scholarly journals Fluctuating dental asymmetry in rabbits with familial nonsyndromic coronal suture synostosis

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Mae A. Hyre ◽  
Seth M. Weinberg ◽  
Gregory M. Cooper ◽  
James Gilbert ◽  
Michael I. Siegel ◽  
...  
Keyword(s):  
Fluctuating Asymmetry ◽  
Early Onset ◽  
Asymmetry Index ◽  
Coronal Suture ◽  
Wild Type ◽  
Standard Size ◽  
Molecular Events ◽  
Parametric Statistics ◽  
Systemic Stress ◽  
The Right

Fluctuating dental asymmetry has been linked to conditions of unstable pre- and peri-natal development. Familial, nonsyndromic craniosynostosis disrupts early craniofacial development through localized excessive calvarial ossification leading to the premature fusion of the calvarial sutures. Such abnormal gene expression may also produce systemic stress resulting in developmental instability, thereby affecting normal trait symmetry. The present study was designed to test this hypothesis by examining fluctuating dental asymmetry in an inbred strain of rabbits with familial, nonsyndromic coronal craniosynostosis.  The mesiodistal (MD) and buccolingual (BL) dimensions of the right and left maxillary first molars were measured in four groups of New Zealand white rabbits (N=176; n=40 with early-onset synostosis, n=65 with delayed-onset synostosis, n=46 in-colony, phenotypically normal rabbits, and n=25 wild-type normal controls). For each variable, raw signed asymmetry was calculated (left-right) and tested for assumptions of fluctuating asymmetry (i.e., normality and non-directionality). Any group that did not meet these assumptions was excluded from further analysis. Using a standard size-adjusted, fluctuating asymmetry index, mean fluctuating asymmetry was calculated and compared across groups with non-parametric statistics.  For the MD dimension, no significant (p > 0.05) group differences in mean fluctuating asymmetry were observed among groups. In contrast, rabbits with early-onset synostosis had significantly (p < 0.05) more fluctuating asymmetry in the BL dimension compared to wild-type controls.  Results demonstrate increased fluctuating dental asymmetry in rabbits with nonsyndromic, early-onset coronal suture synostosis and suggest that the molecular events producing suture synostosis locally may have also have systemic effects. Knowledge of these systemic interactions may contribute to a fuller understanding of the phenotypic spectrum observed in individuals with nonsyndromic craniosynostosis.

Early Neuromotor Behavior in Craniosynostotic Rabbits

2003 ◽  
Vol 40 (5) ◽  
pp. 486-492 ◽  
Author(s):  
Ronal L. Mitchell ◽  
Timothy E. Barbano ◽  
H. Wolfgang Losken ◽  
Michael I. Siegel ◽  
Mark P. Mooney
Keyword(s):  
Early Onset ◽  
Rabbit Model ◽  
Zealand White Rabbit ◽  
Psychomotor Development ◽  
Activity Levels ◽  
Coronal Suture ◽  
Wild Type ◽  
Significant Group ◽  
Delayed Onset ◽  
Neuromotor Development

Objective Clinical studies have shown both abnormal and normal mental and psychomotor development in patients with craniosynostosis. However, a number of confounding variables make study comparisons difficult. For these reasons, the present study describes early neuromotor development in an homogeneous rabbit model of craniosynostosis. Design Fifty-three newborn New Zealand white rabbit kits were used: 13 were wild-type, normal control rabbits; 23 had delayed-onset coronal suture synostosis (onset is approximately 57 to 74 days post conception); and 17 had early-onset coronal suture synostosis (onset is approximately 21 to 25 days post conception). All rabbits were observed individually and blindly in an open field, daily for 2 minutes, from birth through the first 14 days of life. The first day of emergence of 10 different mature behaviors and developmental events (in developmental order of appearance: falling, righting, cliff avoidance, first sign of fur, body elevation, head elevation, circling, dragging, eye opening, and hopping) was recorded for each kit. Daily activity levels (grid crossing), and body weights were also recorded. Results Significant group (p < .05) differences were observed in 9 of 11 measures. Both synostosed groups had significantly (p < .05) accelerated onset of behavior in 8 of 9 measures, compared with wild-type controls. The early-onset synostosis group had significantly (p < .05) accelerated onset in five of eight measures, compared with wild-type controls, and three of eight measures, compared with the delayed-onset synostosis group. Conclusions Synostotic rabbits showed precocious neuromotor development possibly through frontal lobe constrictions and altered brain activity from increased intracranial pressure, although primary genetic effects cannot be ruled out.

scholarly journals Natural Zeitgebers Under Temperate Conditions Cannot Compensate for the Loss of a Functional Circadian Clock in Timing of a Vital Behavior in Drosophila

