Masculinization of Zebrafish Through Partial Depletion of Primordial Germ by Injecting Diluted Oligonucleotides into

Author(s):  
László Orbán ◽  
Jolly M. Saju ◽  
Keh-Weei Tzung ◽  
Woei Chang Liew
Keyword(s):  
2021 ◽  
Vol 7 (8) ◽  
pp. eabd6167
Author(s):  
Capucine L. Grandjean ◽  
Zacarias Garcia ◽  
Fabrice Lemaître ◽  
Béatrice Bréart ◽  
Philippe Bousso

Anti-CD20 antibody (mAb) represents an effective strategy for the treatment of B cell malignancies, possibly involving complement activity, antibody-dependent cellular cytotoxicity and phagocytosis (ADP). While ADP by Kupffer cells deplete circulating tumors, mechanisms targeting non-circulating tumors remain unclear. Using intravital imaging in a model of B cell lymphoma, we establish here the dominance and limitations of ADP in the bone marrow (BM). We found that tumor cells were stably residing in the BM with little evidence for recirculation. To elucidate the mechanism of depletion, we designed a dual fluorescent reporter to visualize phagocytosis and apoptosis. ADP by BM-associated macrophages was the primary mode of tumor elimination but was no longer active after one hour, resulting in partial depletion. Moreover, macrophages were present at low density in tumor-rich regions, targeting only neighboring tumors. Overcoming spatiotemporal bottlenecks in tumor-targeting Ab therapy thus represents a critical path towards the design of optimized therapies.


Nephrology ◽  
2005 ◽  
Vol 10 (5) ◽  
pp. 470-477 ◽  
Author(s):  
YIPING WANG ◽  
DEEPIKA MAHAJAN ◽  
YUET-CHING TAY ◽  
SHISAN BAO ◽  
TIM SPICER ◽  
...  

Blood ◽  
2013 ◽  
Vol 121 (17) ◽  
pp. 3493-3501 ◽  
Author(s):  
Maria Amaya ◽  
Megha Desai ◽  
Merlin Nithya Gnanapragasam ◽  
Shou Zhen Wang ◽  
Sheng Zu Zhu ◽  
...  

Key Points Mi2β exerts a major part of its silencing effect on embryonic and fetal globin genes by positively regulating the BCL11A and KLF1 genes. Partial depletion of Mi2β induces increased γ-globin gene expression in primary human erythroid cells without impairing differentiation.


2018 ◽  
Vol 7 (6) ◽  
pp. 247
Author(s):  
AnaL Rodriguez-Perea ◽  
Johanna Gutierrez-Vargas ◽  
Mauricio Rojas ◽  
GloriaP Cardona-Gomez ◽  
PaulaA Velilla

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Andrew P Holmes ◽  
Ting Yu ◽  
Fahima Syeda ◽  
Nigel A Brown ◽  
Larissa Fabritz ◽  
...  

Introduction and hypothesis: Genetic abnormalities close to the Pitx2 gene correlate more strongly with atrial fibrillation (AF) than any other genetic modification. It is known that Pitx2c mRNA is expressed in the adult left atrium (LA), but its relevance for the electrical integrity of cardiomyocytes throughout the atria remains unresolved. We therefore compared regional action potential (AP) morphology in PITX2c +/- and wild type (WT) littermate mice. Methods: Transmembrane (T) and optical (O) APs were recorded from superfused intact, isolated LA paced at 100ms. TAPs were recorded from three distinct regions on the LA epicardium: 1) the junction with the interatrial septum (S), 2) the medial muscular dome (M) and 3) the lateral wall (L). OAPs were recorded using a custom murine atrial optical mapping system using the Hamamatsu ORCA flash 4 and Di-4-Anepps. Results: OAPs were shorter in Pitx2c deficient LA (AP duration (APD70); WT 13±2ms, n=4 LA vs Pitx2c +/- 9±1ms, n=4 LA, all data as mean±SEM, p<0.05). Simultaneous recordings of OAPs from multiple LA regions showed an AP gradient with longer OAPs at the septum than at the lateral wall, in both genotypes. In WT LA, TAPs were longer and of greater amplitude at the septum than in the other two regions (APD90; S 26±1ms, M 19±1mV and L 19±1ms, APA; S 81±1mV, M 76±2mV and L 76±2mV, n=6 LA, p<0.05). In Pitx2c +/- , TAPs were shorter than WT in all three regions tested and exhibited the same regional patterning (S 20±1ms, M 15±1ms and L 16±1, n=7 LA, p<0.05). The regional AP amplitude gradient was not apparent, or at least shifted more towards the lateral wall, in PITX2c +/- atria (APA; S 77±2mV, M 76±3mV and L 74±2mV, n=7 LA, ns). Conclusion: Partial depletion in Pitx2c mRNA expression causes a uniform APD shortening throughout the LA and loss of regional changes in AP amplitude. Identification of the targets downstream of Pitx2 accounting for these changes will help to better understand the mechanisms conveying AF due to reduced Pitx2 function.


