scholarly journals Recoverin depletion accelerates cone photoresponse recovery

Open Biology ◽  
2015 ◽  
Vol 5 (8) ◽  
pp. 150086 ◽  
Author(s):  
Jingjing Zang ◽  
Jennifer Keim ◽  
Edda Kastenhuber ◽  
Matthias Gesemann ◽  
Stephan C. F. Neuhauss

The neuronal Ca 2+ -binding protein Recoverin has been shown to regulate phototransduction termination in mammalian rods. Here we identify four recoverin genes in the zebrafish genome, rcv1a , rcv1b , rcv2a and rcv2b , and investigate their role in modulating the cone phototransduction cascade. While Recoverin-1b is only found in the adult retina, the other Recoverins are expressed throughout development in all four cone types, except Recoverin-1a, which is expressed only in rods and UV cones. Applying a double flash electroretinogram (ERG) paradigm, downregulation of Recoverin-2a or 2b accelerates cone photoresponse recovery, albeit at different light intensities. Exclusive recording from UV cones via spectral ERG reveals that knockdown of Recoverin-1a alone has no effect, but Recoverin-1a/2a double-knockdowns showed an even shorter recovery time than Recoverin-2a-deficient larvae. We also showed that UV cone photoresponse kinetics depend on Recoverin-2a function via cone-specific kinase Grk7a. This is the first in vivo study demonstrating that cone opsin deactivation kinetics determine overall photoresponse shut off kinetics.

1998 ◽  
Vol 15 (4) ◽  
pp. 643-651 ◽  
Author(s):  
JEFFRY I. FASICK ◽  
THOMAS W. CRONIN ◽  
DAVID M. HUNT ◽  
PHYLLIS R. ROBINSON

To assess the dolphin's capacity for color vision and determine the absorption maxima of the dolphin visual pigments, we have cloned and expressed the dolphin opsin genes. On the basis of sequence homology with other mammalian opsins, a dolphin rod and long-wavelength sensitive (LWS) cone opsin cDNAs were identified. Both dolphin opsin cDNAs were expressed in mammalian COS-7 cells. The resulting proteins were reconstituted with the chromophore 11-cis-retinal resulting in functional pigments with absorption maxima (λmax) of 488 and 524 nm for the rod and cone pigments respectively. These λmax values are considerably blue shifted compared to those of many terrestrial mammals. Although the dolphin possesses a gene homologous to other mammalian short-wavelength sensitive (SWS) opsins, it is not expressed in vivo and has accumulated a number of deletions, including a frame-shift mutation at nucleotide position 31. The dolphin therefore lacks the common dichromatic form of color vision typical of most terrestrial mammals.


2019 ◽  
Vol 4 (1) ◽  
pp. 10
Author(s):  
Patihul Husni ◽  
Mayang K. Dewi ◽  
Norisca A. Putriana ◽  
Rini Hendriani

Scabies is an infectious skin disease caused by mite Sarcoptes scabiei. Neem tree (Azadirachta indica) has the potential to be used as an anti-parasite due to the presence of azadirachtin compound that is commonly found in the seeds. The aim of this study was to evaluate in-vivo effectiveness of neem oil as an anti-scabies. This study used an experimental method.  The effectiveness of the cream as an anti-scabies was tested on New Zealand white rabbits which were infected with scabies. Permethrin cream was used as a positive control and cream base was used as a negative control.  Cream was applied once daily and left for 8 hours. The data were analyzed using Kruskal Wallis and Mann Whitney. Dermal acute irritation test was performed by applying  0.5 g cream on the rabbit dorsal. We found that 5% neem oil cream was effective as an anti-scabies with 20-21 days recovery time. The recovery time is longer than permethrin cream (7-8 days), but shorter compared to negative control with recovery time over 30 days. Primary irritation index for 5% neem oil creams was 0, indicating negligible irritation category. In conclusion, A. indica cream was effective for the treatment of scabies although its recovery time is shorter than permethrin cream.  Keywords: effectiveness test, irritation test, neem oil cream, scabies


2020 ◽  
Vol 48 (12) ◽  
pp. 2901-2910 ◽  
Author(s):  
Hattie C. Cutcliffe ◽  
Keithara M. Davis ◽  
Charles E. Spritzer ◽  
Louis DeFrate

