Department of Bioscience & Bioengineering

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Pseudomonas aeruginosa generally forms strong biofilm during chronic condition of wound. The whole mechanism of biofilm formation works in tandem with quorum sensing circuit of the organism in order to produce virulence. Here we report the draft genome sequence of two diabetic foot ulcer Pseudomonas aeruginosa isolates (VIT PC 7 and VIT PC 9) displaying homoserine lactone, rhamnolipid producing, biofilm phenotype and antibiotic resistance genes related to carbapenem, aminoglycoside, beta- lactamase and tetracycline resistance. The whole genome sequencing library was prepared according to the Oxford Nanopore's SQK-LSK108 kit protocol on Oxford Nanopore's Minion platform. The 7.1 Mb and 6.3-Mb draft genome sequence with GC content of 65.8% and 66.4% respectively provides insight into their resistance mechanism and virulence factors. © 2020 The Authors

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Data in Brief

Comparative data analsysis of two multi-drug resistant homoserine lactone and rhamnolipid producing Pseudomonas aeruginosa from diabetic foot infected patient

Nanosized carriers engineered from red blood cells (RBCs) provide a means for delivering various cargos, including drugs, biologics, and imaging agents. We have engineered nanosized particles from RBCs, doped with the near-infrared (NIR) fluorochrome, indocyanine green (ICG). An important issue related to clinical translation of RBC-derived nanocarriers, including these NIR nanoparticles, is their stability postfabrication. Freezing may provide a method for long-term storage of these and other RBC-derived nanoparticles. Herein, we have investigated the physical and optical stability of these particles in response to a single freeze-thaw cycle. Nanoparticles were frozen to -20 °C, stored frozen for up to 8 weeks, and then thawed at room temperature. Our results show that the hydrodynamic diameter, zeta potential, optical density, and NIR fluorescence emission of these nanoparticles are retained following the freeze-thaw cycle. The ability of these nanoparticles in NIR fluorescence imaging of ovarian cancer cells, as well as their biodistribution in reticuloendothelial organs of healthy Swiss Webster mice after the freeze-thaw cycle is similar to that for freshly prepared nanoparticles. These results indicate that a single cycle of freezing the RBC-derived nanoparticles to -20 °C followed by thawing at room temperature is an effective method to retain the physical and optical characteristics of the nanoparticles, and their interactions with biological systems without the need for use of cryoprotectants. Copyright © 2020 American Chemical Society.

Langmuir

RBC-Derived Optical Nanoparticles Remain Stable after a Freeze-Thaw Cycle

A field study was conducted to understand the physiological responses, yield and grain quality of an old (HUW234) and a modern (HD3118) wheat cultivar exposed to elevated ozone (O3). The cultivars were grown under ambient O3 (NF) and ambient +20 ppb O3 (NF+) conditions using open-top chambers (OTCs). The comparative study of an old and a modern cultivar showed variable physiological responses under elevated O3 exposure. Elevated O3 in old cultivar caused high reductions in Rubisco activity (Vcmax) and electron transport rate (J) compared to modern cultivar with simultaneous reductions in the rate of photosynthesis and chlorophyll fluorescence. In modern cultivar, high stomatal density and conductance caused higher O3 uptake thereby triggering more damage to the adjacent stomatal cells and photosynthetic pigments coupled with reductions in photosynthetic rate and photosynthetic nitrogen use efficiency (PNUE). Modern cultivar also showed relatively high reduction in grain yield compared to old one under NF + treatment. Furthermore, grain quality traits (such as starch, protein and amino acids) of modern cultivar were better than old cultivar under ambient O3, but showed more deterioration under NF + treatment. Results thus indicated that modern cultivar is relatively more susceptible to O3 and showed more negative impacts on plant performance, yield and quality of grains compared to old cultivar. © 2020 Elsevier Ltd

Environmental Pollution

Responses of an old and a modern Indian wheat cultivar to future O3 level: Physiological, yield and grain quality parameters

