Strongborregaard2532
Antimicrobial resistance is a serious public health threat worldwide today. Escherichia coli is known to resist low doses of antibiotics in the presence of sodium salicylate and related compounds by mounting non-heritable transient phenotypic antibiotic resistance (PAR). In the present study, we demonstrate that Bgl+ bacterial strains harboring a functional copy of the β-glucoside (bgl) operon and are actively hydrolyzing plant-derived aromatic β-glucosides such as salicin show PAR to low doses of antibiotics. The aglycone released during metabolism of aromatic β-glucosides is responsible for conferring this phenotype by de-repressing the multiple antibiotics resistance (mar) operon. We also show that prolonged exposure of Bgl+ bacteria to aromatic β-glucosides in the presence of sub-lethal doses of antibiotics can lead to a significant increase in the frequency of mutants that show heritable resistance to higher doses of antibiotics. Although heritable drug resistance in many cases is known to reduce the fitness of the carrier strain, we did not see a cost associated with resistance in the mutants, most of which carry clinically relevant mutations. These findings indicate that the presence of the activated form of the bgl operon in the genome facilitates the survival of bacteria in environments in which both aromatic β-glucosides and antibiotics are present.In Germany, approximately 2% of the population suffers from psoriasis, which is no longer considered only a cutaneous, but rather a systemic disease. Accordingly, common comorbidities and potential joint involvement in psoriasis must be recorded. If necessary, interdisciplinary patient care has to be organized. The use of validated scores is recommended to complete the patient's medical history. The individual treatment should include intensified topical therapies as well as short-term phototherapy in case of an acute phase. In addition to conventional systemic therapies (e.g., fumarates, methotrexate), a number of new therapeutics for psoriasis are in development. Apart from the PDE‑4 inhibitor apremilast, targeted therapies are currently available to block TNF-alpha, IL-17A, the IL-17 receptor and IL-23. Decisions on individualized, patient-centered psoriasis management should be based on assessment of disease severity and the existence of comorbidities. Furthermore, economic aspects should be taken into account.RATIONALE The rapid-onset and long-lasting antidepressant properties of ketamine have prompted investigations into a variety of agents that target N-methyl-D-aspartate receptors (NMDARs) for the treatment of major depressive disorder (MDD). According to the literature, ifenprodil (a GluN2B-containing NMDAR antagonist) can potentiate the antidepressant-like effects of certain antidepressant drugs in mice. Here, we report that a single injection of ifenprodil (3 mg/kg, intraperitoneally (i.p.)) was sufficient to provoke rapid antidepressant-like effects in chronic unpredictable mild stress (CUMS) rats. Moreover, ifenprodil activated mTOR signaling and reversed the CUMS-induced elevation of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the hippocampus after acute administration. Unfortunately, in our study, ifenprodil had no influence on corticosterone levels in the plasma. Our data indicate that ifenprodil per se might exert antidepressant-like effects by modulating neuropthe synthesis of the synaptic protein GluA1 synthesis after acute administration. Moreover, ifenprodil reversed the CUMS-induced elevation of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the hippocampus after acute administration. Unfortunately, ifenprodil had no influence on corticosterone levels in the plasma in our study. CONCLUSIONS Our data indicate that ifenprodil per se might exert antidepressant-like effects through its effects on neuroplasticity and inflammatory processes rather than the typical hormonal factors affected by stressors.The perception of an event is strongly influenced by the context in which it occurs. check details Here, we examined the effect of a rhythmic context on detection of asynchrony in both the auditory and vibrotactile modalities. Using the method of constant stimuli and a two-alternative forced choice (2AFC), participants were presented with pairs of pure tones played either simultaneously or with various levels of stimulus onset asynchrony (SOA). Target stimuli in both modalities were nested within either (i) a regularly occurring, predictable rhythm (ii) an irregular, unpredictable rhythm, or (iii) no rhythm at all. Vibrotactile asynchrony detection had higher thresholds and showed greater variability than auditory asynchrony detection in general. Asynchrony detection thresholds for auditory targets but not vibrotactile targets were significantly reduced when the target stimulus was embedded in a regular rhythm as compared to no rhythm. Embedding within an irregular rhythm produced no such improvement. The observed modality asymmetries are interpreted with regard to the superior temporal resolution of the auditory system and specialized brain circuitry supporting auditory-motor coupling.High-status individuals have been found to be less attuned to the behaviour of others in the social environment, at least in the absence of any specific instructions to pay attention to them. Previous work using neural measures has shown that socioeconomic status (SES) influences the degree to which people are attuned to the actions of others. In particular, individuals from low-SES backgrounds were found to exhibit more mu-suppression, which has been suggested to reflect greater levels of sensorimotor resonance, compared to their high-SES counterparts. However, it is unclear whether such effects on brain activity translate into behaviour. Here, we examined differences in automatic imitation between high-SES and low-SES individuals. The automatic imitation task involves participants making actions in response to a numerical cue, while simultaneously being exposed to an action that is incongruent or congruent with the cued response. Patterns of interference effect reveal the extent to which the congruence of the observed action affects performance of the cued response.