scholarly journals Selective effects of small barriers on river‐resident fish

Author(s):  
P.E. Jones ◽  
T. Champneys ◽  
J. Vevers ◽  
L. Börger ◽  
J.C. Svendsen ◽  
...  
2021 ◽  
Author(s):  
Lucie Oberhauser ◽  
Miriam Stoeber

AbstractThe kappa opioid receptor (KOR) has emerged as a promising therapeutic target for pain and itch treatment. There is growing interest in biased agonists that preferentially activate select signaling pathways downstream of KOR activation on the cellular level due to their therapeutic promise in retaining the analgesic and antipruritic effects and eliminating the sedative and dysphoric effects of KOR signaling on the physiological level. The concept of ligand-selective signaling includes that biased ligands promote KOR to selectively recruit one transducer or regulator protein over another, introducing bias into the signaling cascade at the very receptor-proximal level. Measuring agonist effects directly at the receptor has remained challenging and previous studies have focused on inferring agonist-selective KOR engagement with G protein relative to β-arrestin based on downstream signaling readouts. Here we discuss novel strategies to directly assess ligand-selective effects on receptor activation using KOR-interacting biosensors. The conformation-specific cytoplasmic biosensors are disconnected from the endogenous signaling machinery and provide a direct receptor-proxy readout of ligand effects in living cells. Receptor–biosensor interaction is ligand concentration dependent and can be used to determine relative ligand potency and efficacy. In addition, the biosensors reveal the existence of two dimensions of agonist bias in the cellular context: Firstly, agonists can selectively produce discrete protein-engaged KOR states and secondly, agonists can differ in the precise subcellular location at which they activate KOR. We discuss the value and the limitations of using orthogonal receptor-interacting biosensors in the quest to understand functional selectivity amongst KOR agonists in the cellular context.


2003 ◽  
Vol 188 (4) ◽  
pp. 585-590 ◽  
Author(s):  
Richard M. Winn ◽  
Cristina Gil‐Lamaignere ◽  
Emmanuel Roilides ◽  
Maria Simitsopoulou ◽  
Caron A. Lyman ◽  
...  

1970 ◽  
Vol 122 (3) ◽  
pp. 216-219
Author(s):  
H. Hamel-Messier ◽  
J. de Repentigny ◽  
L. G. Mathieu ◽  
S. Sonea

Author(s):  
R. T. Jones ◽  
W. G. D. Lugton ◽  
S. R. Massey ◽  
R. B. Richardson

AbstractWhen studying the distribution of smoke deposited in the lung, it is necessary to use a tracer which indicates the levels of particulate matter deposited at various sites. Because the site of deposition can be dependent on the particle size of the aerosol, it is important that the tracer should be uniformly distributed with respect to particle size, otherwise the levels of particulate matter may be wrongly estimated. The distributions in the smoke from a cigarette containing flue-cured tobacco of three possible tracers (dotriacontane, hexadecane and decachlorobiphenyl) have been measured; alI three show a slight dependence but probably not sufficient to exclude them from possible use in inhalation studies. However, because of the different environment which exists in the lung, and the possible dependence of the results on the type of tobacco, it should not be assumed that there are no selective effects


Reproduction ◽  
2004 ◽  
Vol 127 (1) ◽  
pp. 35-43 ◽  
Author(s):  
M Amstalden ◽  
D A Zieba ◽  
M R Garcia ◽  
R L Stanko ◽  
T H Welsh ◽  
...  

Experiments were performed to test the hypothesis that lamprey GnRH-III (lGnRH-III) selectively releases FSH. Primary cultures of bovine adenohypophyseal cells were treated with mammalian GnRH (mGnRH) and lGnRH-III (10−9, 10−8, 10−7 and 10−6 M) or control media in Experiment 1. All doses of mGnRH and the two highest doses of lGnRH-III stimulated (P < 0.001) a non-selective release of LH and FSH. In Experiments 2–4, Latin Square designs were utilized in vivo to examine whether physiological and hormonal milieu regulate putative selective effects of lGnRH-III. In Experiments 2 and 3, ovariectomized cows with basal levels of estradiol only (Experiment 2) or in combination with luteal phase levels of progester-one (Experiment 3) were injected with mGnRH and lGnRH-III (0.055, 0.11, 0.165 and 1.1 μg/kg body weight (BW) and saline. All doses of mGnRH released (P < 0.001) LH and FSH, but only the highest dose of lGnRH-III stimulated (P < 0.001) a non-selective release of both LH and FSH (Experiment 3). For Experiments 4A and 4B, intact, mid-luteal phase cows were injected with mGnRH and lGnRH-III (1.1 μg/kg BW; Experiment 4A), lGnRH-III (1.1 and 4.4 μg/kg BW; Experiment 4B) and saline. As before, mGnRH released (P < 0.001) both LH and FSH at all doses. In contrast, lGnRH-III at the highest dose released (P < 0.001) LH but not FSH. These findings suggest that lGnRH-III may act as a weak competitor for the mGnRH receptor and do not support the hypothesis that it selectively releases FSH in cattle.


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