PKM2 regulates the Warburg effect and promotes HMGB1 release in sepsis

Increasing evidence suggests the important role of metabolic reprogramming in the regulation of the innate inflammatory response, but the underlying mechanism remains unclear. Here we provide evidence to support a novel role for the pyruvate kinase M2 (PKM2)-mediated Warburg effect, namely aerobic glycolysis, in the regulation of high-mobility group box 1 (HMGB1) release. PKM2 interacts with hypoxia-inducible factor 1 alpha (HIF1 alpha) and activates the HIF-1 alpha-dependent transcription of enzymes necessary for aerobic glycolysis in macrophages. Knockdown of PKM2, HIF1 alpha and glycolysis-related genes uniformly decreases lactate production and HMGB1 release. Similarly, a potential PKM2 inhibitor, shikonin, reduces serum lactate and HMGB1 levels, and protects mice from lethal endotoxemia and sepsis. Collectively, these findings shed light on a novel mechanism for metabolic control of inflammation by regulating HMGB1 release and highlight the importance of targeting aerobic glycolysis in the treatment of sepsis and other inflammatory diseases

Identification of anthropogenic parameters for a regional nitrogen balance model via field investigation of six ecosystems in China

To evaluate the impact of human behavior (with regard food consumption, waste disposal and farming method) on nitrogen flow, a field investigation was conducted in six typical ecosystems in China. A number of parameters for regional nitrogen balance models were identified during the investigation. The results show that the average per-capita daily protein intake is 107 g. While there is an insignificant difference in total protein intake among the different ecosystems, protein intake from all food groups, except for eggs, is significantly different (P a parts per thousand currency sign 0.05). Differences in diet, along with those in socio-economic conditions, reflect differences in the characteristics of the ecosystems. Regarding per-capita annual potential nitrogen loading from human excrement, a considerable difference exists between the urban rich and the rural poor. In urban areas, approximately 1.02 kg N is returned to farmlands and 5.49 kg N is directly discharged into rivers. In rural regions, on the other hand, approximately 4.33 kg N is returned to farmlands and 1.60 kg N is directly discharged into rivers. Furthermore, urea and mixed fertilizers constitute the most common chemical fertilizers in the study area. Fertilizer diversification is practiced in a range of agricultural lands, paddy-fields and irrigated plains. In the oasis and paddy-field agricultural systems, many of the agricultural by-products (e.g., straw) are burned or mixed with base-fertilizers and plowed into the soil. In irrigated agricultural systems, over 70% of agricultural by-products are recycled as livestock feed. In most instances, livestock excrement is directly reduced in the pasturelands or reused in the fields as manure. Occasionally, as in the case of large-scale breeding, excrements are usually abandoned

The Electronics and Data Acquisition System of the DarkSide Dark Matter Search

It is generally inferred from astronomical measurements that Dark Matter (DM) comprises approximately 27\% of the energy-density of the universe. If DM is a subatomic particle, a possible candidate is a Weakly Interacting Massive Particle (WIMP), and the DarkSide-50 (DS) experiment is a direct search for evidence of WIMP-nuclear collisions. DS is located underground at the Laboratori Nazionali del Gran Sasso (LNGS) in Italy, and consists of three active, embedded components; an outer water veto (CTF), a liquid scintillator veto (LSV), and a liquid argon (LAr) time projection chamber (TPC). This paper describes the data acquisition and electronic systems of the DS detectors, designed to detect the residual ionization from such collisions

An epifluorescent attachment improves whole-plant digital photography of Arabidopsis thaliana expressing red-shifted green fluorescent protein

Filter cubes made with machine-vision dichroic filters and illuminated with a royal blue light emitting diode can be used to produce an epifluorescent digital camera attachment that improves whole organism green fluorescent protein (GFP) photography. Mean pixel intensity responds linearly to purified GFP titration

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40–31.03, P = 1.36 × 10 −54 ) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45–6.96, P = 8.75 × 10 −19 ). Both risk alleles are observed at a low frequency among controls (~2–3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy. © 2018, The Author(s).Peer reviewe

CMS physics technical design report : Addendum on high density QCD with heavy ions

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