Porous Graphene Materials for Energy Storage and Conversion Applications

Porous graphene materials possess a unique structure with interconnected networks, high surface area, and high pore volume. Because of the combination of its remarkable architecture and intrinsic properties, such as high mechanical strength, excellent electrical conductivity, and good thermal stability, porous graphene has attracted tremendous attention in many fields, such as nanocomposites, lithium batteries, supercapacitors, and dye-sensitized solar cells. This chapter reviews synthesis methods, properties, and several key applications of porous graphene materials

Nuclear S-nitrosylation impacts tissue regeneration in zebrafish

The role of the post-translational modifications in tissue regeneration is still not clearly understood. Here, the authors show that many nuclear proteins change S-nitrosylation state in the regenerating zebrafish tailfin, highlighting the importance of Kdm1a S-nitrosylation in the repair process

Identification of a pan-cancer oncogenic microRNA superfamily anchored by a central core seed motif

MicroRNAs modulate tumorigenesis through suppression of specific genes. As many tumour types rely on overlapping oncogenic pathways, a core set of microRNAs may exist, which consistently drives or suppresses tumorigenesis in many cancer types. Here we integrate The Cancer Genome Atlas (TCGA) pan-cancer data set with a microRNA target atlas composed of publicly available Argonaute Crosslinking Immunoprecipitation (AGO-CLIP) data to identify pan-tumour microRNA drivers of cancer. Through this analysis, we show a pan-cancer, coregulated oncogenic microRNA ‘superfamily’ consisting of the miR-17, miR-19, miR-130, miR-93, miR-18, miR-455 and miR-210 seed families, which cotargets critical tumour suppressors via a central GUGC core motif. We subsequently define mutations in microRNA target sites using the AGO-CLIP microRNA target atlas and TCGA exome-sequencing data. These combined analyses identify pan-cancer oncogenic cotargeting of the phosphoinositide 3-kinase, TGFβ and p53 pathways by the miR-17-19-130 superfamily members

Calcium/calmodulin-dependent protein kinase kinase 2 regulates hepatic fuel metabolism

Objective The liver is the primary internal metabolic organ that coordinates whole body energy homeostasis in response to feeding and fasting. Genetic ablation or pharmacological inhibition of calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) has been shown to significantly improve hepatic health and peripheral insulin sensitivity upon overnutrition with high fat diet. However, the precise molecular underpinnings that explain this metabolic protection have remained largely undefined. Methods To characterize the role of CaMKK2 in hepatic metabolism, we developed and challenged liver-specific CaMKK2 knockout (CaMKK2LKO) mice with high fat diet and performed glucose and insulin tolerance tests to evaluate peripheral insulin sensitivity. We used a combination of RNA-Sequencing, glucose and fatty acid istotopic tracer studies, a newly developed Seahorse assay for measuring the oxidative capacity of purified peroxisomes, and a degenerate peptide libarary to identify putative CaMKK2 substrates that mechanistically explain the protective effects of hepatic CaMKK2 ablation. Results Consistent with previous findings, we show that hepatic CaMKK2 ablation significantly improves indices of peripheral insulin sensitivity. Mechanistically, we found that CaMKK2 phosphorylates and regulates GAPDH to promote glucose metabolism and PEX3 to blunt peroxisomal fatty acid catabolism in the liver. Conclusion CaMKK2 is a central metabolic fuel sensor in the liver that significantly contributes to whole body systems metabolism

A new mild hyperthermia device to treat vascular involvement in cancer surgery

Abstract Surgical margin status in cancer surgery represents an important oncologic parameter affecting overall prognosis. The risk of disease recurrence is minimized and survival often prolonged if margin-negative resection can be accomplished during cancer surgery. Unfortunately, negative margins are not always surgically achievable due to tumor invasion into adjacent tissues or involvement of critical vasculature. Herein, we present a novel intra-operative device created to facilitate a uniform and mild heating profile to cause hyperthermic destruction of vessel-encasing tumors while safeguarding the encased vessel. We use pancreatic ductal adenocarcinoma as an in vitro and an in vivo cancer model for these studies as it is a representative model of a tumor that commonly involves major mesenteric vessels. In vitro data suggests that mild hyperthermia (41–46 °C for ten minutes) is an optimal thermal dose to induce high levels of cancer cell death, alter cancer cell’s proteomic profiles and eliminate cancer stem cells while preserving non-malignant cells. In vivo and in silico data supports the well-known phenomena of a vascular heat sink effect that causes high temperature differentials through tissues undergoing hyperthermia, however temperatures can be predicted and used as a tool for the surgeon to adjust thermal doses delivered for various tumor margins

