The North Atlantic right whale Eubalaena glacialis (NARW), currently numbering <410 individuals, is on a trajectory to extinction. Although direct mortality from ship strikes and fishing gear entanglements remain the major threats to the population, reproductive failure, resulting from poor body condition and sublethal chronic entanglement stress, is believed to play a crucial role in the population decline. Using photogrammetry from unmanned aerial vehicles, we conducted the largest population assessment of right whale body condition to date, to determine if the condition of NARWs was poorer than 3 seemingly healthy (i.e. growing) populations of southern right whales E. australis (SRWs) in Argentina, Australia and New Zealand. We found that NARW juveniles, adults and lactating females all had lower body condition scores compared to the SRW populations. While some of the difference could be the result of genetic isolation and adaptations to local environmental conditions, the magnitude suggests that NARWs are in poor condition, which could be suppressing their growth, survival, age of sexual maturation and calving rates. NARW calves were found to be in good condition. Their body length, however, was strongly determined by the body condition of their mothers, suggesting that the poor condition of lactating NARW females may cause a reduction in calf growth rates. This could potentially lead to a reduction in calf survival or an increase in female calving intervals. Hence, the poor body condition of individuals within the NARW population is of major concern for its future viability.
Repeated oesophageal acidification causes lower oesophageal sphincter (LOS) relaxation in the anaesthetized ferret which is mediated by a peripheral neurokinin (NK-1) receptor mechanism. Our aim in this study was to characterize neural pathways in the LOS activated by capsaicin and tachykinin receptor agonists in vitro. Circular muscle strips of LOS (two per animal) from a total of 24 ferrets were maintained in organ baths. Electrical field stimulation (EFS, 50 V, 5-50 Hz) caused frequency-dependent LOS relaxation which was abolished by tetrodotoxin (TTX; 10(-6) M: P < 0.001) and reduced by N(G)-nitro-L-arginine (L-NNA; 10(-4) M: P < 0.01). Substance P and [Sar9, Met (O2)11]-substance P (selective NK-1 agonist) caused dose-dependent relaxation, while the NK-2 receptor agonist [beta-Ala8]-NKA 4-10 evoked excitation. Capsaicin (10(-6) M) caused relaxation and desensitization that was overcome by long recovery periods and substance P dosing (10(-8) M). After pretreatment with the NK-1 receptor antagonist CP 99994 (10(-7) M), substance P (10(-8) M; P < 0.001) and capsaicin (10(-6) M: P < 0.01)-induced relaxations were reduced. In the presence of TTX (10(-6) M), excitation resulted in response to substance P (10(-8) M; P < 0.05) and [Sar9, Met (O2)11]-substance P (10(-8) M; P < 0.001), while the response to [beta-Ala8]-NKA 4-10 (10(-7) M) was unaffected. In the presence of L-NNA (10(-4) M), substance P and [Sar9, Met (O2)11]-substance P-induced relaxations were reduced (10(-8) M; P < 0.01), while the response to [beta-Ala8]-NKA 4-10 (10(-7) M) was unaffected. These results show that functional coupling between capsaicin-sensitive sensory neurones and NANC inhibitory neural pathways occurs via NK-1 receptors in the ferret LOS. NK-2 (and some NK-1) receptors activate non-neural excitatory mechanisms. Substance P and NK-1 receptors coupling sensory and NANC inhibitory neurones may be important in the reflex control of LOS motility.
Many children with fully accommodative esotropia can be weaned out of spectacles during the grade school years. The degree of baseline hyperopia appears to be one of the best predictors of success.
The global pandemic crisis, COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has claimed the lives of millions of people across the world. Development and testing of anti-SARS-CoV-2 drugs or vaccines, are not turned to be realistic in the timeframe needed to combat this pandemic. Thus, rigorous efforts are still ongoing for the drug repurposing as a clinical treatment strategy to control COVID-19. Here we report a comprehensive computational approach to identify the multi-targeted drug molecules against the SARS-CoV-2 proteins, which are crucially involved in the viral-host interaction, replication of the virus inside the host, disease progression and transmission of coronavirus infection. Virtual screening of 72 FDA approved potential antiviral drugs against the target proteins: Spike (S) glycoprotein, human angiotensin-converting enzyme 2 (hACE2), 3-chymotrypsin-like cysteine protease (3CLpro), Cathepsin L, Nucleocapsid protein, RNA-dependent RNA polymerase (RdRp) and nonstructural protein 6 (NSP6) resulted in the selection of seven drugs which preferentially binds to the target proteins. Further, the molecular interactions determined by MD simulation, free energy landscape and the binding free energy estimation, using MM-PBSA revealed that among 72 drug molecules, catechin (flavan-3-ol) can effectively bind to 3CLpro, Cathepsin L, RBD of S protein, NSP-6, and Nucleocapsid protein. It is more conveniently involved in key molecular interactions, showing binding free energy (ΔGbind) in the range of -5.09 kcal/mol (Cathepsin L) to -26.09 kcal/mol (NSP6). At the binding pocket, catechin is majorly stabilized by the hydrophobic interactions, displays ΔEvdW values -7.59 to -37.39 kcal/mol. Thus, the structural insights of better binding affinity and favourable molecular interaction of catechin towards multiple target proteins, signifies that catechin can be potentially explored as a multitargeted agent in the rational design of effective therapies against COVID-19.<br>
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.