination of the uvr-12 mutation with the uvrA1 mutation affecting the first step of excision repair was studied in Salmonella abony. Cells of the uvr-12 mutant were 10 times more uv-sensitive and cells of the uvrA1 mutant were 15 times more uv-sensitive than wild type bacteria. The double ...
Energy Citations Database
Vibrio cholerae mutants sensitive to 2-aminopurine (2AP) but with DNA adenine methylase activity similar to parental cells have been isolated. The mutant strains were sensitive to ultraviolet light (UV), methyl methanesulfonate (MMS) and 9-aminoacridine. The spontaneous mutation frequency of the mutants were not significantly ...
We describe a mutant of Streptococcus pyogenes NCTC 8198 with a multidrug efflux phenotype. A mutant selected with ethidium bromide showed a four-fold rise in MIC of norfloxacin, a 16-fold rise in MIC of ethidium bromide and an eight-fold rise in MIC of acriflavine when compared with the parent strain. The MICs were unaffected by the efflux pump inhibitors ...
In healthy brain, less than 5% of ?-synuclein (?-syn) is phosphorylated at serine 129 (pS129). However, within Parkinson disease (PD) Lewy bodies, 89% of ?-syn is pS129. The effects of pS129 modification on ?-syn distribution and solubility are poorly understood. As ?-syn normally exists in both membrane-bound and cytosolic compartments, we examined the binding and dissociation of pS129 ?-syn and ...
Genetic and enzymatic analysis of 17 L-arabinose nonutilizing mutants of Escherichia coli B/r, together with eight previously analyzed mutants of the B gene, show no relationship between the location of a mutant site in the B gene and its effect on the level of inducib1e L-arabinose isomerase, the product of the adjacent ...
... arose as a repult of the fact that different mutants require different conditions for growth ... workers who may wish to use it as a tool in genetics studies. ...
... 1984. Isolation of Catalase-Deficient Escherichia coli Mutants and Genetic Mapping of katE, a Locus that affects Catalase Activity. J. Bacteriol. ...
Three Agrobacterium tumefaciens mutants with chromosomal mutations that affect bacterial virulence were isolated by transposon mutagenesis. Two of the mutants were avirulent on all hosts tested. The third mutant, Ivr-211, was a host range mutant which was avirulent on Bryophyllum ...
Two mutants are described the affect eye pigment in the Culex tarsalis mosquito. The data indicate that carmine eye car, and black eye ble, are each linked to one of the two autosomes. The expression of the two pigment in individuals homozygous for both mutants is unique in that larvae and pupae have car eyes and young adults show both ...
The pterin (red) eye pigments of wild type and mutant strains are separated using a simple paper chromatography system, and the patterns are analyzed to determine where the metabolic pathway is blocked in each mutant. Crosses of these strains are followed for two generations to provide data that students analyze to determine the mode of inheritance of each ...
NSDL National Science Digital Library
To improve sorghum for cellulosic bioenergy uses, brown midrib mutants are being investigated for their ability to increase the conversion efficiency of biomass. brown midrib 6 and 12 (bmr6 and 12) mutants affect monolignol biosynthesis resulting in reduced lignin content and altered lignin composi...
Technology Transfer Automated Retrieval System (TEKTRAN)
Enterococcus faecalis transposon insertion mutants were screened for attenuated killing of the nematode model host Caenorhabditis elegans. The genes disrupted in the attenuated mutants encode a variety of factors including transcriptional regulators, transporters, and damage control and repair systems. Five of nine mutants tested were ...
The following topics are discussed: advantages of yeasts for easily manipulated model systems for studies on molecular biology of eukaryotes; induction of x-ray-resistant mutants by radiations and chemicals; genetics of uv- sensitive mutants; loci of genes affecting radiosensitivity; gene interactions in multiple ...
Mutants of Azotobacter vinelandii affected in N2 fixation in the presence of 1 microM Na2MoO4 (conventional system), 50 nM V2O5, or under Mo deficiency (alternative system) have been isolated after Tn5 mutagenesis with the suicide plasmid pSUP1011. These mutants can be grouped into at least four broad phenotypic classes. ...