Generation of an in vitro 3D PDAC stroma rich spheroid model

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic/stromal reaction, which contributes to the poor clinical outcome of this disease. Therefore, greater understanding of the stroma development and tumor-stroma interactions is highly required. Pancreatic stellate cells (PSC) are myofibroblast-like cells that located in exocrine areas of the pancreas, which as a result of inflammation produced by PDAC migrate and accumulate in the tumor mass, secreting extracellular matrix components and producing the dense PDAC stroma. Currently, only a few orthotopic or ectopic animal tumor models, where PDAC cells are injected into the pancreas or subcutaneous tissue layer, or genetically engineered animals offer tumors that encompass some stromal component. Herein, we report generation of a simple 3D PDAC in vitro micro-tumor model without an addition of external extracellular matrix, which encompasses a rich, dense and active stromal compartment. We have achieved this in vitro model by incorporating PSCs into 3D PDAC cell culture using a modified hanging drop method. It is now known that PSCs are the principal source of fibrosis in the stroma and interact closely with cancer cells to create a tumor facilitatory environment that stimulates local and distant tumor growth. The 3D micro-stroma models are highly reproducible with excellent uniformity, which can be used for PDAC-stroma interaction analysis and high throughput automated drug-screening assays. Additionally, the increased expression of collagenous regions means that molecular based perfusion and cytostaticity of gemcitabine is decreased in our Pancreatic adenocarcinoma stroma spheroids (PDAC-SS) model when compared to spheroids grown without PSCs. We believe this model will allow an improved knowledge of PDAC biology and has the potential to provide an insight into pathways that may be therapeutically targeted to inhibit PSC activation, thereby inhibiting the development of fibrosis in PDAC and interrupting PSC-PDAC cell interactions so as to inhibit cancer progression

Engineering solventogenic clostridia

Solventogenic clostridia are strictly anaerobic, endospore forming bacteria that produce a large array of primary metabolites, like butanol, by anaerobically degrading simple and complex carbohydrates, including cellulose and hemicellulose. Two genomes have been sequenced and some genetic tools have been developed, but more are now urgently needed. Genomic tools for designing, and assessing the impact of, genetic modifications are well developed. Early efforts to metabolically engineer these organisms suggest that they are promising organisms for biorefinery applications. Pathway engineering efforts have resulted in interesting strains, but global engineering of their transcriptional machinery has produced better outcomes. Future efforts are expected to undertake the development of complex multigenic phenotypes, such as aerotolerance, solvent tolerance, high-cell density fermentations, abolished sporulation without impacting product formation, and genetic stability for continuous bioprocessing. Section snippets Introduction: solventogenic clostridia: from outcasts to workhorses? The development of renewable chemicals and biofuel technologies has been on the scientific and technological agenda in the US and worldwide for over 35 years now, but never quite with the urgency and high priority of the past two years, when finally this technology has been elevated to a high priority status from being underappreciated (as many working in this field have experienced) by the broader scientific community, industry, and the funding agencies. Significantly, combustion of The tools: to transform, overexpress, knockout (KO), knockdown (KD), to report, and to analyze in vivo fluxes, and the transcriptome Although not as easy to employ, as reliable, and as fast as in well established model organisms (like Escherichia coli and Bacillus subtilis), solventogenic clostridia have now reasonably developed tools that have been recently reviewed, for example [15]. Briefly, transformation by electroporation and means to overcome the restriction system in C. acetobutylicum and plasmids to overexpress genes was published over 15 years ago [16], and this approach has been adapted to other clostridia. How to fix the major generic issues: aerointolerance, low cell densities, and limited sustainable viability The major advantage of butyric acid and related clostridia is their powerful central primary metabolism (Figure 1). Specific carbon fluxes are very good (e.g. [13, 14]), but cell densities are relatively low (around a max of 10–11 of absorbance at 600 nm (A600)), and the ability to sustain them viable over prolonged time periods is limited. Significantly, while anaerobiosis is essential for their powerful primary metabolism, their typically low aerotolerance complicates bioprocessing. The issue How to make them grow on complex cellulosic substrates: the cellulosome and how to fix it Cellulolytic clostridial degrade cellulose via the cellulosome [38]. This enzymatic complex is generally bound to the cell surface, contains motifs that bind to insoluble cellulose, and is made up of various cellulases that cleave oligosaccharides from insoluble cellulose. There are several sequenced organisms that contain complete and functional cellulosomes (coded by 11 to ca. 26 genes), and of notable interest are cellulolytic clostridia (incl. C. phytofermentans, C. thermocellum, and C. To undo the sporulation, and thus increase productivity and simplify bioprocessing: differentiation engineering? The metabolism of C. acetobutylicum and of other solventogenic clostridia is biphasic in batch culture: first producing acetate and butyrate and later butanol, acetone, and ethanol. During growth, the production of acids lowers the pH of the culture, which combined with butyrate accumulation shifts the metabolism toward solvent production. Solvent formation is associated with re-uptake of the acids that are then converted into solvents (Figure 1). Solvent formation coincides with initiation o

Synthesis and characterization of modified graphene for energy storage applications

This thesis presents the synthesis and characterization of modified graphene materials and investigates their role in sustainable energy storage applications by using both experimental methods and density functional theory simulations. The outcomes obtained provide a better understanding of the structure-property relationship in modified graphene and its role in electrochemical process in rechargeable batteries, benefiting the development of high-performance electrode materials