scholarly journals Splice variants of DOMINO controlDrosophilacircadian behavior and pacemaker neuron maintenance

2018 ◽  
Author(s):  
Zhenxing Liu ◽  
Ye Niu ◽  
Vu H. Lam ◽  
Joanna C. Chiu ◽  
Yong Zhang
Keyword(s):  
Protein Expression ◽  
Splice Variants ◽  
Circadian Clocks ◽  
Circadian Period ◽  
Daily Rhythms ◽  
Pacemaker Neurons ◽  
Constitutive Activation ◽  
Pigment Dispersing Factor ◽  
Period Lengthening ◽  
Circadian Behavior

AbstractCircadian clocks control daily rhythms in physiology. InDrosophila, the small ventral lateral neurons (sLNvs) expressing PIGMENT DISPERSING FACTOR (PDF) are the master pacemaker neurons. Despite the importance of sLNvs and PDF in circadian behavior, little is known about factors that control sLNvs maintenance and PDF accumulation. Here, we identify theDrosophilaSWI2/SNF2 protein DOMINO (DOM) as a key regulator of circadian behavior. Depletion of DOM eliminates morning anticipation and impairs rhythmicity. Interestingly, the two splice variants of DOM, DOM-A and DOM-B have distinct circadian functions. DOM-A depletion leads to arrhythmic behavior, while DOM-B knockdown lengthens circadian period. Both DOM-A and DOM-B bind to the promotor regions of key pacemaker genesperiodandtimeless, and regulate their protein expression. Furthermore, we identify that DOM-A is required for the maintenance of sLNvs and transcription ofpdf. Lastly, constitutive activation of PDF-receptor signaling rescued the arrhythmia and period lengthening of DOM downregulation. Taken together, our findings reveal that splice variants of DOM play distinct roles in circadian rhythms through regulating abundance of pacemaker proteins and sLNvs maintenance.

scholarly journals The Circadian Clock, the Brain, and COVID-19: The Cases of Olfaction and the Timing of Sleep

2021 ◽  
pp. 074873042110312
Author(s):  
Rachel S. Herz ◽  
Erik D. Herzog ◽  
Martha Merrow ◽  
Sara B. Noya
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Function ◽  
Human Brain ◽  
Circadian Clock ◽  
Clinical Data ◽  
Circadian Clocks ◽  
Olfactory Sensitivity ◽  
Daily Rhythms ◽  
Sense Of Smell ◽  
The Brain

Daily rhythms of behavior and neurophysiology are integral to the circadian clocks of all animals. Examples of circadian clock regulation in the human brain include daily rhythms in sleep-wake, cognitive function, olfactory sensitivity, and risk for ischemic stroke, all of which overlap with symptoms displayed by many COVID-19 patients. Motivated by the relatively unexplored, yet pervasive, overlap between circadian functions and COVID-19 neurological symptoms, this perspective piece uses daily variations in the sense of smell and the timing of sleep and wakefulness as illustrative examples. We propose that time-stamping clinical data and testing may expand and refine diagnosis and treatment of COVID-19.

Tenascin-c protein expression and mRNA splice variants in thyroid carcinoma

2006 ◽  
Vol 80 (2) ◽  
pp. 177-182 ◽  
Author(s):  
S. Tseleni-Balafouta ◽  
H. Gakiopoulou ◽  
G. Fanourakis ◽  
G. Voutsinas ◽  
D. Balafoutas ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Protein Expression ◽  
Splice Variants ◽  
C Protein ◽  
Mrna Splice ◽  
Tenascin C

Regulation of desmocollin transcription in mouse preimplantation embryos

Development ◽  
1995 ◽  
Vol 121 (3) ◽  
pp. 743-753 ◽  
Author(s):  
J.E. Collins ◽  
J.E. Lorimer ◽  
D.R. Garrod ◽  
S.C. Pidsley ◽  
R.S. Buxton ◽  
...  
Keyword(s):  
Protein Expression ◽  
Molecular Mechanisms ◽  
Inner Cell Mass ◽  
Splice Variants ◽  
Cell Mass ◽  
Cumulus Cells ◽  
Early Embryo ◽  
Preimplantation Embryos ◽  
Cell Stage ◽  
Cleavage Stages

