scholarly journals Peptide–Peptide Co-Assembly: A Design Strategy for Functional Detection of C-peptide, A Biomarker of Diabetic Neuropathy

2020 ◽  
Vol 21 (24) ◽  
pp. 9671
Author(s):  
Kiat Hwa Chan ◽  
Jaehong Lim ◽  
Joo Eun Jee ◽  
Jia Hui Aw ◽  
Su Seong Lee

Diabetes-related neuropathy is a debilitating condition that may be averted if it can be detected early. One possible way this can be achieved at low cost is to utilise peptides to detect C-peptide, a biomarker of diabetic neuropathy. This depends on peptide-peptide co-assembly, which is currently in a nascent stage of intense study. Instead, we propose a bead-based triple-overlay combinatorial strategy that can preserve inter-residue information during the screening process for a suitable complementary peptide to co-assemble with C-peptide. The screening process commenced with a pentapeptide general library, which revealed histidine to be an essential residue. Further screening with seven tetrapeptide focused libraries led to a table of self-consistent peptide sequences that included tryptophan and lysine at high frequencies. Three complementary nonapeptides (9mer com-peptides), wpkkhfwgq (Trp-D), kwkkhfwgq (Lys-D), and KWKKHFWGQ (Lys-L) (as a negative control) were picked from this table for co-assembly studies with C-peptide. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) and circular dichroism (CD) spectroscopies were utilized to study inter-peptide interactions and changes in secondary structures respectively. ATR-FTIR studies showed that there is indeed inter-peptide interaction between C-peptide and the tryptophan residues of the 9mer com-peptides. CD studies of unaggregated and colloidal C-peptide with the 9mer com-peptides suggest that the extent of co-assembly of C-peptide with Trp-D is greatest, followed by Lys-D and Lys-L. These results are promising and indicate that the presented strategy is viable for designing and evaluating longer complementary peptides, as well as complementary peptides for co-assembly with other polypeptides of interest and importance. We discuss the possibility of designing complementary peptides to inhibit toxic amyloidosis with this approach.

Author(s):  
Shancy Augustine ◽  
Pan Gu ◽  
Xiangjun Zheng ◽  
Toshikazu Nishida ◽  
Z. Hugh Fan

There is a need for low-cost immunoassays that measure the presence and concentration of multiple harmful agents in one device. Currently, comparable immunoassays employ a one-analyte-per-test format that is time consuming and not cost effective for the requirement of detecting multiple analytes in a single sample. For instance, if a spectrum of harmful agents, including E. coli O157, cholera toxin, and Salmonella typhimurium, should be simultaneously monitored in foods and drinking water, then a one-analyte-per-test would be inefficient. This work demonstrates a platform capable of simultaneous detection of multiple analytes in a single, low-cost, microvalve array-enabled multiplexed immunoassay. This multiplexed immunoassay platform is demonstrated in a prototype COC (cyclic olefin copolymer) device with a 2×3 array in which 6 analytes can be detected simultaneously. In order to contain and regulate the flow of reagents in the multichannel device, an array of microfluidic valves actuated by a thermally expandable material and microfabricated resistors have been developed to direct the flow to the necessary assay sites. The microvalve-based immunoassay is shown to be reliable, easy to operate, and compatible with large-scale integration. The all-plastic microvalves use paraffin wax as the thermally sensitive material which drastically reduces power consumption by latching upon closing so that pulsed power is required only to close and latch the microvalve until it is necessary to re-open the valve. The multiplexed detection scheme has been demonstrated by using three proteins, C reactive protein (CRP) and transferrin, both of which are biomarkers associated with traumatic brain injury (TBI) as well as bovine serum albumin (BSA) as the negative control. Since there are no external bulky pneumatic accessories required to operate/latch the microvalves in the device, this compact, thermally actuated and latching microvalve-enabled multiplexed immunoassay has the potential to realize a portable, low power, battery operated microfluidic device for biological assays.


Diabetes Care ◽  
2006 ◽  
Vol 30 (1) ◽  
pp. 71-76 ◽  
Author(s):  
K. Ekberg ◽  
T. Brismar ◽  
B.-L. Johansson ◽  
P. Lindstrom ◽  
L. Juntti-Berggren ◽  
...  

Today in communication field, many antennas have been evolved for various applications. The most popularly used antennas are micro-strip antennas. These antennas can be easily fabricated at reasonably low cost. Hence, these antennas are gaining lot of importance in recent times. Many techniques have been in use for micro strip antennas to improve the performance of the antenna parameters. The design of these antennas is slowly moving towards high frequencies, where there is lot of advantage with bandwidth. In this paper a normal and E shaped inset micro-strip antenna in Ku-Band is simulated and the results are presented. It is noted that CST-MS 2015 tool has been used to get the simulation results.


