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1.
Front Microbiol ; 14: 1243818, 2023.
Article in English | MEDLINE | ID: mdl-37808276

ABSTRACT

The emergence of antibiotic resistance is a growing threat to human health, and therefore, alternatives to existing compounds are urgently needed. In this context, a novel fluorescent photoactivatable diarylacetylene has been identified and characterised for its antibacterial activity, which preferentially eliminates Gram-positive over Gram-negative bacteria. Experiments confirmed that the Gram-negative lipopolysaccharide-rich outer surface is responsible for tolerance, as strains with reduced outer membrane integrity showed increased susceptibility. Additionally, bacteria deficient in oxidative damage repair pathways also displayed enhanced sensitivity, confirming that reactive oxygen species production is the mechanism of antibacterial activity. This new diarylacetylene shows promise as an antibacterial agent against Gram-positive bacteria that can be activated in situ, potentially for the treatment of skin infections.

2.
RNA ; 24(11): 1481-1495, 2018 11.
Article in English | MEDLINE | ID: mdl-30065024

ABSTRACT

RNA editing diversifies genomically encoded information to expand the complexity of the transcriptome. In ectothermic organisms, including Drosophila and Cephalopoda, where body temperature mirrors ambient temperature, decreases in environmental temperature lead to increases in A-to-I RNA editing and cause amino acid recoding events that are thought to be adaptive responses to temperature fluctuations. In contrast, endothermic mammals, including humans and mice, typically maintain a constant body temperature despite environmental changes. Here, A-to-I editing primarily targets repeat elements, rarely results in the recoding of amino acids, and plays a critical role in innate immune tolerance. Hibernating ground squirrels provide a unique opportunity to examine RNA editing in a heterothermic mammal whose body temperature varies over 30°C and can be maintained at 5°C for many days during torpor. We profiled the transcriptome in three brain regions at six physiological states to quantify RNA editing and determine whether cold-induced RNA editing modifies the transcriptome as a potential mechanism for neuroprotection at low temperature during hibernation. We identified 5165 A-to-I editing sites in 1205 genes with dynamically increased editing after prolonged cold exposure. The majority (99.6%) of the cold-increased editing sites are outside of previously annotated coding regions, 82.7% lie in SINE-derived repeats, and 12 sites are predicted to recode amino acids. Additionally, A-to-I editing frequencies increase with increasing cold-exposure, demonstrating that ADAR remains active during torpor. Our findings suggest that dynamic A-to-I editing at low body temperature may provide a neuroprotective mechanism to limit aberrant dsRNA accumulation during torpor in the mammalian hibernator.


Subject(s)
Brain/metabolism , Hibernation/genetics , Mammals/genetics , RNA Editing , Temperature , Animals , Evolution, Molecular , Gene Expression Profiling , Gene Expression Regulation , RNA, Messenger/genetics , Sciuridae , Torpor/genetics , Transcriptome
3.
Behav Modif ; 42(1): 108-125, 2018 01.
Article in English | MEDLINE | ID: mdl-28073293

ABSTRACT

Researchers have yet to identify the conditions under which people diagnosed with autism spectrum disorder demonstrate restricted interests; it is possible that the impression of restricted interests is strengthened when a limited variety of items are included in a client's preference assessments. This study will extend past research on preferences of children with autism by (a) examining participants' preferences for unreplenished (familiar) play or leisure items versus items that are replenished frequently, (b) assessing if participants who prefer replenished items select items with properties that are matched or unmatched to their most preferred unreplenished item, and (c) assessing if participants who show an exclusive preference for unreplenished items will select replenished items during response-restriction and enhanced-replenished pool manipulations. Participants were four adolescents with autism and a caregiver-reported history of restricted interests. One participant selected both unreplenished (familiar) items and replenished (novel) items without further manipulations. The remaining three participants only selected replenished-matched leisure items after additional manipulations. Results are discussed in terms of the ethical and practical importance of assessing a range of potential reinforcers, particularly with clients who demonstrate restricted interests.


Subject(s)
Autism Spectrum Disorder/physiopathology , Choice Behavior/physiology , Leisure Activities , Schools , Adolescent , Humans , Male
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