2021 ◽  
pp. 074873042199811
Author(s):  
Franziska Ruf ◽  
Oliver Mitesser ◽  
Simon Tii Mungwa ◽  
Melanie Horn ◽  
Dirk Rieger ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Time Window ◽  
Fruit Fly ◽  
Diel Activity ◽  
Wild Type ◽  
Statistical Measures ◽  
Clock Mutant ◽  
Full Complement ◽  
The Right

The adaptive significance of adjusting behavioral activities to the right time of the day seems obvious. Laboratory studies implicated an important role of circadian clocks in behavioral timing and rhythmicity. Yet, recent studies on clock-mutant animals questioned this importance under more naturalistic settings, as various clock mutants showed nearly normal diel activity rhythms under seminatural zeitgeber conditions. We here report evidence that proper timing of eclosion, a vital behavior of the fruit fly Drosophila melanogaster, requires a functional molecular clock under quasi-natural conditions. In contrast to wild-type flies, period01 mutants with a defective molecular clock showed impaired rhythmicity and gating in a temperate environment even in the presence of a full complement of abiotic zeitgebers. Although period01 mutants still eclosed during a certain time window during the day, this time window was much broader and loosely defined, and rhythmicity was lower or lost as classified by various statistical measures. Moreover, peak eclosion time became more susceptible to variable day-to-day changes of light. In contrast, flies with impaired peptidergic interclock signaling ( Pdf01 and han5304 PDF receptor mutants) eclosed mostly rhythmically with normal gate sizes, similar to wild-type controls. Our results suggest that the presence of natural zeitgebers is not sufficient, and a functional molecular clock is required to induce stable temporal eclosion patterns in flies under temperate conditions with considerable day-to-day variation in light intensity and temperature. Temperate zeitgebers are, however, sufficient to functionally rescue a loss of PDF-mediated clock-internal and -output signaling

scholarly journals COMPLEMENTATION ANALYSIS OF LINKED CIRCADIAN CLOCK MUTANTS OF NEUROSPORA CRASSA

Genetics ◽  
1976 ◽  
Vol 82 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Jerry F Feldman ◽  
Marian N Hoyle
Keyword(s):  
Linkage Group ◽  
Circadian Clock ◽  
Neurospora Crassa ◽  
Period Length ◽  
Complementation Analysis ◽  
Wild Type ◽  
The Right

ABSTRACT A fourth mutant of Neurospora crassa, designated frq-4, has been isolated in which the period length of the circadian conidiation rhythm is shortened to 19.3 ± 0.3 hours. This mutant is tightly linked to the three previously isolated frq mutants, and all four map to the right arm of linkage group VII about 10 map units from the centromere. Complementation tests suggest, but do not prove, that all four mutations are allelic, since each of the four mutants is co-dominant with the frq  + allele—i.e., heterokaryons have period lengths intermediate between the mutant and wild-type—and since heterokaryons between pairs of mutants also have period lengths intermediate between those of the two mutants.

scholarly journals Agrobacterium-Mediated Transformation of Aspergillus awamori in the Absence of Full-Length VirD2, VirC2, or VirE2 Leads to Insertion of Aberrant T-DNA Structures

2004 ◽  
Vol 186 (7) ◽  
pp. 2038-2045 ◽  
Author(s):  
Caroline B. Michielse ◽  
Arthur F. J. Ram ◽  
Paul J. J. Hooykaas ◽  
Cees A. M. J. J. van den Hondel
Keyword(s):  
Single Copy ◽  
Full Length ◽  
Aspergillus Awamori ◽  
Wild Type ◽  
Dna Structures ◽  
Dna Integration ◽  
Virulence Proteins ◽  
Type Transformation ◽  
The Right ◽  
Transposon Insertions

ABSTRACT Reductions to 2, 5, and 42% of the wild-type transformation efficiency were found when Agrobacterium mutants carrying transposon insertions in virD2, virC2, and virE2, respectively, were used to transform Aspergillus awamori. The structures of the T-DNAs integrated into the host genome by these mutants were analyzed by Southern and sequence analyses. The T-DNAs of transformants obtained with the virE2 mutant had left-border truncations, whereas those obtained with the virD2 mutant had truncated right ends. From this analysis, it was concluded that the virulence proteins VirD2 and VirE2 are required for full-length T-DNA integration and that these proteins play a role in protecting the right and left T-DNA borders, respectively. Multicopy and truncated T-DNA structures were detected in the majority of the transformants obtained with the virC2 mutant, indicating that VirC2 plays a role in correct T-DNA processing and is required for single-copy T-DNA integration.

