Unbinding Pathways from the Glucocorticoid Receptor Shed Light on the Reduced Sensitivity of Glucocorticoid Ligands to a Naturally Occurring, Clinically Relevant Mutant Receptor

2013 ◽  
Vol 56 (17) ◽  
pp. 7003-7014 ◽  
Author(s):  
Anna Maria Capelli ◽  
Agostino Bruno ◽  
Antonio Entrena Guadix ◽  
Gabriele Costantino
2012 ◽  
Vol 443 (2) ◽  
pp. 477-484 ◽  
Author(s):  
Min Tan ◽  
Wei Yan ◽  
Ru-Juan Liu ◽  
Meng Wang ◽  
Xin Chen ◽  
...  

aaRSs (aminoacyl-tRNA synthetases) establish the rules of the genetic code by catalysing the formation of aminoacyl-tRNA. The quality control for aminoacylation is achieved by editing activity, which is usually carried out by a discrete editing domain. For LeuRS (leucyl-tRNA synthetase), the CP1 (connective peptide 1) domain is the editing domain responsible for hydrolysing mischarged tRNA. The CP1 domain is universally present in LeuRSs, except MmLeuRS (Mycoplasma mobile LeuRS). The substitute of CP1 in MmLeuRS is a nonapeptide (MmLinker). In the present study, we show that the MmLinker, which is critical for the aminoacylation activity of MmLeuRS, could confer remarkable tRNA-charging activity on the inactive CP1-deleted LeuRS from Escherichia coli (EcLeuRS) and Aquifex aeolicus (AaLeuRS). Furthermore, CP1 from EcLeuRS could functionally compensate for the MmLinker and endow MmLeuRS with post-transfer editing capability. These investigations provide a mechanistic framework for the modular construction of aaRSs and their co-ordination to achieve catalytic efficiency and fidelity. These results also show that the pre-transfer editing function of LeuRS originates from its conserved synthetic domain and shed light on future study of the mechanism.


2018 ◽  
Vol 16 (1) ◽  
pp. 128-151
Author(s):  
Mikołaj Deckert ◽  
Marek Molenda

Abstract This article looks into the interface of temporality and quantification. Drawing on the principles of Cognitive Linguistics, we use experimental as well as corpus methods to provide evidence on how the conceptual organisation and linguistic coding of content can play a role in meaning construction. With that broad agenda in mind, a major objective is to shed light on the construct of conventionalisation. For that purpose, construal coding variants are examined with a focus on nominal phrases that express time quantities. The examination involves two construal types (termed “cumulative” and “fractional”) that differ primarily in their prominence configurations, across three granularity levels of time conceptualisation. Our main finding – that the fractional and cumulative constructions are asymmetrically conventionalised – is contextualised through a qualitative analysis of naturally-occurring data to identify additional language use patterns and offer explanatory hypotheses.


2016 ◽  
Vol 60 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Pawan Jolly ◽  
Pedro Estrela ◽  
Michael Ladomery

There are an increasing number of applications that have been developed for oligonucleotide-based biosensing systems in genetics and biomedicine. Oligonucleotide-based biosensors are those where the probe to capture the analyte is a strand of deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or a synthetic analogue of naturally occurring nucleic acids. This review will shed light on various types of nucleic acids such as DNA and RNA (particularly microRNAs), their role and their application in biosensing. It will also cover DNA/RNA aptamers, which can be used as bioreceptors for a wide range of targets such as proteins, small molecules, bacteria and even cells. It will also highlight how the invention of synthetic oligonucleotides such as peptide nucleic acid (PNA) or locked nucleic acid (LNA) has pushed the limits of molecular biology and biosensor development to new perspectives. These technologies are very promising albeit still in need of development in order to bridge the gap between the laboratory-based status and the reality of biomedical applications.


2004 ◽  
Vol 4 (2) ◽  
pp. 207-262 ◽  
Author(s):  
Daniel Fessler

AbstractCross-cultural comparisons can a) illuminate the manner in which cultures differentially highlight, ignore, and group various facets of emotional experience, and b) shed light on our evolved species-typical emotional architecture. In many societies, concern with shame is one of the principal factors regulating social behavior. Three studies conducted in Bengkulu (Indonesia) and California explored the nature and experience of shame in two disparate cultures. Study 1, perceived term use frequency, indicated that shame is more prominent in Bengkulu, a collectivistic culture, than in California, an individualistic culture. Study 2, comparing naturally occurring shame events (Bengkulu) with reports thereof (California), revealed that shame is associated with guilt-like accounts in California but not in Bengkulu, and subordinance events in Bengkulu but not in California; published reports suggest that the latter pattern is prominent worldwide. Study 3 mapped the semantic domain of shame using a synonym task; again, guilt was prominent in California, subordinance in Bengkulu. Because shame is overshadowed by guilt in individualistic cultures, and because these cultures downplay aversive emotions associated with subordinance, a fuller understanding of shame is best arrived at through the study of collectivistic cultures such as Bengkulu. After reviewing evolutionary theories on the origins and functions of shame, I evaluate these perspectives in light of facets of this emotion evident in Bengkulu and elsewhere. The available data are consistent with the proposition that shame evolved from a rank-related emotion and, while motivating prestige competition, cooperation, and conformity, nevertheless continues to play this role in contemporary humans.


Foods ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 372 ◽  
Author(s):  
Quintieri ◽  
Fanelli ◽  
Caputo

Microbial multidrug resistance (MDR) is a growing threat to public health mostly because it makes the fight against microorganisms that cause lethal infections ever less effective. Thus, the surveillance on MDR microorganisms has recently been strengthened, taking into account the control of antibiotic abuse as well as the mechanisms underlying the transfer of antibiotic genes (ARGs) among microbiota naturally occurring in the environment. Indeed, ARGs are not only confined to pathogenic bacteria, whose diffusion in the clinical field has aroused serious concerns, but are widespread in saprophytic bacterial communities such as those dominating the food industry. In particular, fresh dairy products can be considered a reservoir of Pseudomonas spp. resistome, potentially transmittable to consumers. Milk and fresh dairy cheeses products represent one of a few “hubs” where commensal or opportunistic pseudomonads frequently cohabit together with food microbiota and hazard pathogens even across their manufacturing processes. Pseudomonas spp., widely studied for food spoilage effects, are instead underestimated for their possible impact on human health. Recent evidences have highlighted that non-pathogenic pseudomonads strains (P. fluorescens, P. putida) are associated with some human diseases, but are still poorly considered in comparison to the pathogen P. aeruginosa. In addition, the presence of ARGs, that can be acquired and transmitted by horizontal genetic transfer, further increases their risk and the need to be deeper investigated. Therefore, this review, starting from the general aspects related to the physiological traits of these spoilage microorganisms from fresh dairy products, aims to shed light on the resistome of cheese-related pseudomonads and their genomic background, current methods and advances in the prediction tools for MDR detection based on genomic sequences, possible implications for human health, and the affordable strategies to counteract MDR spread.


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