scholarly journals A modified silent substitution electroretinography protocol to separate photoreceptor subclass function in lightly sedated dogs

2020 ◽  
Author(s):  
E. N. Wise ◽  
M. L. Foster ◽  
J. Kremers ◽  
F. M. Mowat
Keyword(s):  
Silent Substitution

Likelihood Models of Somatic Mutation and Codon Substitution in Cancer Genes

Genetics ◽  
2003 ◽  
Vol 165 (2) ◽  
pp. 695-705 ◽  
Author(s):  
Ziheng Yang ◽  
Simon Ro ◽  
Bruce Rannala
Keyword(s):  
Amino Acid ◽  
Gene Mutation ◽  
Somatic Mutation ◽  
Mutation Rates ◽  
Functional Domains ◽  
Cancer Gene ◽  
Structural Domains ◽  
Specific Amino Acid ◽  
Silent Substitution ◽  
Codon Substitution

Abstract The role of somatic mutation in cancer is well established and several genes have been identified that are frequent targets. This has enabled large-scale screening studies of the spectrum of somatic mutations in cancers of particular organs. Cancer gene mutation databases compile the results of many studies and can provide insight into the importance of specific amino acid sequences and functional domains in cancer, as well as elucidate aspects of the mutation process. Past studies of the spectrum of cancer mutations (in particular genes) have examined overall frequencies of mutation (at specific nucleotides) and of missense, nonsense, and silent substitution (at specific codons) both in the sequence as a whole and in a specific functional domain. Existing methods ignore features of the genetic code that allow some codons to mutate to missense, or stop, codons more readily than others (i.e., by one nucleotide change, vs. two or three). A new codon-based method to estimate the relative rate of substitution (fixation of a somatic mutation in a cancer cell lineage) of nonsense vs. missense mutations in different functional domains and in different tumor tissues is presented. Models that account for several potential influences on rates of somatic mutation and substitution in cancer progenitor cells and allow biases of mutation rates for particular dinucleotide sequences (CGs and dipyrimidines), transition vs. transversion bias, and variable rates of silent substitution across functional domains (useful in detecting investigator sampling bias) are considered. Likelihood-ratio tests are used to choose among models, using cancer gene mutation data. The method is applied to analyze published data on the spectrum of p53 mutations in cancers. A novel finding is that the ratio of the probability of nonsense to missense substitution is much lower in the DNA-binding and transactivation domains (ratios near 1) than in structural domains such as the linker, tetramerization (oligomerization), and proline-rich domains (ratios exceeding 100 in some tissues), implying that the specific amino acid sequence may be less critical in structural domains (e.g., amino acid changes less often lead to cancer). The transition vs. transversion bias and effect of CpG dinucleotides on mutation rates in p53 varied greatly across cancers of different organs, likely reflecting effects of different endogenous and exogenous factors influencing mutation in specific organs.

scholarly journals Contribution of human melanopsin retinal ganglion cells to steady-state pupil responses

2010 ◽  
Vol 277 (1693) ◽  
pp. 2485-2492 ◽  
Author(s):  
Sei-ichi Tsujimura ◽  
Kazuhiko Ukai ◽  
Daisuke Ohama ◽  
Atsuo Nuruki ◽  
Kazutomo Yunokuchi
Keyword(s):  
Steady State ◽  
Retinal Ganglion Cells ◽  
Ganglion Cells ◽  
Pupil Diameter ◽  
Retinal Ganglion ◽  
Silent Substitution ◽  
Conventional View ◽  
Rods And Cones ◽  
Direct Measurements ◽  
Stimulation System

The recent discovery of melanopsin-containing retinal ganglion cells (mRGCs) has led to a fundamental reassessment of non-image forming processing, such as circadian photoentrainment and the pupillary light reflex. In the conventional view of retinal physiology, rods and cones were assumed to be the only photoreceptors in the eye and were, therefore, considered responsible for non-image processing. However, signals from mRGCs contribute to this non-image forming processing along with cone-mediated luminance signals; although both signals contribute, it is unclear how these signals are summed. We designed and built a novel multi-primary stimulation system to stimulate mRGCs independently of other photoreceptors using a silent-substitution technique within a bright steady background. The system allows direct measurements of pupillary functions for mRGCs and cones. We observed a significant change in steady-state pupil diameter when we varied the excitation of mRGC alone, with no change in luminance and colour. Furthermore, the change in pupil diameter induced by mRGCs was larger than that induced by a variation in luminance alone: that is, for a bright steady background, the mRGC signals contribute to the pupillary pathway by a factor of three times more than the L- and M-cone signals.

