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Human enteroids as a tool to study conventional and ultra-high dose rate radiation. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Katarina C Klett,Briana C Martin-Villa,Victoria S Villarreal,Stavros Melemenidis,Vignesh Viswanathan,Rakesh Manjappa,M Ramish Ashraf,Luis Soto,Brianna Lau,Suparna Dutt,Erinn B Rankin,Billy W Loo,Sarah C Heilshorn
Radiation therapy, one of the most effective therapies to treat cancer, is highly toxic to healthy tissue. The delivery of radiation at ultra-high dose rates, FLASH radiation therapy (FLASH), has been shown to maintain therapeutic anti-tumor efficacy while sparing normal tissues compared to conventional dose rate irradiation (CONV). Though promising, these studies have been limited mainly to murine
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Preliminary study to identify CXCR4 inhibitors as potential therapeutic agents for Alzheimer's and Parkinson's diseases. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Rahul Tripathi,Pravir Kumar
Neurodegenerative disorders (NDDs) are known to exhibit genetic overlap and shared pathophysiology. This study aims to find the shared genetic architecture of Alzheimer's disease (AD) and Parkinson's disease (PD), two major age-related progressive neurodegenerative disorders. The gene expression profiles of GSE67333 (containing samples from AD patients) and GSE114517 (containing samples from PD patients)
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Collagen microgel to simulate the adipocyte microenvironment for in vitro research on obesity. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Natalia Moreno-Castellanos,Elías Cuartas-Gómez,Oscar Vargas-Ceballos
Obesity is linked to adipose tissue dysfunction, a dynamic endocrine organ. Two-dimensional cultures present technical hurdles hampering their ability to follow individual or cell groups for metabolic disease research. Three-dimensional type I collagen microgels with embedded adipocytes have not been thoroughly investigated to evaluate adipogenic maintenance as instrument for studying metabolic disorders
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A high-throughput sensory assay for parasitic and free-living nematodes. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Leonardo R Nunn,Terry D Juang,David J Beebe,Nicolas J Wheeler,Mostafa Zamanian
Sensory pathways first elucidated in Caenorhabditis elegans are conserved across free-living and parasitic nematodes, even though each species responds to a diverse array of compounds. Most nematode sensory assays are performed by tallying observations of worm behavior on two-dimensional planes using agarose plates. These assays have been successful in the study of volatile sensation but are poorly
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Continuum interpretation of mechano-adaptation in micropatterned epithelia informed by in vitro experiments. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Bernard L Cook,Patrick W Alford
Epithelial tissues adapt their form and function following mechanical perturbations, or mechano-adapt, and these changes often result in reactive forces that oppose the direction of the applied change. Tissues subjected to ectopic tensions, for example, employ behaviors that lower tension, such as increasing proliferation or actomyosin turnover. This oppositional behavior suggests that the tissue has
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Dynamic modelling predicts lactate and IL-1β as interventional targets in metabolic-inflammation-clock regulatory loop in glioma. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Shalini Sharma,Pruthvi Gowda,Kirti Lathoria,Mithun K Mitra,Ellora Sen
In an attempt to understand the role of dysregulated circadian rhythm in glioma, our recent findings highlighted the existence of a feed-forward loop between tumour metabolite lactate, pro-inflammatory cytokine IL-1β and circadian CLOCK. To further elucidate the implication of this complex interplay, we developed a mathematical model that quantitatively describes this lactate dehydrogenase A (LDHA)-IL-1β-CLOCK/BMAL1
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3D quantitative assessment for nuclear morphology in osteocytic spheroid with optical clearing technique. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Takashi Inagaki,Jeonghyun Kim,Kosei Tomida,Eijiro Maeda,Takeo Matsumoto
In recent years, three-dimensional (3D) cell culture has been attracting attention as a cell culture model that mimics an environment closer to that of a living organism. It is known that there is a close relationship between cell nuclear shape and cellular function, which highlights the importance of cell nucleus shape analysis in the 3D culture. On the other hand, it is difficult to observe the cell
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Altered physical phenotypes of leukemia cells that survive chemotherapy treatment. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Chau Ly,Heather Ogana,Hye Na Kim,Samantha Hurwitz,Eric J Deeds,Yong-Mi Kim,Amy C Rowat
The recurrence of cancer following chemotherapy treatment is a major cause of death across solid and hematologic cancers. In B-cell acute lymphoblastic leukemia (B-ALL), relapse after initial chemotherapy treatment leads to poor patient outcomes. Here we test the hypothesis that chemotherapy-treated versus control B-ALL cells can be characterized based on cellular physical phenotypes. To quantify physical
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Diagnostics of ovarian cancer via metabolite analysis and machine learning. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Jerry Z Yao,Igor F Tsigelny,Santosh Kesari,Valentina L Kouznetsova
