The rate of production of bacterial gene products is known to vary with the rate of cell growth, the concentrations of many cellular proteins are altered during times of decreased growth rate. In addition, proteins whose in vivo levels show no significant alterations with changes in cell doubling time must be synthesized at rates that vary in direct proportion to the growth rate of the cell. In certain instances, growth-rate dependent gene regulation has been shown to occur at the transcriptional or translational level. Another potentially important element in the regulation of gene expression is the stability of messenger RNA. We report here the effect of bacterial growth rate on the half lives of four different monocistronic Escherichia coli mRNA species. The stabilities of two of these species, the transcripts of the ompA and cat genes, exhibited a marked dependence on cell growth rate, whereas the half lives of the transcripts of the lpp and bla genes are constant over a broad range of cell doubling times. Our results indicate that E. coli can alter the rate of synthesis of certain proteins by modulating mRNA stability in response to changes in the rate of cell growth.

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Translational stop codons were introduced at various locations in the protein-coding regions of the monocistronic bla and ompA gene transcripts of Escherichia coli, and the decay characteristics of the upstream and downstream mRNA segments were analyzed. Premature termination of translation at codon position 26 reduced the stability of both the translated and ribosome-free segments of bla mRNA, whereas release of ribosomes just 30 codons further downstream resulted in normal stability for both segments. Normal stability of an untranslated bla gene mRNA segment required its linkage to a ribosome-bound segment of bla gene mRNA. These findings indicate that depriving an mRNA segment of ribosomes does not necessarily render it more susceptible to degradation. However, premature termination of translation at a location that allows ribosomes to traverse only a short segment of bla mRNA can lead to destabilization of the entire transcript.

BackgroundIn myocardial infarction (MI), pre-hospital delay is associated with increased mortality and decreased possibility of revascularisation. We assessed pre-hospital delay in patients with first time MI in a northern Swedish population and identified determinants of a pre-hospital delay ≥ 2 h.MethodsA total of 89 women (mean age 72.6 years) and 176 men (mean age 65.8 years) from a secondary prevention study were enrolled in an observational study after first time MI between November 2009 and March 2012. Total pre-hospital delay was defined as the time from the onset of symptoms suggestive of MI to admission to the hospital. Decision time was defined as the time from the onset of symptoms until the call to Emergency Medical Services (EMS). The time of symptom onset was assessed during the episode of care, and the time of call to EMS and admission to the hospital was based on recorded data. The first medical contact was determined from a mailed questionnaire. Determinants associated with pre-hospital delay ≥ 2 h were identified by multivariable logistic regression.ResultsThe median total pre-hospital delay was 5.1 h (IQR 18.1), decision time 3.1 h (IQR 10.4), and transport time 1.2 h (IQR 1.0). The first medical contact was to primary care in 52.3 % of cases (22.3 % as a visit to a general practitioner and 30 % by telephone counselling), 37.3 % called the EMS, and 10.4 % self-referred to the hospital. Determinants of a pre-hospital delay ≥ 2 h were a visit to a general practitioner (OR 10.77, 95 % CI 2.39–48.59), call to primary care telephone counselling (OR 3.82, 95 % CI 1.68–8.68), chest pain as the predominant presenting symptom (OR 0.24, 95 % CI 0.08–0.77), and distance from the hospital (OR 1.03, 95 % CI 1.02–1.04). Among patients with primary care as the first medical contact, 67.0 % had a decision time ≥ 2 h, compared to 44.7 % of patients who called EMS or self-referred (p = 0.002).ConclusionsPre-hospital delay in patients with first time MI is prolonged considerably, particularly when primary care is the first medical contact. Actions to shorten decision time and increase the use of EMS are still necessary.Electronic supplementary materialThe online version of this article (doi:10.1186/s12872-016-0271-x) contains supplementary material, which is available to authorized users.

BackgroundPeriventricular leukomalacia (PVL) is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia–ischemia (HI) and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.MethodsImmunohistochemistry on brain sections from neonatal mice was performed to evaluate the extent of brain injury in wild-type and T cell and B cell-deficient neonatal mice (Rag1−/− mice) using a mouse model of HI-induced preterm brain injury. Flow cytometry was performed to determine the presence of different types of immune cells in mouse brains following HI. In addition, immunostaining for CD3 T cells and CD20 B cells was performed on postmortem preterm human infant brains with PVL.ResultsMature lymphocyte-deficient Rag1−/− mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3+ T cells and CD20+ B cells were observed in the postmortem preterm infant brains with PVL. Flow cytometry analysis of mouse brains after HI-induced injury showed increased frequency of CD3+ T, αβT and B cells at 7 days after HI in the ipsilateral (injured) hemisphere compared to the contralateral (control, uninjured) hemisphere.ConclusionLymphocytes were found in the injured brain after injury in both mice and humans, and lack of mature lymphocytes protected neonatal mice from HI-induced brain white matter injury. This finding provides insight into the pathology of perinatal brain injury and suggests new avenues for the development of therapeutic strategies.