Biochemical characterization of 70 temperature-sensitive (ts) mutants of rabies virus has been done by following the appearance of viral proteins and RNA molecules in infected cells at both permissive and nonpermissive temperature. The presence or absence of the nucleocapsid protein (N) was demonstrated by treating infected cells with anti-N fluorescent antibodies. At 33 ...
The morphological relations of 31 flower mutants that appeared after x- ray treatmaent of dormant seeds of P. sativm are discussed. Only one of these mutants is fertile, three others show a significantiy reduced fertility, and the rest are sterile. In 2 mutants the transition from the vegetative to the reproductive phase does ...
Root hairs are an excellent model system to study cell developmental processes as they are easily accessible, single-celled, long tubular extensions of root epidermal cells. In a genetic approach to identify loci important for root hair development, we have isolated eight der (deformed root hairs) mutants from an ethylmethanesulfonate (EMS)-mutagenized Arabidopsis population. ...
Chloroplast ribosomes isolated from a spectinomycin-resistant mutant (spr-1-27-3) of Chlamydomonas reinhardtii that displays non-Mendelian inheritance fail to bind labeled antibiotic, in contrast to ribosomes from wild-type cells. In vitro resistance of this mutant appears to result from the absence of a specific protein in the small subunit of the ...
A new screening procedure was used to isolate 14 gib mutants of Gibberella fujikuroi with modifications in the production of gibberellins. The production of carotenoids and gibberellins was investigated in the gib mutants and in representative car mutants with various modifications of carotenoid biosynthesis. The determinations of ...
Simple de novo screens in Arabidopsis thaliana have previously identified mutants that affect endosperm development but viable-embryo mutants have not been identified. Our strategy to identify autonomous embryo development was to uncouple embryo and endosperm fertilisation. This involved a male-sterile mutant ...
Bacteria are common inhabitants of leaf surfaces, and they can affect the plants on which they live (eg., inciting disease or ice formation, altering plant growth). This report describes randomly generated insertional mutants of Pseudomonas syringae that exhibited decreased abilities to grow or survive on leaves, and the characteristics of these epiphytic ...
ABSTRACT To investigate the biocontrol mechanisms by which the antagonistic Fusarium oxysporum strain Fo47 is active against Fusarium wilt, a Fot1 transposon-mediated insertional mutagenesis approach was adopted to generate mutants affected in their antagonistic activity. Ninety strains in which an active Fot1 copy had transposed were identified with a ...
Flavonoids are low molecular weight secondary plant metabolites with a myriad of functions. As flavonoids affect auxin transport (an important growth-controlling hormone) and are biologically active in eukaryotes, flavonoid mutants were expected to have undescribed architectural phenotypes. The Arabidopsis thaliana transparent testa (tt) ...
Natively disordered proteins are a growing class of anomalies to the structure-function paradigm. The natively disordered protein alpha-synuclein is the primary component of Lewy bodies, the cellular hallmark of Parkinson's disease. We noticed a dramatic difference in dilute solution 1H-15N Heteronuclear Single Quantum Coherence (HSQC) spectra of wild-type alpha-synuclein and two disease-related ...
Parkinson disease (PD) is a neurodegenerative disease with motor as well as non-motor signs in the gastrointestinal tract that include dysphagia, gastroparesis, prolonged gastrointestinal transit time, constipation and difficulty with defecation. The gastrointestinal dysfunction commonly precedes the motor symptoms by decades. Most PD is sporadic and of unknown etiology, but a fraction is ...
Human ?-Synuclein (?Syn) is a natively unfolded protein whose aggregation into amyloid fibrils is involved in the pathology of Parkinson disease. A full comprehension of the structure and dynamics of early intermediates leading to the aggregated states is an unsolved problem of essential importance to researchers attempting to decipher the molecular mechanisms of ?Syn aggregation and formation of ...
Identification of unique features of cancer cells is important for defining specific and efficient therapeutic targets. Mutant p53 is present in nearly half of all cancer cases, forming a promising target for pharmacological reactivation. In addition to being defective for the tumor-suppressor function, mutant p53 contributes to malignancy by blocking a ...