The molecular mechanisms regulating the biogenesis of the first desmosomes to form during mouse embryogenesis have been studied. A sensitive modification of a reverse transcriptase-cDNA amplification procedure has been used to detect transcripts of the desmosomal adhesive cadherin, desmocollin. Sequencing of cDNA amplification products confirmed that two splice variants, a and b, of the DSC2 gene are transcribed coordinately. Transcripts were identified in unfertilized eggs and cumulus cells and in cleavage stages up to the early 8-cell stage, were never detected in compact 8-cell embryos, but were evident again either from the 16-cell morula or very early blastocyst (approx 32-cells) stages onwards. These two phases of transcript detection indicate DSC2 is encoded by maternal and embryonic genomes. Previously, we have shown that desmocollin protein synthesis is undetectable in eggs and cleavage stages but initiates at the early blastocyst stage when desmocollin localises at, and appears to regulate assembly of, nascent desmosomes that form in the trophectoderm but not in the inner cell mass (Fleming, T. P., Garrod, D. R. and Elsmore, A. J. (1991), Development 112, 527–539). Maternal DSC2 mRNA is therefore not translated and presumably is inherited by blastomeres before complete degradation. Our results suggest, however, that initiation of embryonic DSC2 transcription regulates desmocollin protein expression and thereby desmosome formation. Moreover, data from blastocyst single cell analyses suggest that embryonic DSC2 transcription is specific to the trophectoderm lineage. Inhibition of E-cadherin-mediated cell-cell adhesion did not influence the timing of DSC2 embryonic transcription and protein expression. However, isolation and culture of inner cell masses induced an increase in the amount of DSC2 mRNA and protein detected. Taken together, these results suggest that the presence of a contact-free cell surface activates DSC2 transcription in the mouse early embryo.

scholarly journals Splice variants of DOMINO control Drosophila circadian behavior and pacemaker neuron maintenance

PLoS Genetics ◽  
2019 ◽  
Vol 15 (10) ◽  
pp. e1008474 ◽  
Author(s):  
Zhenxing Liu ◽  
Christine A. Tabuloc ◽  
Yongbo Xue ◽  
Yao Cai ◽  
Pearson Mcintire ◽  
...  
Keyword(s):  
Splice Variants ◽  
Pacemaker Neuron ◽  
Circadian Behavior

scholarly journals Compromised barrier integrity of human feto-placental vessels from gestational diabetic pregnancies is related to downregulation of occludin expression

Diabetologia ◽  
2020 ◽  
Vol 64 (1) ◽  
pp. 195-210
Author(s):  
Stephany Daniela Villota ◽  
Maria Toledo-Rodriguez ◽  
Lopa Leach
Keyword(s):  
Gene Expression ◽  
Protein Expression ◽  
Splice Variants ◽  
Fold Increase ◽  
Lifestyle Changes ◽  
Protein Isoforms ◽  
Lower Percentage ◽  
Systematic Sampling ◽  
Regulation Of Expression ◽  
Gene And Protein Expression