Ovarian cancer (OC) is the second most common cancer of the female reproductive system. Due to the asymptomatic nature of early stages of OC and an increasingly poor prognosis in later stages, methods of screening for OC are much desired. Furthermore, screening and diagnosis processes, in order to justify use on asymptomatic patients, must be convenient and non-invasive. Recent developments in machine-learning
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Triple-negative breast cancer cells invade adipocyte/preadipocyte-encapsulating geometrically inverted mammary organoids. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 David R Mertz,Eric Parigoris,Jason Sentosa,Ji-Hoon Lee,Soojung Lee,Celina G Kleer,Gary Luker,Shuichi Takayama
This paper describes the manufacture of geometrically inverted mammary organoids encapsulating primary mammary preadipocytes and adipocytes. Material manipulation in an array of 192 hanging drops induces cells to self-assemble into inside-out organoids where an adipose tissue core is enveloped by a cell-produced basement membrane, indicated by laminin V staining and then a continuous layer of mammary
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The lymphatic endothelium-derived follistatin: activin A axis regulates neutrophil motility in response to Pseudomonas aeruginosa. Integr. Biol. (IF 2.5) Pub Date : 2023-04-11 Patrick H McMinn,Adeel Ahmed,Anna Huttenlocher,David J Beebe,Sheena C Kerr
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
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A novel integrated experimental and computational approach to unravel fibroblast motility in response to chemical gradients in 3D collagen matrices. Integr. Biol. (IF 2.5) Pub Date : 2022-12-30 Nieves Movilla,Inês G Gonçalves,Carlos Borau,Jose Manuel García-Aznar
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
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Mapping of structural arrangement of cells and collective calcium transients: an integrated framework combining live cell imaging using confocal microscopy and UMAP-assisted HDBSCAN-based approach. Integr. Biol. (IF 2.5) Pub Date : 2022-12-30 Suman Gare,Soumita Chel,T K Abhinav,Vaibhav Dhyani,Soumya Jana,Lopamudra Giri
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
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Phylogenetic analysis, computer modeling and catalytic prediction of an Amazonian soil β-glucosidase against a soybean saponin. Integr. Biol. (IF 2.5) Pub Date : 2022-12-30 Andrea I Hernandez,Raíza Dos Santos Azevedo,Adriano V Werhli,Karina Dos Santos Machado,Bruna F Nornberg,Luis F Marins
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
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A kidney proximal tubule model to evaluate effects of basement membrane stiffening on renal tubular epithelial cells. Integr. Biol. (IF 2.5) Pub Date : 2022-12-30 Dan Wang,Snehal Sant,Craig Lawless,Nicholas Ferrell
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
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Simultaneous screening of zebrafish larvae cardiac and respiratory functions: a microfluidic multi-phenotypic approach. Integr. Biol. (IF 2.5) Pub Date : 2022-12-01 Arezoo Khalili,Ellen van Wijngaarden,Georg R Zoidl,Pouya Rezai
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
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Bioengineered and functionalized silk proteins accelerate wound healing in rat and human dermal fibroblasts. Integr. Biol. (IF 2.5) Pub Date : 2022-12-01 Chitra Manoharan,Dyna Susan Thomas,Rasalkar Sandhya Yashwant,Manjunatha Panduranga Mudagal,Suresh Janadri,Gourab Roy,Vijayan Kunjupillai,Rakesh Kumar Mishra,Ravikumar Gopalapillai
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
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In silico analysis of metabolic effects of bipolar disorder on prefrontal cortex identified altered GABA, glutamate-glutamine cycle, energy metabolism and amino acid synthesis pathways. Integr. Biol. (IF 2.5) Pub Date : 2022-10-14 Hamza Umut Karakurt,Pınar Pir
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
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A hybrid model to study how late long-term potentiation is affected by faulty molecules in an intraneuronal signaling network regulating transcription factor CREB. Integr. Biol. (IF 2.5) Pub Date : 2022-08-03 Ali Emadi,Mustafa Ozen,Ali Abdi
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
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Comparative biological network analysis for differentially expressed proteins as a function of bacilysin biosynthesis in Bacillus subtilis. Integr. Biol. (IF 2.5) Pub Date : 2022-08-03 Meltem Kutnu,Elif Tekin İşlerel,Nurcan Tunçbağ,Gülay Özcengiz
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
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Early biomolecular changes in brain microvascular endothelial cells under Epstein-Barr virus influence: a Raman microspectroscopic investigation. Integr. Biol. (IF 2.5) Pub Date : 2022-07-11 Omkar Indari,Deeksha Tiwari,Manushree Tanwar,Rajesh Kumar,Hem Chandra Jha
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
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Biomarkers of mitochondrial origin: a futuristic cancer diagnostic. Integr. Biol. (IF 2.5) Pub Date : 2022-07-11 Sukanya Gayan,Gargee Joshi,Tuli Dey
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
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In silico target-based strain engineering of Saccharomyces cerevisiae for terpene precursor improvement. Integr. Biol. (IF 2.5) Pub Date : 2022-04-08 Kalaivani Paramasivan,Aneesha Abdulla,Nabarupa Gupta,Sarma Mutturi
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
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Contracting scars from fibrin drops Integr. Biol. (IF 2.5) Pub Date : 2022-02-19 Robinson S, Parigoris E, Chang J, et al.
