Integrative Biology : Quantitative Biosciences From Nano to Macro

The lymphatic system plays an active role during infection, however the role of lymphatic-neutrophil interactions in host-defense responses is not well understood. During infection with pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus and Yersinia pestis, neutrophils traffic from sites of infection through the lymphatic vasculature, to draining lymph nodes to interact with resident lymphocytes. This process is poorly understood, in part, due to the lack of in vitro models of the lymphatic system...

Fibroblasts play an essential role in tissue repair and regeneration as they migrate to wounded areas to secrete and remodel the extracellular matrix. Fibroblasts recognize chemical substances such as growth factors, which enhance their motility towards the wounded tissues through chemotaxis. Although several studies have characterized single-cell fibroblast motility before, the migration patterns of fibroblasts in response to external factors have not been fully explored in 3D environments. We present a study that combines experimental and computational efforts to characterize the effect of chemical stimuli on the invasion of 3D collagen matrices by fibroblasts...

Saponins are amphipathic glycosides with detergent properties present in vegetables. These compounds, when ingested, can cause difficulties in absorbing nutrients from food and even induce inflammatory processes in the intestine. There is already some evidence that saponins can be degraded by β-glucosidases of the GH3 family. In the present study, we evaluated, through computational tools, the possibility of a β-glucosidase (AMBGL17) obtained from a metagenomic analysis of the Amazonian soil, to catalytically interact with a saponin present in soybean...

Live cell calcium (Ca2+) imaging is one of the important tools to record cellular activity during in vitro and in vivo preclinical studies. Specially, high-resolution microscopy can provide valuable dynamic information at the single cell level. One of the major challenges in the implementation of such imaging schemes is to extract quantitative information in the presence of significant heterogeneity in Ca2+ responses attained due to variation in structural arrangement and drug distribution. To fill this gap, we propose time-lapse imaging using spinning disk confocal microscopy and machine learning-enabled framework for automated grouping of Ca2+ spiking patterns...

The kidney tubule consists of a single layer of epithelial cells supported by the tubular basement membrane (TBM), a thin layer of specialized extracellular matrix (ECM). The mechanical properties of the ECM are important for regulating a wide range of cell functions including proliferation, differentiation and cell survival. Increased ECM stiffness plays a role in promoting multiple pathological conditions including cancer, fibrosis and heart disease. How changes in TBM mechanics regulate tubular epithelial cell behavior is not fully understood...

Multi-phenotypic screening of multiple zebrafish larvae plays an important role in enhancing the quality and speed of biological assays. Many microfluidic platforms have been presented for zebrafish phenotypic assays, but multi-organ screening of multiple larvae, from different needed orientations, in a single device that can enable rapid and large-sample testing is yet to be achieved. Here, we propose a multi-phenotypic quadruple-fish microfluidic chip for simultaneous monitoring of heart activity and fin movement of 5-7-day postfertilization zebrafish larvae trapped in the chip...

Wound healing is an intrinsic process directed towards the restoration of damaged or lost tissue. The development of a dressing material having the ability to control the multiple aspects of the wound environment would be an ideal strategy to improve wound healing. Though natural silk proteins, fibroin, and sericin have demonstrated tissue regenerative properties, the efficacy of bioengineered silk proteins on wound healing is seldom assessed. Furthermore, silk proteins sans contaminants, having low molecular masses, and combining with other bioactive factors can hasten the wound healing process...

During chemotherapy, structural and mechanical changes in malignant cells have been observed in several cancers, including leukaemia and pancreatic and prostate cancer. Such cellular changes may act as physical biomarkers for chemoresistance and cancer recurrence. This study aimed to determine how exposure to paclitaxel affects the intracellular stiffness of human oesophageal cancer of South African origin in vitro. A human oesophageal squamous cell carcinoma cell line WHCO1 was cultured on glass substrates (2D) and in collagen gels (3D) and exposed to paclitaxel for up to 48 h...

Bipolar disorder (BP) is a lifelong psychiatric condition, which often disrupts the daily life of the patients. It is characterized by unstable and periodic mood changes, which cause patients to display unusual shifts in mood, energy, activity levels, concentration and the ability to carry out day-to-day tasks. BP is a major psychiatric condition, and it is still undertreated. The causes and neural mechanisms of bipolar disorder are unclear, and diagnosis is still mostly based on psychiatric examination, furthermore the unstable character of the disorder makes diagnosis challenging...

