Irradiation Induced Injury Reduces Energy Metabolism in Small Intestine of Tibet Minipigs

Background

The radiation-induced energy metabolism dysfunction related to injury and radiation doses is largely elusive. The purpose of this study is to investigate the early response of energy metabolism in small intestinal tissue and its correlation with pathologic lesion after total body X-ray irradiation (TBI) in Tibet minipigs.

Methods and Results

30 Tibet minipigs were assigned into 6 groups including 5 experimental groups and one control group with 6 animals each group. The minipigs in these experimental groups were subjected to a TBI of 2, 5, 8, 11, and 14 Gy, respectively. Small intestine tissues were collected at 24 h following X-ray exposure and analyzed by histology and high performance liquid chromatography (HPLC). DNA contents in this tissue were also examined. Irradiation causes pathologic lesions and mitochondrial abnormalities. The Deoxyribonucleic acid (DNA) content-corrected and uncorrected adenosine-triphosphate (ATP) and total adenine nucleotides (TAN) were significantly reduced in a dose-dependent manner by 2–8 Gy exposure, and no further reduction was observed over 8 Gy.

Conclusion

TBI induced injury is highly dependent on the irradiation dosage in small intestine and inversely correlates with the energy metabolism, with its reduction potentially indicating the severity of injury.     

Modeling the Effects of Harvest Alternatives on Mitigating Oak Decline in a Central Hardwood Forest Landscape

Oak decline is a process induced by complex interactions of predisposing factors, inciting factors, and contributing factors operating at tree, stand, and landscape scales. It has greatly altered species composition and stand structure in affected areas. Thinning, clearcutting, and group selection are widely adopted harvest alternatives for reducing forest vulnerability to oak decline by removing susceptible species and declining trees. However, the long-term, landscape-scale effects of these different harvest alternatives are not well studied because of the limited availability of experimental data. In this study, we applied a forest landscape model in combination with field studies to evaluate the effects of the three harvest alternatives on mitigating oak decline in a Central Hardwood Forest landscape. Results showed that the potential oak decline in high risk sites decreased strongly in the next five decades irrespective of harvest alternatives. This is because oak decline is a natural process and forest succession (e.g., high tree mortality resulting from intense competition) would eventually lead to the decrease in oak decline in this area. However, forest harvesting did play a role in mitigating oak decline and the effectiveness varied among the three harvest alternatives. The group selection and clearcutting alternatives were most effective in mitigating oak decline in the short and medium terms, respectively. The long-term effects of the three harvest alternatives on mitigating oak decline became less discernible as the role of succession increased. The thinning alternative had the highest biomass retention over time, followed by the group selection and clearcutting alternatives. The group selection alternative that balanced treatment effects and retaining biomass was the most viable alternative for managing oak decline. Insights from this study may be useful in developing effective and informed forest harvesting plans for managing oak decline.     

Granulin Exacerbates Lupus Nephritis via Enhancing Macrophage M2b Polarization

Background and Aims

Lupus nephritis (LN), with considerable morbidity and mortality, is one of the most severe manifestations of systemic lupus erythematosus (SLE). Yet, the pathogenic mechanisms of LN have not been clearly elucidated, and efficient therapies are still in great need. Granulin (GRN), a multifunctional protein linked to inflammatory diseases, has recently been reported to correlate with the disease activity of autoimmune diseases. However, the role of GRN in the pathogenic process of LN still remains obscure. In this study, we explored its potential role and underlying mechanism in the pathogenesis of LN.

Methodology/Principal Findings

We found that serum GRN levels were significantly up-regulated and were positively correlated with the severity of LN. Overexpression of GRN in vivo by transgenic injection remarkably exacerbated LN, whereas down-regulation of GRN with shRNA ameliorated LN, firmly demonstrating the critical role of GRN in the pathogenesis of LN. Notably, macrophage phenotype analysis revealed that overexpression of GRN could enhance macrophage polarization to M2b, a key mediator of the initiation and progression of LN. On the contrary, down-regulation of GRN resulted in impaired M2b differentiation, thus ameliorating LN. Moreover, we found that MAPK signals were necessary for the effect of GRN on macrophage M2b polarization.

Conclusion/Significance

We first demonstrated that GRN could aggravate lupus nephritis (LN) via promoting macrophage M2b polarization, which might provide insights into the pathogenesis of LN as well as potential therapeutic strategies against LN.     

Oxaliplatin and Its Enantiomer Induce Different Condensation Dynamics of Single DNA Molecules

The interactions of DNA with oxaliplatin (Pt(R,R-DACH)) or its enantiomer (Pt(S,S-DACH)) were investigated using magnetic tweezers and atomic force microscope. In the process of DNA condensation induced by Pt-DACH, only diadducts and micro-loops are formed at low Pt-DACH concentrations, while at high Pt-DACH concentrations, besides the diadducts and micro-loops, long-range cross-links are also formed. The diadduct formation rate of Pt(R,R-DACH) is higher than that of Pt(S,S-DACH). However, the proportions of micro-loops and long-range cross-links for Pt(S,S-DACH) are higher than those for Pt(R,R-DACH). We propose a model to explain these differences between the effect of Pt(R,R-DACH) and that of Pt(S,S-DACH) on DNA condensation. The study has strong implications for the understanding of the effect of chirality on the interaction between Pt-DACH and DNA and the kinetics of DNA condensation induced by platinum complexes.     

