Department of Bioscience & Bioengineering

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The response of a granular alignment held between fixed end walls to an impulse was introduced in the works of Nesterenko between 1983 and the years that followed. He showed analytically and experimentally that a granular chain admits a propagating solitary wave. In his analytic work, under small precompression compared to the local strain, he showed that one finds a propagating solitary wave. The solitary wave was also seen experimentally but at zero and vanishingly small precompressions. Under stronger precompression a possible Korteweg–de Vries (KdV) solitary wave was suggested though never observed. Later, others confirmed the solitary wave result at zero loading. Sen and Manciu reported seeing the solitary wave behavior in numerical simulations and in 2001 proposed an accurate solution which obtained the solitary wave at zero precompression as seen in some experiments and in numerics. Simulations showed an oscillatory tail following the solitary wave at small precompressions. In an experimental study in 1997, Costé, Falcon and Fauve and later Nesterenko et al. reported seeing propagation of a wave with an oscillatory tail. The oscillatory tail eventually consumed the solitary wave with increasing precompression. How can one reconcile Nesterenko’s solitary wave for the weakly precompressed system with Sen and Manciu’s solitary wave solution for zero precompression? Here we show that there is a separate solitary wave phase at a certain weak but finite loading regime which is distinct from Sen and Manciu’s work and this may be the reason why Nesterenko’s analytic theory seems to admit a solitary wave at finite loadings. We also offer insights into why the KdV solution is not seen. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

World University root node

Granular Matter

Revisiting Nesterenko’s solitary wave in the precompressed granular alignment held between fixed ends

Cowpea is sensitive to drought and heat stress, particularly at the reproductive stages of development. Both stresses limit growth and yield, and their effect is more devastating when occurring concurrently. Dehydration-responsive element-binding protein 2A (DREB2A) is an important signaling hub integrating information about two different abiotic stresses, drought and heat. We identified VuDREB2A as a canonical DREB ortholog in cowpea, activating downstream stress-responsive genes by binding to DREs in their promoter. Post-translational modification of a negative regulatory domain (NRD) within the VuDREB2A protein prevents its degradation. Targeted deletion of the NRD produces a stable and constitutively active form VuDREB2A-CA. However, there is very little evidence of its practical utility under field conditions. This study overexpressed the VuDREB2A-CA in a popular cowpea variety and conducted drought- and heat-tolerance experiments across various stress regimes. Transgenic cowpea exhibited significant tolerance with consistently higher yield when exposed to over 30-d drought stress and 3-d exposure to high temperature (28&nbsp;°C˗52&nbsp;°C) without any pleiotropic alterations. The transgenic lines showed higher <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/photosynthetic-efficiency">photosynthetic efficiency</a>, <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/plant-osmotic-adjustment">osmotic adjustment</a>, antioxidant defense, <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/critical-thermal-maximum">thermotolerance</a>, and significantly higher survival and increased biomass than the wild type. Late <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/embryogenesis">embryogenesis</a> abundant 5, <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/heat-shock-protein-70">heat shock protein 70</a>, <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/dehydrin">dehydrin</a>, mitogen-activated protein kinase 2/4, <a href="https://www.sciencedirect.com/topics/agricultural-and-biological-sciences/isoflavonoid">isoflavonoid</a> <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/reductase">reductase</a>, and myoinositol phosphate <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/synthase">synthase</a> were upregulated in transgenic lines under drought and heat stress. Through <a href="https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/gene-expression-profiling">transcriptome analysis</a> of the transgenic lines, we found significant up-regulation of various stress-responsive cowpea genes, having DRE in their promoter. Our results suggest that overexpression of VuDREB2A could improve cowpea production under drought and high temperatures.