The Gram-positive bacterium Bacillus subtilis produces a diverse range of secondary metabolites with different structures and activities. Among them, bacilysin is an enzymatically synthesized dipeptide that consists of L-alanine and L-anticapsin. Previous research by our group has suggested bacilysin's role as a pleiotropic molecule in its producer, B. subtilis PY79. However, the nature of protein interactions in the absence of bacilysin has not been defined. In the present work, we constructed a protein-protein interaction subnetwork by using Omics Integrator based on our recent comparative proteomics data obtained from a bacilysin-silenced strain, OGU1...

Systems biology analysis of intracellular signaling networks has tremendously expanded our understanding of normal and diseased cell behaviors and has revealed paths to finding proper therapeutic molecular targets. When it comes to neurons in the human brain, analysis of intraneuronal signaling networks provides invaluable information on learning, memory and cognition-related disorders, as well as potential therapeutic targets. However, neurons in the human brain form a highly complex neural network that, among its many roles, is also responsible for learning, memory formation and cognition...

The brain microvascular endothelial cells (ECs) play an important role in protecting the brain from hazardous pathogens. However, some viral pathogens can smartly modulate the endothelial pathways to gain entry inside the brain. Further, these viruses can cause endothelial dysfunction which could develop serious neurological ailments. Epstein-Barr virus (EBV), an oncogenic virus, has also been linked to various neurological disorders. The virus primarily infects epithelial and B cells, however, it also has a tendency to infect ECs and cause endothelial activation...

Cancer is a highly fatal disease without effective early-stage diagnosis and proper treatment. Along with the oncoproteins and oncometabolites, several organelles from cancerous cells are also emerging as potential biomarkers. Mitochondria isolated from cancer cells are one such biomarker candidates. Cancerous mitochondria exhibit different profiles compared with normal ones in morphology, genomic, transcriptomic, proteomic and metabolic landscape. Here, the possibilities of exploring such characteristics as potential biomarkers through single-cell omics and Artificial Intelligence (AI) are discussed...

Macrophages are white blood cells that play disparate roles in homeostasis and immune responses. They can reprogram their phenotypes to pro-inflammatory (M1) or anti-inflammatory (M2) states in response to their environment. About 8-15% of the macrophage transcriptome has circadian oscillations, including genes closely related to their functioning. As circadian rhythms are associated with cellular phenotypes, we hypothesized that polarization of macrophages to opposing subtypes might differently affect their circadian rhythms...

Heterogeneity among cancer cells and in the tumor microenvironment (TME) is thought to be a significant contributor to the heterogeneity of clinical therapy response observed between patients and can evolve over time. A primary example of this is multiple myeloma (MM), a generally incurable cancer where such heterogeneity contributes to the persistent evolution of drug resistance. However, there is a paucity of functional assays for studying this heterogeneity in patient samples or for assessing the influence of the patient TME on therapy response...

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Systems-based metabolic engineering enables cells to enhance product formation by predicting gene knockout and overexpression targets using modeling tools. FOCuS, a novel metaheuristic tool, was used to predict flux improvement targets in terpenoid pathway using the genome-scale model of Saccharomyces cerevisiae, iMM904. Some of the key knockout target predicted includes LYS1, GAP1, AAT1, AAT2, TH17, KGD-m, MET14, PDC1 and ACO1. It was also observed that the knockout reactions belonged either to fatty acid biosynthesis, amino acid synthesis pathways or nucleotide biosynthesis pathways...

Patients with diabetes are unable to produce a sufficient amount of insulin to properly regulate their blood glucose levels. One potential method of treating diabetes is to increase the number of insulin-secreting beta cells in the pancreas to enhance insulin secretion. It is known that during pregnancy, pancreatic beta cells proliferate in response to the pregnancy hormone, prolactin (PRL). Leveraging this proliferative response to PRL may be a strategy to restore endogenous insulin production for patients with diabetes...

With high drug attrition, protein-protein interaction (PPI) network models are attractive as efficient methods for predicting drug outcomes by analyzing proteins downstream of drug targets. Unfortunately, these methods tend to overpredict associations and they have low precision and prediction performance; performance is often no better than random (AUROC ~0.5). Typically, PPI models identify ranked phenotypes associated with downstream proteins, yet methods differ in prioritization of downstream proteins. Most methods apply global approaches for assessing all phenotypes...

This paper describes a microscale fibroplasia and contraction model that is based on fibrin-embedded lung fibroblasts and provides a convenient visual readout of fibrosis. Cell-laden fibrin microgel drops are formed by aqueous two-phase microprinting. The cells deposit extracellular matrix (ECM) molecules such as collagen while fibrin is gradually degraded. Ultimately, the cells contract the collagen-rich matrix to form a compact cell-ECM spheroid. The size of the spheroid provides the visual readout of the extent of fibroplasia...