Mitochondrial Dysfunction and β-Cell Failure in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is the most common human endocrine disease and is characterized by peripheral insulin resistance and pancreatic islet β-cell failure. Accumulating evidence indicates that mitochondrial dysfunction is a central contributor to β-cell failure in the evolution of T2DM. As reviewed elsewhere, reactive oxygen species (ROS) produced by β-cell mitochondria as a result of metabolic stress activate several stress-response pathways. This paper focuses on mechanisms whereby ROS affect mitochondrial structure and function and lead to β-cell failure. ROS activate UCP2, which results in proton leak across the mitochondrial inner membrane, and this leads to reduced β-cell ATP synthesis and content, which is a critical parameter in regulating glucose-stimulated insulin secretion. In addition, ROS oxidize polyunsaturated fatty acids in mitochondrial cardiolipin and other phospholipids, and this impairs membrane integrity and leads to cytochrome c release into cytosol and apoptosis. Group VIA phospholipase A2 (iPLA2β) appears to be a component of a mechanism for repairing mitochondrial phospholipids that contain oxidized fatty acid substituents, and genetic or acquired iPLA2β-deficiency increases β-cell mitochondrial susceptibility to injury from ROS and predisposes to developing T2DM. Interventions that attenuate ROS effects on β-cell mitochondrial phospholipids might prevent or retard development of T2DM

Highly efficient synthesis of LTA-type aluminophosphate molecular sieve by improved ionothermal method

This work was supported by the National Natural Science Foundation of China (Grant No. 21306072, 21203081) and Development Program of Lanzhou University of Technology for excellent teachers (Grant No. Q201113). WZ thanks EPSRC for financial support to upgrade the SEM facilities (No. EP/F019580/1). We cordially thank the Reviewers and Editors for providing us with valuable comments and suggestions.LTA-type aluminophosphate molecular sieve has been successfully synthesized by improvedionothermal method from a gel containing low-dosage ionic liquids. The optimum syntheticconditions of this material are refined. The resultant LTA molecular sieves were characterized byXRD, SEM, TG-DTA, CHN elemental analysis, solution 13C NMR, EDX, TEM and N2physisorption. The composition of the resulting LTA-type molecular sieves is determined to be(Al12P12O48)(C4H9NO)2(C8H15N2+)2(F-)2, for which morpholine together with1-butyl-3-methylimidazolium cations act as the structure-directing agent. The high zeolite yield, as well as the high specific surface area and micropore volume for the calcined LTA-type materials imply that these zeolitic materials have a high potential in applications.PostprintPeer reviewe

Prediction of corrosion failure probability of buried oil and gas pipeline based on an RBF neural network

Risk assessment is critical to ensure the safe operation of oil and gas pipeline systems. The core content of such risk assessment is to determine the failure probability of the pipelines quantitatively and accurately. Hence, this study combines the MATLAB neural network toolbox and adopts an Radial Basis Functions (RBF) neural network with a strong non-linear mapping relationship to build a corrosion failure probability prediction model for buried oil and gas gathering and transmission pipelines. Based on the hazard identification of pipeline corrosion failure, the model summarizes the causes of corrosion failure and determines the input and output vectors of the neural network based on the fault tree. According to the selected learning samples, through the design and training of network parameters, the RBF neural network that can predict the system failure probability is finally obtained. Taking the failure probability of 30 groups of high-pressure gathering and transmission pipelines of gas storage as an example, the capability of inputting the probability of the bottom event and outputting the probability of the top event is demonstrated through training data. Our results show that the calculated failure probability based on the fault tree analysis model is consistent with the predicted failure probability based on the RBF neural network model. Hence, the RBF neural network model is shown to be reliable in predicting the corrosion failure probability of buried pipelines

Neurospheres from rat adipose-derived stem cells could be induced into functional Schwann cell-like cells in vitro

<p>Abstract</p> <p>Background</p> <p>Schwann cells (SC) which are myelin-forming cells in peripheral nervous system are very useful for the treatment of diseases of peripheral nervous system and central nervous system. However, it is difficult to obtain sufficient large number of SC for clinical use, so alternative cell systems are desired.</p> <p>Results</p> <p>Using a procedure similar to the one used for propagation of neural stem cells, we could induce rat adipose-derived stem cells (ADSC) into floating neurospheres. In addition to being able to differentiate into neuronal- and glial-like cells, neurospheres could be induced to differentiate into SC-like cells. SC-like cells were bi- or tri-polar in shape and immunopositive for nestin and SC markers p75, GFAP and S-100, identical to genuine SC. We also found that SC-like cells could induce the differentiation of SH-SY5Y neuroblastoma cells efficiently, perhaps through secretion of soluble substances. We showed further that SC-like cells could form myelin structures with PC12 cell neurites in vitro.</p> <p>Conclusion</p> <p>These findings indicated that ADSC could differentiate into SC-like cells in terms of morphology, phenotype and functional capacities. SC-like cells induced from ADSC may be useful for the treatment of neurological diseases.</p

