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  1. Sriram S, Natiq H, Rajagopal K, Krejcar O, Krejcar O
    Math Biosci Eng, 2023 Jan;20(2):2908-2919.
    PMID: 36899564 DOI: 10.3934/mbe.2023137
    Investigating the effect of changes in neuronal connectivity on the brain's behavior is of interest in neuroscience studies. Complex network theory is one of the most capable tools to study the effects of these changes on collective brain behavior. By using complex networks, the neural structure, function, and dynamics can be analyzed. In this context, various frameworks can be used to mimic neural networks, among which multi-layer networks are a proper one. Compared to single-layer models, multi-layer networks can provide a more realistic model of the brain due to their high complexity and dimensionality. This paper examines the effect of changes in asymmetry coupling on the behaviors of a multi-layer neuronal network. To this aim, a two-layer network is considered as a minimum model of left and right cerebral hemispheres communicated with the corpus callosum. The chaotic model of Hindmarsh-Rose is taken as the dynamics of the nodes. Only two neurons of each layer connect two layers of the network. In this model, it is assumed that the layers have different coupling strengths, so the effect of each coupling change on network behavior can be analyzed. As a result, the projection of the nodes is plotted for several coupling strengths to investigate how the asymmetry coupling influences the network behaviors. It is observed that although no coexisting attractor is present in the Hindmarsh-Rose model, an asymmetry in couplings causes the emergence of different attractors. The bifurcation diagrams of one node of each layer are presented to show the variation of the dynamics due to coupling changes. For further analysis, the network synchronization is investigated by computing intra-layer and inter-layer errors. Calculating these errors shows that the network can be synchronized only for large enough symmetric coupling.
  2. Andoy-Galvan JA, Sriram S, Kiat TJ, Xin LZ, Shin WJ, Chinna K
    F1000Res, 2023;12:550.
    PMID: 37868299 DOI: 10.12688/f1000research.125203.1
    Background: Doctors with a normal BMI and healthy living habits have shown to be more confident and effective in providing realistic guidance and obesity management to their patients. This study investigated obesogenic tendencies of medical students as they progress in their medical studies. Methods: A cohort of forty-nine medical students enrolled in a five-year cohort study and was followed up after one year. At the initiation of the cohort, socio-demography and information on anthropometry, accommodation, eating behavior, stress and sleeping habits of the students had been recorded. Follow-up data was collected using a standardized self-administered questionnaire. Results: Thirty-seven percent of the students in the cohort are either obese or overweight in the one-year period.. A year of follow-up suggests that there is an increase in BMI among the male students (P=0.008) and the changes are associated with changes in accommodation (P=0.016), stress levels (P=0.021), and sleeping habits (P=0.011). Conclusion: Medical education system should seriously consider evaluating this aspect in the curriculum development to help our future medical practitioners practice a healthy lifestyle and be the initiator of change in the worsening prevalence of obesity worldwide.
  3. Thekkeparambil Chandrabose S, Sriram S, Subramanian S, Cheng S, Ong WK, Rozen S, et al.
    Stem Cell Res Ther, 2018 03 20;9(1):68.
    PMID: 29559008 DOI: 10.1186/s13287-018-0796-2
    BACKGROUND: While a shift towards non-viral and animal component-free methods of generating induced pluripotent stem (iPS) cells is preferred for safer clinical applications, there is still a shortage of reliable cell sources and protocols for efficient reprogramming.

    METHODS: Here, we show a robust episomal and xeno-free reprogramming strategy for human iPS generation from dental pulp stem cells (DPSCs) which renders good efficiency (0.19%) over a short time frame (13-18 days).

    RESULTS: The robustness of DPSCs as starting cells for iPS induction is found due to their exceptional inherent stemness properties, developmental origin from neural crest cells, specification for tissue commitment, and differentiation capability. To investigate the epigenetic basis for the high reprogramming efficiency of DPSCs, we performed genome-wide DNA methylation analysis and found that the epigenetic signature of DPSCs associated with pluripotent, developmental, and ecto-mesenchymal genes is relatively close to that of iPS and embryonic stem (ES) cells. Among these genes, it is found that overexpression of PAX9 and knockdown of HERV-FRD improved the efficiencies of iPS generation.

    CONCLUSION: In conclusion, our study provides underlying epigenetic mechanisms that establish a robust platform for efficient generation of iPS cells from DPSCs, facilitating industrial and clinical use of iPS technology for therapeutic needs.

