A species-specific frequency filter through specific inhibition, not specific excitation

2002 ◽  
Vol 188 (3) ◽  
pp. 239-248 ◽  
Author(s):  
Stumpner A.
Parasitology ◽  
2015 ◽  
Vol 142 (9) ◽  
pp. 1239-1248 ◽  
Author(s):  
LIANET MONZOTE ◽  
ALEXANDRA LACKOVA ◽  
KATRIN STANIEK ◽  
OSMANY CUESTA-RUBIO ◽  
LARS GILLE

SUMMARYNemorosone (Nem) and guttiferone A (GutA) are acyl phloroglucinol derivatives (APD) that are present in different natural products. For both compounds anti-cancer and anti-microbial properties have been reported. In particular, an anti-leishmanial activity of both compounds was demonstrated. The aim of this study was to explore the possible role of mitochondria in the anti-leishmanial activity of Nem and GutA in comparison with their action on mammalian mitochondria. Both APD inhibited the growth of promastigotes ofLeishmania tarentolae(LtP) with half maximal inhibitory concentration (IC50) values of 0·67 ± 0·17 and 6·2 ± 2·6μm; while IC50values for cytotoxicity against peritoneal macrophages from BALB/c mice were of 29·5 ± 3·7 and 9·2 ± 0·9μm, respectively. Nemorosone strongly inhibited LtP oxygen consumption, caused species-specific inhibition (P< 0·05) of succinate:ubiquinone oxidoreductase (complex II) from LtP-mitochondria and significantly increased (P< 0·05) the mitochondrial superoxide production. In contrast, GutA caused only a moderate reduction of respiration in LtP and triggered less superoxide radical production in LtP compared with Nem. In addition, GutA inhibited mitochondrial complex III in bovine heart submitochondrial particles, which is possibly involved in its mammalian toxicity. Both compounds demonstrated at low micromolar concentrations an effect on the mitochondrial membrane potential in LtP. The present study suggests that Nem caused its anti-leishmanial action due to specific inhibition of complexes II/III of mitochondrial respiratory chain ofLeishmaniaparasites that could be responsible for increased production of reactive oxygen species that triggers parasite death.


2014 ◽  
Vol 289 (20) ◽  
pp. 13801-13809 ◽  
Author(s):  
Bhuvaneshwari Mahalingam ◽  
Johannes F. Van Agthoven ◽  
Jian-Ping Xiong ◽  
José Luis Alonso ◽  
Brian D. Adair ◽  
...  

2008 ◽  
Vol 284 (9) ◽  
pp. 5819-5826 ◽  
Author(s):  
Mario Perković ◽  
Stanislaw Schmidt ◽  
Daniela Marino ◽  
Rebecca A. Russell ◽  
Benjamin Stauch ◽  
...  

2016 ◽  
Vol 113 (9) ◽  
pp. 2508-2513 ◽  
Author(s):  
Melville J. Wohlgemuth ◽  
Cynthia F. Moss

This study investigated auditory stimulus selectivity in the midbrain superior colliculus (SC) of the echolocating bat, an animal that relies on hearing to guide its orienting behaviors. Multichannel, single-unit recordings were taken across laminae of the midbrain SC of the awake, passively listening big brown bat, Eptesicus fuscus. Species-specific frequency-modulated (FM) echolocation sound sequences with dynamic spectrotemporal features served as acoustic stimuli along with artificial sound sequences matched in bandwidth, amplitude, and duration but differing in spectrotemporal structure. Neurons in dorsal sensory regions of the bat SC responded selectively to elements within the FM sound sequences, whereas neurons in ventral sensorimotor regions showed broad response profiles to natural and artificial stimuli. Moreover, a generalized linear model (GLM) constructed on responses in the dorsal SC to artificial linear FM stimuli failed to predict responses to natural sounds and vice versa, but the GLM produced accurate response predictions in ventral SC neurons. This result suggests that auditory selectivity in the dorsal extent of the bat SC arises through nonlinear mechanisms, which extract species-specific sensory information. Importantly, auditory selectivity appeared only in responses to stimuli containing the natural statistics of acoustic signals used by the bat for spatial orientation—sonar vocalizations—offering support for the hypothesis that sensory selectivity enables rapid species-specific orienting behaviors. The results of this study are the first, to our knowledge, to show auditory spectrotemporal selectivity to natural stimuli in SC neurons and serve to inform a more general understanding of mechanisms guiding sensory selectivity for natural, goal-directed orienting behaviors.


2021 ◽  
Vol 17 (1) ◽  
pp. e1009183
Author(s):  
Chorong Park ◽  
Chen Peng ◽  
M. Julhasur Rahman ◽  
Sherry L. Haller ◽  
Loubna Tazi ◽  
...  

The antiviral protein kinase R (PKR) is an important host restriction factor, which poxviruses must overcome to productively infect host cells. To inhibit PKR, many poxviruses encode a pseudosubstrate mimic of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2), designated K3 in vaccinia virus. Although the interaction between PKR and eIF2α is highly conserved, some K3 orthologs from host-restricted poxviruses were previously shown to inhibit PKR in a species-specific manner. To better define this host range function, we compared the sensitivity of PKR from 17 mammals to inhibition by K3 orthologs from closely related orthopoxviruses, a genus with a generally broader host range. The K3 orthologs showed species-specific inhibition of PKR and exhibited three distinct inhibition profiles. In some cases, PKR from closely related species showed dramatic differences in their sensitivity to K3 orthologs. Vaccinia virus expressing the camelpox virus K3 ortholog replicated more than three orders of magnitude better in human and sheep cells than a virus expressing vaccinia virus K3, but both viruses replicated comparably well in cow cells. Strikingly, in site-directed mutagenesis experiments between the variola virus and camelpox virus K3 orthologs, we found that different amino acid combinations were necessary to mediate improved or diminished inhibition of PKR derived from different host species. Because there is likely a limited number of possible variations in PKR that affect K3-interactions but still maintain PKR/eIF2α interactions, it is possible that by chance PKR from some potential new hosts may be susceptible to K3-mediated inhibition from a virus it has never previously encountered. We conclude that neither the sensitivity of host proteins to virus inhibition nor the effectiveness of viral immune antagonists can be inferred from their phylogenetic relatedness but must be experimentally determined.


2018 ◽  
Vol 1438 (1) ◽  
pp. 3-17 ◽  
Author(s):  
Zhixun Zhao ◽  
Xueliang Zhu ◽  
Na Wu ◽  
Xiaodong Qin ◽  
Caiyun Huang ◽  
...  

1996 ◽  
Vol 241 (1) ◽  
pp. 114-120 ◽  
Author(s):  
Georgina Garza-Ramos ◽  
Ruy PErez-Montfort ◽  
Arturo Rojo-DomInguez ◽  
Marietta Tuena GOmez-Puyou ◽  
Armando GOmez-Puyou

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