A chilling-sensitive mutant of Arabidopsis thaliana was isolated and subjected to genetic, physiological, and biochemical analysis. The chilling-sensitive nature of the mutant line is due to a single recessive nuclear mutation at a locus designated chs1. In contrast to wild-type plants, which are not adversely affected by low ...
In the present study, animals with a genetic defect in copper metabolism were used as a model organism to study the role of copper in reproduction and to determine whether the disturbances in copper and zinc metabolism affect the testicular tissue and gamete quality in males. Mice with an X-linked mosaic mutation (Atp7a(mo-ms)) exhibit pathological features characteristic of ...
The relationship between corrected skull width and the presence and size of an interfrontal bone is discussed with regard to the effect of certain mutant genes in the mouse known to affect the development of the neural tube. All genes reviewed which increase the incidence of the interfrontal bone and affect the neural tube also change ...
The goal of this project was the elucidation of the pathway of starch biosynthesis in the developing maize endosperm with mutants affecting the process constituting the experimental probes. Studies involving a total of seven different loci were undertaken...
The goal of this project was the elucidation of the pathway of starch biosynthesis in the developing maize endosperm with mutants affecting the process constituting the experimental probes. Studies involving a total of seven different loci were undertaken, with a concentration on four of these. The four studies focus on the following: brittle endosperm1 ...
DOE Information Bridge
Electrophysiological analysis of the Drosophila behavioral mutants Eag and Sh and the double mutant Eag Sh indicates that the products of both genes take part in the control of potassium currents in the membranes of both nerve and muscle. In voltage-clamped larval muscle fibers, Sh affects the transient A current, whereas Eag reduces ...
Photosynthesis rates and photosynthate partitioning were determined for WT and two "isogenic" barley mutants (H. vulgare cv. Steptoe) deficient in NADH:NR activity. The two mutations were at separate loci, with nar1 affecting the NR structural gene and nar2, which is pleiotropic, affecting the moly...
The nth gene of Escherichia coli affects the production of endonuclease III, a glycosylase-endonuclease that attacks DNA damaged by oxidizing agents or by ionizing radiation. An nth insertion mutant and a deletion mutant were studied. nth is located between add and tyrS on the linkage map of E. coli K-12 and was 97% linked to tyrS in a ...
Four rotavirus SA11 temperature-sensitive (ts) mutants and seven rotavirus RRV ts mutants, isolated at the National Institutes of Health (NIH) and not genetically characterized, were assigned to reassortment groups by pairwise crosses with the SA11 mutant group prototypes isolated and characterized at Baylor College of Medicine (BCM). ...
Defective �X174 H protein-mediated DNA piloting indirectly influences the entire viral lifecycle. Faulty piloting can mask the H protein's other functions or inefficient penetration may be used to explain defects in post-piloting phenomena. For example, optimal synthesis of other viral proteins requires de novo H protein biosynthesis. As low protein concentrations affect ...
The molecular basis of the uroporphyrinogen decarboxylase defect in eleven yeast 'uroporphyric' mutants was investigated. Uroporphyrinogen decarboxylase, an enzyme of the haem-biosynthetic pathway, catalyses the decarboxylation of uroporphyrinogen to coproporphyrinogen and is encoded by the HEM12 gene in the yeast Saccharomyces cerevisiae. The mutations were identified by ...
The pectinolytic enterobacterium Erwinia chrysanthemi 3937 causes a systemic disease in its natural host, the African violet (Saintpaulia: ionantha). It produces two structurally unrelated siderophores, chrysobactin and achromobactin. Chrysobactin makes a large contribution to invasive growth of the bacterium in its host. Insertion mutants of a chrysobactin-defective strain ...
Outer membrane alterations were characterized in spontaneous mutants of the Erwinia chrysanthemi 3937jRH, which were selected for resistance to bacteriophage phi EC2. All but one of the mutants analyzed were affected in their lipopolysaccharide (LPS) structure, lacking the entire heterogeneous region of apparent high molecular weight ...
