Department of Bioscience & Bioengineering

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IIT Jodhpur

We present a study of the dynamics of a system of masses connected by springs and repelling by a 1∕r potential in 1D. The present study focuses on the dynamics in the regime where the repulsive force dominates the dynamics of the system. We conjecture that such a system may be approximately modeled by an alignment of repelling rigid bar magnets that are sufficiently far apart from each other. We show that except for cases where the repulsive potential is very weak, most of the energy due to a velocity perturbation at system initiation of magnitude v0(0) generates a propagating solitary wave in the system. Dynamical simulations show that this solitary wave shows no measurable tendency to thermalize over extended simulation time scales, thereby yielding an effectively non-ergodic system. Part of the energy generates low-amplitude persistent oscillations which do not show any measurable interaction with the solitary wave. We find that the solitary wave propagation speed vSW∝v0 2 for various coupling strengths. We further demonstrate that owing to the repulsion between the adjacent particles, these solitary waves are mutually repulsive, i.e., they cannot cross each other and hence there is no phase change associated with their mutual interactions. We use the data driven Dynamic Mode Decomposition technique to develop a simple approximate way to represent the propagating solitary wave. Additionally, we compute fluctuations in the kinetic energy of the system at late times and show that the energy fluctuations increase drastically when the effects of v0 and the coupling associated with the repulsive interactions become competitive. © 2020 Elsevier B.V.

World University root node

Physica A: Statistical Mechanics and its Applications

Dynamics in a confined mass–spring chain with 1∕r repulsive potential: Strongly nonlinear regime

Floriculture is an integral part of modern agriculture. Genetic transformation techniques pave way for the development of biotechnology assisted novel varieties which are appealing to customers. Customer preference in floriculture changes rapidly with time. Recently discovered CRISPR/Cas genome editing technique is useful in editing key genes attributing to a trait with the enhanced aesthetic appeal of plants. This chapter primarily discusses the application of biotechnology-based tools for improvement of floriculture plants to keep up with consumer appeal.

CRISPR/Cas Genome Editing

Improvement of Floriculture Crops Using Genetic Modification and Genome Editing Techniques

Boron is one of the most vital minerals for the growth of the human body, as it helps in managing several harmful bone conditions such as osteoporosis and arthritis. The doping of boron in various quantities into the bioglass system has a noteworthy influence on its structure, glass formation factors, cell viability, and biodegradability. In the present study, in vitro bioactivity of B2O3 containing 45S5 glass was systematically investigated using a sol-gel route and its mechanical and biological properties were evaluated. B2O3 concentrations of 1, 2.5, and 5 wt.% were added to replace the content of silica in the composition of 45S5 without altering the concentration of the other constituents. The crystallization behavior of the glass and the sintered samples was evaluated by XRD analysis. In vitro bioactivity testing was performed in simulated body fluid (SBF) and FESEM analysis was carried out to observe the microstructure in static in vitro condition. The biocompatibility nature of the as-prepared bioglass powders was ascertained via MTT assay. Results revealed a higher in vitro bioactivity in the B2O3 containing 45S5 glass as compared with 45S5 bioglass. © 2020, Australian Ceramic Society.

Journal of the Australian Ceramic Society

Effect of addition of B2O3 to the sol-gel synthesized 45S5 bioglass

Evaluation of the biological properties of silanized graphene oxide is important in the context of biomedical applications of the material. In this study, we have evaluated the toxicity, immunogenicity and other biological properties like osteogenicity of silanized graphene oxide (SiGO). Graphene oxide (GO) was silanized using a common silanizing agent namely (3-aminopropyl) triethoxysilane (APTES). Silanization was confirmed through infrared spectroscopy and elemental mapping. Post-silanization, we did not observe any significant changes in the morphology of GO. Silanization leads to an increase in the interlayer distance and disorder in the lattice. Study of in vitro toxicity of SiGO on three different cell lines namely primary human dermal fibroblast, murine embryonic fibroblast and human osteosarcoma cell lines revealed that toxicity of SiGO was significantly less than GO. We further showed that in vitro immune activation of macrophage was less in the case of SiGO in comparison to GO. Profiling of osteogenic differentiation of human mesenchymal stem cell revealed that SiGO is less osteogenic than GO. Study of acute toxicity in the murine model indicated that GO was hepatotoxic at experimental concentration whereas SiGO did not show any significant toxicity. This study implied that SiGO is a better biocompatible material than GO. © 2020 Elsevier B.V.