Abstract Aims/hypothesis Reduced occupancy of junctional occludin is a feature of human placental vessels in the diabetic milieu. However, the functional consequence of this and whether this loss is due to differential expression of occludin splice variants is not known. Our study aimed to investigate the effects of gestational diabetes mellitus (GDM), and its treatment, on endothelial junctional integrity, gene and protein expression of occludin splice variants, and potential regulation of expression by microRNAs (miRNAs). Methods Term placentas were obtained from normal pregnancies (n = 21), and pregnancies complicated by GDM where glucose levels were controlled by diet (n = 11) or metformin (n = 6). Gene and microRNA (miRNA) expression were determined by quantitative real-time PCR; protein expression by immunoblotting; endothelial junctional occupancy by fluorescence microscopy and systematic sampling; and paracellular leakage by perfusion of placental microvascular beds with 76 Mr dextran. Transfection studies of miRNAs that target OCLN were performed in HUVECs, and the trans-endothelial electrical resistance and tracer permeability of the HUVECs were measured. Results All three predicted OCLN gene splice variants and two occludin protein isoforms were found in human placental samples. In placental samples from diet-controlled GDM (d-GDM) pregnancies we found a lower percentage of conduit vessels showing occludin immunoreactivity (12%, p < 0.01), decreased levels of the fully functional occludin isoform-A protein (29%), and differential gene expression of OCLN variant 2 (33% decrease), variant 3 (3.3-fold increase). These changes were not seen in samples from the group with metformin-controlled GDM. In d-GDM placentas, increased numbers of conduit microvessels demonstrated extravasation of 76 Mr dextran (2.0-fold). In d-GDM expression of one of the five potential miRNAs targeting OCLN, miR-181a-5p, expression was 2.1-fold that in normal pregnancies. Experimental overexpression of miR-181a-5p in HUVECs from normal pregnancies resulted in a highly significant downregulation of OCLN variant 1 (69%) and variant 2 (46%) gene expression, with decreased trans-endothelial resistance (78%) and increase in tracer permeability (1.3-fold). Conclusions/interpretation Downregulation of expression of OCLN variant 2 and the fully functional occludin isoform-A protein are a feature of placentas in d-GDM pregnancies. These may be behind the loss of junctional occludin and the increased extravasation of exogenous dextran observed. miR-181a-5p was in part responsible for the downregulation of occludin in placentas from d-GDM pregnancies. Induced overexpression of miR-181a-5p compromised the integrity of the endothelial barrier. Our data suggest that, despite good glucose control, the adoption of lifestyle changes alone during a GDM pregnancy may not be enough to prevent an alteration in the expression of occludin and the subsequent functional consequences in placentas and impaired vascular barrier function in offspring.

Overexpression of survivin in pediatric Hodgkin lymphoma tumor cells: Characterization of protein expression and splice-variants transcription profile

2019 ◽  
Vol 108 ◽  
pp. 24-31 ◽  
Author(s):  
Mario Alejandro Lorenzetti ◽  
María Jimena Mosna ◽  
Elena Noemí De Matteo ◽  
Mercedes García Lombardi ◽  
Sandra Lorena Colli ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hodgkin Lymphoma ◽  
Tumor Cells ◽  
Splice Variants ◽  
Transcription Profile ◽  
Pediatric Hodgkin Lymphoma

scholarly journals Metabolite-mediated TOR signaling regulates the circadian clock inArabidopsis

2019 ◽  
Vol 116 (51) ◽  
pp. 25395-25397 ◽  
Author(s):  
Nan Zhang ◽  
Yanyan Meng ◽  
Xu Li ◽  
Yu Zhou ◽  
Liuyin Ma ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Circadian Clocks ◽  
Circadian Period ◽  
Energy Status ◽  
Vitamin B3 ◽  
Tor Signaling ◽  
Energy Sensor ◽  
Tor Kinase ◽  
Effect Of Glucose ◽  
Kinase A

Circadian clocks usually run with a period close to 24 h, but are also plastic and can be entrained by external environmental conditions and internal physiological cues. Two key nutrient metabolites, glucose and vitamin B3 (nicotinamide), can influence the circadian period in both mammals and plants; however, the underlying molecular mechanism is still largely unclear. We reveal that the target of rapamycin (TOR) kinase, a conserved central growth regulator, is essential for glucose- and nicotinamide-mediated control of the circadian period inArabidopsis. Nicotinamide affects the cytosolic adenosine triphosphate concentration, and blocks the effect of glucose-TOR energy signaling on period length adjustment, meristem activation, and root growth. Together, our results uncover a missing link between cellular metabolites, energy status, and circadian period adjustment, and identify TOR kinase as an essential energy sensor to coordinate circadian clock and plant growth.

scholarly journals Adaptive diversification in the cellular circadian behavior of Arabidopsis leaf- and root-derived cells

2021 ◽  
Author(s):  
Shunji Nakamura ◽  
Tokitaka Oyama
Keyword(s):  
Environmental Changes ◽  
Cell Types ◽  
Cellular Level ◽  
Circadian System ◽  
Circadian Clocks ◽  
Intrinsic Properties ◽  
Adaptive Diversification ◽  
Local Environments ◽  
Fluctuating Environments ◽  
Circadian Behavior