1987 ◽  
Vol 252 (6) ◽  
pp. G768-G775
Author(s):  
P. E. Miller ◽  
J. W. Adelson

Recent studies demonstrating nonparallel regulated secretion of prestored digestive enzymes in tightly linked groups consistent with the exocytosis mechanism led us to predict that digestive enzymes would be found to be secreted from heterogeneous sources within the exocrine pancreas (J. W. Adelson, and P.E. Miller, Science Wash. DC 228: 993-996, 1985). We explored whether the gland was heterogeneous with respect to its sources of prestored secretory proteins with a double isotopic label method not dependent on activity of secreted digestive enzymes. Rabbit pancreatic proteins were double labeled in vivo by injection of each animal with chemically identical but isotopically distinct mixtures of 3H- and 14C-labeled amino acids, which were administered separately or together on consecutive days after partial depletion of prestored proteins by administration of cholecystokinin (CCK), methacholine chloride, or saline in a protocol in which order of both isotope and secretagogue administration was varied. Three days after labeling, proteins were recovered by collection from cannulated pancreatic ducts of anesthetized animals after stimulation with alternating increasing doses of CCK and methacholine chloride. Pooled secretory data were analyzed to determine whether secretagogue pretreatment resulted in specific and heterogeneous sequestration of proteins after synthesis; data after final secretory stimulation with methacholine chloride and CCK were individually analyzed to determine whether presequestered proteins were mobilized from heterogeneous compartments during secretion. Correlation and regression analysis of isotopic outputs and variance analysis of specific radioactivities of secreted proteins showed sequestration into and secretion from heterogeneous pools of secretory proteins, directly confirming out hypothesis. These results provide a cell biological mechanism explaining regulated nonparallel secretion of digestive enzymes.


1999 ◽  
Vol 276 (6) ◽  
pp. L891-L899 ◽  
Author(s):  
Soichiro Kanoh ◽  
Mitsuko Kondo ◽  
Jun Tamaoki ◽  
Hideki Shirakawa ◽  
Kazutetsu Aoshiba ◽  
...  

To elucidate the effect of FK506 on Ca2+ oscillations in airway epithelium, we investigated cultured cow tracheal epithelial cells with a Ca2+ image-analysis system. ATP (1 μM) induced long-lasting Ca2+ oscillations, having nearly constant peak values (300–400 nM) and intervals (20–40 s) in subconfluent cells but not in confluent cells. These responses were gradually attenuated and abolished by the addition of FK506. Rapamycin, which binds the FK506-binding protein (FKBP), likewise inhibited Ca2+ oscillations, whereas cyclosporin A, a calcineurin inhibitor, did not. Treatment of cells with FK506 decreased Ca2+ content in thapsigargin-sensitive stores, suggesting that the partial depletion of the stores causes the inhibition of Ca2+ oscillations. Immunocytochemistry revealed the existence of cytoplasmic FKBP-like immunoreactivities. The expression of a 12-kDa FKBP was greater in subconfluent cells than in confluent cells as determined by Western blotting, suggesting that the 12-kDa FKBP may be one of the factors that regulates Ca2+ oscillations. Therefore, FK506 possesses an inhibitory action on the Ca2+ response via intracellular FKBP but not via calcineurin, which may result in modification of airway epithelial functions.


1994 ◽  
Vol 358 ◽  
Author(s):  
D. Stievenard ◽  
D. Deresmes

ABSTRACTPorous silicon is known to be sensitive to moisture. Using an aluminium-porous p+ silicon junction, we have realized a sensor which dc current increases up to two orders of magnitude in the presence of ammoniac. We have tested a series of various gases and we show that if the dipole moment of the molecule is zero, there is no effect on the dc current. To interpret quantitatively this phenomenon, we assume that the conductivity is governed by the width of a channel resulting from the partial depletion of silicon located between two pores. This depleted region is due to the charges trapped on surface states associated with the Si-SiO2 interface where SiO2 is the native silicon oxide. When some gas is adsorbed, we propose there is a passivation of the interface states (mainly dangling bonds), leading to a decrease of the depleted region, i.e. an increase of the width of the channel and thus an increase of the current. The adsorbed gas gives a dipole layer at the surface of the pore. This layer has no influence on the depleted region. It stabilizes electrons or holes at the porous Si surface, allowing a stable charge state of the dangling bonds.


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