Significance On the basis of amino acid sequence, a polypeptide folds into unique structure. In contrast, aggregation-prone proteins often misfold distinct aggregate conformations. Interestingly, each conformation can dictate different phenotypic consequences, such as cellular toxicity. However, underlying mechanism origin structural diversity protein aggregates has been critical open question. Using intrinsically disordered domain yeast prion Sup35, we revealed diversification is triggered...

Summary The yeast prion [ PSI + ] represents an aggregated state of the translation termination factor Sup35 resulting in tendency ribosomes to readthrough stop codons. In this study, we constructed auxotrophic chromosomal marker, ura3‐197 (nonsense allele), applicable selection for loss psi – ]. Unlike strains, strains exhibit nonsense suppression allele and are not viable presence 5‐fluoroorotic acid (5‐FOA) that is converted a toxic material by product Ura3. We selected 20...

<b>Objective:</b> Mutations of the genes encoding subunits potassium voltage-gated channel, <i>KCNQ2</i> and <i>KCNQ3</i>, have been identified in patients with benign familial neonatal seizures (BFNS). This study set out to determine frequency microchromosomal deletions or <i>KCNQ3</i> associated BFNS. <b>Methods:</b> The subjects were BFNS (n = 22). Microdeletions sought by multiplex ligation-dependent probe amplification then confirmed fluorescence situ hybridization characterized...

The [PSI+] element of the budding yeast is an aggregated form translation release factor Sup35 that propagated and transmitted cytoplasmically in a manner analogous to mammalian prions. N-terminal Sup35, necessary for [PSI+], contains oligopeptide repeats multiple Gln/Asn residues.We replaced Gln/Asn-rich prion with non-Gln/Asn from heterologous strains. These repeat Sup35s novel variant, [PHI+], appeared de novo 103 times more frequent than [PSI+]. [PHI+] was stably inherited non-Mendelian...

Prions are infectious, self-propagating protein conformations.Rnq1 is required for the yeast Saccharomyces cerevisiae prion [PIN ؉ ], which necessary de novo induction of a second prion, [PSI ].Here we isolated ]-eliminating mutant, Rnq1⌬100, that deletes nonprion domain Rnq1.Rnq1⌬100 inhibits not only ] propagation but also [URE3] and huntingtin's polyglutamine aggregate in background [pin ؊ background.Rnq1⌬100, however, does eliminate ].These findings interpreted as showing possible...

Abstract Background: Tropomyosin is an actin‐binding protein, which thought to stabilize actin filaments and influence many aspects of F‐actin. In fission yeast, the cdc8 gene encodes tropomyosin, product Cdc8p known be essential for formation F‐actin contractile ring hence cytokinesis in mitotic cell cycle. Results: We isolated yeast mutants that were defective fusion during conjugation. One them turned out carry a point mutation . found original temperature‐sensitive mutant frequently...

[PIN+] is the prion form of Rnq1 protein unknown function in Saccharomyces cerevisiae. A glutamine/asparagine (Q/N)-rich C-terminal domain necessary for propagation [PIN+], whereas N-terminal region non-Q/N-rich and considered nonprion domain. Here, we isolated numerous single-amino-acid mutations Rnq1, phenotypically similar to Rnq1Δ100, which inhibit [PSI+] state, but not [pin−] when overproduced. The dynamics aggregates was analyzed by semi-denaturing detergent-agarose gel electrophoresis...

[PIN+] is the prion form of Rnq1 in Saccharomyces cerevisiae and necessary for de novo induction a second prion, [PSI+]. The function Rnq1, however, little understood. limited availability defective rnq1 alleles impedes study its structure-function relationship by genetic analysis. In this study, we isolated mutants that are stable maintenance prion. Since there no phenotype available applicable to direct selection or screening loss-of-function mutants, took advantage inhibitory agent,...

An examination was made of the release isoniazid, anhyrous caffeine, theophylline, salicylic acid and indomethacin from hydroxypropylmethylcellulose (HPMC) matrices, results were usually found to follow first order kinetics. rate drug influenced by solubility drug, viscosity content HPMC. As increased, also conversely, as and/or HPMC decreased. A multiple regression analysis used determine relationship between response (release rate) factors (drug solubility, content), a statistically...

The yeast prion [PSI+] represents an aggregated state of the translational release factor Sup35 (eRF3) and deprives termination complexes functional Sup35, resulting in nonsense codon suppression. Protein-remodeling Hsp104 is involved thermotolerance propagation, however structure-and-function relationship for remains unclear. In this study, we engineered 58 chromosomal hsp104 mutants that affect residues considered structurally or functionally relevant to remodeling activity, yet most...