The plant circadian system is based on self-sustained cellular oscillations and is utilized to adapt to daily and seasonal environmental changes. The cellular circadian clocks in the above- and belowground plant organs are subjected to diverse local environments. Individual cellular clocks are affected by other cells/tissues in plants, and the intrinsic properties of cellular clocks remain to be elucidated. In this study, we showed the circadian properties of leaf- and root-derived cells of a CCA1::LUC Arabidopsis transgenic plant and demonstrated that the cells in total isolation from other cells harbor a genuine circadian clock. Quantitative and statistical analyses for individual cellular bioluminescence rhythms revealed a difference in amplitude and precision of light/dark entrainment between the two cell-types, suggesting that leaf-derived cells have a clock with a stronger persistence against fluctuating environments. Circadian systems in the leaves and roots are diversified to adapt to their local environments at the cellular level.

Contribution of constitutive activation of Akt to the pathogenesis of mantle cell lymphoma (MCL) independent of PTEN protein expression

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8101-8101
Author(s):  
C. Economopoulou ◽  
A. Psyrri ◽  
E. Liakata ◽  
S. Papageorgiou ◽  
P. Economopoulou ◽  
...  
Keyword(s):  
Protein Expression ◽  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Pten Protein ◽  
Akt Activation ◽  
Constitutive Activation ◽  
Protein Levels ◽  
Phosphorylated Akt ◽  
Mantle Cell

8101 Background: To determine whether the PI3K/Akt signaling pathway is involved in the pathogenesis of mantle cell lymphoma (MCL), we investigated the phosphorylation status of Akt in primary MCL cases and cell lines. We also sought to determine whether loss of the phosphatase PTEN is the mechanism of Akt activation in MCL. Methods: We evaluated the protein levels of Akt, phosphorylated Akt and PTEN in 15 primary MCL cases and 2 cell lines by immunoblotting Results: Akt was phosphorylated in 3 of 15 MCL cases and in 2 of 2 mantle cell lymphoma cell lines. PTEN protein was expressed in 15 of 15 primary mantle cell lymphoma cases and in 2 of 2 MCL cell lines. Conclusions: We conclude that constitutive activation of the PI3K/Akt pathway contributes to the pathogenesis of MCL. Loss of PTEN protein expression is not the responsible mechanism for Akt activation. Alternative mechanisms of Akt activation are being evaluated to identify markers predictive for response to PI3K/Akt inhibitors in MCL. No significant financial relationships to disclose.

scholarly journals Mutations in EID1 and LNK2 caused light-conditional clock deceleration during tomato domestication

2018 ◽  
Vol 115 (27) ◽  
pp. 7135-7140 ◽  
Author(s):  
Niels A. Müller ◽  
Lei Zhang ◽  
Maarten Koornneef ◽  
José M. Jiménez-Gómez
Keyword(s):  
Clock Gene ◽  
Genetic Basis ◽  
Allelic Variation ◽  
Genomic Region ◽  
Circadian Period ◽  
Circadian Phase ◽  
Signatures Of Selection ◽  
Period Lengthening ◽  
Phytochrome B1 ◽  
Light Input

Circadian period and phase of cultivated tomato (Solanum lycopersicum) were changed during domestication, likely adapting the species to its new agricultural environments. Whereas the delayed circadian phase is mainly caused by allelic variation of EID1, the genetic basis of the long circadian period has remained elusive. Here we show that a partial deletion of the clock gene LNK2 is responsible for the period lengthening in cultivated tomatoes. We use resequencing data to phylogenetically classify hundreds of tomato accessions and investigate the evolution of the eid1 and lnk2 mutations along successive domestication steps. We reveal signatures of selection across the genomic region of LNK2 and different patterns of fixation of the mutant alleles. Strikingly, LNK2 and EID1 are both involved in light input to the circadian clock, indicating that domestication specifically targeted this input pathway. In line with this, we show that the clock deceleration in the cultivated tomato is light-dependent and requires the phytochrome B1 photoreceptor. Such conditional variation in circadian rhythms may be key for latitudinal adaptation in a variety of species, including crop plants and livestock.

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