Real-time determination of kinetics of adsorption of lead(II) onto palm shell-based activated carbon using ion selective electrode

In this study, the kinetics of adsorption of Pb(II) from aqueous solution onto palm shell-based activated carbon (PSAC) were investigated by employing ion selective electrode (ISE) for real-time Pb(II) and pH monitoring. Usage of ISE was very appropriate for real-time adsorption kinetics data collection as it facilitated recording of adsorption data at very specific and short time intervals as well as provided consistent kinetics data. Parameters studied were initial Pb(II) concentration and agitation speed. It was found that increases in initial Pb(II) concentration and agitation speed resulted in higher initial rate of adsorption. Pseudo first-order, pseudo second-order, Elovich, intraparticle diffusion and liquid film diffusion models were used to fit the adsorption kinetics data. It was suggested that chemisorption was the rate-controlling step for adsorption of Pb(II) onto PSAC since the adsorption kinetics data fitted both the pseudo second-order and Elovich models well.     

First cervical vertebra (atlas) fracture mechanism studies using finite element method.

Injury mechanisms and stress distribution patterns are important in the clinical evaluation of spinal injuries. Recognition and interpretation of the failure patterns help to determine spinal instability and consequently the choice of treatment. Although, the biomechanics responses of the atlas have received much attention, it has not been investigated using theoretical modeling. Mathematical techniques such as finite element model will provide further understanding to the injury mechanisms of the atlas, which is important for the prevention, diagnosis, and treatment of spinal injuries. In the present study, a detailed three-dimensional finite element model of the human atlas (C1) was constructed, with the geometrical data obtained using a three-dimensional digitizer. Anterior arch, superior/inferior articular processes, transverse processes, posterior arch and posterior tubercule were modeled using eight-noded brick elements. Using the material properties from literature, the 7808-finite element model was exercised under three simulated axial compressive mode of pressure loading and boundary conditions to investigate the sites of failure reported in vivo and in vitro. This report demonstrates high concentration of localized stress at the anterior and posterior archs of the atlas, which agrees well with those reported in the literature. Furthermore, under simulated hyperextension, our results agreed well with the experimental findings, which show that the groove of the posterior arch is subjected to enormous bending moment. The close agreement of the failure location provided confidence to perform further analysis and in vitro experiments. These results may be potentially used to supplement experimental research in understanding the clinical biomechanics of the atlas.     

Src kinases relax adherens junctions between the neighbors of apoptotic cells to permit apical extrusion

Epithelia can eliminate apoptotic cells by apical extrusion. This is a complex morphogenetic event where expulsion of the apoptotic cell is accompanied by rearrangement of its immediate neighbors to form a rosette. A key mechanism for extrusion is constriction of an actomyosin network that neighbor cells form at their interface with the apoptotic cell. Here we report a complementary process of cytoskeletal relaxation that occurs when cortical contractility is down-regulated at the junctions between those neighbor cells themselves. This reflects a mechanosensitive Src family kinase (SFK) signaling pathway that is activated in neighbor cells when the apoptotic cell relaxes shortly after injury. Inhibiting SFK signaling blocks both the expulsion of apoptotic cells and the rosette formation among their neighbor cells. This reveals the complex pattern of spatially distinct contraction and relaxation that must be established in the neighboring epithelium for apoptotic cells to be extruded.     

Altered expression of Alzheimer's disease-related genes in the cerebellum of autistic patients: a model for disrupted brain connectome and therapy

Autism and Alzheimer''s disease (AD) are, respectively, neurodevelopmental and degenerative diseases with an increasing epidemiological burden. The AD-associated amyloid-β precursor protein-α has been shown to be elevated in severe autism, leading to the ‘anabolic hypothesis'' of its etiology. Here we performed a focused microarray analysis of genes belonging to NOTCH and WNT signaling cascades, as well as genes related to AD and apoptosis pathways in cerebellar samples from autistic individuals, to provide further evidence for pathological relevance of these cascades for autism. By using the limma package from R and false discovery rate, we demonstrated that 31% (116 out of 374) of the genes belonging to these pathways displayed significant changes in expression (corrected P-values <0.05), with mitochondria-related genes being the most downregulated. We also found upregulation of GRIN1, the channel-forming subunit of NMDA glutamate receptors, and MAP3K1, known activator of the JNK and ERK pathways with anti-apoptotic effect. Expression of PSEN2 (presinilin 2) and APBB1 (or F65) were significantly lower when compared with control samples. Based on these results, we propose a model of NMDA glutamate receptor-mediated ERK activation of α-secretase activity and mitochondrial adaptation to apoptosis that may explain the early brain overgrowth and disruption of synaptic plasticity and connectome in autism. Finally, systems pharmacology analyses of the model that integrates all these genes together (NOWADA) highlighted magnesium (Mg²⁺) and rapamycin as most efficient drugs to target this network model in silico. Their potential therapeutic application, in the context of autism, is therefore discussed.     