Plant Physiology and Biochemistry

Enhanced osmotic adjustment, antioxidant defense, and photosynthesis efficiency under drought and heat stress of transgenic cowpea overexpressing an engineered DREB transcription factor

Cowpea is a significant grain legume crop primarily grown in sub-Saharan Africa, Asia, and South America. Drought and nutrient deficiency affect the growth and yield of cowpea. To address this challenge, we studied the phyto-beneficial effects of stress-tolerant rhizobacteria on the biomass yield of cowpea under water- and nutrient-deficit conditions. Among the bacteria isolated, two rhizobacillus genotypes, C8 (Priestia filamentosa; basonym: Bacillus filamentosus) and C29 (Priestia aryabhattai; basonym: Bacillus aryabhattai) were evaluated for the improvement of seed germination and growth of cowpea under stress. Our study revealed that C8 protected cowpea from stress by facilitating phosphorus and potassium uptake, protecting it from oxidative damage, reducing transpiration, and enhancing CO2 assimilation. A 17% increase in root biomass upon C8 inoculation was concomitant with the induction of stress tolerance genes in cowpea roots predominantly involved in growth and metabolic processes, cell wall organization, ion homeostasis, and cellular responses to phosphate starvation. Our results indicate a metabolic alteration in cowpea root triggered by P. filamentosa, leading to efficient nutrient reallocation in the host plant. We propose inoculation with P. filamentosa as an effective strategy for improving the yield of cowpea in low-input agriculture, where chemical fertilization and irrigation are less accessible to resource-poor farmers.

Planta

<a href="https://scholar.google.com/citations?view_op=view_citation&amp;hl=en&amp;user=GLOX0tAAAAAJ&amp;sortby=pubdate&amp;citation_for_view=GLOX0tAAAAAJ:ULOm3_A8WrAC">Rhizosphere Priestia species altered cowpea root transcriptome and enhanced growth under drought and nutrient deficiency</a>

Priestia species isolated from the cowpea rhizosphere altered the transcriptome of cowpea roots by colonization and enhanced nutrient uptake, antioxidant mechanisms, and photosynthesis, protecting cowpea from drought and nutrient deficiency. Cowpea is a significant grain legume crop primarily grown in sub-Saharan Africa, Asia, and South America. Drought and nutrient deficiency affect the growth and yield of cowpea. To address this challenge, we studied the phyto-beneficial effects of stress-tolerant rhizobacteria on the biomass yield of cowpea under water- and nutrient-deficit conditions. Among the bacteria isolated, two rhizobacillus genotypes, C8 (Priestia filamentosa; basonym: Bacillus filamentosus) and C29 (Priestia aryabhattai; basonym: Bacillus aryabhattai) were evaluated for the improvement of seed germination and growth of cowpea under stress. Our study revealed that C8 protected cowpea from stress by facilitating phosphorus and potassium uptake, protecting it from oxidative damage, reducing transpiration, and enhancing CO2 assimilation. A 17% increase in root biomass upon C8 inoculation was concomitant with the induction of stress tolerance genes in cowpea roots predominantly involved in growth and metabolic processes, cell wall organization, ion homeostasis, and cellular responses to phosphate starvation. Our results indicate a metabolic alteration in cowpea root triggered by P. filamentosa, leading to efficient nutrient reallocation in the host plant. We propose inoculation with P. filamentosa as an effective strategy for improving the yield of cowpea in low-input agriculture, where chemical fertilization and irrigation are less accessible to resource-poor farmers.

Rhizosphere Priestia species altered cowpea root transcriptome and enhanced growth under drought and nutrient deficiency

A convergent, robust one-pot three-component approach for the synthesis of dihydrofuro[3,2-c]coumarins (DHFCs) was developed via the reaction of aryl/hetryl aldehydes, substituted phenacyl bromides and 4-hydroxycoumarin using N,N-diisopropyl ethyl ammonium acetate (DIPEAc) as the promoting medium. By virtue of its operational simplicity, efficiency, and wide substrate scope, the herein documented methodology constitutes a very attractive protocol addressing access to diversely substituted fused coumarin derivatives in a cost- and time-effective manner. Moreover, in silico pharmacophore modelling divulges the selective binding of the synthesized DHFC derivatives at the highly conserved active site catalytic cleft of Trichomonas vaginalis purine nucleoside phosphorylase (TvPNP), the indispensable enzyme of the protozoan purine salvage pathway and the potent anti-trichomoniasis drug target. The strong ligand binding is corroborated by excellent free energy of binding (ΔGbinding) profiles and further confirmed by all-atomistic molecular dynamics simulation analysis and deep learning based binding affinity (pKd) predictions. The docked conformations of DHFC derivatives at the active site catalytic cleft of TvPNP are structurally reminiscent of previously reported co-crystallized conformation of FormycinA (PDB ID: <a href="http://xlink.rsc.org/?pdb=1Z36">1Z36</a>), albeit the DHFC derivatives demonstrated stronger binding propensities. Detailed quantitative structure–function analysis, presented herein, may elucidate the potential role of the synthesized DHFC derivatives as future anti-trichomoniasis therapeutic leads.