Source localization of S-cone and L/M-cone driven signals using silent substitution flash stimulation

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Sascha Klee ◽  
Jens Liebermann ◽  
Jens Haueisen
Keyword(s):  
Source Localization ◽  
Element Model ◽  
Selective Excitation ◽  
Dipole Localization ◽  
Silent Substitution ◽  
Grand Average ◽  
Compartment Boundary ◽  
Main Components ◽  
Flash Stimulation ◽  
Stimulation Of

AbstractThis study aimed to analyze the neuronal sources of the visual evoked potentials after flash stimulation of the S- and the L/M-cone driven channels of the visual system. For 11 volunteers a 64-channel electroencephalography (EEG) was recorded during selective excitation of both color opponent channels. Individual and grand average data were analyzed topographically. Source localization was carried out using a realistically shaped three compartment boundary element model (BEM) and a mirrored moving dipole model. We found two main components (N1, P1) in all subjects, as well as a third late component in most subjects. For these components significant latency differences (N1=33 ms, P1=22 ms; p<0.05) between both color opponent channels were found. The results showed no differences in the topography and no differences in dipole localization between both color channels. Talairach coordinates of grand averages indicated activation in area 18. Comparison of results of separately stimulated eyes revealed no differences. Our findings showed that neural processing occurs in the same areas of the visual cortex for stimuli with different spectral properties. The signals of S- and L/M-cone driven channels are transmitted in distinct pathways to the cortex. Thus, the observed latency differences might be caused by different anatomical and functional properties of these pathways.

scholarly journals L- and M-Cone isolating ERGs: LED versus CRT stimulation

2008 ◽  
Vol 25 (3) ◽  
pp. 327-331 ◽  
Author(s):  
I.J. MURRAY ◽  
J. KREMERS ◽  
N.R.A. PARRY
Keyword(s):  
Retinal Area ◽  
Silent Substitution ◽  
Close Resemblance ◽  
Spectral Overlap ◽  
Careful Control ◽  
Temporal Profiles

Using double silent substitution, it is possible to generate L-cone and M-cone isolating electroretinograms (ERGs) on a CRT. A major limitation of the technique is that the depth of modulation of cone classes is limited by the restricted luminance of the phosphors and their spectral overlap. To address this problem we have ported the technique to a four-color LED Ganzfeld stimulus (Diagnosis ColorDome). This allows higher retinal illuminances, higher contrasts, and triple silent substitution. With careful control over the retinal area stimulated, we show that the same data can be recorded from both CRT and LED stimuli when luminance, size and cone contrast are kept constant. Importantly, the different temporal profiles of the two devices do not influence the ERG amplitude and phase plots. We present data over a much wider range of luminances (up to about 10000 trolands) and contrasts with the LED stimulator than previously reported with CRT screens. We conclude that the close resemblance between data obtained with an LED stimulator and with a CRT screen indicate that the differences have a purely physiological origin.

The Krüppel-like transcription factor 6 gene in sporadic pituitary tumours.