Materials Science and Engineering C

Silanization improves biocompatibility of graphene oxide

Objective: In the last few decades, the consumption of cannabis-based products for recreational purposes has dramatically increased. Unfortunately, cannabis consumption has been associated with the incidences of cardiovascular diseases. Hence, there is a necessity for understanding the plausible mechanics of cardiophysiological changes due to cannabis consumption. Accordingly, the current study was designed to understand the suitability of the recurrence quantification analysis (RQA) method in detecting the changes in the heart rate variability (HRV) time-series signals due to the consumption of cannabis (bhang). Further, a machine learning model has been proposed for the automated detection of the cannabis takers. Materials and Methods: The RQA of the HRV time-series signals from 200 healthy Indian male paddy-field workers were carried out. The obtained parameters were statistically analyzed using the Mann-Whitney U test. Further, the decision trees, weight-based feature ranking, and dimensionality reduction methods were employed for identifying the relevant features for the development of a suitable machine learning model. Results: Observable changes in the patterns of the recurrence plots among the bhang consuming and non-consuming groups were noticed. However, there were no significant differences in the RQA parameters. Among the developed machine learning models, the SVM model obtained from the “Information gain ratio” feature selection method exhibited the highest accuracy (%) of 69.09 ± 9.33. Conclusion: Our study suggests that the RQA method is not as effective as the time and frequency domain methods for detecting the alterations in the HRV time-series signals due to cannabis consumption. The SVM model was found to be the best model for the automated detection of cannabis takers. The selection of the features by the information gain ratio method played an important role in the development of the optimized SVM model. © 2020 AGBM

IRBM

Comparing the HRV Time-Series Signals Acquired from Cannabis Consuming and Non-Consuming Indian Paddy-Field Workers by Recurrence Quantification Analysis

Epigenetic deregulation remarkably triggers mechanisms associated with tumor aggressiveness like epithelial–mesenchymal transition (EMT). Since EMT is a highly complex, but also reversible event, epigenetic processes such as DNA methylation or chromatin alterations must be involved in its regulation. It was recently described that loss of the cell cycle regulator p21 was associated with a gain in EMT characteristics and an upregulation of the master EMT transcription factor ZEB1. In this study, in silico analysis was performed in combination with different in vitro and in vivo techniques to identify and verify novel epigenetic targets of ZEB1, and to proof the direct transcriptional regulation of SETD1B by ZEB1. The chorioallantoic-membrane assay served as an in vivo model to analyze the ZEB1/SETD1B interaction. Bioinformatical analysis of CRC patient data was used to examine the ZEB1/SETD1B network under clinical conditions and the ZEB1/SETD1B network was modeled under physiological and pathological conditions. Thus, we identified a self-reinforcing loop for ZEB1 expression and found that the SETD1B associated active chromatin mark H3K4me3 was enriched at the ZEB1 promoter in EMT cells. Moreover, clinical evaluation of CRC patient data showed that the simultaneous high expression of ZEB1 and SETD1B was correlated with the worst prognosis. Here we report that the expression of chromatin modifiers is remarkably dysregulated in EMT cells. SETD1B was identified as a new ZEB1 target in vitro and in vivo. Our study demonstrates a novel example of an activator role of ZEB1 for the epigenetic landscape in colorectal tumor cells. © 2020, The Author(s).

Fulltext

Cell Death and Disease

EMT transcription factor ZEB1 alters the epigenetic landscape of colorectal cancer cells

Identification of cancer subtypes is critically important for understanding the heterogeneity present in tumors. Integrating information from multiple sources, homogeneous groups for cancer can be identified. However, there is a lack of computational approaches to identify histological subtypes among the patients suffering from different types of cancers. Assigning weight to the biomarkers prior to the integration of multiple information sources for the same set of samples can play an important role in cancer subtypes identification, which has not been explored previously. Sub-typing of cancers can help in analyzing shared molecular profiles between different histological subtypes of solid tumors. A novel method for feature weighting based on robust regression fit is developed in this study. The weight is utilized to find similarity between patients individually from each of the information sources. Here, miRNA and mRNA expression profiles across the same set of samples have been used. Patient-similarity networks, that are generated from each of the expression profiles are then integrated using the approach of Similarity Network Fusion. Finally, Spectral clustering is applied on the fused network to identify similar groups of patients that represent a cancer subtype. The effectiveness of the proposed method has been demonstrated on different data sets. IEEE

IEEE/ACM Transactions on Computational Biology and Bioinformatics

A Feature Weighting-Assisted Approach for Cancer Subtypes Identification from Paired Expression profiles

Unraveling the large number of various signals in the brain under the influence of physical and chemical cues that govern the formation of individual neurons, axons, dendrites, and their functional synapses during the development of neural network is a challenging task. To understand this task, microfluidic devices equipped with microchannels for reconstitution of cell/tissue-culture environments have been studied. Microfluidic devices are emerging as powerful tools in neurobiology, since they are capable of controlling and manipulating the microenvironment of the brain in a precise manner. They can enhance the physiological relevance of three-dimensional (3D) cell culture by allowing spatial control over fluids in micrometer-sized channels. Recent technological advancement in designing microfluidic platforms for studying neural communication, disease progression, and detection of neurotransmitters enhance our fundamental knowledge and understanding. However, more such advanced and innovative interventions are required. This Viewpoint focuses on highlighting a few of them with future scope of further advancement in this field. © 2019 American Chemical Society.

