Flow-driven voltage generation in carbon nanotubes

The flow of various liquids and gases over single-walled carbon nanotube bundles induces an electrical signal (voltage/current) in the sample along the direction of the flow. The electrical response generated by the flow of liquids is found to be logarithmic in the flow speed over a wide range. In contrast, voltage generated by the flow of gas is quadratically dependent on the gas flow velocity. It was found that the underlying physics for the generation of electrical signals by liquids and gases are different. For the liquid, the Coulombic interaction between the ions in the liquid and the charge carriers in the nanotube plays a key role while electrical signal generation due to gas flow is due to an interplay of Bernoulli's principle and Seebeck effect. Unlike the liquid case which is specific to the nanotubes, the gas flow effect can be seen for a variety of solids ranging from single and multi-walled carbon nanotubes, graphite and doped semiconductors

Thiol stabilized copper nanoparticles exert antimicrobial properties by preventing cell division in Escherichia coli

The uses of metallic nanoparticles have gained importance as one of the therapeutic options to treat infections. Here, we synthesized stable copper nanoparticles (CuNPs) using Thiosalicylic acid and assessed their antimicrobial activities against various Gram-negative bacteria. The synthesized CuNPs had absorption maxima of 570 nM with a size range of 5-11 nM and face-centred cubic (Fcc) crystal structure. The bacterial cells in their planktonic and sessile forms were susceptible to CuNPs. The nanoparticles did not show any cytotoxicity to murine macrophages (RAW264.7) below 60 µg/mL. However, the expression of oxidative stress defence gene ahpC revealed the possibility of ROS generation upon treatment with CuNPs. Interestingly, the cell division proteins like, FtsZ and FtsI were destabilized in the presence of CuNPs which in turn inhibited bacterial cell division. In conclusion, it may be stated that the synthesized CuNPs can kill bacteria by arresting cell division and/or by ROS generation

Thiol stabilized copper nanoparticles exert antimicrobial properties by preventing cell division in Escherichia coli

151-157The uses of metallic nanoparticles have gained importance as one of the therapeutic options to treat infections. Here, we synthesized stable copper nanoparticles (CuNPs) using Thiosalicylic acid and assessed their antimicrobial activities against various Gram-negative bacteria. The synthesized CuNPs had absorption maxima of 570 nM with a size range of 5-11 nM and face-centred cubic (Fcc) crystal structure. The bacterial cells in their planktonic and sessile forms were susceptible to CuNPs. The nanoparticles did not show any cytotoxicity to murine macrophages (RAW264.7) below 60 µg/mL. However, the expression of oxidative stress defence gene ahpC revealed the possibility of ROS generation upon treatment with CuNPs. Interestingly, the cell division proteins like, FtsZ and FtsI were destabilized in the presence of CuNPs which in turn inhibited bacterial cell division. In conclusion, it may be stated that the synthesized CuNPs can kill bacteria by arresting cell division and/or by ROS generation

The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins.

The long term side effects of any newly introduced drug is a subject of intense research, and often raging controversies. One such example is the dipeptidyl peptidase-IV (DPP4) inhibitor used for treating type 2 diabetes, which is inconclusively implicated in increased susceptibility to acute pancreatitis. Previously, based on a computational analysis of the spatial and electrostatic properties of active site residues, we have demonstrated that phosphoinositide-specific phospholipase C (PI-PLC) from Bacillus cereus is a prolyl peptidase using in vivo experiments. In the current work, we first report the inhibition of the native activity of PI-PLC by two DPP4 inhibitors - vildagliptin (LAF-237) and K-579. While vildagliptin inhibited PI-PLC at micromolar concentrations, K-579 was a potent inhibitor even at nanomolar concentrations. Subsequently, we queried a comprehensive, non-redundant set of 5000 human proteins (50% similarity cutoff) with known structures using serine protease (SPASE) motifs derived from trypsin and DPP4. A pancreatic lipase and a gastric lipase are among the proteins that are identified as proteins having promiscuous SPASE scaffolds that could interact with DPP4 inhibitors. The presence of such scaffolds in human lipases is expected since they share the same catalytic mechanism with PI-PLC. However our methodology also detects other proteins, often with a completely different enzymatic mechanism, that have significantly congruent domains with the SPASE motifs. The reported elevated levels of serum lipase, although contested, could be rationalized by inhibition of lipases reported here. In an effort to further our understanding of the spatial and electrostatic basis of DPP4 inhibitors, we have also done a comprehensive analysis of all 76 known DPP4 structures liganded to inhibitors till date. Also, the methodology presented here can be easily adopted for other drugs, and provide the first line of filtering in the identification of pathways that might be inadvertently affected due to promiscuous scaffolds in proteins

