Doubly robust estimates for binary longitudinal data analysis with missing response and missing covariates

Longitudinal studies often feature incomplete response and covariate data. Likelihood-based methods such as the expectation-maximization algorithm give consistent estimators for model parameters when data are missing at random (MAR) provided that the response model and the missing covariate model are correctly specified; however, we do not need to specify the missing data mechanism. An alternative method is the weighted estimating equation, which gives consistent estimators if the missing data and response models are correctly specified; however, we do not need to specify the distribution of the covariates that have missing values. In this article, we develop a doubly robust estimation method for longitudinal data with missing response and missing covariate when data are MAR. This method is appealing in that it can provide consistent estimators if either the missing data model or the missing covariate model is correctly specified. Simulation studies demonstrate that this method performs well in a variety of situations.     

NO serves as a signaling intermediate downstream of H2O2 to modulate dynamic microtubule cytoskeleton during responses to VD-toxins in Arabidopsis

Although hydrogen peroxide (H₂O₂) and nitric oxide (NO) can act as an upstream signaling molecule to modulate the dynamic microtubule cytoskeleton during the defense responses to Verticillium dahliae (VD) toxins in Arabidopsis, it is not known the relationship between these two signaling molecules. Here, we show that VD-toxin-induced NO accumulation was dependent on prior H₂O₂ production, NO is downstream of H₂O₂ in the signaling process, and that H₂O₂ acted synergistically with NO to modulate the dynamic microtubule cytoskeleton responses to VD-toxins in Arabidopsis.     

Exogenous Glycine Betaine Reduces Drought Damage by Mediating Osmotic Adjustment and Enhancing Antioxidant Defense in <i>Phoebe hunanensis</i>

Drought stress negatively impacts growth and physiological processes in plants. The foliar application of glycine betaine (GB) is an effective and low-cost approach to improve the drought tolerance of trees. This study examined the effect of exogenously applied GB on the cell membrane permeability, osmotic adjustment, and antioxidant enzyme activities of Phoebe hunanensis Hand.-Mazz under drought stress. Two levels (0 and 800 mL) of water irrigation were tested under different applied GB concentrations (0, 50, 100, and 200 mM). Drought stress decreased the relative water content by 58.5% while increased the electric conductivity, malondialdehyde, proline, soluble proteins, soluble sugars, and antioxidant enzyme activities (superoxide dismutase, catalase, peroxidase) by up to 62.9%, 42.4%, 87.0%, 19.1%, 60.5%, 68.3%, 71.7%, and 83.8%, respectively, on the 25^th day. The foliar application of GB, especially at 100 mM, increased the relative water content of P. hunanensis leaves under drought stress. The concentration of GB from 50 to 100 mM effectively alleviated the improvement of cell membrane permeability and inhibited the accumulation of membrane lipid peroxidation products. Under drought stress, the concentrations of proline, soluble proteins, and soluble sugars in the leaves of P. hunanensis increased as the applied GB concentration was increased and the water stress time was prolonged. Exogenously applied GB decreased oxidative stress and improved antioxidant enzyme activities as compared with treatments without GB application. Furthermore, the physiological and biochemical indexes of P. hunanensis showed a certain dose effect on exogenous GB concentration. These results suggest that GB helps maintain the drought tolerance of P. hunanensis.     

RIP3 blockade prevents immune-mediated hepatitis through a myeloid-derived suppressor cell dependent mechanism

Autoimmune hepatitis (AIH) is an immune-mediated chronic inflammatory liver disease, and its pathogenesis is not fully understood. Our previous study discovered that receptor interacting protein kinase 3 (RIP3) is correlated with serum transaminase levels in AIH patients. However, its role and underlying mechanism in AIH are poorly understood. Here, we detected the increased expression and activation of RIP3 in livers of patients and animal models with AIH. The inhibition of RIP3 kinase by GSK872 prevented concanavalin A (ConA)-induced immune-mediated hepatitis (IMH) by reduced hepatic proinflammatory cytokines and immune cells including Th17 cells and macrophages. Further experiments revealed that RIP3 inhibition resulted in an increase in CD11b⁺Gr1⁺ myeloid-derived suppressor cells (MDSCs) with immunoregulatory properties in the liver, spleen, and peripheral blood. Moreover, the depletion of Gr-1⁺ MDSCs abrogated the protective effect and immune suppression function of GSK872 in ConA-induced IMH. Altogether, our data demonstrate that RIP3 blockade prevents ConA-induced IMH through promoting MDSCs infiltration. Inhibition of RIP3 kinase may be a novel therapeutic avenue for AIH treatment.     

