A MUTATIONAL ANALYSIS OF THE TRIPLO-LETHAL REGION OF DROSOPHILA MELANOGASTER

ABSTRACT The extensive analysis of the impact of segmental aneuploidy by LINDSLEY et al. (1972) showed that there are relatively few haplo-lethal loci in the genome and that, with one exception, all loci are triplo-viable. The exceptional locus, which lies in salivary gland chromosome region 83D-E, is associated with lethality when present in either one or three doses in an otherwise diploid individual (DENEU 1976). The genetic nature of the phenomenon has been studied by examining the rates of induction, by ionizing radiation and chemical mutagens, of mutations affecting the dose-sensitive behavior. For both types of mutagens, the frequency of inactivation of the locus is relatively low, and a high proportion of such mutations is associated with chromosomal deficiencies. These data indicate that the locus is infrequently and perhaps never inactivated by a DNA base-pair substitution and thus that the triplo-lethal phenomenon is not associated with a "typical" structural gene. It is possible that the triplo-lethal locus is very small, is reiterated or otherwise complex or is functionally insensitive to base-pair substitutions. The result that all mutations that complement a duplication of the triplo-lethal locus are lethal in heterozygous combination with a normal third chromosome argues that triplo- and haplo-lethality are concomitants of the same phenomenon. Salivary gland chromosome analysis of newly induced deficiencies and duplications localizes the locus to 83D4,5-83E1,2, and further cytogenetic manipulation shows that the dose-sensitive behavior is independent of the position of the locus in the genome.

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Disease-Induced Changes in Salivary Gland Function and the Composition of Saliva

Journal of Dental Research ◽

10.1177/00220345211004842 ◽

2021 ◽

pp. 002203452110048

Author(s):

G.B. Proctor ◽

A.M. Shaalan

Keyword(s):

Salivary Gland ◽

Sjögren Syndrome ◽

Healthy Population ◽

Sjogren Syndrome ◽

Salivary Gland Function ◽

Salivary Gland Dysfunction ◽

Gland Function ◽

And Function ◽

The Impact ◽

Saliva Composition

Although the physiological control of salivary secretion has been well studied, the impact of disease on salivary gland function and how this changes the composition and function of saliva is less well understood and is considered in this review. Secretion of saliva is dependent upon nerve-mediated stimuli, which activate glandular fluid and protein secretory mechanisms. The volume of saliva secreted by salivary glands depends upon the frequency and intensity of nerve-mediated stimuli, which increase dramatically with food intake and are subject to facilitatory or inhibitory influences within the central nervous system. Longer-term changes in saliva secretion have been found to occur in response to dietary change and aging, and these physiological influences can alter the composition and function of saliva in the mouth. Salivary gland dysfunction is associated with different diseases, including Sjögren syndrome, sialadenitis, and iatrogenic disease, due to radiotherapy and medications and is usually reported as a loss of secretory volume, which can range in severity. Defining salivary gland dysfunction by measuring salivary flow rates can be difficult since these vary widely in the healthy population. However, saliva can be sampled noninvasively and repeatedly, which facilitates longitudinal studies of subjects, providing a clearer picture of altered function. The application of omics technologies has revealed changes in saliva composition in many systemic diseases, offering disease biomarkers, but these compositional changes may not be related to salivary gland dysfunction. In Sjögren syndrome, there appears to be a change in the rheology of saliva due to altered mucin glycosylation. Analysis of glandular saliva in diseases or therapeutic interventions causing salivary gland inflammation frequently shows increased electrolyte concentrations and increased presence of innate immune proteins, most notably lactoferrin. Altering nerve-mediated signaling of salivary gland secretion contributes to medication-induced dysfunction and may also contribute to altered saliva composition in neurodegenerative disease.

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Choline Acetyltransferase Induces the Functional Regeneration of the Salivary Gland in Aging SAMP1/Kl -/- Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22010404 ◽

2021 ◽

Vol 22 (1) ◽

pp. 404

Author(s):

Nguyen Khanh Toan ◽

Nguyen Chi Tai ◽

Soo-A Kim ◽

Sang-Gun Ahn

Keyword(s):

Salivary Gland ◽

Choline Acetyltransferase ◽

Salivary Flow ◽

Salivary Secretion ◽

Functional Markers ◽

Tooth Structure ◽

Saliva Secretion ◽

Gland Function ◽

The Impact

Salivary gland dysfunction induces salivary flow reduction and a dry mouth, and commonly involves oral dysfunction, tooth structure deterioration, and infection through reduced salivation. This study aimed to investigate the impact of aging on the salivary gland by a metabolomics approach in an extensive aging mouse model, SAMP1/Klotho -/- mice. We found that the salivary secretion of SAMP1/Klotho -/- mice was dramatically decreased compared with that of SAMP1/Klotho WT (+/+) mice. Metabolomics profiling analysis showed that the level of acetylcholine was significantly decreased in SAMP1/Klotho -/- mice, although the corresponding levels of acetylcholine precursors, acetyl-CoA and choline, increased. Interestingly, the mRNA and protein expression of choline acetyltransferase (ChAT), which is responsible for catalyzing acetylcholine synthesis, was significantly decreased in SAMP1/Klotho -/- mice. The overexpression of ChAT induced the expression of salivary gland functional markers (α–amylase, ZO-1, and Aqua5) in primary cultured salivary gland cells from SAMP1/Klotho +/+ and -/- mice. In an in vivo study, adeno-associated virus (AAV)-ChAT transduction significantly increased saliva secretion compared with the control in SAMP1/Klotho -/- mice. These results suggest that the dysfunction in acetylcholine biosynthesis induced by ChAT reduction may cause impaired salivary gland function