Antimicrobial Peptides Designed against the Ω-Loop of Class A β-Lactamases to Potentiate the Efficacy of β-Lactam Antibiotics

Class A serine β-lactamases (SBLs) have a conserved non-active site structural domain called the omega loop (Ω-loop), in which a glutamic acid residue is believed to be directly involved in the hydrolysis of β-lactam antibiotics by providing a water molecule during catalysis. We aimed to design and characterise potential pentapeptides to mask the function of the Ω-loop of β-lactamases and reduce their efficacy, along with potentiating the β-lactam antibiotics and eventually decreasing β-lactam resistance. Considering the Ω-loop sequence as a template, a group of pentapeptide models were designed, validated through docking, and synthesised using solid-phase peptide synthesis (SPPS). To check whether the β-lactamases (BLAs) were inhibited, we expressed specific BLAs (TEM-1 and SHV-14) and evaluated the trans-expression through a broth dilution method and an agar dilution method (HT-SPOTi). To further support our claim, we conducted a kinetic analysis of BLAs with the peptides and employed molecular dynamics (MD) simulations of peptides. The individual presence of six histidine-based peptides (TSHLH, ETHIH, ESRLH, ESHIH, ESRIH, and TYHLH) reduced β-lactam resistance in the strains harbouring BLAs. Subsequently, we found that the combinational effect of these peptides and β-lactams sensitised the bacteria towards the β-lactam drugs. We hypothesize that the antimicrobial peptides obtained might be considered among the novel inhibitors that can be used specifically against the Ω-loop of the β-lactamases

The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins

The long term side effects of any newly introduced drug is a subject of intense research, and often raging controversies. One such example is the dipeptidyl peptidase-IV (DPP4) inhibitor used for treating type 2 diabetes, which is inconclusively implicated in increased susceptibility to acute pancreatitis. Previously, based on a computational analysis of the spatial and electrostatic properties of active site residues, we have demonstrated that phosphoinositide-specific phospholipase C (PI-PLC) from Bacillus cereus is a prolyl peptidase using in vivo experiments. In the current work, we first report the inhibition of the native activity of PI-PLC by two DPP4 inhibitors - vildagliptin (LAF-237) and K-579. While vildagliptin inhibited PI-PLC at micromolar concentrations, K-579 was a potent inhibitor even at nanomolar concentrations. Subsequently, we queried a comprehensive, non-redundant set of 5000 human proteins (50% similarity cutoff) with known structures using serine protease (SPASE) motifs derived from trypsin and DPP4. A pancreatic lipase and a gastric lipase are among the proteins that are identified as proteins having promiscuous SPASE scaffolds that could interact with DPP4 inhibitors. The presence of such scaffolds in human lipases is expected since they share the same catalytic mechanism with PI-PLC. However our methodology also detects other proteins, often with a completely different enzymatic mechanism, that have significantly congruent domains with the SPASE motifs. The reported elevated levels of serum lipase, although contested, could be rationalized by inhibition of lipases reported here. In an effort to further our understanding of the spatial and electrostatic basis of DPP4 inhibitors, we have also done a comprehensive analysis of all 76 known DPP4 structures liganded to inhibitors till date. Also, the methodology presented here can be easily adopted for other drugs, and provide the first line of filtering in the identification of pathways that might be inadvertently affected due to promiscuous scaffolds in proteins

Ethylenediamine functionalized-single-walled nanotube (f-SWNT)-assisted in vitro delivery of the oncogene suppressor p53 gene to breast cancer MCF-7 cells

A gene delivery concept based on ethylenediamine-functionalized single-walled carbon nanotubes (f-SWCNTs) using the oncogene suppressor p53 gene as a model gene was successfully tested in vitro in MCF-7 breast cancer cells. The f-SWCNTs-p53 complexes were introduced into the cell medium at a concentration of 20 μg mL−1 and cells were exposed for 24, 48, and 72 hours. Standard ethidium bromide and acridine orange assays were used to detect apoptotic cells and indicated that a significantly larger percentage of the cells (approx 40%) were dead after 72 hours of exposure to f-SWCNTs-p53 as compared to the control cells, which were exposed to only p53 or f-SWCNTs, respectively. To further support the uptake and expression of the genes within the cells, green fluorescent protein-tagged p53, attached to the f-SWCNTs was added to the medium and the complex was observed to be strongly expressed in the cells. Moreover, caspase 3 activity was found to be highly enhanced in cells incubated with the f-SWCNTs-p53 complex, indicating strongly induced apoptosis. This system could be the foundation for novel gene delivery platforms based on the unique structural and morphological properties of multi-functional nanomaterials