ACS Chemical Neuroscience

Three-Dimensional Microfluidic Platform with Neural Organoids: Model System for Unraveling Synapses

Traumatic brain injury (TBI) and spinal cord injury (SCI) cause millions of deaths and permanent or prolonged physical disabilities around the globe every year. It generally happens due to various incidents, such as accidents during sports, war, physical assault, and strokes which result in severe damage to brain and spinal cord. If this remains untreated, traumatic CNS injuries may lead to early development of several neurodegenerative diseases like Alzheimer's, Parkinson, multiple sclerosis, and other mental illnesses. The initial physical reaction, which is also termed as the primary phase, includes swelling, followed by inflammation as a result of internal haemorrhage causing damage to indigenous tissue, i.e., axonal shear injury, rupture of blood vessels, and partial impaired supply of oxygen and essential nutrients in the neurons, thereby initiating a cascade of events causing secondary injuries such as hypoxia, hypotension, cognitive impairment, seizures, imbalanced calcium homeostasis and glutamate-induced excitotoxicity resulting in concomitant neuronal cell death and cumulative permanent tissue damage. In the modern era of advanced biomedical technology, we are still living with scarcity of the clinically applicable comparative non-invasive therapeutic strategies for regeneration or functional recovery of neurons or neural networks after a massive CNS injury. One of the key reasons for this scarcity is the limited regenerative ability of neurons in CNS. Growth-impermissive glial scar and the lack of a synthetic biocompatible platform for proper neural tissue engineering and controlled supply of drugs further retard the healing process. Injectable or implantable hydrogel materials, consisting majorly of water in its porous three-dimensional (3D) structure, can serve as an excellent drug delivery platform as well as a transplanted cell-supporting scaffold medium. Among the various neuro-compatible bioinspired materials, we are limiting our discussion to the recent advancement of engineered biomaterials comprising mainly of peptides and proteins due to their growing demand, low immunogenicity and versatility in the fabrication of neuro regenerative medicine. In this article, we try to explore all the recent scientific avenues that are developing gradually to make peptide and peptide-conjugated biomaterial hydrogels as a therapeutic and supporting scaffold for treating CNS injuries. © 2020 The Royal Society of Chemistry.

Soft Matter

Recent trends in the development of peptide and protein-based hydrogel therapeutics for the healing of CNS injury

Background: Neurocysticercosis (NCC) is infection by cestode Taenia solium/pork tapeworm. Sero-diagnosis of NCC is still a challenge. Radiological imaging (CT/MRI) are cost intensive, requires technical expertise and resource intensive. Hence, its availability is restricted in endemic zone. Existing Enzyme electro immune transfer blot (EITB) antigens are difficult to make and is not standardized for endemic population. Therefore, there is a definite need for easy and reliable EITB tool. Methods: T. solium metacestode were harvested from naturally infected swine post slaughter. The cyst fluid/vesicular fluid was aspirated and processed with ultracentrifugation and immune blot was performed with this antigen. Results: A total of 406 cases [rural 256 (NCC 78, seizures other than NCC 108 and healthy controls 70); urban 150 (NCC 41, seizures other than NCC 59 and healthy controls 50)] were enrolled. Positive EITB (detection of band <50 kDa) was significantly associated with NCC patients of urban population only (p < 0.001) but not in rural populations (p = 0.292). However, identification of 15 kDa band had significant association with NCC both in urban and rural populations with overall sensitivity of 91.5% and specificity of 91.6%. Presence of 35 kDa band was associated with multiple NCC (p < 0.001). The study shows that 15 kDa reactive band on EITB is highly sensitive and specific for diagnosis of NCC in endemic population. Conclusions: Presence of 35 kDa band on EITB was associated with infection by multiple cysticerci. The observations demand purification of cyst fluid antigens to develop simple and easy to execute test in field studies. © 2020

Clinica Chimica Acta

Evaluation of Taenia solium cyst fluid-based enzyme linked immunoelectro transfer blot for Neurocysticercosis diagnosis in urban and highly endemic rural population of North India