AbstractThis 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
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Phosphatases are predicted to govern prolactin-mediated JAK–STAT signaling in pancreatic beta cells Integr. Biol. (IF 2.5) Pub Date : 2022-02-01 Ariella D Simoni,Holly A Huber,Senta K Georgia,Stacey D Finley
Abstract 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)
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Nanofiber curvature with Rho GTPase activity increases mouse embryonic fibroblast random migration velocity Integr. Biol. (IF 2.5) Pub Date : 2022-01-12 Bowers D, Brown J.
AbstractMechanotransduction arises from information encoded in the shape of materials such as curvature. It induces activation of small GTPase signaling affecting cell phenotypes including differentiation. We carried out a set of preliminary experiments to test the hypothesis that curvature (1/radius) would also affect cell motility due to signal pathway crosstalk. High molecular weight poly (methyl
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Evolution and emergence: higher order information structure in protein interactomes across the tree of life Integr. Biol. (IF 2.5) Pub Date : 2021-12-22 Klein B, Hoel E, Swain A, et al.
AbstractThe internal workings of biological systems are notoriously difficult to understand. Due to the prevalence of noise and degeneracy in evolved systems, in many cases the workings of everything from gene regulatory networks to protein–protein interactome networks remain black boxes. One consequence of this black-box nature is that it is unclear at which scale to analyze biological systems to
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From random to predictive: a context-specific interaction framework improves selection of drug protein–protein interactions for unknown drug pathways Integr. Biol. (IF 2.5) Pub Date : 2022-01-01 Jennifer L Wilson,Alessio Gravina,Kevin Grimes
Abstract 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
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Immune cell mediated cabozantinib resistance for patients with renal cell carcinoma. Integr. Biol. (IF 2.5) Pub Date : 2021-12-30 Keon Young Park,Hunter O Hefti,Peng Liu,Karina M Lugo-Cintrón,Sheena C Kerr,David J Beebe
Renal cell carcinoma (RCC) is the third most common genitourinary cancer in the USA. Despite recent advances in the treatment for advanced and metastatic clear cell RCC (ccRCC), the 5-year relative survival rate for the distant disease remains at 12%. Cabozantinib, a tyrosine kinase inhibitor (TKI), which is one of the first-line therapies approved to treat advanced ccRCC as a single agent, is now
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Pervasive cytoquakes in the actomyosin cortex across cell types and substrate stiffness. Integr. Biol. (IF 2.5) Pub Date : 2021-12-15 Yu Shi,Shankar Sivarajan,Katherine M Xiang,Geran M Kostecki,Leslie Tung,John C Crocker,Daniel H Reich
The actomyosin cytoskeleton enables cells to resist deformation, crawl, change their shape and sense their surroundings. Despite decades of study, how its molecular constituents can assemble together to form a network with the observed mechanics of cells remains poorly understood. Recently, it has been shown that the actomyosin cortex of quiescent cells can undergo frequent, abrupt reconfigurations
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Translatable pathways classification (TransPath-C) for inferring processes germane to human biology from animal studies data: example application in neurobiology. Integr. Biol. (IF 2.5) Pub Date : 2021-12-15 Molly J Carroll,Natàlia Garcia-Reyero,Edward J Perkins,Douglas A Lauffenburger
How to translate insights gained from studies in one organismal species for what is most likely to be germane in another species, such as from mice to humans, is a ubiquitous challenge in basic biology as well as biomedicine. This is an especially difficult problem when there are few molecular features that are obviously important in both species for a given phenotype of interest. Neuropathologies
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A quantitative view of strategies to engineer cell-selective ligand binding Integr. Biol. (IF 2.5) Pub Date : 2021-11-01 Zhixin Cyrillus Tan,Brian T Orcutt-Jahns,Aaron S Meyer
Abstract A critical property of many therapies is their selective binding to target populations. Exceptional specificity can arise from high-affinity binding to surface targets expressed exclusively on target cell types. In many cases, however, therapeutic targets are only expressed at subtly different levels relative to off-target cells. More complex binding strategies have been developed to overcome
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Creation of a synthesis-friendly inflammation-inducible promoter suitable for cell therapy Integr. Biol. (IF 2.5) Pub Date : 2021-10-08 Jadav A, Truong K.
