Publications by authors named "Moyed H"

Deficiency of otoferlin causes profound prelingual deafness in humans and animal models. Here, we closely analyzed developmental deficits and degenerative mechanisms in knock-out ( ) mice over the course of 48 weeks. We found otoferlin to be required for proper synapse development in the immature rodent cochlea: In absence of otoferlin, synaptic pruning was delayed, and postsynaptic boutons appeared enlarged at 2 weeks of age.

View Article and Find Full Text PDF

Normal hearing and synaptic transmission at afferent auditory inner hair cell (IHC) synapses require otoferlin. Deafness DFNB9, caused by mutations in the gene encoding otoferlin, might be treated by transferring wild-type otoferlin cDNA into IHCs, which is difficult due to the large size of this transgene. In this study, we generated two adeno-associated viruses (AAVs), each containing half of the otoferlin cDNA Co-injecting these dual-AAV2/6 half-vectors into the cochleae of 6- to 7-day-old otoferlin knock-out () mice led to the expression of full-length otoferlin in up to 50% of IHCs.

View Article and Find Full Text PDF

The multi-C domain protein otoferlin is required for hearing and mutated in human deafness. Some OTOF mutations cause a mild elevation of auditory thresholds but strong impairment of speech perception. At elevated body temperature, hearing is lost.

View Article and Find Full Text PDF

Active zones (AZs) of inner hair cells (IHCs) indefatigably release hundreds of vesicles per second, requiring each release site to reload vesicles at tens per second. Here, we report that the endocytic adaptor protein 2μ (AP-2μ) is required for release site replenishment and hearing. We show that hair cell-specific disruption of AP-2μ slows IHC exocytosis immediately after fusion of the readily releasable pool of vesicles, despite normal abundance of membrane-proximal vesicles and intact endocytic membrane retrieval.

View Article and Find Full Text PDF

Objective: Slowly ramping down initial current intensity after a minimal interval of stimulation is the de facto standard for sham stimulation in transcranial electrical stimulation research. The aim of this study is to further investigate the effectiveness of this method of blinding.

Methods: We have investigated the time course of the cutaneous perception during 10 min of anodal, cathodal, and sham transcranial direct current stimulation, probing the perceived strength and site of the perceived sensation.

View Article and Find Full Text PDF

The hip locus of Escherichia coli affects the frequency of persistence to the lethal consequences of selective inhibition of either DNA or peptidoglycan synthesis. Regulation of the hip operon, which consists of a regulatory region and two genes, hipB and hipA, was examined with strains containing a hip-lac transcriptional fusion placed in single copy at the lambda att site. Disruption of the hip locus increased activity from the fusion 16-fold.

View Article and Find Full Text PDF

High-frequency persistence to the lethal effects of inhibition of either DNA or peptidoglycan synthesis, the Hip phenotype, results from mutations at the hip locus of Escherichia coli K-12. The nucleotide sequence of DNA fragments which complement these mutations revealed an operon consisting of a possible regulatory region, including sequences with modest homology to an E. coli promoter, and two open reading frames which are translated both in vitro and in vivo.

View Article and Find Full Text PDF

Mutations in hipA, a gene of Escherichia coli K-12, greatly reduce the lethality of selective inhibition of peptidoglycan synthesis. These mutations have also been found to reduce the lethality that accompanies either selective inhibition of DNA synthesis or heat shock of strains defective in htpR. In addition, the mutant alleles of hipA are responsible for a reversible cold-sensitive block in cell division and synthesis of macromolecules, particularly peptidoglycan.

View Article and Find Full Text PDF

The hipA gene at 33.8 min on the Escherichia coli chromosome controls the frequency of persistence upon inhibition of murein synthesis; for strains bearing hipA+ the frequency is 10(-6), and for hipA- strains the frequency is 10(-2). hip+ has been cloned by selection for a kanamycin resistance determinant at 33.

View Article and Find Full Text PDF

Except for a small fraction of persisters, 10(-6) to 10(-5), Escherichia coli K-12 is killed by prolonged inhibition of murein synthesis. The progeny of persisters are neither more resistant to inhibition of murein synthesis nor more likely to persist than normal cells. Mutants have been isolated in which a larger fraction, 10(-2), persists.