AbstractOsteoarthritis (OA) is a disease characterized by the degeneration of cartilage tissue, and is a leading cause of disability in the United States. The clinical diagnosis of OA includes the presence of pain and radiographic imaging findings, which typically do not present until advanced stages of the disease when treatment is difficult. Therefore, identifying new methods of OA detection that are sensitive to earlier pathological changes in cartilage, which may be addressed prior to the development of irreversible OA, is critical for improving OA treatment. A potentially promising avenue for developing early detection methods involves measuring the tissue’s in vivo mechanical response to loading, as changes in mechanical function are commonly observed in ex vivo studies of early OA. However, thus far the mechanical function of cartilage has not been widely assessed in vivo. Therefore, the purpose of this study was to develop a novel methodology that can be used to measure an in vivo mechanical property of cartilage: the characteristic recovery time. Specifically, in this study we quantified the characteristic recovery time of cartilage thickness after exercise in relatively young subjects with asymptomatic cartilage. Additionally, we measured baseline cartilage thickness and T1rho and T2 relaxation times (quantitative MRI) prior to exercise in these subjects to assess whether baseline MRI measures are predictive of the characteristic recovery time, to understand whether or not the characteristic recovery time provides independent information about cartilage’s mechanical state. Our results show that the mean recovery strain response across subjects was well-characterized by an exponential approach with a characteristic time of 25.2 min, similar to literature values of human characteristic times measured ex vivo. Further, we were unable to detect a statistically significant linear relationship between the characteristic recovery time and the baseline metrics measured here (T1rho relaxation time, T2 relaxation time, and cartilage thickness). This might suggest that the characteristic recovery time has the potential to provide additional information about the mechanical state of cartilage not captured by these baseline MRI metrics. Importantly, this study presents a noninvasive methodology for quantifying the characteristic recovery time, an in vivo mechanical property of cartilage. As mechanical response may be indicative of cartilage health, this study underscores the need for future studies investigating the characteristic recovery time and in vivo cartilage mechanical response at various stages of OA.


2019 ◽  
Author(s):  
Nicholas M. Tran ◽  
Karthik Shekhar ◽  
Irene E. Whitney ◽  
Anne Jacobi ◽  
Inbal Benhar ◽  
...  

SummaryNeuronal types in the central nervous system differ dramatically in their resilience to injury or insults. Here we studied the selective resilience of mouse retinal ganglion cells (RGCs) following optic nerve crush (ONC), which severs their axons and leads to death of ~80% of RGCs within 2 weeks. To identify expression programs associated with differential resilience, we first used single-cell RNA-seq (scRNA-seq) to generate a comprehensive molecular atlas of 46 RGC types in adult retina. We then tracked their survival after ONC, characterized transcriptomic, physiological, and morphological changes that preceded degeneration, and identified genes selectively expressed by each type. Finally, using loss- and gain-of-function assays in vivo, we showed that manipulating some of these genes improved neuronal survival and axon regeneration following ONC. This study provides a systematic framework for parsing type-specific responses to injury, and demonstrates that differential gene expression can be used to reveal molecular targets for intervention.


2021 ◽  
Author(s):  
Nirthieca Suthakaran ◽  
Sanjana Chandran ◽  
Michael Iacobelli ◽  
David Binninger

Unlike the mammalian brain, Drosophila melanogaster can tolerate several hours of hypoxia without any tissue injury by entering a protective coma known as spreading depression. However, when oxygen is reintroduced, there is an increased production of reactive oxygen species (ROS) that causes oxidative damage. Methionine sulfoxide reductase (MSR) acts to restore functionality to oxidized methionine residues. In the present study, we have characterized in vivo effects of MSR deficiency on hypoxia tolerance throughout the lifespan of Drosophila. Flies subjected to sudden hypoxia that lacked MSR activity exhibited a longer recovery time and a reduced ability to survive hypoxic stress as they approached senescence. However, when hypoxia was induced slowly, MSR deficient flies recovered significantly quicker throughout their entire adult lifespan. In addition, the wildtype and MSR deficient flies had nearly 100% survival rates throughout their lifespan. Neuroprotective signaling mediated by decreased apoptotic pathway activation, as well as gene reprogramming and metabolic downregulation are possible reasons for why MSR deficient flies have faster recovery time and a higher survival rate upon slow induction of spreading depression. Our data are the first to suggest important roles of MSR and longevity pathways in hypoxia tolerance exhibited by Drosophila.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Adonis Z Wu ◽  
Cheng Wang ◽  
Katie Spoonamore ◽  
Thomas Everett ◽  
Zhenhui Chen ◽  
...  