Department of Chemistry

New Journal of Chemistry

Convenient multicomponent synthesis of furo[3,2-c]coumarins in the promoting medium DIPEAc and assessment of their therapeutic potential through in silico pharmacophore based target screening

Recurrent spells of droughts are more common than a single drought, with intermittent moist recovery intervals. While the detrimental effects of the first drought on plant structure and physiology are unavoidable, if survived, plants can memorize the first drought to present a more robust response to the following droughts. This includes a partial stomatal opening in the watered recovery interval, higher levels of osmoprotectants and ABA, and attenuation of photosynthesis in the subsequent exposure. Short-term drought memory is regulated by ABA and other phytohormone signaling with transcriptional memory behavior in various genes. High levels of methylated histones are deposited at the drought-tolerance genes. During the recovery interval, the RNA polymerase is stalled to be activated by a pause-breaking factor in the subsequent drought. Drought leads to DNA demethylation near drought-response genes, with genetic control of the process. Progenies of the drought-exposed plants can better adapt to drought owing to the inheritance of particular methylation patterns. However, a prolonged watered recovery interval leads to loss of drought memory, mediated by certain demethylases and chromatin accessibility factors. Small RNAs act as critical regulators of drought memory by altering transcript levels of drought-responsive target genes. Further studies in the future will throw more light on the genetic control of drought memory and the interplay of genetic and epigenetic factors in its inheritance. Plants from extreme environments can give queues to understanding robust memory responses at the ecosystem level.

How do plants remember drought?

The role of commensal bacterial microbiota in the pathogenesis of human malignancies has been a research field of incomparable progress in recent years. Although breast tissue is commonly assumed to be sterile, recent studies suggest that human breast tissue may contain a bacterial microbiota. In this study, we used an immune-competent orthotopic breast cancer mouse model to explore the existence of a unique and independent bacterial microbiota in breast tumors. We observed some similarities in breast cancer microbiota with skin; however, breast tumor microbiota was mainly enriched with Gram-negative bacteria, serving as a primary source of lipopolysaccharide (LPS). In addition, dextran sulfate sodium (DSS) treatment in late-stage tumor lesions increased LPS levels in the breast tissue environment. We also discovered an increased expression of S100A7 and low level of TLR4 in late-stage tumors with or without DSS as compared to early-stage tumor lesions. The treatment of breast cancer cells with LPS increased the expression of S100A7 in breast cancer cells in vitro. Furthermore, S100A7 overexpression downregulated TLR4 and upregulated RAGE expression in breast cancer cells. Analysis of human breast cancer samples also highlighted the inverse correlation between S100A7 and TLR4 expression. Overall, these findings suggest that the commensal microbiota of breast tissue may enhance breast tumor burden through a novel LPS/S100A7/TLR4/RAGE signaling axis. © 2021 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Molecular oncology

Lipopolysaccharide from the commensal microbiota of the breast enhances cancer growth: role of S100A7 and TLR4