AbstractThe development of ‘smart’ cell-based therapeutics requires cells that first recognize conditions consistent with disease (e.g. inflammation) and then subsequently release therapeutic proteins, thereby reducing potential toxicity from otherwise continuous expression. Promoters containing NF-κB response elements are often used as reporters of inflammation; however, endogenous promoters have
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Corrigendum to: A novel two-layer-integrated microfluidic device for high-throughput yeast proteomic dynamics analysis at the single-cell level Integr. Biol. (IF 2.5) Pub Date : 2021-10-01 Kaiyue Chen,Nan Rong,Shujing Wang,Chunxiong Luo
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Spatiotemporal model of cellular mechanotransduction via Rho and YAP Integr. Biol. (IF 2.5) Pub Date : 2021-07-17 Javor K Novev, Mathias L Heltberg, Mogens H Jensen, Amin Doostmohammadi
How cells sense and respond to mechanical stimuli remains an open question. Recent advances have identified the translocation of Yes-associated protein (YAP) between nucleus and cytoplasm as a central mechanism for sensing mechanical forces and regulating mechanotransduction. We formulate a spatiotemporal model of the mechanotransduction signalling pathway that includes coupling of YAP with the cell
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Engineering and standardization of posttranscriptional biocircuitry in Saccharomyces cerevisiae Integr. Biol. (IF 2.5) Pub Date : 2021-07-16 John McCarthy
This short review considers to what extent posttranscriptional steps of gene expression can provide the basis for novel control mechanisms and procedures in synthetic biology and biotechnology. The term biocircuitry is used here to refer to functionally connected components comprising DNA, RNA or proteins. The review begins with an overview of the diversity of devices being developed and then considers
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Machine learning-assisted imaging analysis of a human epiblast model Integr. Biol. (IF 2.5) Pub Date : 2021-07-30 Resto Irizarry A, Esfahani S, Zheng Y, et al.
AbstractThe human embryo is a complex structure that emerges and develops as a result of cell-level decisions guided by both intrinsic genetic programs and cell–cell interactions. Given limited accessibility and associated ethical constraints of human embryonic tissue samples, researchers have turned to the use of human stem cells to generate embryo models to study specific embryogenic developmental
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Bioengineered 3D electrospun nanofibrous scaffold with human liver cells to study alcoholic liver disease in vitro Integr. Biol. (IF 2.5) Pub Date : 2021-06-28 Das P, DiVito M, Wertheim J, et al.
AbstractAlcohol injury induces hepatic fibrosis which gradually progresses to cirrhosis, sometimes may lead to liver cancer. Animal models are less efficient in mimicking responses of human liver cells, whereas in vitro models discussed so far are majorly based on rodent cells. In this work, a coculture of primary human hepatocytes (PHHs) with LX-2 cells was established on the unmodified (C:F_0:0)
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A time-resolved experimental–mathematical model for predicting the response of glioma cells to single-dose radiation therapy Integr. Biol. (IF 2.5) Pub Date : 2021-06-01 Junyan Liu, David A Hormuth, Tessa Davis, Jianchen Yang, Matthew T McKenna, Angela M Jarrett, Heiko Enderling, Amy Brock, Thomas E Yankeelov
To develop and validate a mechanism-based, mathematical model that characterizes 9L and C6 glioma cells’ temporal response to single-dose radiation therapy in vitro by explicitly incorporating time-dependent biological interactions with radiation.
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Cell surface integrin α5ß1 clustering negatively regulates receptor tyrosine kinase signaling in colorectal cancer cells via glycogen synthase kinase 3 Integr. Biol. (IF 2.5) Pub Date : 2021-05-26 Starchenko A, Graves-Deal R, Brubaker D, et al.
