Interaction of Fluoroquinolones in Their Different Prototropic States with DNA: Diversity in the Nature of Binding and the Role of External Chemical Stimulus on Drug Displacement

2019 ◽  
Vol 4 (3) ◽  
pp. 892-905
Author(s):  
Ishita Das ◽  
Mintu Halder
2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Zhengxiang Zhang ◽  
Yunxiang Tao ◽  
Qingling Hua ◽  
Juan Cai ◽  
Xiaobing Ye ◽  
...  

Small nucleolar RNAs (snoRNAs) play a crucial role during colorectal cancer (CRC) development. The study of SNORA71A is few, and its role in CRC is unknown. This study focused on screening abnormal snoRNAs in CRC and exploring the role of key snoRNA in CRC. The expression pattern of snoRNAs in 3 CRC and 3 normal colon tissues was detected via small RNA sequencing. The six candidate snoRNAs were identified by quantitative PCR (qPCR). Subsequently, the expression level of SNORA71A was further verified through the Cancer Genome Atlas (TCGA) data analysis and qPCR. The CCK8 and transwell assays were used to detect the functional role of SNORA71A in CRC cells. The integrated analysis of snoRNA expression profile indicated that a total 107 snoRNAs were significantly differentially expressed (DE) in CRC tissues compared with normal tissues, including 45 upregulated and 62 downregulated snoRNAs. Bioinformatics analysis revealed that the DE snoRNAs were mainly implicated in “detection of chemical stimulus involved in sensory perception of smell” and “sensory perception of smell” in the biological process. The DE snoRNAs were preferentially enriched in “olfactory transduction” and “glycosphingolipid biosynthesis-ganglio series pathway.” The expression of SNORA71A was upregulated in CRC tissues and cells. SNORA71A expression showed statistically significant correlations with TNM stage ( P = 0.0196 ) and lymph node metastasis ( P = 0.0189 ) and can serve as biomarkers for CRC. Importantly, SNORA71A significantly facilitated the CRC cell proliferation, migration, and invasion. Our findings indicate that SNORA71A screened by sequencing acted as an oncogene and promoted proliferation, migration, and invasion ability of CRC cells.


PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2150 ◽  
Author(s):  
Valeria Sfara ◽  
Gastón A. Mougabure-Cueto ◽  
Paola A. González-Audino

Insects under different stimuli from the environment modify behavioural responses due to changes in the sensitivity of neurons at the peripheral and/or at the central level of the nervous system. This phenomenon is called neuronal plasticity, and sensory adaptation is an example of it. An insect repellent is a chemical that produces oriented movements of the insects away from its source. In this work we studied the modulation of the behavioural and electrical response to the repellent N, N-diethyl-3-methylbenzamide (DEET) in males of the German cockroachB. germanicaproduced by previous exposure to the same repellent.Methods.We determined repellency using a circular arena, one half of which was treated with DEET. The time spent by insects in each half of the arena was measured, and a repellency coefficient (RC) was calculated. The RCs of pre-exposed and non-pre-exposed insects were compared. To determine a possible role of nitric oxide in the modulation of the response to DEET after pre-exposure, the nitric oxide donor S-nitroso-acetyl-cysteine (SNAC) was applied on cockroaches’ antennae. The electrical activity of the cockroaches’ antennae in response to DEET was recorded using electroantennogram (EAG) technique. The response to DEET was recorded also after a long stimulation with the same repellent, and after topical application of SNAC and dbcGMP (a cGMP analogue) on the antennae.Results.We found that previous exposure ofB. germanicamales to the repellent DEET produced an increase of the repellency at the behavioural level, measured as RC. A possible role of nitric oxide (NO) in the transduction pathway of this phenomenon is suggested, since treatment of the cockroaches with the NO donor SNAC also produced an increase of the repellency elicited by DEET. On the other hand, the response of the cockroaches’ antennae exposed to DEET was determined electrophysiologically. The electrical activity in response to DEET decreased when the insects’ antennae were stimulated with a long pulse of the repellent. The activity of the antennae was restored after 10 min. Treatment of the antennae either with SNAC or dbGMPc also produced a decrease in the response of the antennae to the repellent.Discussion.The previous exposure to a chemical stimulus can modify the behaviour associated to the same stimulus, increasing or decreasing the behavioural response. In the case of DEET we found that pre-exposure increased DEET repellency in male cockroaches. We also found NO involvement in a similar phenomenon. On the other hand, the test showed that DEET is perceived by insects’ antennae as an odour. A long exposure of the antennae to DEET caused a transient decrease in the response of the antennae to the same compound. The same effect was achieved by treating the antennae with SNAC or dbcGMP, suggesting the involvement of the NO/cGMP system in the transduction pathway of the sensory adaptation phenomenon elicited by an odour in this species.