Introduction: We have identified a de novo mutation of LMNA ( LMNA -R545H) in a 34-year-old man with high-grade atrioventricular block. Studies in HEK-293 cells showed that LMNA -R545H reduced the amplitude and resulted in a shift in gating kinetics of the voltage-gated sodium current ( I Na ). These results have not been confirmed in cardiomyocytes. Hypothesis: (1) LMNA -R545H mutation replicates the electrocardiogram (ECG) phenotypes in vivo and (2) there is downregulation of I Na in cardiomyocytes. Methods: We used CRISPR/Cas9 to generate a knock-in mouse model with LMNA -R545H mutation. Isolated cardiomyocytes were used for whole-cell voltage-clamp studies of I Na . Results: Panel (A) shows P, PR, QTc intervals were significantly prolonged and the standard deviation (SD) of the RR intervals was increased during anesthesia in Lmna (R545H+/+) but not in Lmna (R545H+) mice compared with the wild-type control littermates (WT, N=5-8). In Langendorff perfused hearts, the sinus node recovery time (SNRT) and effective refractory period (ERP) were significantly prolonged in the Lmna (R545H+/+) compared with both WT and Lmna (R545H+) . Lmna (R545H+/+) cardiomyocytes showed decreased I Na current density (-20.1±2.3 pA/pF vs. -30.3±3.9 pA/pF, -40 mV, n=7-8, p<.05, Panel B) and prolonged the recovery time constant from I Na inactivation (τ, 36.3±2.2 ms vs. 22.9±1.6 ms, each n=5, p<.05, Panel C). There were no difference in Nav1.5 protein and mRNA levels between the Lmna (R545H+/+) and WT hearts. Conclusions: Homozygous LMNA -R545H mutation leads to reduced I Na , prolonged PR and QTc intervals, and increased sinus arrhythmias.


2002 ◽  
Vol 24 (2) ◽  
pp. 100-108 ◽  
Author(s):  
Kathryn Nightingale ◽  
Roger Nightingale ◽  
Deborah Stutz ◽  
Gregg Trahey

Acoustic Radiation Force Impulse (ARFI) imaging is a method for characterizing local variations in tissue mechanical properties. In this method, a single ultrasonic transducer array is used to both apply temporally short localized radiation forces within tissue and to track the resulting displacements through time. Images of tissue displacement immediately after force cessation, maximum tissue displacement, the time it takes for the tissue to reach its maximum displacement, and the recovery time constant of the tissue are generated from the ARFI data sets. The information in each of these images demonstrates good agreement with matched B-mode images. The study presented here was designed to evaluate the relationship between changes in these ARFI parameters with known tissue mechanical properties in vivo. Utilizing a modified Siemens Elegra scanner with a 75L40 transducer array, ARFI images of vastus medialis muscle were generated in three of the authors under four levels of activation (0, 5.7, 14.5, and 23.3 N-m). Four ARFI datasets were acquired for each loading condition. The observed trends were that displacement magnitude, the time it took for the tissue to reach its maximum displacement, and recovery time constant decreased with increasing load (i.e., increasing muscle stiffness). Significant differences were observed between load levels and subjects for all parameters (p<0.01). The results indicate that ARFI imaging may be capable of quantifying tissue stiffness in real-time measurements, although further investigation is required.


1990 ◽  
Vol 5 (5) ◽  
pp. 429-439 ◽  
Author(s):  
Gregory M. Zinkl ◽  
Linnette Maier ◽  
Kent Studer ◽  
Randall Sapp ◽  
De-Mao Chen ◽  
...  

AbstractWe examined a white-eyed strain of the norpA mutant (norpA;cn bw) and white (w)norpA+ controls using microspectrophotometry (MSP), electron microscopy (EM), and electroretinography (ERG). These studies revealed that light mediates receptor demise in norpA even though norpA lacks phototransduction. Rhodopsin and the rhabdomere which houses it decrease with increasing age in norpA but not in w with rearing on a 12 h light/12-h dark cycle or in constant light. At higher temperature in norpA;cn bw and w reared in constant light, visual pigment decreases, rhabdomeres diminish, and cells die. Importantly, dark rearing blocked visual pigment loss in norpA;cn bw; the M-potential, an ERG reflection of visual pigment level, corroborated this finding. MSP showed that norpA's visual pigment loss was not due to acute loss of metarhodopsin, rhodopsin's photoproduct. NorpA blocks certain processes expected to be light elicited. The alteration of visual pigment as a function of time of day, present in w controls, is absent in white-eyed norpA, suggesting that light-induced depolarization may be necessary to entrain the rhythm. Microspectrofluorometry using the fluorescent dye, Lucifer yellow, suggested that norpA lacks a light-induced uptake mechanism; using control flies, we determined the stimulus parameters required for uptake in vivo. An attempt to “cure” norpA;cn bw by replacement “therapy” using phospholipase C, missing in norpA's phototransduction cascade, was largely unsuccessful.


2009 ◽  
Vol 104 (11) ◽  
pp. 1318-1325 ◽  
Author(s):  
Daniel R. Potter ◽  
John Jiang ◽  
Edward R. Damiano

Sign in / Sign up

Export Citation Format

Share Document