Objective: Taenia solium is a neglected tropical disease; larvae of this parasite infect central nervous system i.e. Neurocysticercosis, and adults mature and survive into intestine i.e. Taeniasis. Globally more than 50 million people are at the risk of infection. This is one of the main etiological agents for onset of new early epilepsy in developing countries. However, there is no vaccine available to protect human from its infection. Hence, there is an urgent need for a good vaccine. Methods: We applied immune-informatics approach to design a multi-epitope chimeric vaccine consisting of both B and T-cell epitopes. Results: From the whole transcriptome of Taenia, we identified five suitable peptides present on cell membrane, epitope identification on these peptides were done by using various immunoinformatic software. Physiochemical properties were determined and the tertiary structure of vaccine was predicted, validated and refined, and to increase antigenicity we added linker to them. Best-modeled protein-complex was used for docking study with TLR1-2, TLR4, TLR3 and TLR7 and stability of molecular complex was determined by molecular dynamics simulation. Conclusions: Overall, we attempted to design an efficient subunit chimeric vaccine, which could stimulate humoral and cellular immune responses and could protect against both neurocysticercosis and taeniasis. © 2020, © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Expert Review of Vaccines

Development of multi-epitope chimeric vaccine against Taenia solium by exploring its proteome: an in silico approach

Human immune cell toll-like receptors (TLRs) provide a novel chance for the development of the vaccine adjuvant engaging TLR signaling. A library of peptides was developed and peptides structure was generated through homology modeling and refinement. Further, these peptides were subjected to receptor-ligand interaction study against human immune cell TLRs using Schrödinger-suite software. Here, we identified the most potent ligands for each human immune cell receptor and identified it as a potent adjuvant. This work portrays the ability of binding of different known protein adjuvants with human TLRs 1‐–10. The significance of the study deals with the identification of adjuvant (ligand) for human TLRs individually which assist in the development of the optimal highly immunogenic vaccine. © 2020 Elsevier B.V.

International Journal of Biological Macromolecules

Receptor-ligand based molecular interaction to discover adjuvant for immune cell TLRs to develop next-generation vaccine

Nonlinear normal mode solutions of the β-FPUT chain with fixed boundaries are presented in terms of the Jacobi sn function. Exact solutions for the two particle chain are found for arbitrary linear and nonlinear coupling strengths. Solutions for the N-body chain are found for the case of purely nonlinear couplings. Three distinct solution types are presented: a linear analogue, a chaotic amplitude mapping, and a localized nonlinear mode. The relaxation of perturbed modes are also explored using l1-regularized least squares regression to estimate the free energy functional near the nonlinear normal mode solution. The perturbed modes are observed to decay sigmoidally towards a quasi-equilibrium state and a logarithmic relationship between the perturbation strength and mode lifetime is found. © 2020 Elsevier B.V.

Physica A: Statistical Mechanics and its Applications

Nonlinear normal modes in the β-Fermi-Pasta–Ulam-Tsingou chain

Nanoparticles are promising bioengineering platforms facilitating various consumer product formulations, including packaged food, electrical, biosensor and biomedical tools. The unique surface and physicochemical properties of amorphous nanosilica supports advanced nano-biomolecular applications for various manufacturing, biotechnology, and healthcare industries including cosmetics, packaging, implants, drug delivery systems and cancer diagnostics. The increased technological and economic benefits of amorphous nanosilica, raises concerns regarding their adverse biological effects on humans. The cellular mechanisms underlying amorphous nanosilica internalization, evasion of biological barriers, inadvertent nano-bio interactions and unexpected long term exposure effects must be taken into consideration from the diverse ecosystems and human safety aspects. Recent research studies reveal cytotoxic, inflammatory and immunomodulatory effects of amorphous nanosilica particles. Our review focuses on studies demonstrating hazardous impact of amorphous nanosilica/bio-systems interface on the cellular and biochemical processes. The review further seeks to evaluate amorphous nanosilica-induced cytotoxicity, innate immune responses, inflammation and immune related dysfunctions, and discuss open research questions related to the use of amorphous nanosilica in biomedicine. © 2020 Elsevier B.V.