We introduce a novel agent based model where each agent carries an effective viral load that captures the instantaneous state of infection of the agent. We simulate the spread of a pandemic and subsequently validate it by using publicly available COVID-19 data. Our simulation tracks the temporal evolution of a virtual city or community of agents in terms of contracting infection, recovering asymptomatically, or getting hospitalized. The virtual community is divided into family groups with 2–6 individuals in each group. Agents interact with other agents in virtual public places like at grocery stores, on public transportation and in offices. We initially seed the virtual community with a very small number of infected individuals and then monitor the disease spread and hospitalization over a period of fifty days, which is a reasonable time-frame for the initial spread of a pandemic. An uninfected or asymptomatic agent is randomly selected from a random family group in each simulation step for visiting a random public space. Subsequently, an uninfected agent contracts infection if the public place is occupied by other infected agents. We have calibrated our simulation rounds according to the size of the population of the virtual community for simulating realistic exposure of agents to a contagion. Our simulation results are consistent with the publicly available hospitalization and ICU patient data from three distinct regions of varying sizes in New York state. Our model can predict the trend in epidemic spread and hospitalization from a set of simple parameters and could be potentially useful in predicting the disease evolution based on available data and observations about public behavior. Our simulations suggest that relaxing the social distancing measures may increase the hospitalization numbers by some 30% or more. © 2021 Elsevier B.V.

Physica A: Statistical Mechanics and its Applications

An agent-based model of spread of a pandemic with validation using COVID-19 data from New York State

Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy to combat the growth of cisplatin-resistant (CR) NSCLC cells. We have shown that treatment with the plant-derived, non-psychotropic small molecular weight molecule, cannabidiol (CBD), significantly induced apoptosis of CR NSCLC cells. In addition, CBD treatment significantly reduced tumor progression and metastasis in a mouse xenograft model and suppressed cancer stem cell properties. Further mechanistic studies demonstrated the ability of CBD to inhibit the growth of CR cell lines by reducing NRF-2 and enhancing the generation of reactive oxygen species (ROS). Moreover, we show that CBD acts through Transient Receptor Potential Vanilloid-2 (TRPV2) to induce apoptosis, where TRPV2 is expressed on human lung adenocarcinoma tumors. High expression of TRPV2 correlates with better overall survival of lung cancer patients. Our findings identify CBD as a novel therapeutic agent targeting TRPV2 to inhibit the growth and metastasis of this aggressive cisplatin-resistant phenotype in NSCLC. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Cancers

Cannabidiol inhibits tumorigenesis in cisplatin-resistant non-small cell lung cancer via TRPV2

Background: Molecular mechanisms underlying inflammation-associated breast tumor growth are poorly studied. S100A7, a pro-inflammatory molecule has been shown to enhance breast cancer growth and metastasis. However, the S100A7-mediated molecular mechanisms in enhancing tumor growth and metastasis are unclear. Methods: Human breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3 (1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effects of S100A7/cPLA2 inhibition on the recruitment of various immune cells. Results: In this study, we found that S100A7 and cPLA2 are highly expressed and correlate with decreased overall survival in breast cancer patients. Further mechanistic studies revealed that S100A7/RAGE signaling promotes the expression of cPLA2 to mediate its oncogenic effects. Pharmacological inhibition of cPLA2 suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models including transgenic and humanized patient-derived xenograft (PDX) mouse models. The attenuation of cPLA2 signaling reduced S100A7-mediated recruitment of immune-suppressive myeloid cells in the tumor microenvironment (TME). Interestingly, we discovered that the S100A7/cPLA2 axis enhances the immunosuppressive microenvironment by increasing prostaglandin E2 (PGE2). Furthermore, CO-Detection by indEXing (CODEX) imaging-based analyses revealed that cPLA2 inhibition increased the infiltration of activated and proliferating CD4+ and CD8+ T cells in the TME. In addition, CD163+ tumor associated-macrophages were positively associated with S100A7 and cPLA2 expression in malignant breast cancer patients. Conclusions: Our study provides new mechanistic insights on the cross-talk between S100A7/cPLA2 in enhancing breast tumor growth and metastasis by generating an immunosuppressive TME that inhibits the infiltration of cytotoxic T cells. Furthermore, our studies indicate that S100A7/cPLA2 could be used as novel prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing aggressive breast cancer. © 2022, The Author(s).