Bacteroides thetaiotaomicron, an obligate anaerobe found in high numbers in human colons, can utilize a variety of polysaccharides. To determine which type of polysaccharide contributes most to the nutrition of B. thetaiotaomicron in vivo, we isolated and characterized transposon-generated mutants deficient in the ability to use different polysaccharides. Some ...
Multiple molecular cues guide neuronal axons to their targets during development. Previous studies in vitro have shown that mechanical stimulation also can affect axon growth; however, whether mechanical force contributes to axon guidance in vivo is unknown. We investigated the role of muscle contractions in the guidance of zebrafish peripheral Rohon-Beard (RB) sensory axons ...
Multiple molecular cues guide neuronal axons to their targets during development. Previous studies in vitro have shown that mechanical stimulation also can affect axon growth, however whether mechanical force contributes to axon guidance in vivo is unknown. We have investigated the role of muscle contractions in the guidance of zebrafish peripheral Rohon-Beard (RB) sensory ...
The testa of higher plant seeds protects the embryo against adverse environmental conditions. Its role is assumed mainly by controlling germination through dormancy imposition and by limiting the detrimental activity of physical and biological agents during seed storage. To analyze the function of the testa in the model plant Arabidopsis, we compared mutants ...
BackgroundAlpha-synuclein is a presynaptic protein with a proposed role in neurotransmission and dopamine homeostasis. Abnormal accumulation of ?-synuclein aggregates in dopaminergic neurons of the substantia nigra is diagnostic of sporadic Parkinson's disease, and mutations in the protein are linked to early onset forms of the disease. The folded conformation of the protein varies depending upon ...
We have completed the initial genetic and phenotypic characterization of several classes of new mutants that affect CAB gene expression. The doc mutants (for dark overexpression of cab) are characterized by elevated levels of CAB gene expression in the dark; however, unlike the previously isolated de-etiolated ...
The synthesis of viral-specified glycoproteins, and their appearance on cell surfaces, were compared for cells infected either with syncytial mutants of HSV-1 or with the parental strains from which the mutants were derived. The mutants MP and tsB5, representatives of two different viral genes that affect fusion, ...
We have analyzed the response to vernalization and light quality of six classes of late-flowering mutants (fb, fca, fe, fg, ft, and fy) previously isolated following mutagenesis of the early Landsberg race of Arabidopsis thaliana (L.) Heynh. When grown in continuous fluorescent illumination, four mutants (fca, fe, ft, and fy) and the Landsberg wild type ...
The dwarf pea (Pisum sativum) mutants lka and lkb are brassinosteroid (BR) insensitive and deficient, respectively. The dwarf phenotype of the lkb mutant was rescued to wild type by exogenous application of brassinolide and its biosynthetic precursors. Gas chromatography-mass spectrometry analysis of the endogenous sterols in this ...
Two Rhizobium phaseoli mutants affected in cytochrome expression were obtained by Tn5-mob mutagenesis of the wild-type strain (CE3). Mutant strain CFN031 expressed sevenfold less cytochrome o in culture, expressed cytochrome aa3 under microaerophilic culture conditions, in contrast to strain CE3, and was affected ...
Cells colicinogenic for the colicin plasmids E1 or E2 (Col E1 and Col E2, respectively) were selected for a loss of colicin production after infection with bacteriophage Mu. Extrachromosomal deoxyribonucleic acid that was larger than the original colicin plasmids was found in such cells. A small insertion mutant in Col E1 deoxyribonucleic acid affecting ...
Melibiose carrier mutants, isolated by growing cells on melibiose plus the non-metabolizable competitive inhibitor thiomethyl-beta-galactoside (TMG), were studied to determine sugar and cation recognition abnormalities. Most of the mutants show good transport of melibiose but have lost the recognition of TMG. In addition, most mutants ...
We devised a positive selection procedure for bacterial mutants incapable of producing acid from sugars by fermentation. The method relied on the production of elemental bromine from a mixture of bromide and bromate under acidic conditions. When wild-type Escherichia coli cells were plated on media containing a fermentable sugar and an equimolar mixture of bromide and bromate, ...