Analysing CYP2D6*4 Allele frequency in Patients with Schizophrenia

2017 ◽  
Vol 41 (S1) ◽  
pp. S101-S102
Author(s):  
V. Djordjevic ◽  
T. Jevtovic Stoimenov
Keyword(s):  
Allele Frequency ◽  
Plasma Concentrations ◽  
Clinical Severity ◽  
Genotype Distribution ◽  
Healthy Individuals ◽  
Wild Type ◽  
Specific Pcr ◽  
Significant Difference ◽  
Schizophrenic Patients ◽  
The Right

IntroductionSchizophrenia is treated with antipsychotics and other psychotropic medications, many of which are substrates for the highly polymorphic CYP2D6 enzyme. The most frequent variant allele is CYP2D6*4- leading cause of poor metabolism (PM) phenotype. PM causes the reduction of therapeutic response, increase the risk of adverse drug reactions and increase the plasma concentration of both drug and its metabolites above the levels of toxicity.The AimAnalysing CYP2D6*4 allele frequency among schizophrenic patients for further individualisation and rationalisation of therapy.Patients and methodsResearch was conducted on 38 schizophrenic patients and 110 healthy individuals. CYP2D6*4 allele was detected with allele specific PCR.ResultsBoth wild type allele carriers are 55% of the schizophrenic patients, 45% are wild type/*4heterozygous, and *4/*4 homozygous are not identified. There is a statistically significant difference in the genotype distribution (P < 0.05) between schizophrenic patients and healthy individuals. Significantly higher *4 allele frequency (37%) comparing to healthy individuals (P < 0.0001) indicates the necessary caution in administration of CYP2D6 substrates. A lower frequency of PMs in schizophrenic patients than in healthy individuals could be explained with CYP2D6 neuroactive substrate metabolism. Forty-five percent of the schizophrenic patients are intermediate metabolisers carrying the higher risk of adverse response to CYP2D6 substrates comparing to wild type homozygous. As none of the analyzed patients was PM, exceeded plasma concentrations of medications above toxic levels are not expected when administrating the right dosage.ConclusionAltered CYP2D6 metabolism may contribute to the vulnerability, clinical severity and treatment outcome of schizophrenia.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Foamy Virus Integration

2004 ◽  
Vol 78 (5) ◽  
pp. 2472-2477 ◽  
Author(s):  
Thomas Juretzek ◽  
Teresa Holm ◽  
Kathleen Gärtner ◽  
Sylvia Kanzler ◽  
Dirk Lindemann ◽  
...  
Keyword(s):  
Infectious Virus ◽  
High Titer ◽  
Foamy Virus ◽  
Wild Type ◽  
Foamy Viruses ◽  
Unintegrated Dna ◽  
Particle Export ◽  
The Right ◽  
Virus Integration ◽  
Transcription And Replication

ABSTRACT It had been suggested that during integration of spumaretroviruses (foamy viruses) the right (U5) end of the cDNA is processed, while the left (U3) remains uncleaved. We confirmed this hypothesis by sequencing two-long terminal repeat (LTR) circle junctions of unintegrated DNA. Based on an infectious foamy virus molecular clone, a set of constructs harboring mutations at the 5′ end of the U3 region in the 3′ LTR was analyzed for particle export, reverse transcription, and replication. Following transient transfection some mutants were severely impaired in generating infectious virus, while others replicated almost like the wild type. The replication competence of the mutants was unrelated to the cleavability of the newly created U3 end. This became obvious with two mutants both belonging to the high-titer type. One mutant containing a dinucleotide artificially transferred from the right to the left end was trimmed upon integration, while another one with an unrelated dinucleotide in that place was not. The latter construct in particular showed that the canonical TG motif at the beginning of the provirus is not essential for foamy virus integration.

Volumetric reduction in various cortical regions of elderly patients with early-onset and late-onset mania

2010 ◽  
Vol 23 (1) ◽  
pp. 149-154 ◽  
Author(s):  
Shou-Hung Huang ◽  
Shang-Ying Tsai ◽  
Jung-Lung Hsu ◽  
Yi-Lin Huang
Keyword(s):  
Elderly Patients ◽  
Early Onset ◽  
Late Onset ◽  
Cingulate Gyrus ◽  
Posterior Cingulate Gyrus ◽  
Left Caudate ◽  
Cortical Regions ◽  
The Right ◽  
Bipolar Patients ◽  
Left Middle

ABSTRACTBackground: Few studies have examined alterations of the brain in elderly bipolar patients. As late-onset mania is associated with increased cerebrovascular morbidity and neurological damage compared with typical/early-onset mania, we investigated differences in the volume of various cortical regions between elderly patients with early-onset versus late-onset mania.Methods: We recruited 44 bipolar patients aged over 60 years, who underwent volumetric magnetic resonance imaging at 1.5 T. The analytic method is based on the hidden Markov random field model with an expectation-maximization algorithm. We determined the volume of each cortical region as a percentage of the total intracranial volume. The cutoff age for defining early versus late onset was 45 years.Results: The study participants consisted of 25 patients with early-onset mania and 19 patients with late-onset mania; their mean ages were 65.7 years and 62.8 years, respectively. The demographic variables of the two groups were comparable. The volumes of the left caudate nucleus (p = 0.022) and left middle frontal gyrus (p = 0.013) were significantly greater and that of the right posterior cingulate gyrus (p = 0.019) was significantly smaller in the late-onset group. More patients with late-onset mania had comorbid cerebrovascular disease (p = 0.072).Conclusions: The right posterior cingulate gyrus is smaller and the left caudate nucleus and left middle frontal gyrus are larger in patients with late-onset mania compared with those with early-onset mania. Volumetric change in brain regions may vary in elderly bipolar patients with early and late-onset mania.

scholarly journals A New Fluctuating Asymmetry Index, or the Solution for the Scaling Effect?

