Individual Streptomyces species have the genetic potential to produce a diverse array of natural products of commercial, medical and veterinary interest. However, these products are often not detectable under laboratory culture conditions. To harness their full biosynthetic potential, it is important to develop a detailed understanding of the regulatory networks that orchestrate their metabolism. Here we integrate nucleotide resolution genome-scale measurements of the transcriptome and translatome of Streptomyces coelicolor, the model antibiotic-producing actinomycete. Our systematic study determines 3,570 transcription start sites and identifies 230 small RNAs and a considerable proportion (∼21%) of leaderless mRNAs; this enables deduction of genome-wide promoter architecture. Ribosome profiling reveals that the translation efficiency of secondary metabolic genes is negatively correlated with transcription and that several key antibiotic regulatory genes are translationally induced at transition growth phase. These findings might facilitate the design of new approaches to antibiotic discovery and development.
We evaluated the predictive value of serum biomarkers and various clinical risk scales for the 28-day mortality of community-acquired pneumonia (CAP). Serum biomarkers including procalcitonin (PCT) and C-reactive protein (CRP) were evaluated in the emergency department. Scores for the pneumonia severity index (PSI); CURB65 (confusion, urea, respiration, blood pressure; age >65 years); Infectious Disease Society of America (IDSA) and American Thoracic Society (ATS) guidelines for severe CAP; Acute Physiology, Chronic Health Evaluation (APACHE) II; Sequential Organ Failure Assessment (SOFA); and quick SOFA (qSOFA) were calculated. Receiver-operating characteristic curves for 28-day mortality were calculated for each predictor using cut-off values, and we applied logistic regression models and area under the curve (AUC) analysis to compare the performance of predictors. Of the 125 enrolled patients, 13 died within 28 days. The AUCs of the PCT and CRP were 0.83 and 0.77, respectively. Using a PCT level >5.6 μg/L as the cut-off, the sensitivity and specificity for mortality were 76.9% and 90.2%, respectively. The three pneumonia severity scales showed an AUC of 0.86 (PSI), 0.87 (IDSA/ATS) and 0.77 (CURB65). The AUCs of the APACHE II, SOFA and qSOFA scores were 0.85, 0.83 and 0.81, respectively. The models combining CRP and/or PCT with PSI or the IDSA/ATS guidelines demonstrated superior performance to those of either PSI or the IDAS/ATS guidelines alone. In conclusion, serum PCT is a reliable single predictor for short-term mortality. Inclusion of CRP and/or PCT could significantly improve the performance of the PSI and IDAS/ATS guidelines.
Microglia plays a critical role in the brain and protects neuronal cells from toxins. However, over-activation of microglia leads to deleterious effects. Lipopolysaccharide (LPS) has been reported to affect neuronal cells via activation of microglia as well as directly to initiate neuroinflammation. In the present study, we evaluated the anti-inflammatory and anti-oxidative effect of anthocyanins against LPS-induced neurotoxicity in an animal model and in cell cultures. Intraperitoneal injections of LPS (250 μg/kg/day for 1 week) induce ROS production and promote neuroinflammation and neurodegeneration which ultimately leads to memory impairment. However, anthocyanins treatment at a dose of 24 mg/kg/day for 2 weeks (1 week before and 1 week co-treated with LPS) prevented ROS production, inhibited neuroinflammation and neurodegeneration, and improved memory functions in LPS-treated mice. Both histological and immunoblot analysis indicated that anthocyanins reversed the activation of JNK, prevented neuroinflammation by lowering the levels of inflammatory markers (p-NF-kB, TNF-α, and IL-1β), and reduced neuronal apoptosis by reducing the expression of Bax, cytochrome c, cleaved caspase-3, and cleaved PARP-1, while increasing the level of survival proteins p-Akt, p-GSK3β, and anti-apoptotic Bcl-2 protein. Anthocyanins treatment increased the levels of memory-related pre- and post-synaptic proteins and improved the hippocampus-dependent memory in the LPS-treated mice. Overall, this data suggested that consumption of naturally derived anti-oxidant agent such as anthocyanins ameliorated several pathological events in the LPS-treated animal model and we believe that anthocyanins would be a safe therapeutic agent for slowing the inflammation-induced neurodegeneration in the brain against several diseases such as Alzheimer's disease and Parkinson's disease.
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