1990 ◽  
Vol 69 (3) ◽  
pp. 1159-1164 ◽  
Author(s):  
D. Georgopoulos ◽  
Z. Bshouty ◽  
M. Younes ◽  
N. R. Anthonisen

After voluntary hyperventilation, normal humans do not develop a significant ventilatory depression despite low arterial CO2 tension, a phenomenon attributed to activation of a brain stem mechanism referred to as the "afterdischarge." Afterdischarge is one of the factors that promote ventilatory stability. It is not known whether physiological stimuli, such as hypoxia, are able to activate the afterdischarge in humans. To test this, breath-by-breath ventilation (VI) was measured in nine young adults during and immediately after a brief period (35-51 s) of acute hypoxia (end-tidal O2 tension 55 Torr). Hypoxia was terminated by switching to 100% O2 (end-tidal O2 tension of first posthypoxic breath greater than 100 Torr). Brief hypoxia increased VI and decreased end-tidal CO2 tension. In all subjects, termination of hypoxia was followed by a gradual ventilatory decay; hyperoxic VI remained higher than the normoxic baseline for several breaths and, despite the negative chemical stimulus of hyperoxia and hypocapnia, reached a new steady state without an apparent undershoot. We conclude that brief hypoxia is able to activate the afterdischarge mechanism in conscious humans. This contrasts sharply with the ventilatory undershoot that follows relief of sustained hypoxia, thereby suggesting that sustained hypoxia inactivates the afterdischarge mechanism. The present findings are of relevance to the pathogenesis of periodic breathing in a hypoxic environment. Furthermore, brief exposure to hypoxia might be useful for evaluation of the role of afterdischarge in other disorders associated with unstable breathing.


1936 ◽  
Vol 27 (3) ◽  
pp. 423-429 ◽  
Author(s):  
D. N. Roy

The intimate association between a blood meal and ovulation in all female mosquitos, with the exception of a few (de Buck, Roubaud) has been clearly recognised; but the peculiar manner in which the presence of blood in the stomach can influence the formation of eggs is not understood. Two explanations may be suggested: it may either act as a physico-chemical stimulus to the ovarian follicles, or certain constituents in the blood may furnish some nutrient material for the development of the eggs.


2013 ◽  
Vol 103 (6) ◽  
pp. 675-682 ◽  
Author(s):  
C.D. Rogers ◽  
K.A. Evans ◽  
J. Parker ◽  
V.A. Pappa

AbstractWheat bulb fly (WBF) larvae use chemotaxis to orientate towards host-plant root exudates. This study aimed to investigate the role of the primary plant metabolite carbon dioxide (CO2) in host-plant location by WBF. Arena based behavioural experiments were used to identify whether CO2 induced chemotaxis (directional movement in response to a chemical stimulus) or kinesis (non-directional movement in response to a stimulus) from WBF larvae. No chemotactic response was observed when larvae were presented to a point source of CO2. However, elevated levels of CO2 induced kinesis, with both track length and tortuosity (number of twists and turns in the movement path) increasing at elevated CO2 levels of 1000–2000 ppm, demonstrating increased searching behaviour. Soil emission of CO2 was quantified to compare soil levels with those identified as eliciting behavioural effects on the larvae. Samples removed from soil gave a mean CO2 concentration of 557 (±46) ppm, which is lower than the lowest concentration of CO2 found to induce a behavioural response and higher than the lowest CO2 concentration tested, which was found not to alter behaviour. It is proposed that increased CO2 concentrations in the soil act as a behavioural trigger, inducing intensive searching of an area by WBF larvae. This increases the likelihood of finding more host-specific identifiers, such as secondary metabolites when near a potential host-plant.