2016 ◽  
Author(s):  
Eric Mwangi Irungu ◽  
Peter Waweru Mwangi ◽  
Frederick O Bukachi

Organophosphate poisoning represents a major and growing global health problem especially in the developing countries and cardiotoxicity is the major cause of death. Thus, a compelling need to develop novel low cost efficacious agents to manage this condition. Objective To evaluate the methanol extract of Withania somnifera as a pre-treatment agent in the prevention of the cardiotoxic effects of diazinon in Sprague Dawley rats Materials and Methods Twenty one (21) adult rats were randomized to receive 200 mg/kg methanol extract of Withania somnifera (test group), vehicle (negative control) or 200 [mu]g/kg Neostigmine as pre-treatment 30 minutes prior to the oral administration of 200 mg/kg Diazinon. Baseline and post-treatment electrocardiograms (ECGs) were recorded by the Powerlab data acquisition system (ML865 AD instruments, Sydney, Australia). The experimental data were expressed as median [plusmn] the inter-quartile range and analysed using the Kruskal [minus] Wallis non[minus]parametric test and followed by Mann[minus]Whitney U post hoc test in cases of significance, which was set at p < 0.05. Statistical Package for Social Sciences (SPSS) version 17 software was used for analysis. Results Pre-treatment with the methanol extract of W. somnifera had significant effect on the following diazinon-induced electrocardiographic changes; RR interval (0.026 (0.007 [minus] 0.065) vs. 0.035 (0.019 [minus] 0.050) vs. 0.090 (0.071 [minus] 0.01), p = 0.031),heart rate ([minus]54.235 (115.317 [minus] ([minus]19.857)) vs. [minus]96.136 ([minus]96.472 [minus] ([minus]43.879)) vs. [minus]174.361 ([minus]189.775 [minus] ([minus]129.469)), p = 0.014), PR interval (0.006 (0.004 [minus] 0.008) vs. 0.003 (0.001 [minus] 0.004) vs. 0.009 (0.006 [minus] 0.015), p = 0.019), QRS interval (0.005 (0.001 [minus] 0.008) vs. [minus]0.002 ([minus]0.005 [minus] 0.001) vs. 0.007 (0.003 [minus] 0.011), p = 0.023) and ST height ([minus]34.830 ([minus]63.578 [minus] 4.215) vs. [minus]22.330 ([minus]38.383[minus]([minus]4.159)) vs. [minus]73.156 ([minus]214.022[minus] ([minus]52.449)), p = 0.023). It however had no significant effect on the QTc interval changes ([minus]0.005 ([minus]0.011 [minus] 0.003) vs. [minus]0.005 ([minus]0.015 [minus] 0.065) vs. [minus]0.021 ([minus]0.060[minus] ([minus]0.006)), p = 0.174). Conclusion The efficacy of pre-treatment with the methanol extract of Withania somnifera was comparable to that of pre-treatment with Neostigmine a commonly used carbamate drug. Thus, it is a potentially viable low cost treatment option for organophosphate poisoning in resource-limited settings.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Cassandra M. Wilkinson ◽  
Jennifer I. Burrell ◽  
Jonathan W. P. Kuziek ◽  
Sibi Thirunavukkarasu ◽  
Brian H. Buck ◽  
...  

Abstract In this study, we demonstrated the use of low-cost portable electroencephalography (EEG) as a method for prehospital stroke diagnosis. We used a portable EEG system to record data from 25 participants, 16 had acute ischemic stroke events, and compared the results to age-matched controls that included stroke mimics. Delta/alpha ratio (DAR), (delta + theta)/(alpha + beta) ratio (DBATR) and pairwise-derived Brain Symmetry Index (pdBSI) were investigated, as well as head movement using the on-board accelerometer and gyroscope. We then used machine learning to distinguish between different subgroups. DAR and DBATR increased in ischemic stroke patients with increasing stroke severity (p = 0.0021, partial η2 = 0.293; p = 0.01, partial η2 = 0.234). Also, pdBSI decreased in low frequencies and increased in high frequencies in patients who had a stroke (p = 0.036, partial η2 = 0.177). Using classification trees, we were able to distinguish moderate to severe stroke patients and from minor stroke and controls, with a 63% sensitivity, 86% specificity and accuracy of 76%. There are significant differences in DAR, DBATR, and pdBSI between patients with ischemic stroke when compared to controls, and these effects scale with severity. We have shown the utility of a low-cost portable EEG system to aid in patient triage and diagnosis as an early detection tool.


Diabetes ◽  
2004 ◽  
Vol 53 (6) ◽  
pp. 1556-1563 ◽  
Author(s):  
A. A.F. Sima ◽  
W. Zhang ◽  
Z.-G. Li ◽  
Y. Murakawa ◽  
C. R. Pierson

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