View Article and Find Full Text PDF

Escherichia coli K-12 strains that carry the Tn10 tetracycline resistance determinant (tet) on multicopy plasmids are hypersensitive to 5a,6-anhydrotetracycline and heated chlortetracycline, two tetracycline derivatives that are relatively more effective as inducers of tet gene expression than as inhibitors of bacterial growth. Twenty spontaneous mutations that confer resistance to anhydrotetracycline (Atr) and resistance to heated chlortetracycline (Ctr) were isolated and characterized. All of these Atr mutations are located in the Tn10 tet region; the majority (18 of 20) have no effect on tetR repressor function.

View Article and Find Full Text PDF

We inserted the Tn10 tetracycline resistance determinant (tet) into the multicopy plasmid pACYC177, and we examined the phenotype of Escherichia coli K-12 strains harboring these plasmids. In agreement with others, we find that Tn10 tet exhibits a negative gene dosage effect. Strains carrying multicopy Tn10 tet plasmids are 4- to 12-fold less resistant to tetracycline than are strains with a single copy of Tn10 in the bacterial chromosome.

View Article and Find Full Text PDF

Of 50 strains of Escherichia coli isolated from blood cultures of bacteremic patients, 14 (28%) were unable to grow on minimal medium at 42 degrees C, compared to only 2 of 50 nonbacteremic strains. In 7 of the 14 bacteremic strains, growth at 42 degrees C was restored by adding nicotinic acid. These unique temperature-sensitive auxotrophic patterns warrant evaluation as a marker correlating with clinical pathogenicity in E.

View Article and Find Full Text PDF

Using a set of overlapping deletion mutants in the tetracycline-resistance transposon Tn10, it has been established that certain regions of the Tn10 genome exert a powerful inhibition on translocation of an intact Tn10 element into the bacterial genome. Such inhibition is strongly temperature dependent: at 37 degrees C translocation is inhibited by at least a factor of 100; no inhibition of translocation is detected at 30 degrees C.

View Article and Find Full Text PDF

The purified enzyme xanthosine-5'-monophosphate (XMP) aminase from Escherichia coli strain B-96 is shown to possess catalytic activity with either glutamine or ammonia as a substrate. This enzyme, which possesses identical subunits, has the following properties: (a) a pH optimum of 8.3 for both aminase and amidotransferase; (b) an apparent K-m for both glutamine and NH3 of 1 mM; (c) an amidotransferase that is approximately 2 times more active than the aminase; (d) a linear relationship between velocity and enzyme concentrationfor both activities; (e) inhibition of both activities by the glutamine analogue 6-diazo-5-oxo-L-norleucine, but the amidotransferase is more sensitive than the aminase; and (f) inhbiition of both activities by the adenosine analogue, psicofuranine, but again the amidotransferase activity is more sensitive than the aminase.

View Article and Find Full Text PDF

3-Methyleneoxindole (MO), an oxidation product of the plant auxin indole-3-acetic acid, can selectively inhibit the replication of herpes-, mengo-, polioviruses, and Sindbis virus. The antiviral action of MO, a sulfhydryl binding compound, is neutralized by 2-mercaptoethanol if the latter is added soon after exposure of infected cells to MO. If addition of 2-mercaptoethanol is delayed, the antiviral action of MO appears to be irreversible.

View Article and Find Full Text PDF

A 100-fold purification of a reduced triphosphopyridine nucleotide/3-methyleneoxindole reductase of peas has been achieved using conventional protein fractionation procedures. Reduced diphosphopyridine nucleotide is 25-fold less effective than reduced triphosphopyridine nucleotide as the reductant. The preparation is free of other reductase activities including those linking the oxidation of reduced pyridine nucleotide coenzymes to the reduction of cytochrome c; vitamins K(1), K(2), and K(3); O(2); nitrate; oxidized glutathione; and thiazolyl blue tetrazolium.

View Article and Find Full Text PDF

Extracts of pea seedlings (Pisum sativum, variety Alaska) oxidize indole-3-acetic acid to a bacteriostatic compound which has been identified as 3-hydroxymethyloxindole. At physiological pH this compound is readily dehydrated to 3-methyleneoxindole, another bacteriostatic agent. The extracts of pea seedlings also contain a reduced triphosphopyridine nucleotide-linked enzyme which reduces 3-methyleneoxindole to 3-methyloxindole, a non-toxic compound.

View Article and Find Full Text PDF