Prediction of the Mechanism of Action of Fusaricidin on Bacillus subtilis

Long-term use of antibiotics has engendered a large number of resistant pathogens, which pose a serious threat to human health. Here, we investigated the mechanism of fusaricidin antibacterial activity toward Bacillus subtilis and characterized the pathways responsible for drug resistance. We found that σ^w, an extracytoplasmic function sigma factor, plays an important role in the resistance to fusaricidins during the initial 5 minutes of drug addition. Approximately 18 genes were induced more than 3-fold, of which 66.7% are known to be regulated by σ^w. Over the following 3 h, fusaricidins induced 194 genes more than three-fold, and most were associated with classes of antibiotic-responsive stimulons. Moreover, the fusaricidin treatment increased the catabolism of fatty and amino acids but strongly repressed glucose decomposition and gluconeogenesis. In summary, our data provide insight into the mechanism of fusaricidin activity, on which we based our suggested strategies for the development of novel antibiotic agents.     

Extraskeletal myxoid chondrosarcoma in the lung: asymptomatic lung mass with severe anemia

ABSTRACT: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft-tissue sarcoma, which primarily occurs deep in the extremities, especially in skeletal muscle, or tendon. EMC of the pleura has been described, however, no case of primary EMC arising from lung has been previously reported. We describe herein, a 51-year-old Asian female initially manifested with signs of severe anemia who presented with a lung mass unrelated to pleura that was morphologically typical EMC, with strong immunoreactivity for vimentin and NSE. Two weeks after resection, the anemia was cured. The patient continued with follow-up, without sign of abnormality 32 months after operation.Virtual slidesThe virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2882199847396682.     

Molecular characterization and expression analysis of a complement component 3 in the sea cucumber (Apostichopus japonicus)

The complement system has been discovered in invertebrates and vertebrates, and plays a crucial role in the innate defense against common pathogens. As a central component in the complement system, complement component 3 (C3) is an intermediary between innate and adaptive immune system. In this study, a new isoform of C3 in the sea cucumber Apostichopus japonicus, termed AjC3-2 was identified. Its open reading frame (ORF) is 5085?bp and encodes for 1695 amino acids with a putative signal peptide of 20 amino acid residues. The mature protein molecular weight of AjC3-2 was 187.72?kDa. It has a conserved thioester site and a linker R(689)RRR(692) where AjC3-2 is splitted into β and α chain during posttranslational modification. The expression patterns of two distinct sea cucumber C3 genes, AjC3-2 and AjC3, were similar. During the different development stages from unfertilized egg to juvenile of the sea cucumber, the highest expression levels of AjC3-2 and AjC3 genes were both found in late auricularia. In the adult, the highest expression of these two genes was observed in the coelomocytes and followed by the body wall. AjC3-2 and AjC3 genes expression increased significantly at 6?h after the LPS challenge. These results indicated that these two C3 genes play a pivotal role in immune responses to the bacterial infection in sea cucumber.     

Observations on the division characterization of diploid nuclear in <Emphasis Type="Italic">Porphyra</Emphasis> (Bangiales,Rhodophyta)

Nuclear divisions of carpospores, conchocelis and conchospores of Porphyra yezoensis, P. haitanensis, P. katadai var. hemiphylla and P. oligospermatangia from China were investigated. The observations showed diploid chromosome numbers of 2n = 6 for P. yezoensis and P. oligospermatangia, and 2n = 10 for P. haitanensis and P. katadai var. hemiphylla. For all four species, somatic pairing of chromosome sets was observed in late prophase. Sister chromosomes separated at anaphase as mitosis took place in carpospores, conchocelis filamentous cells, conchosporangial branch cells and sporangial cells (conchospore formation). Chromosome configurations of tetrad and ring-shaped in conchospore germination were observed, demonstrating the occurrence of meiosis. The characteristics of diploid nuclear division in 2n = 6 species are the same as those of 2n = 10 species. The influence of somatic pairing on nuclear division of diploid cells in Porphyra was discussed.     

The Immunoregulation Effect of Alpha 1-Antitrypsin Prolong β-Cell Survival after Transplantation

Islet transplantation has considerable potential as a cure for diabetes. However, the difficulties that arise from inflammation and the immunological rejection of transplants must be addressed for islet transplantation to be successful. Alpha 1-antitrypsin (AAT) inhibits the damage on β cells caused by inflammatory reactions and promotes β-cell survival and proliferation. This protein also induces specific immune tolerance to transplanted β cells. However, whether the expression of AAT in β cells themselves could eliminate or decrease immunological rejection of transplants is not clear. Therefore, we established a β cell line (NIT-hAAT) that stably expresses human AAT. Interestingly, in a cytotoxic T lymphocyte (CTL)-killing assay, we found that hAAT reduced apoptosis and inflammatory cytokine production in NIT-1 cells and regulated the Th1/Th2 cytokine balance in vitro. In vivo transplantation of NIT-hAAT cells into mice with diabetes showed hAAT inhibited immunological rejection for a short period of time and increased the survival of transplanted β cells. This study demonstrated that hAAT generated remarkable immunoprotective and immunoregulation effects in a model of β cell islet transplantation for diabetes model.