  4. Al-Ahdal SA, Ahmad Kayani AB, Md Ali MA, Chan JY, Ali T, Adnan N, et al.
    Int J Mol Sci, 2019 Jul 23;20(14).
    PMID: 31340481 DOI: 10.3390/ijms20143595
    We employed dielectrophoresis to a yeast cell suspension containing amyloid-beta proteins (Aβ) in a microfluidic environment. The Aβ was separated from the cells and characterized using the gradual dissolution of Aβ as a function of the applied dielectrophoretic parameters. We established the gradual dissolution of Aβ under specific dielectrophoretic parameters. Further, Aβ in the fibril form at the tip of the electrode dissolved at high frequency. This was perhaps due to the conductivity of the suspending medium changing according to the frequency, which resulted in a higher temperature at the tips of the electrodes, and consequently in the breakdown of the hydrogen bonds. However, those shaped as spheroidal monomers experienced a delay in the Aβ fibril transformation process. Yeast cells exposed to relatively low temperatures at the base of the electrode did not experience a positive or negative change in viability. The DEP microfluidic platform incorporating the integrated microtip electrode array was able to selectively manipulate the yeast cells and dissolve the Aβ to a controlled extent. We demonstrate suitable dielectrophoretic parameters to induce such manipulation, which is highly relevant for Aβ-related colloidal microfluidic research and could be applied to Alzheimer's research in the future.
  5. Sriram S, Kang NY, Subramanian S, Nandi T, Sudhagar S, Xing Q, et al.
    Stem Cell Res Ther, 2021 02 05;12(1):113.
    PMID: 33546754 DOI: 10.1186/s13287-021-02171-6
    BACKGROUND: Despite recent rapid progress in method development and biological understanding of induced pluripotent stem (iPS) cells, there has been a relative shortage of tools that monitor the early reprogramming process into human iPS cells.

    METHODS: We screened the in-house built fluorescent library compounds that specifically bind human iPS cells. After tertiary screening, the selected probe was analyzed for its ability to detect reprogramming cells in the time-dependent manner using high-content imaging analysis. The probe was compared with conventional dyes in different reprogramming methods, cell types, and cell culture conditions. Cell sorting was performed with the fluorescent probe to analyze the early reprogramming cells for their pluripotent characteristics and genome-wide gene expression signatures by RNA-seq. Finally, the candidate reprogramming factor identified was investigated for its ability to modulate reprogramming efficiency.

    RESULTS: We identified a novel BODIPY-derived fluorescent probe, BDL-E5, which detects live human iPS cells at the early reprogramming stage. BDL-E5 can recognize authentic reprogramming cells around 7 days before iPS colonies are formed and stained positive with conventional pluripotent markers. Cell sorting of reprogrammed cells with BDL-E5 allowed generation of an increased number and higher quality of iPS cells. RNA sequencing analysis of BDL-E5-positive versus negative cells revealed early reprogramming patterns of gene expression, which notably included CREB1. Reprogramming efficiency was significantly increased by overexpression of CREB1 and decreased by knockdown of CREB1.

    CONCLUSION: Collectively, BDL-E5 offers a valuable tool for delineating the early reprogramming pathway and clinically applicable commercial production of human iPS cells.

  6. Chan JY, Ahmad Kayani AB, Md Ali MA, Kok CK, Ramdzan Buyong M, Hoe SLL, et al.
    Electrophoresis, 2019 10;40(20):2728-2735.
    PMID: 31219180 DOI: 10.1002/elps.201800442
    This paper presents the development and experimental analysis of a curved microelectrode platform for the DEP deformation of breast cancer cells (MDA-MB-231). The platform is composed of arrays of curved DEP microelectrodes which are patterned onto a glass slide and samples containing MDA-MB-231 cells are pipetted onto the platform's surface. Finite element method is utilised to characterise the electric field gradient and DEP field. The performance of the system is assessed with MDA-MB-231 cells in a low conductivity 1% DMEM suspending medium. We applied sinusoidal wave AC potential at peak to peak voltages of 2, 5, and 10 Vpp at both 10 kHz and 50 MHz. We observed cell blebbing and cell shrinkage and analyzed the percentage of shrinkage of the cells. The experiments demonstrated higher percentage of cell shrinkage when cells are exposed to higher frequency and peak to peak voltage electric field.
  7. Chan JY, Ahmad Kayani AB, Md Ali MA, Kok CK, Yeop Majlis B, Hoe SLL, et al.
    Biomicrofluidics, 2018 Jan;12(1):011503.
    PMID: 29531634 DOI: 10.1063/1.5010158
    The recent advancement of dielectrophoresis (DEP)-enabled microfluidic platforms is opening new opportunities for potential use in cancer disease diagnostics. DEP is advantageous because of its specificity, low cost, small sample volume requirement, and tuneable property for microfluidic platforms. These intrinsic advantages have made it especially suitable for developing microfluidic cancer diagnostic platforms. This review focuses on a comprehensive analysis of the recent developments of DEP enabled microfluidic platforms sorted according to the target cancer cell. Each study is critically analyzed, and the features of each platform, the performance, added functionality for clinical use, and the types of samples, used are discussed. We address the novelty of the techniques, strategies, and design configuration used in improving on existing technologies or previous studies. A summary of comparing the developmental extent of each study is made, and we conclude with a treatment of future trends and a brief summary.
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