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To demonstrate the potential of P. putida as a heterologous host, we introduced BGCs encoding the synthesis of prodigiosin and glidobactin A, two bioactive natural products synthesized from a combination of PKS and NRPS enzymology. Engineered strains exhibited robust production of both compounds after a single chromosomal integration of the corresponding BGC. Next, we took advantage of a set of genome-editing tools to increase titers by modifying transcription and translation of the BGCs and increasing the availability of auxiliary proteins required for PKS and NRPS activity. Lastly, we discovered genetic modifications to P. putida that affect natural product synthesis, including a strategy for removing a carbon sink that improves product titers. These efforts resulted in production strains capable of producing 1.1 g/L prodigiosin and 470 mg/L glidobactin A.Insulin resistance (IR) is a state when the physiological amount of insulin is not sufficient to evoke proper action, that is, glucose uptake. Numerous conditions lead to IR, including epigenetic components. Epigenetic modifications, associated with obesity and IR are one of the main mechanisms leading to IR pathogenesis. The adipose tissue samples (subcutaneous (SAT) and visceral (VAT)) were collected during abdominal surgery from 40 patients of a wide range of BMI, age, and insulin resistance ratios (F = 9, M = 31). IR was induced in 3T3-L1 adipocytes and human adipocytes collected from SAT and VAT of healthy subjects. Global and site-specific histone modifications (H3K4me3 and H3K9/14ac) were determined. We found lower histone modifications in adipose tissue of IR patients. Furthermore, numerous genes regulating insulin action (PPARG, SLC2A4, ADIPOQ) were differently marked by histone methylation and acetylation. Moreover, we noticed that epigenetic changes appear as soon as 72 h following IR induction. The epigenetic changes appeared to be mediated through the SIRT family. Based on obtained results, the histone marks related to insulin resistance mostly concerned PPARG and SLC2A4 genes. Furthermore, our results proved a vital role of the SIRT family in insulin action and IR pathogenesis.
Health literacy is increasingly recognized as an essential determinant for the health of the population. Liver patients report perceived stigma to be a considerable problem. Little is however known about liver health literacy in the general population and to what extent liver disease is considered stigmatizing in comparison with other chronic diseases. We aimed to explore these knowledge gaps.
We performed an exploratory e-survey in a statistically representative sample of 500 Swedes from the general population. A questionnaire developed for this purpose investigated awareness, attention, knowledge and attitudes towards liver health and compared some aspects with other common health problems.
Few worry (23%), think (28%), discuss with their doctor (31%) or hear about liver health in the news (19%). Few (18%) had a liver test in the last year and knew (23%) what is considered a normal liver test. More knew what is considered normal blood pressure (89%), blood sugar (74%) and BMI (73%). Few (22%) talk about liver health, mainly (50%) because abuse is presumed. Many (36%) believe that cirrhosis is only caused by alcohol, 31% that the liver produces urine and 21% that you can survive without a liver. Only mental illness (78%) and obesity (74%) were considered more stigmatizing than liver cirrhosis (61%).
The study confirms often held views that liver health receives less attention than many other health areas. Knowledge about liver health is generally poor, and liver cirrhosis carries significant social stigma. Improving public awareness and knowledge about liver health, and thereby ameliorating stigma, should be essential parts of policy objectives and action plans to improve liver health in Europe.
This research was supported by a general grant from the Bengt Ihre Foundation.
This research was supported by a general grant from the Bengt Ihre Foundation.Neonatal sepsis is common, lethal, and hard to diagnose. In combination with clinical findings and blood culture, biomarkers are crucial to make the correct diagnose. A Swedish national inquiry indicated that neonatologists were not quite satisfied with the available biomarkers. We assessed the kinetics of 15 biomarkers simultaneously ferritin, fibrinogen, granulocyte colony-stimulating factor (G-CSF), interferon (IFN)-γ, interleukin (IL)-1β, -6, -8, -10, macrophage inflammatory protein (MIP)-1β, procalcitonin, resistin, serum amyloid A (SAA), tumor necrosis factor (TNF)-α, tissue plasminogen activator-3 and visfatin. The goal was to observe how quickly they rise in response to infection, and for how long they remain elevated. From a neonatal intensive care unit, newborns ≥28 weeks gestational age were recruited. Sixty-eight newborns were recruited to the study group (SG), and fifty-one to the control group (CG). The study group subjects were divided into three subgroups depending on clinical findings confirmkers studied. It is also readily available methodologically, making it a prime candidate for clinical use.The proneural gene Ascl1 promotes formation of both neurons and oligodendrocytes from neural stem cells (NSCs), but it remains to be analyzed how its different functions are coordinated. Oxythiaminechloride It was previously shown that Ascl1 enhances proliferation of NSCs when its expression oscillates but induces differentiation into transit-amplifying precursor cells and neurons when its expression is up-regulated and sustained. By time-lapse imaging and immunohistological analyses, we found that Ascl1 expression oscillated in proliferating oligodendrocyte precursor cells (OPCs) at lower levels than in transit-amplifying precursor cells and was repressed when OPCs differentiated into mature oligodendrocytes. Induction of sustained overexpression of Ascl1 reduced oligodendrocyte differentiation and promoted neuronal differentiation. These results suggest that oscillatory expression of Ascl1 plays an important role in proliferating OPCs during oligodendrocyte formation.
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