Immunoglobulin G Locus Events in Soft Tissue Sarcoma Cell Lines

Recently immunoglobulins (Igs) have been found to be expressed by cells other than B lymphocytes, including various human carcinoma cells. Sarcomas are derived from mesenchyme, and the knowledge about the occurrence of Ig production in sarcoma cells is very limited. Here we investigated the phenomenon of immunoglobulin G (IgG) expression and its molecular basis in 3 sarcoma cell lines. The mRNA transcripts of IgG heavy chain and kappa light chain were detected by RT-PCR. In addition, the expression of IgG proteins was confirmed by Western blot and immunofluorescence. Immuno-electron microscopy localized IgG to the cell membrane and rough endoplasmic reticulum. The essential enzymes required for gene rearrangement and class switch recombination, and IgG germ-line transcripts were also identified in these sarcoma cells. Chromatin immunoprecipitation results demonstrated histone H3 acetylation of both the recombination activating gene and Ig heavy chain regulatory elements. Collectively, these results confirmed IgG expression in sarcoma cells, the mechanism of which is very similar to that regulating IgG expression in B lymphocytes

CAMKs support development of acute myeloid leukemia.

BACKGROUND: We recently identified the human leukocyte immunoglobulin-like receptor B2 (LILRB2) and its mouse ortholog-paired Ig-like receptor (PirB) as receptors for several angiopoietin-like proteins (Angptls). We also demonstrated that PirB is important for the development of acute myeloid leukemia (AML), but exactly how an inhibitory receptor such as PirB can support cancer development is intriguing. RESULTS: Here, we showed that the activation of Ca (2+)/calmodulin-dependent protein kinases (CAMKs) is coupled with PirB signaling in AML cells. High expression of CAMKs is associated with a poor overall survival probability in patients with AML. Knockdown of CAMKI or CAMKIV decreased human acute leukemia development in vitro and in vivo. Mouse AML cells that are defective in PirB signaling had decreased activation of CAMKs, and the forced expression of CAMK partially rescued the PirB-defective phenotype in the MLL-AF9 AML mouse model. The inhibition of CAMK kinase activity or deletion of CAMKIV significantly slowed AML development and decreased the AML stem cell activity. We also found that CAMKIV acts through the phosphorylation of one of its well-known target (CREB) in AML cells. CONCLUSION: CAMKs are essential for the growth of human and mouse AML. The inhibition of CAMK signaling may become an effective strategy for treating leukemia

Genetic Ablation of PLA2G6 in Mice Leads to Cerebellar Atrophy Characterized by Purkinje Cell Loss and Glial Cell Activation

Infantile neuroaxonal dystrophy (INAD) is a progressive, autosomal recessive neurodegenerative disease characterized by axonal dystrophy, abnormal iron deposition and cerebellar atrophy. This disease was recently mapped to PLA2G6, which encodes group VI Ca2+-independent phospholipase A2 (iPLA2 or iPLA2β). Here we show that genetic ablation of PLA2G6 in mice (iPLA2β-/-) leads to the development of cerebellar atrophy by the age of 13 months. Atrophied cerebella exhibited significant loss of Purkinje cells, as well as reactive astrogliosis, the activation of microglial cells, and the pronounced up-regulation of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Moreover, glial cell activation and the elevation in TNF-α and IL-1β expression occurred before apparent cerebellar atrophy. Our findings indicate that the absence of PLA2G6 causes neuroinflammation and Purkinje cell loss and ultimately leads to cerebellar atrophy. Our study suggests that iPLA2β-/- mice are a valuable model for cerebellar atrophy in INAD and that early anti-inflammatory therapy may help slow the progression of cerebellar atrophy in this deadly neurodegenerative disease

An Analytical Mechanical Model of Corti in the Cochlea

The organ of Corti (OC) in the cochlea is a significant structure for feeling sound. The components of OC and the interaction of the part with the surroundings contribute to the fact that the passive tuning of the cochlear macrostructure is unclear. Based on the interaction between the basilar membrane (BM), tectorial membrane (TM), reticular lamina (RL), and various parts of OC, a mechanical model of the cochlea is established to study the motion patterns of each part under the action of a certain pressure. The variational principle is applied to the calculation of the analytical expression of the displacement of the BM. The results of the analytical solution differ little from the experimental value, and the variation trend is consistent, which presents the correctness of the model. The parameter sensitivity analysis is carried out for obtaining the interaction principle and the primary and secondary roles of each component in the process of the sense of sound. The results show that the absence of the TM and the decrease in the stiffness of the outer hair cells (OHCs) and OHC bundles will shift vibratory response patterns to lower frequencies, in which the lack of TM will result in the greatest reduction of CF. The absence of RL exerts a negative influence on the CF as well as the amplitude of BM and thereby loss of hearing. Therefore, both TM and RL are essential structures during the process of the sense of sound. At the same time, the resonance frequency at the base of the BM is concentrated on the high-frequency segment, while the apex of the BM is mainly in the low frequency. Different points of BM correspond to different CF, which demonstrates the frequency selectivity of the BM