Reference gene selection and validation for mRNA expression analysis by RT-qPCR in murine M1- and M2-polarized macrophage

Molecular Biology Reports - Murine bone marrow-derived macrophages (M0) and M1- and M2-polarized macrophages are being widely used as a laboratory model for polarized macrophages related molecular...     

Over-Expression of Masson Pine PmPT1 Gene in Transgenic Tobacco Confers Tolerance Enhancement to Pi Deficiency by Ameliorating P Level and the Antioxidants

Plant Molecular Biology Reporter - Previously, we cloned the full sequence of masson pine (Pinus massoniana) phosphate transporter gene (PmPT1) from a phosphorus (Pi) deficiency tolerant strain. To...     

Randomization inference with general interference and censoring

Interference occurs between individuals when the treatment (or exposure) of one individual affects the outcome of another individual. Previous work on causal inference methods in the presence of interference has focused on the setting where it is a priori assumed that there is “partial interference,” in the sense that individuals can be partitioned into groups wherein there is no interference between individuals in different groups. Bowers et al. (2012, Political Anal, 21, 97–124) and Bowers et al. (2016, Political Anal, 24, 395–403) consider randomization-based inferential methods that allow for more general interference structures in the context of randomized experiments. In this paper, extensions of Bowers et al. that allow for failure time outcomes subject to right censoring are proposed. Permitting right-censored outcomes is challenging because standard randomization-based tests of the null hypothesis of no treatment effect assume that whether an individual is censored does not depend on treatment. The proposed extension of Bowers et al. to allow for censoring entails adapting the method of Wang et al. (2010, Biostatistics, 11, 676–692) for two-sample survival comparisons in the presence of unequal censoring. The methods are examined via simulation studies and utilized to assess the effects of cholera vaccination in an individually randomized trial of 73 000 children and women in Matlab, Bangladesh.     

Cover Image

Synthetic microbial communities have become a focus of biotechnological research since they can overcome several of the limitations of single-specie cultures. A paradigmatic example is Clostridium cellulovorans DSM 743B, which can decompose lignocellulose but cannot produce butanol. Clostridium beijerinckii NCIMB 8052 however, is unable to use lignocellulose but can produce high amounts of butanol from simple sugars. In our previous studies, both organisms were cocultured to produce butanol by consolidated bioprocessing. However, such consolidated bioprocessing implementation strongly depends on pH regulation. Since low pH (pH 4.5–5.5) is required for butanol fermentation, C. cellulovorans cannot grow well and saccharify sufficient lignocellulose to feed both strains at a pH below 6.4. To overcome this bottleneck, this study engineered C. cellulovorans by adaptive laboratory evolution, inactivating cell wall lyases genes (Clocel_0798 and Clocel_2169), and overexpressing agmatine deiminase genes (augA, encoded by Cbei_1922) from C. beijerinckii NCIMB 8052. The generated strain WZQ36: 743B*6.0*3△lyt0798△lyt2169-(pXY1-P_thl-augA) can tolerate a pH of 5.5. Finally, the alcohol aldehyde dehydrogenase gene adhE1 from Clostridium acetobutylicum ATCC 824 was introduced into the strain to enable butanol production at low pH, in coordination with solvent fermentation of C. beijerinckii in consortium. The engineered consortium produced 3.94 g/L butanol without pH control within 83 hr, which is more than 5-fold of the level achieved by wild consortia under the same conditions. This exploration represents a proof of concept on how to combine metabolic and evolutionary engineering to coordinate coculture of a synthetic microbial community.     

Ribosomal protein S7 regulates arsenite-induced GADD45α expression by attenuating MDM2-mediated GADD45α ubiquitination and degradation

The stress-responding protein, GADD45α, plays important roles in cell cycle checkpoint, DNA repair and apoptosis. In our recent study, we demonstrate that GADD45α undergoes a dynamic ubiquitination and degradation in vivo, which process can be blocked by the cytotoxic reagent, arsenite, resulting in GADD45α accumulation to activate JNKs cell death pathway, thereby revealing a novel mechanism for the cellular GADD45α functional regulation. But the factors involved in GADD45α stability modulations are unidentified. Here, we demonstrated that MDM2 was an E3 ubiquitin ligase for GADD45α. One of MDM2-binding partner, ribosomal protein S7, interacted with and stabilized GADD45α through preventing the ubiquitination and degradation of GADD45α mediated by MDM2. This novel function of S7 is unrelated to p53 but seems to depend on S7/MDM2 interaction, for the S7 mutant lacking MDM2-binding ability lost its function to stabilize GADD45α. Further investigations indicated that arsenite treatment enhanced S7–MDM2 interaction, resulting in attenuation of MDM2-dependent GADD45α ubiquitination and degradation, thereby leading to GADD45α-dependent cell death pathway activation. Silencing S7 expression suppressed GADD45α-dependent cytotoxicity induced by arsenite. Our findings thus identify a novel function of S7 in control of GADD45α stabilization under both basal and stress conditions and its significance in mediating arsenite-induced cellular stress.