A positive selection procedure was devised for bacterial mutants incapable of producing acid from sugars by fermentation. The method relied on the production of elemental bromine from a mixture of bromide and bromate under acidic conditions. When wild-type Escherichia coli cells were plated on media containing a fermentable sugar and an equimolar mixture of bromide and ...
A new type of norfloxacin-resistant mutant of Pseudomonas aeruginosa PAO was isolated. This mutant showed cross resistance to imipenem and chloramphenicol and hypersusceptibility to beta-lactam and aminoglycoside antibiotics. The new norfloxacin resistance gene nfxC was mapped near catA (46 min) on the PAO chromosome. Norfloxacin accumulation was decreased ...
Cells with a genetic defect affecting a biological activity and/or a cell phenotype are generally called "cell mutants" and are a highly useful tool in genetic, biochemical, as well as cell biological research. To investigate peroxisome biogenesis and human peroxisome biogenesis disorders, more than a dozen complementation groups of Chinese hamster ovary ...
A DNA-dependent ATPase has previously been purified from bacteriophage T4-infected Escherichia coli. A mutant phage strain lacking this enzyme has been isolated and characterized. Although the mutant strain produced no detectable DNA-dependent ATPase, growth properties were not affected. Burst sizes were similar for the ...
Mutations in superoxide dismutase 1 (SOD1, EC 1.15.1.1) cause familial amyotrophic lateral sclerosis (fALS); with aggregated forms of mutant protein accumulating in spinal cord tissues of transgenic mouse models and human patients. Mice over-expressing wild-type human SOD1 (WT hSOD1) do not develop ALS-like disease, but co-expression of WT enzyme at high levels with ...
A series 11 gamma-ray-induced mutants at the dihydrofolate reductase (dhfr) locus in Chinese hamster ovary cells has been examined for the types of DNA sequence change brought about by this form of ionizing radiation. All 11 mutants were found to have suffered major structural changes affecting the dhfr gene. In eight of the ...
Mutants of Azotobacter vinelandii affected in N/sub 2/ fixation in the presence of 1 ..mu..M Na/sub 2/MoO/sub 4/ (conventional system), 50 nM V/sub 2/O/sub 5/, or under Mo deficiency (alternative system) have been isolated after Tn5 mutagenesis with the suicide plasmid pSUP1011. These mutants are grouped into four broad phenotypic ...
Among 150 temperature-sensitive Saccharomyces cerevisiae mutants which we have isolated, 15 are specifically affected in ribonucleic acid (RNA) synthesis. Four of these mutants exhibit particularly drastic changes and were chosen for a more detailed study. In these four mutants, RNA synthesis is immediately blocked ...
The work described in this dissertation deals with the effect of cytochrome b on the biogenesis and assembly of the subunits of complex III in the mitochondrial membrane of the yeast Saccharomyces cerevisiae. The cytochrome b-mutants (Box mutants of S. cerevisiae form an excellent system to study such a role of cytochome B. The amounts of cytochrome c/sub ...
The ubiquitous bacterial RNA-binding protein Hfq is involved in stress resistance and pathogenicity. In Sinorhizobium meliloti, Hfq is essential for the establishment of symbiosis with Medicago sativa and for nitrogen fixation. A proteomic analysis identifies 55 proteins with significantly affected expression in the hfq mutant; most of them are involved in ...
We have identified several genes that are required for various morphogenetic processes during gastrulation and tail formation. Two genes are required in the anterior region of the body axis: one eyed pinhead (oep) and dirty nose (dns).oep mutant embryos are defective in prechordal plate formation and the specification of anterior and ventral structures of the central nervous ...
A previously undescribed forward chemical genetic screen using hydrolases affecting the extracellular matrix is introduced. The developed screen takes advantage of the power of chemical genetics and combines it with the known substrate specificity of glycosylhydrolases, resulting in the selection of conditional mutants that exhibit structural defects in ...
The cooperative developmental system of the social amoeba Dictyostelium discoideum is susceptible to exploitation by cheaters-strains that make more than their fair share of spores in chimerae. Laboratory screens in Dictyostelium have shown that the genetic potential for facultative cheating is high, and field surveys have shown that cheaters are abundant in nature, but the cheating mechanisms are ...
