Sphingosine kinase 1 regulates HMGB1 translocation by directly interacting with calcium/calmodulin protein kinase II-δ in sepsis-associated liver injury

Previously, we confirmed that sphingosine kinase 1 (SphK1) inhibition improves sepsis-associated liver injury. High-mobility group box 1 (HMGB1) translocation participates in the development of acute liver failure. However, little information is available on the association between SphK1 and HMGB1 translocation during sepsis-associated liver injury. In the present study, we aimed to explore the effect of SphK1 inhibition on HMGB1 translocation and the underlying mechanism during sepsis-associated liver injury. Primary Kupffer cells and hepatocytes were isolated from SD rats. The rat model of sepsis-associated liver damage was induced by intraperitoneal injection with lipopolysaccharide (LPS). We confirmed that Kupffer cells were the cells primarily secreting HMGB1 in the liver after LPS stimulation. LPS-mediated HMGB1 expression, intracellular translocation, and acetylation were dramatically decreased by SphK1 inhibition. Nuclear histone deacetyltransferase 4 (HDAC4) translocation and E1A-associated protein p300 (p300) expression regulating the acetylation of HMGB1 were also suppressed by SphK1 inhibition. HDAC4 intracellular translocation has been reported to be controlled by the phosphorylation of HDAC4. The phosphorylation of HDAC4 is modulated by CaMKII-δ. However, these changes were completely blocked by SphK1 inhibition. Additionally, by performing coimmunoprecipitation and pull-down assays, we revealed that SphK1 can directly interact with CaMKII-δ. The colocalization of SphK1 and CaMKII-δ was verified in human liver tissues with sepsis-associated liver injury. In conclusion, SphK1 inhibition diminishes HMGB1 intracellular translocation in sepsis-associated liver injury. The mechanism is associated with the direct interaction of SphK1 and CaMKII-δ.Subject terms: Hepatotoxicity, Sepsis     

A Microarray-Based Analysis Reveals that a Short Photoperiod Promotes Hair Growth in the Arbas Cashmere Goat

Many animals exhibit different behaviors in different seasons. The photoperiod can have effects on migration, breeding, fur growth, and other processes. The cyclic growth of the fur and feathers of some species of mammals and birds, respectively, is stimulated by the photoperiod as a result of hormone-dependent regulation of the nervous system. To further examine this phenomenon, we evaluated the Arbas Cashmere goat (Capra hircus), a species that is often used in this type of research. The goats were exposed to an experimentally controlled short photoperiod to study the regulation of cyclic cashmere growth. Exposure to a short photoperiod extended the anagen phase of the Cashmere goat hair follicle to increase cashmere production. Assessments of tissue sections indicated that the short photoperiod significantly induced cashmere growth. This conclusion was supported by a comparison of the differences in gene expression between the short photoperiod and natural conditions using gene chip technology. Using the gene chip data, we identified genes that showed altered expression under the short photoperiod compared to natural conditions, and these genes were found to be involved in the biological processes of hair follicle growth, structural composition of the hair follicle, and the morphogenesis of the surrounding skin appendages. Knowledge about differences in the expression of these genes as well as their functions and periodic regulation patterns increases our understanding of Cashmere goat hair follicle growth. This study also provides preliminary data that may be useful for the development of an artificial method to improve cashmere production by controlling the light cycle, which has practical significance for livestock breeding.     

Nature of Novel 2D van der Waals Heterostructures for Superior Potassium Ion Batteries

Novel 2D van der Waals heterostructures with innovative bimetallic oxychloride (Bi‐ and Sb‐based oxychloride) nanosheets that are well dispersed on reduced graphene oxide nanosheets, are established through element engineering for superior potassium ion battery (PIBs) anodes. This material displays an exceptional electrochemical performance, obtaining a discharge capacity as high as 360 mAh g^?1 at 100 mA g^?1 after running 1000 cycles for over 9 months with a capacity preservation percentage of 88.5% and achieving a discharge capacity as high as 319 mAh g^?1 at 1000 mA g^?1, in addition to the low charge/discharge plateaus for anodes and promising full cell performance. More significantly, the nature of such 2D van der Waals heterostructures, including the element engineering for morphology control, the function of each component of heterostructures, the mechanism of potassium ion storage, and the process of K⁺ intercalation accompanied with the lattice distortion and chemical bond breakages, is explored in depth. This study is critical for not only paving the way for the practical application of PIBs but also shedding light on fundamentals of potassium ion storage in 2D van der Waals heterostructures.     