2021 ◽  
Vol 11 ◽  
Author(s):  
Anne-Clémence Vion ◽  
Tijana Perovic ◽  
Charlie Petit ◽  
Irene Hollfinger ◽  
Eireen Bartels-Klein ◽  
...  

Vascular networks form, remodel and mature under the influence of multiple signals of mechanical or chemical nature. How endothelial cells read and interpret these signals, and how they integrate information when they are exposed to both simultaneously is poorly understood. Here, we show using flow-induced shear stress and VEGF-A treatment on endothelial cells in vitro, that the response to the magnitude of a mechanical stimulus is influenced by the concentration of a chemical stimulus, and vice versa. By combining different flow levels and different VEGF-A concentrations, front-rear polarity of endothelial cells against the flow direction was established in a flow and VEGF-A dose-response while their alignment with the flow displayed a biphasic response depending on the VEGF-A dose (perpendicular at physiological dose, aligned at no or pathological dose of VEGF-A). The effect of pharmaceutical inhibitors demonstrated that while VEGFR2 is essential for both polarity and orientation establishment in response to flow with and without VEGF-A, different downstream effectors were engaged depending on the presence of VEGF-A. Thus, Src family inhibition (c-Src, Yes, Fyn together) impaired alignment and polarity without VEGF-A while FAK inhibition modified polarity and alignment only when endothelial cells were exposed to VEGF-A. Studying endothelial cells in the aortas of VEGFR2Y949F mutant mice and SRCiEC–KO mice confirmed the role of VEGFR2 and specified the role of c-SRC in vivo. Endothelial cells of VEGFR2Y949F mutant mice lost their polarity and alignment while endothelial cells from SRCiEC–KO mice only showed reduced polarity. We propose here that VEGFR2 is a sensor able to integrate chemical and mechanical information simultaneously and that the underlying pathways and mechanisms activated will depend on the co-stimulation. Flow alone shifts VEGFR2 signaling toward a Src family pathway activation and a junctional effect (both in vitro and in vivo) while flow and VEGF-A together shift VEGFR2 signaling toward focal adhesion activation (in vitro) both modifying cell responses that govern orientation and polarity.


JAMA ◽  
1966 ◽  
Vol 195 (12) ◽  
pp. 1005-1009 ◽  
Author(s):  
D. J. Fernbach
Keyword(s):  

JAMA ◽  
1966 ◽  
Vol 195 (3) ◽  
pp. 167-172 ◽  
Author(s):  
T. E. Van Metre

2018 ◽  
Vol 41 ◽  
Author(s):  
Winnifred R. Louis ◽  
Craig McGarty ◽  
Emma F. Thomas ◽  
Catherine E. Amiot ◽  
Fathali M. Moghaddam

AbstractWhitehouse adapts insights from evolutionary anthropology to interpret extreme self-sacrifice through the concept of identity fusion. The model neglects the role of normative systems in shaping behaviors, especially in relation to violent extremism. In peaceful groups, increasing fusion will actually decrease extremism. Groups collectively appraise threats and opportunities, actively debate action options, and rarely choose violence toward self or others.


2018 ◽  
Vol 41 ◽  
Author(s):  
Kevin Arceneaux

AbstractIntuitions guide decision-making, and looking to the evolutionary history of humans illuminates why some behavioral responses are more intuitive than others. Yet a place remains for cognitive processes to second-guess intuitive responses – that is, to be reflective – and individual differences abound in automatic, intuitive processing as well.


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