The cooperative developmental system of the social amoeba Dictyostelium discoideum is susceptible to exploitation by cheaters�strains that make more than their fair share of spores in chimerae. Laboratory screens in Dictyostelium have shown that the genetic potential for facultative cheating is high, and field surveys have shown that cheaters are abundant in nature, but the cheating mechanisms ...
A new mutant strain of Escherichia coli in which phosphorylation is uncoupled from electron transport was isolated. The new mutant strain has a similar phenotype to the uncB mutant described previously; results from reconstitution experiments in vitro indicate that the new mutation also affects a component of the ...
Parkinson's disease (PD) is the most common motor disorder affecting the elderly. PD is characterized by the formation of Lewy bodies and death of dopaminergic neurons. The mechanisms underlying PD are unknown, but the discoveries that mutations in alpha-synuclein can cause familial PD and that alpha-synuclein accumulates in Lewy bodies suggest that alpha-synuclein ...
We have identified three allelic, maternal-effect mutations that affect developmental and behavioral timing in Caenorhabditis elegans. They result in a mean lengthening of embryonic and postembryonic development, the cell cycle period and life span, as well as the periods of the defecation, swimming and pumping cycles. These mutants also display a number ...
Three groups of mutants defective in trimethylamine oxide (TMAO) reduction were isolated from Salmonella typhimurium LT2 subjected to transposition mutagenesis with Mu d(Apr lac). Mutants were identified by their acidic reaction on a modified MacConkey-TMAO medium. Group I consisted of pleiotropic chlorate-resistant mutants which were ...
Histidine kinase (HK) phosphorelay signaling is a major mechanism by which fungi sense their environment. The maize pathogen Cochliobolus heterostrophus has 21 HK genes, 4 candidate response regulator (RR) genes (SSK1, SKN7, RIM15, REC1), and 1 gene (HPT1) encoding a histidine phosphotransfer domain protein. Because most HKs are expected to signal through RRs, these were chosen for deletion. ...
Growing evidence shows that mutant p53 proteins, which are present in many human tumors, gain oncogenic activities that can actively contribute to tumorigenesis. Mutant p53 proteins have been extensively shown to affect the expression of several genes involved in various aspects of cancer biology. We show here the ChIP-on-chip analysis ...
Antennae are known to be olfactory organs in Drosophila. The leg-aristae-wing complex (lawc) mutation causes a homeotic transformation of the arista (the fifth element of antenna) into tarsal elements. To test how the homeotic transformation of the arista into the tarsus can affect behavior, we studied the olfactory response in the lawc mutants. The data ...
A new mutation of Chlamydomonas reinhardi, cr-1, is characterized. The mutation exhibits Mendelian inheritance and affects the sedimentation velocity and formation of intact chloroplast ribosomes. The mutant grows reasonably well when supplied with sodium acetate as a carbon source, but poorly when forced to grow photosynthetically using carbon dioxide. ...
BackgroundTwo isoforms of the enzyme adenosine kinase (AdK), which differ at their N-terminal ends, are found in mammalian cells. However, there is no information available regarding the unique functional aspects or regulation of these isoforms.ResultsWe show that the two AdK isoforms differ only in their first exons and the promoter regions; hence they arise via differential splicing of their ...
The tricarboxylic acid (TCA) cycle aconitase gene acnA from Streptomyces viridochromogenes T�494 was cloned and analyzed. AcnA catalyzes the isomerization of citrate to isocitrate in the TCA cycle, as indicated by the ability of acnA to complement the aconitase-deficient Escherichia coli mutant JRG3259. An acnA mutant was unable to develop aerial ...
Although induced mutations in traditional laboratory animals have been valuable as models for human diseases, they have some important limitations. Here we propose a complementary approach to discover genes and mechanisms that might contribute to human disorders: the analysis of evolutionary mutant models whose adaptive phenotypes mimic maladaptive human diseases. If the type ...