Characterisation of dissolved organic matter in Parisian urban aquatic systems: predominance of hydrophilic and proteinaceous structures

Understanding the nature of organic matter is a necessary first step in assessing contaminant bioavailability and allowing water supply managers to optimise the treatment train in the aim of providing safe and inexpensive drinking water. This study provides further insight into the composition, structure and functional groups of dissolved organic matter (DOM) (both hydrophobic and hydrophilic) from urban aquatic systems by means of various analytical techniques (DAX-8/XAD-4 fractionation, elemental analysis, UV and FTIR spectroscopies, ¹³C and ¹⁵N isotopic analysis, size exclusion chromatography and Pyrolysis-GC-MS). The analytical range chosen for this study constitutes a powerful tool in the characterisation of DOM in urban water. The inclusion of information from one technique to the next might not only serve as a support to each one, but also as a complement. The DOM fraction from treated effluent and, more generally, DOM from urban water (i.e. receiving treated effluent) display a strong hydrophilic characteristic [i.e. low humic substance (HS) content, low SUVA], along with a high distribution in molecular weights observed by SEC and low average molecular weight. Due to the origin of this DOM, proteinaceous structures constitute the main compounds, as observed by FTIR and Py-GC-MS. Such characteristics (i.e. heterogeneity, low average molecular weight and diverse functional groups, which make up a total of N) could explain that DOM from treated effluent displayed a strong reactive potential metals pollutants as previously demonstrated.     

Activation of potassium channels by hypoxia and reoxygenation in the human lung adenocarcinoma cell line A549

Active oxygen species are generated in cells during pathophysiologic conditions such as illflammation and postischemic reperfusion. If oxygen radical scavengers are added before reperfusion, then the magnitude of injury is reduced. We inves-tigated whether free radicals generated following exposure to hypoxia and reoxygenation activate voltage-dependent K⁺ ion channels in tumor cells in vitro. Using the technique of whole cell voltage clamping, we recorded currents from two families of potassium (K⁺) channels that were activated following reoxygenation. One of these groups possessed the electrophysical characteristics of a tetraethylammonium (TEA)-sensitive delayed rectifier channel and the other possessed characteristics of a Tea-insensitive slow inactivating channel. We present evidence which suggests that K⁺ channels are activated following reoxygenation but not during the hypoxia phase. The K⁺ currents decayed with time following reoxygenation. The decay characteristics of the K⁺ currents depended on the duration and level of hypoxia to which the cells were exposed. To determine whether activation of K⁺ channels by reoxygenation was initiated by free radicals, we pretreated cells with N-Acetyl L-Cysteine (NAC), a free radical scavenger, and found that this pretreatment abolished the currents induced by reoxygenation. We also present evidence that free radicals do not directly act on the channel itself, but activate a protein kinase which, in turn, activates the K⁺ channels. Taken together, these results indicate that one of the early responses to oxidative stress is the activation of K⁺ currents. © 1993 Wiley-Liss, Inc.     

The effects of dispersal limitation and topographic heterogeneity on beta diversity and phylobetadiversity in a subtropical forest

We assessed the effects of topographic heterogeneity and stem density on species composition between grains of different sizes (20 × 20, 50 × 50, and 100 × 100 m), based on partial Mantel tests. Similarity in species composition was measured by the abundance-based Jaccard index (C_J) and by an index that incorporates phylogenetic information into C_J (pC_J). Plants were divided into five groups, arbor, subarbor, and shrub according to life form and two other groups: species that produce dry fruits (PDF) and that produce fleshy fruits (PFF). C_J and pC_J between any two grains at each grain size were calculated separately for these groups and for all species combined. In order to examine what influences C_J and pC_J, we analyzed their correlations with topographic heterogeneity variables and two dispersal limitation-related variables (stem and topographic resistance). Our data indicate that at all three grain sizes, C_J and pC_J decrease with increasing distance for all plant groups. Dispersal limitation and topographic heterogeneity were both important at 20 × 20 and 50 × 50 m grain sizes for C_J and pC_J of all plant groups; and at 100 × 100 m grain size, topographic heterogeneity dominates over dispersal limitation for some plant groups. C_J and pC_J of PDFs are less negatively correlated with stem resistance than those of PFFs. We conclude that both beta diversity and phylobetadiversity are dependent on plant groups and grain sizes.