Quantitative secretome and glycome of primary human adipocytes during insulin resistance

Adipose tissue is both an energy storage depot and an endocrine organ. The impaired regulation of the secreted proteins of adipose tissue, known as adipocytokines, observed during obesity contributes to the onset of whole-body insulin resistance and the pathobiology of type 2 diabetes mellitus (T2DM). In addition, the global elevation of the intracellular glycosylation of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc) via either genetic or pharmacological methods is sufficient to induce insulin resistance in both cultured cells and animal models. The elevation of global O-GlcNAc levels is associated with the altered expression of many adipocytokines. We have previously characterized the rodent adipocyte secretome during insulin sensitive and insulin resistant conditions. Here, we characterize and quantify the secretome and glycome of primary human adipocytes during insulin responsive and insulin resistant conditions generated by the classical method of hyperglycemia and hyperinsulinemia or by the pharmacological manipulation of O-GlcNAc levels. Using a proteomic approach, we identify 190 secreted proteins and report a total of 20 up-regulated and 6 down-regulated proteins that are detected in both insulin resistant conditions. Moreover, we apply glycomic techniques to examine (1) the sites of N-glycosylation on secreted proteins, (2) the structures of complex N- and O-glycans, and (3) the relative abundance of complex N- and O-glycans structures in insulin responsive and insulin resistant conditions. We identify 91 N-glycosylation sites derived from 51 secreted proteins, as well as 155 and 29 released N- and O-glycans respectively. We go on to quantify many of the N- and O-glycan structures between insulin responsive and insulin resistance conditions demonstrating no significant changes in complex glycosylation in the time frame for the induction of insulin resistance. Thus, our data support that the O-GlcNAc modification is involved in the regulation of adipocytokine secretion upon the induction of insulin resistance in human adipocytes.     

Systematic re-evaluation of intraoperative motor-evoked potential suppression in scoliosis surgery

Background

Motor- (MEP) and somatosensory-evoked potentials (SSEP) are susceptible to the effects of intraoperative environmental factors.

Methods

Over a 5-year period, 250 patients with adolescent idiopathic scoliosis (AIS) who underwent corrective surgery with IOM were retrospectively analyzed for MEP suppression (MEPS).

Results

Our results show that four distinct groups of MEPS were encountered over the study period. All 12 patients did not sustain any neurological deficits postoperatively. However, comparison of groups 1 and 2 suggests that neither the duration of anesthesia nor speed of surgical or anesthetic intervention were associated with recovery to a level beyond the criteria for MEPS. For group 3, spontaneous MEPS recovery despite the lack of surgical intervention suggests that anesthetic intervention may play a role in this process. However, spontaneous MEPS recovery was also seen in group 4, suggesting that in certain circumstances, both surgical and anesthetic intervention was not required. In addition, neither the duration of time to the first surgical manoeuver nor the duration of surgical manoeuver to MEPS were related to recovery of MEPS. None of the patients had suppression of SSEPs intraoperatively.

Conclusion

This study suggests that in susceptible individuals, MEPS may rarely occur unpredictably, independent of surgical or anesthetic intervention. However, our findings favor anesthetic before surgical intervention as a proposed protocol. Early recognition of MEPS is important to prevent false positives in the course of IOM for spinal surgery.

     

Regulation of Cellular Senescence by Polycomb Chromatin Modifiers through Distinct DNA Damage- and Histone Methylation-Dependent Pathways

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PRODUCTION OF 7-DEOXY-OKADAIC ACID BY A NEW CALEDONIAN STRAIN OF PROROCENTRUM LIMA (DINOPHYCEAE)

7-Deoxy-okadaic acid and okadaic acid were identified as the major diarrhetic shellfish poisoning (DSP) toxins produced by a New Caledonian strain of Prorocentrum lima Ehrenberg. Dinophysistoxin-1 was not produced by this strain. The cellular concentrations of 7-deoxy-okadaic acid were about one tenth that of okadaic acid and were maximal (∼1.4 pg·cell ^{− 1}) during the stationary growth phase of batch culture. Autolytic hydrolysis of cell extracts did not increase the concentrations of 7-deoxy-okadaic acid, whereas okadaic acid production increased more than 4-fold, indicating that 7-deoxy-okadaic acid, unlike okadaic acid, is not directly derived from large sulfated precursors. 7-Deoxy-okadaic acid could be detected by liquid chromatography-selected reaction monitoring mass spectrometry, HPLC-fluorescence detection after derivatization with 9-anthryldiazomethane (ADAM), and inhibition of protein phosphatases. The solvent washes currently used for solid-phase clean-up of ADAM-derivatized DSP samples elute derivatized 7-deoxy-okadaic acid, indicating that the current sample clean-up protocol for HPLC-fluorescence detection would miss any contamination by this toxin.