Toxicology

Amorphous nanosilica induced toxicity, inflammation and innate immune responses: A critical review

The intricate interplay between malignant cells and host cellular and non-cellular components play crucial role in different stages of tumor development, progression, and metastases. Tumor and stromal cells communicate to each other through receptors such as integrins and secretion of signaling molecules like growth factors, cytokines, chemokines and inflammatory mediators. Chemokines mediated signaling pathways have emerged as major mechanisms underlying multifaceted roles played by host cells during tumor progression. In response to tumor stimuli, host cells-derived chemokines further activates signaling cascades that support the ability of tumor cells to invade surrounding basement membrane and extra-cellular matrix. The host-derived chemokines act on endothelial cells to increase their permeability and facilitate tumor cells intravasation and extravasation. The tumor cells-host neutrophils interaction within the vasculature initiates chemokines driven recruitment of inflammatory cells that protects circulatory tumor cells from immune attack. Chemokines secreted by tumor cells and stromal immune and non-immune cells within the tumor microenvironment enter the circulation and are responsible for formation of a “pre-metastatic niche” like a “soil” in distant organs whereby circulating tumor cells “seed’ and colonize, leading to formation of metastatic foci. Given the importance of host derived chemokines in cancer progression and metastases several drugs like Mogamulizumab, Plerixafor, Repertaxin among others are part of ongoing clinical trial which target chemokines and their receptors against cancer pathogenesis. In this review, we focus on recent advances in understanding the complexity of chemokines network in tumor microenvironment, with an emphasis on chemokines secreted from host cells. We especially summarize the role of host-derived chemokines in different stages of metastases, including invasion, dissemination, migration into the vasculature, and seeding into the pre-metastatic niche. We finally provide a brief description of prospective drugs that target chemokines in different clinical trials against cancer. © Copyright © 2020 Hussain, Peng, Cherian, Song, Ahirwar and Ganju.

Frontiers in Immunology

The roles of stroma-derived chemokine in different stages of cancer metastases

Background: Ibrutinib is a Bruton’s tyrosine kinase (BTK) and interleukin-2-inducible kinase (ITK) inhibitor used for treating chronic lymphocytic leukaemia (CLL) and other cancers. Although ibrutinib is known to inhibit the growth of breast cancer cell growth in vitro, its impact on the treatment and metastasis of breast cancer is unclear. Methods: Using an orthotopic mouse breast cancer model, we show that ibrutinib inhibits the progression and metastasis of breast cancer. Results: Ibrutinib inhibited proliferation of cancer cells in vitro, and Ibrutinib-treated mice displayed significantly lower tumour burdens and metastasis compared to controls. Furthermore, the spleens and tumours from Ibrutinib-treated mice contained more mature DCs and lower numbers of myeloid-derived suppressor cells (MDSCs), which promote disease progression and are linked to poor prognosis. We also confirmed that ex vivo treatment of MDSCs with ibrutinib switched their phenotype to mature DCs and significantly enhanced MHCII expression. Further, ibrutinib treatment promoted T cell proliferation and effector functions leading to the induction of antitumour TH1 and CTL immune responses. Conclusions: Ibrutinib inhibits tumour development and metastasis in breast cancer by promoting the development of mature DCs from MDSCs and hence could be a novel therapeutic agent for the treatment of breast cancer. © 2020, The Author(s), under exclusive licence to Cancer Research UK.

British Journal of Cancer

Ibrutinib treatment inhibits breast cancer progression and metastasis by inducing conversion of myeloid-derived suppressor cells to dendritic cells

Centrosomes, the main microtubule organizing centers (MTOCs) of metazoan cells, contain an older “mother” and a younger “daughter” centriole. Stem cells either inherit the mother or daughter-centriole-containing centrosome, providing a possible mechanism for biased delivery of cell fate determinants. However, the mechanisms regulating centrosome asymmetry and biased centrosome segregation are unclear. Using 3D-structured illumination microscopy (3D-SIM) and live-cell imaging, we show in fly neural stem cells (neuroblasts) that the mitotic kinase Polo and its centriolar protein substrate Centrobin (Cnb) accumulate on the daughter centriole during mitosis, thereby generating molecularly distinct mother and daughter centrioles before interphase. Cnb’s asymmetric localization, potentially involving a direct relocalization mechanism, is regulated by Polo-mediated phosphorylation, whereas Polo’s daughter centriole enrichment requires both Wdr62 and Cnb. Based on optogenetic protein mislocalization experiments, we propose that the establishment of centriole asymmetry in mitosis primes biased interphase MTOC activity, necessary for correct spindle orientation. © 2020 Gallaud et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.