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ChemInform Abstract: Targeting DNA Base Pair Mismatch with Artificial Nucleobases. Advances and Perspectives in Triple Helix Strategy

ChemInform ◽

10.1002/chin.201117262 ◽

2011 ◽

Vol 42 (17) ◽

pp. no-no

Author(s):

Vincent Malnuit ◽

Maria Duca ◽

Rachid Benhida

Keyword(s):

Base Pair ◽

Triple Helix ◽

Base Pair Mismatch ◽

Dna Base ◽

Dna Base Pair

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Varying DNA Base-Pair Size in Subangstrom Increments: Evidence for a Loose, Not Large, Active Site in Low-Fidelity Dpo4 Polymerase

Biochemistry ◽

10.1021/bi051961z ◽

2006 ◽

Vol 45 (9) ◽

pp. 2772-2778 ◽

Cited By ~ 48

Author(s):

Shin Mizukami ◽

Tae Woo Kim ◽

Sandra A. Helquist ◽

Eric T. Kool

Keyword(s):

Active Site ◽

Base Pair ◽

Dna Base ◽

Dna Base Pair

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Substituent effect of large conjugate groups on the DNA base pair derivatives: Density functional study

International Journal of Quantum Chemistry ◽

10.1002/qua.20602 ◽

2005 ◽

Vol 104 (1) ◽

pp. 79-86 ◽

Cited By ~ 1

Author(s):

Fancui Meng ◽

Huanjie Wang ◽

Weiren Xu ◽

Chengbu Liu

Keyword(s):

Base Pair ◽

Substituent Effect ◽

Density Functional ◽

Functional Study ◽

Density Functional Study ◽

Dna Base ◽

Dna Base Pair

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GENETIC INVOLVEMENT OF INTERLEUKIN 4 FOR ASTHMA AND IDENTIFICATION OF POTENTIAL PHYTOCHEMICAL SCAFFOLD THROUGH MOLECULAR DOCKING STUDIES

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2018v10i1.24704 ◽

2018 ◽

Vol 10 (1) ◽

pp. 43 ◽

Cited By ~ 1

Author(s):

S. Sarithamol ◽

Divya V. ◽

Sunitha V. R. ◽

Suchitra Surendran ◽

V. L. Pushpa ◽

...

Keyword(s):

Molecular Docking ◽

Small Molecules ◽

In Silico ◽

Mutational Analysis ◽

Chromosome Region ◽

Specific Treatment ◽

Docking Studies ◽

Interleukin 4 ◽

Receptor Interaction ◽

Drug Candidates

Objective: Interleukin 4, an important cytokine, has the major role in the immunomodulatory responses associated with asthma. The present study focused on the involvement of single nucleotide polymorphism variation (SNP) of interleukin 4 (IL4) in the development of disease, asthma and designing small molecules for the inhibition of IL4 through in silico strategy.Methods: Identification of disease causing SNP will be a wise approach towards the phenotype specific treatment. A human origin deleterious no synonymous SNP of IL4 were found out in the chromosome region 5q31-q33 (rs199929962) (T/C). Proteins of the corresponding nucleotide variation were identified and were subjected to characterization studies for selecting the most appropriate one for further mutational analysis and molecular docking studies.Results: Influence of microbes on SNP variation of IL4 gene leading to asthma was found to be insignificant by metagenomic studies. Gene responsive drugs were identified through environmental factor analysis. The drug candidates including corticosteroids were subjected to protein interaction studies by in silico means. The pharmacophoric feature derived from drug receptor interaction was utilized for virtual screening on a dataset of anti-inflammatory phytomolecules. The scaffolds of ellagic acid and quercetin were identified as potential nonsteroidal entities which can shield the asthmatic activities.Conclusion: Developing small molecules using these scaffolds taking interleukin 4 as a target will be an adequate solution for steroid resistant asthma.

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Spo0A-Dependent Activation of an Extended −10 Region Promoter in Bacillus subtilis

Journal of Bacteriology ◽

10.1128/jb.188.4.1411-1418.2006 ◽

2006 ◽

Vol 188 (4) ◽

pp. 1411-1418 ◽

Cited By ~ 13

Author(s):

Guangnan Chen ◽

Amrita Kumar ◽

Travis H. Wyman ◽

Charles P. Moran

Keyword(s):

Bacillus Subtilis ◽

Base Pair ◽

Promoter Activity ◽

Mutational Analysis ◽

Dna Binding Protein ◽

Base Pairs ◽

Dnase I Footprinting ◽

Level Of Activity ◽

High Level ◽

Activity Dependent

ABSTRACT At the onset of endospore formation in Bacillus subtilis the DNA-binding protein Spo0A directly activates transcription from promoters of about 40 genes. One of these promoters, Pskf, controls expression of an operon encoding a killing factor that acts on sibling cells. AbrB-mediated repression of Pskf provides one level of security ensuring that this promoter is not activated prematurely. However, Spo0A also appears to activate the promoter directly, since Spo0A is required for Pskf activity in a ΔabrB strain. Here we investigate the mechanism of Pskf activation. DNase I footprinting was used to determine the locations at which Spo0A bound to the promoter, and mutations in these sites were found to significantly reduce promoter activity. The sequence near the −10 region of the promoter was found to be similar to those of extended −10 region promoters, which contain a TRTGn motif. Mutational analysis showed that this extended −10 region, as well as other base pairs in the −10 region, is required for Spo0A-dependent activation of the promoter. We found that a substitution of the consensus base pair for the nonconsensus base pair at position −9 of Pskf produced a promoter that was active constitutively in both ΔabrB and Δspo0A ΔabrB strains. Therefore, the base pair at position −9 of Pskf makes its activity dependent on Spo0A binding, and the extended −10 region motif of the promoter contributes to its high level of activity.

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