2003 ◽  
pp. 397-402 ◽  
Author(s):  
V V Vax ◽  
M Gueorguiev ◽  
I I Dedov ◽  
A B Grossman ◽  
M Korbonits
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Pituitary Adenomas ◽  
Small Subset ◽  
Tumour Suppressor Genes ◽  
Pituitary Neoplasms ◽  
Pituitary Tumours ◽  
Cell Cycle Protein ◽  
Exon 2 ◽  
Silent Substitution

The oncogenes and/or tumour suppressor genes which may be involved in the transformation process for the vast majority of pituitary tumours remain unknown. There is substantial evidence for derangement of cell cycle control in such tumours, but cell cycle protein mutations identified in other human malignancies are restricted to only a very small subset of sporadic pituitary neoplasms. Krüppel-like factors are DNA-binding transcriptional regulators with diverse effects including the upregulation of the cell cycle protein p21(WAF1/CIP1). It has been reported that the Krüppel-like transcription factor 6 (KLF6) gene is mutated in a proportion (15-55%) of human prostate cancers, and more recent data are emerging regarding mutated KLF6 in nasopharyngeal carcinomas, astrocytoid gliomas and colorectal cancer. We therefore speculated that other tumours such as pituitary adenomas might also harbour such mutations that may be involved in the control of cell proliferation in the pituitary. The aim of the current study was thus to analyse the KLF6 gene for mutations in sporadic pituitary tumours. We analysed 60 pituitary adenomas (15 GH-, four ACTH-, two PRL-secreting and 39 non-functioning) with direct sequence analysis of exons 2 and 3 of the KLF6 gene, the region where most of the previously described mutations are located. Three non-functioning pituitary adenomas of the 60 pituitary tumours (5%) had two identical sequence changes in exon 2 (missense mutation Val165Met, 523G-->A and a silent substitution in Ser77Ser codon 261C-->T). Analysis of genomic DNA extracted from peripheral lymphocytes in one patient confirmed these changes to be present in the germline and they therefore probably represent polymorphisms, although we cannot exclude the possibility that these are predisposing germline mutations. We conclude that mutations of the KLF6 gene are unlikely to play an important role in sporadic pituitary tumorigenesis.

scholarly journals Prevalence of AIP mutations in a large series of sporadic Italian acromegalic patients and evaluation of CDKN1B status in acromegalic patients with multiple endocrine neoplasia

2010 ◽  
Vol 163 (3) ◽  
pp. 369-376 ◽  
Author(s):  
G Occhi ◽  
G Trivellin ◽  
F Ceccato ◽  
P De Lazzari ◽  
G Giorgi ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Collaborative Study ◽  
Point Mutations ◽  
Pituitary Tumors ◽  
Copy Number Variations ◽  
Age At Diagnosis ◽  
Interacting Protein ◽  
Silent Substitution ◽  
Endocrine Neoplasia ◽  
High Age

BackgroundGermline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene and the p27KIP1 encoding gene CDKN1B have been associated with two well-defined hereditary conditions, familial isolated pituitary adenoma (FIPA) and multiple endocrine neoplasia type 4 (MEN4). Somatotropinomas are present in most AIP mutated FIPA kindreds, as well as in two-thirds of MEN4 patients who carry pituitary tumors.MethodsGermline DNA samples of 131 Italian sporadic acromegalic patients including 38 individuals with multiple tumors, and of six FIPA families (four homogeneous for prolactinomas and two heterogeneous with prolactin/nonfunctioning pituitary adenomas) were collected in a multicentric collaborative study. The prevalence of AIP and CDKN1B gene point mutations and copy number variations were evaluated.ResultsTwo novel (IVS3+1G>A and c.871G>A) and one previously described (c.911G>A) AIP mutations were detected in four apparently sporadic cases (3.1%) with relatively high age at diagnosis (49±18, range 30–67). No mutations/rearrangements were detected in FIPA families. The highly conserved c.871G>A substitution was detected in a patient who also carried a MEN1 mutation suggesting that she is a double heterozygote. The possible pathogenic effect on AIP splicing of the silent substitution c.144G>A found in another patient was ruled out using a minigene-based approach. CDKN1B mutations/rearrangements were neither identified in patients with multiple neoplasia nor in FIPA families.ConclusionAIP is mutated in about 3% of apparently sporadic acromegalic patients. The relatively high age at diagnosis, as well as its sporadic presentation, suggests that these patients are carriers of mutations with reduced pathogenicity. p27KIP1 is unlikely to represent the common unifying nonendocrine etiology for acromegaly and cancer.