Two excision-deficient mutants of Neurospora crassa contain normal levels of two enzymes, a single-strand specific endonuclease, which attack uv- irradiated DNA. Mutants of N. crassa have been obtained in which the activity of the latter enzyme as well as an activity with native DNA are simultaneously affected. These ...
We have identified a number of genes in Rhizobium meliloti that affect outer membrane lipopolysaccharides (LPS). These include three genes defined by mutants with different patterns of resistance to a panel of bacteriophages, of which Class 2 and 3 are closely linked to each other but not to Class 1 or 4;another gene, closely linked to Class 2 and 3, ...
Type-A Arabidopsis (Arabidopsis thaliana) response regulators (ARRs) are a family of 10 genes that are rapidly induced by cytokinin and are highly similar to bacterial two-component response regulators. We have isolated T-DNA insertions in six of the type-A ARRs and constructed multiple insertional mutants, including the arr3,4,5,6,8,9 hextuple mutant. ...
The development of root hairs serves as an excellent model to study cell growth using both cytological and genetic approaches. In the past, we have characterized LRX1, an extracellular protein of Arabidopsis consisting of an LRR-domain and a structural extensin domain. LRX1 is specifically expressed in root hairs and lrx1 mutants show severe deficiencies in root hair ...
To study the functions of DNA topoisomerase I and Hpr1 protein, a suppressor mutant of the temperature-sensitive growth of an hpr1 top1-5{sup ts} double mutant was isolated. The isolated triple mutant showed cold-sensitive growth. By complementation of this phenotype, the suppressor gene was cloned. DNA sequencing showed it to be GCR3, ...
The mechanisms controlling oxalate biosynthesis and calcium oxalate formation in plants remain largely unknown. As an initial step toward gaining insight into these regulatory mechanisms we initiated a mutant screen to identify plants that over-accumulate crystals of calcium oxalate. Four new mutants were identified, from an ethyl methanesulfonate ...
Two mutants of Streptococcus lactis ATCC 11454 have been isolated which possess an impaired lactose-fermenting capacity; galactose utilization is also affected, but to a lesser extent. Although the Embden-Meyerhof-Parnas pathway is the major, if not the sole, pathway of carbohydrate metabolism in the three strains, the fermentation end products of the ...
Escherichia coli mutants lacking alcohol dehydrogenase (adh mutants) cannot synthesize the fermentation product ethanol and are unable to grow anaerobically on glucose and other hexoses. Similarly, phosphotransacetylase-negative mutants (pta mutants) neither excrete acetate nor grow anaerobically. However, when a ...
Arabidopsis has three cytokinin receptors genes: CRE1, AHK2, and AHK3. Availability of plants that are homozygous mutant for these three genes indicates that cytokinin receptors in the haploid cells are dispensable for the development of male and female gametophytes. The triple mutants form a few flowers but never set seed, indicating that reproductive ...
Arabidopsis has three cytokinin receptors genes: CRE1, AHK2 and AHK3. Availability of plants that are homozygous mutant for these three genes indicates that cytokinin receptors in the haploid cells are dispensable for the development of male and female gametophytes. The triple mutants form a few flowers but never set seed, indicating that reproductive ...
A mutant of Pseudomonas fluorescens strain B52 deficient in the synthesis of the fluorescent pigment, pyoverdine, was isolated. Absence of pyoverdine and other siderophores was confirmed by gel filtration, a specific siderophore assay, and inhibition studies with the iron chelator EDDA. Both parent and mutant synthesized additional outer membrane proteins ...
Bacillus subtilis mutants with temperature-sensitive growth on complex media were screened for defects in phospholipid metabolism. One mutant was isolated that showed temperature-sensitive net synthesis of phosphatidylethanolamine. The mutant did not accumulate phosphatidylserine at the nonpermissive temperature. In the presence of ...
BackgroundAberrant hyperphosphorylation of tau protein has been implicated in a variety of neurodegenerative disorders. Although a number of protein kinases have been shown to phosphorylate tau in vitro and in vivo, the molecular mechanisms by which tau phosphorylation is regulated pathophysiologically are largely unknown. Recently, a growing body of evidence suggests a link between tau ...