Symmetry ◽  
2015 ◽  
Vol 7 (2) ◽  
pp. 327-335 ◽  
Author(s):  
Cino Pertoldi ◽  
Torsten Kristensen
Keyword(s):  
Fluctuating Asymmetry ◽  
Asymmetry Index ◽  
Scaling Effect

scholarly journals A Novel AURKA Mutant-Induced Early-Onset Severe Hepatocarcinogenesis Greater than Wild-Type via Activating Different Pathways in Zebrafish

Cancers ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 927 ◽  
Author(s):  
Zhong-Liang Su ◽  
Chien-Wei Su ◽  
Yi-Luen Huang ◽  
Wan-Yu Yang ◽  
Bonifasius Putera Sampurna ◽  
...  
Keyword(s):  
Early Onset ◽  
Transgenic Fish ◽  
Aurora A Kinase ◽  
Mitotic Progression ◽  
Wild Type ◽  
Proliferation Markers ◽  
Long Latency ◽  
Important Regulator ◽  
Low Incidence ◽  
Screening Platform

Aurora A kinase (AURKA) is an important regulator in mitotic progression and is overexpressed frequently in human cancers, including hepatocellular carcinoma (HCC). Many AURKA mutations were identified in cancer patients. Overexpressing wild-type Aurka developed a low incidence of hepatic tumors after long latency in mice. However, none of the AURKA mutant animal models have ever been described. The mechanism of mutant AURKA-mediated hepatocarcinogenesis is still unclear. A novel AURKA mutation with a.a.352 Valine to Isoleucine (V352I) was identified from clinical specimens. By using liver-specific transgenic fish overexpressing both the mutant and wild-type AURKA, the AURKA(V352I)-induced hepatocarcinogenesis was earlier and much more severe than wild-type AURKA. Although an increase of the expression of lipogenic enzyme and lipogenic factor was observed in both AURKA(V352I) and AURKA(WT) transgenic fish, AURKA(V352I) has a greater probability to promote fibrosis at 3 months compared to AURKA(WT). Furthermore, the expression levels of cell cycle/proliferation markers were higher in the AURKA(V352I) mutant than AURKA(WT) in transgenic fish, implying that the AURKA(V352I) mutant may accelerate HCC progression. Moreover, we found that the AURKA(V352I) mutant activates AKT signaling and increases nuclear β-catenin, but AURKA(WT) only activates membrane form β-catenin, which may account for the differences. In this study, we provide a new insight, that the AURKA(V352I) mutation contributes to early onset hepatocarcinogenesis, possibly through activation of different pathways than AURKA(WT). This transgenic fish may serve as a drug-screening platform for potential precision medicine therapeutics.

scholarly journals The Structure and Function of the DNA from Bacteriophage Lambda

1966 ◽  
Vol 49 (6) ◽  
pp. 29-57 ◽  
Author(s):  
David S. Hogness
Keyword(s):  
Early Gene ◽  
Second Step ◽  
Wild Type ◽  
Gene Orientation ◽  
Variant Gene ◽  
Position And Orientation ◽  
The Right ◽  
And Function ◽  
Lambda Dna

The position and orientation of genes in lambda and lambda dg DNA are described. The position of six genes located in the right half of isolated lambda DNA was found to be -(N, iλ)--O-P---Q-R-(right end of DNA), which is their order on the genetic map of the vegetative phage. The order of the three genes of the galactose operon (k, t, and e) located in the left half of lambda dg DNA was found to be (left end of DNA)----k-t-e-, consistent with Campbell's model (5) for the formation of this variant. Gene orientation, defined as the direction of transcription along the DNA, is inferred to be from right to left for the galactose operon in lambda dg DNA. The strand of lambda DNA which functions as template in transcription of N, an "early" gene required for normal replication of lambda DNA, was determined as a first step in ascertaining the orientation of this gene. The method includes isolation of each strand, formation of each of two heteroduplex molecules consisting of one strand from wild-type and one from an N mutant) and comparison of their N activities. The second step, which consists of ascertaining the 5'-to-3' direction of each strand, is discussed, as is a determination of the orientation of gene R.

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