scholarly journals Sequence Diversity of the oprI Gene, Coding for Major Outer Membrane Lipoprotein I, among rRNA Group I Pseudomonads

1998 ◽  
Vol 180 (24) ◽  
pp. 6551-6556 ◽  
Author(s):  
Daniel De Vos ◽  
Christiane Bouton ◽  
Alain Sarniguet ◽  
Paul De Vos ◽  
Marc Vauterin ◽  
...  
Keyword(s):  
Outer Membrane ◽  
The Other ◽  
Widespread Distribution ◽  
Phylogenetic Marker ◽  
Silent Substitution ◽  
Group I ◽  
Gene Coding ◽  
Outer Membrane Lipoprotein ◽  
Membrane Lipoprotein

ABSTRACT The sequence of oprI, the gene coding for the major outer membrane lipoprotein I, was determined by PCR sequencing for representatives of 17 species of rRNA group I pseudomonads, with a special emphasis on Pseudomonas aeruginosa andPseudomonas fluorescens. Within the P. aeruginosa species, oprI sequences for 25 independent isolates were found to be identical, except for one silent substitution at position 96. The oprI sequences diverged more for the other rRNA group I pseudomonads (85 to 91% similarity with P. aeruginosa oprI). An accumulation of silent and also (but to a much lesser extent) nonsilent substitutions in the different sequences was found. A clustering according to the respective presence and/or positions of the HaeIII, PvuII, andSphI sites could also be obtained. A sequence cluster analysis showed a rather widespread distribution of P. fluorescens isolates. All other rRNA group I pseudomonads clustered in a manner that was in agreement with other studies, showing that the oprI gene can be useful as a complementary phylogenetic marker for classification of rRNA group I pseudomonads.

scholarly journals Pulses of melanopsin-directed contrast produce highly reproducible pupilresponses that are insensitive to a change in background radiance

2018 ◽  
Author(s):  
Harrison McAdams ◽  
Aleksandra Sasha Igdalova ◽  
Manuel Spitschan ◽  
David H. Brainard ◽  
Geoffrey K. Aguirre
Keyword(s):  
Blue Light ◽  
Human Subjects ◽  
Clinical Pathology ◽  
Primary Interest ◽  
High Reproducibility ◽  
Pupil Response ◽  
Silent Substitution ◽  
Temporal Shape ◽  
Pupil Constriction ◽  
Average Pupil

AbstractPurposeTo measure the pupil response to pulses of melanopsin-directed contrast, and compare this response to those evoked by cone-directed contrast and spectrally-narrowband stimuli.Methods3-second unipolar pulses were used to elicit pupil responses in human subjects across 3 sessions. Thirty subjects were studied in Session 1, and most returned for Sessions 2 and 3. The stimuli of primary interest were “silent substitution” cone‐ and melanopsin-directed modulations. Red and blue narrowband pulses delivered using the post-illumination pupil response (PIPR) paradigm were also studied. Sessions 1 and 2 were identical, while Session 3 involved modulations around higher radiance backgrounds. The pupil responses were fit by a model whose parameters described response amplitude and temporal shape.ResultsGroup average pupil responses for all stimuli overlapped extensively across Sessions 1 and 2, indicating high reproducibility. Model fits indicate that the response to melanopsin-directed contrast is prolonged relative to that elicited by cone-directed contrast. The group average cone‐ and melanopsin-directed pupil responses from Session 3 were highly similar to those from Sessions 1 and 2, suggesting that these responses are insensitive to background radiance over the range studied. The increase in radiance enhanced persistent pupil constriction to blue light.ConclusionsThe group average pupil response to stimuli designed through silent substitution provides a reliable probe of the function of a melanopsin-mediated system in humans. As disruption of the melanopsin system may relate to clinical pathology, the reproducibility of response suggests that silent substitution pupillometry can test if melanopsin signals differ between clinical groups.

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