The Gpg1 protein is a Ggamma subunit mimic implicated in the G-protein glucose-signaling pathway Saccharomyces cerevisiae, and its function largely unknown. Here we report that blocks maintenance of [PSI(+)], an aggregated prion form translation termination factor Sup35. Although GPG1 gene normally not expressed, over-expression inhibits propagation only [PSI(+)] but also [PIN(+)], [URE3] prions, toxic polyglutamine aggregate S. cerevisiae. Over-expression does affect expression activity...

[PIN(+)] is a prion form of Rnq1 in Saccharomyces cerevisiae and necessary for the de novo induction second prion, [PSI(+)]. We previously isolated truncated Rnq1, named Rnq1Delta100, as [PSI(+)]-eliminating factor S. cerevisiae. Rnq1Delta100 deletes N-terminal non-prion domain eliminates [PSI(+)] yeast. Here we found that transmissible to absence full-length forming novel variant [RNQ1Delta100(+)]. [RNQ1Delta100(+)] has similar properties it stimulates eliminated by null hsp104Delta...

Our rapid method of microwave-mediated saponification for preparing lysoglycosphingolipids from their parent glycosphingolipids was also able to prepare lysogangliosides or modified lysogangliosides, which were identified by delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometric (DE MALDI-TOF MS) analysis. When GM3, GM2, and GM1 isolated adult human brain gangliosides subjected the saponification, GM3 found give rise only lyso-GM3 containing...

Prions are epigenetic modifiers that cause partially loss-of-function phenotypes of the proteins in Saccharomyces cerevisiae. The molecular chaperone network supports prion propagation cell has seen a great progress last decade. However, cellular machinery to activate or deactivate states remains an enigma, largely due insufficient knowledge prion-regulating factors. Here, we report overexpression [PSI(+) ]-inducible Q/N-rich protein, Lsm4, eliminates three major prions ], [URE3], and...

Prion diseases are progressive fatal neurodegenerative illnesses caused by the accumulation of transmissible abnormal prion protein (PrP). To find treatments for diseases, we searched substances from natural resources that inhibit PrP formation in prion-infected cells. We found high-molecular-weight components insect cuticle extracts reduced levels. The chemical nature these was consistent with melanin. In fact, synthetic melanin produced tyrosine or 3-hydroxy-l-tyrosine inhibited formation....

We found a de novo missense mutation of the gene encoding α1 subunit neuro-nal voltage-gated sodium channel, SCN1A, in patient with repetitive focal seizures. At 5 months age, had first seizure characterized by loss consciousness and clonic convulsions left hand followed secondary generalization lasting for 20 minutes association pyrexia. Although valproate was administered, she has generalized seizures every month, mostly elevated body temperature. Since 32 also different type fearful...

No remedies for prion disease have been established, and the conversion of normal to abnormal protein, a key event in disease, is still unclear. Here we found that substances beetle grub hemolymph, after they were browned by aging month or heating hours, reduced protein (PrP) levels RML prion-infected cells. Active anti-prion components hemolymph resistant protease treatment had molecular weights larger than 100 kDa. Aminoguanidine abolished its activity, suggesting Maillard reaction...

A temperature-sensitive poly(N-isopropylacrylamide) (NIPA) gel containing dextran sulfate was synthesized. Dextran entrapped in the crosslinked poly(NIPA). This hybrid showed a reversible volume change with temperature. The phase transition temperature of almost same as that poly(NIPA) regardless fraction sulfate. ionized copolymer increased degree ionization. water-sorption capacity content. Exclusion and separation proteins were found possible gels various contents.

The cytoplasmic [PSI+] element of budding yeast represents the prion conformation translation release factor eRF-3 (Sup35). Prions are transmissible agents caused by self-seeded highly ordered aggregates (amyloids). Much interest lies in understanding how prions developed and transmitted. However, cellular mechanism involved clearance is unknown. Recently we have reported that excess misfolded multi-transmembrane protein, Dip5ΔC-v82, eliminates [PSI+]. In this study, showed loss was...

Prions are infectious, self-propagating protein conformations. [PSI+], [RNQ+] and [URE3] well characterized prions in Saccharomyces cerevisiae represent the aggregated states of translation termination factor Sup35, a functionally unknown Rnq1, regulator nitrogen metabolism Ure2, respectively. Overproduction Sup35 induces de novo appearance [PSI+] prion or strain, but not non-prion strain. However, themselves, as overexpression mutant Rnq1 protein, Rnq1Δ100, Lsm4, hamper maintenance [PSI+]....