AbstractAs a key process within the tissue microenvironment, integrin signaling can influence cell functional responses to growth factor stimuli. We show here that clustering of integrin α5ß1 at the plasma membrane of colorectal cancer-derived epithelial cells modulates their ability to respond to stimulation by receptor tyrosine kinase (RTK)-activating growth factors EGF, NRG and HGF, through GSK3-mediated
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Hyperglycemia minimally alters primary self-renewing human colonic epithelial cells while TNFα-promotes severe intestinal epithelial dysfunction Integr. Biol. (IF 2.5) Pub Date : 2021-05-15 Johanna S Dutton, Samuel S Hinman, Raehyun Kim, Peter J Attayek, Mallory Maurer, Christopher S Sims, Nancy L Allbritton
Hyperglycemia is thought to increase production of inflammatory cytokines and permeability of the large intestine. Resulting intestinal inflammation is then often characterized by excess secretion of tumor necrosis factor alpha (TNFα). Thus, hyperglycemia in hospitalized patients suffering from severe trauma or disease is frequently accompanied by TNFα secretion, and the combined impact of these insults
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Insights into therapeutic targets and biomarkers using integrated multi-‘omics’ approaches for dilated and ischemic cardiomyopathies Integr. Biol. (IF 2.5) Pub Date : 2021-05-10 Austė Kanapeckaitė, Neringa Burokienė
At present, heart failure (HF) treatment only targets the symptoms based on the left ventricle dysfunction severity; however, the lack of systemic ‘omics’ studies and available biological data to uncover the heterogeneous underlying mechanisms signifies the need to shift the analytical paradigm towards network-centric and data mining approaches. This study, for the first time, aimed to investigate
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Mechanistic dissection of spatial organization in NF-κB signaling pathways by hybrid simulations Integr. Biol. (IF 2.5) Pub Date : 2021-04-24 Yinghao Wu, Kalyani Dhusia, Zhaoqian Su
The nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is one of the most important transcription factors involved in the regulation of inflammatory signaling pathways. Inappropriate activation of these pathways has been linked to autoimmunity and cancers. Emerging experimental evidences have been showing the existence of elaborate spatial organizations for various molecular components
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Microbial-based magnetic nanoparticles production: a mini-review Integr. Biol. (IF 2.5) Pub Date : 2021-04-07 Chmykhalo V, Belanova A, Belousova M, et al.
AbstractThe ever-increasing biomedical application of magnetic nanoparticles (MNPs) implies increasing demand in their scalable and high-throughput production, with finely tuned and well-controlled characteristics. One of the options to meet the demand is microbial production by nanoparticles-synthesizing bacteria. This approach has several benefits over the standard chemical synthesis methods, including
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A reconfigurable microscale assay enables insights into cancer-associated fibroblast modulation of immune cell recruitment Integr. Biol. (IF 2.5) Pub Date : 2021-04-05 Yu J, Piazza A, Sparks S, et al.
AbstractInnate immune cell infiltration into neoplastic tissue is the first line of defense against cancer and can play a deterministic role in tumor progression. Here, we describe a series of assays, using a reconfigurable microscale assay platform (i.e. Stacks), which allows the study of immune cell infiltration in vitro with spatiotemporal manipulations. We assembled Stacks assays to investigate
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Interactivity of biochemical and physical stimuli during epigenetic conditioning and cardiomyocytic differentiation of stem and progenitor cells derived from adult hearts Integr. Biol. (IF 2.5) Pub Date : 2021-03-11 Zeng W, Doran P.
AbstractMixed populations of cardiosphere-derived stem and progenitor cells containing proliferative and cardiomyogenically committed cells were obtained from adult rat hearts. The cells were cultured in either static 2D monolayers or dynamic 3D scaffold systems with fluid flow. Cardiomyocyte lineage commitment in terms of GATA4 and Nkx2.5 expression was significantly enhanced in the dynamic 3D cultures
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Oxygenation as a driving factor in epithelial differentiation at the air–liquid interface Integr. Biol. (IF 2.5) Pub Date : 2021-03-03 Kouthouridis S, Goepp J, Martini C, et al.
AbstractCulture at the air–liquid interface is broadly accepted as necessary for differentiation of cultured epithelial cells towards an in vivo-like phenotype. However, air–liquid interface cultures are expensive, laborious and challenging to scale for increased throughput applications. Deconstructing the microenvironmental parameters that drive these differentiation processes could circumvent these
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Patterns of virus growth across the diversity of life Integr. Biol. (IF 2.5) Pub Date : 2021-02-22 Jin T, Yin J.
AbstractAlthough viruses in their natural habitats add up to less than 10% of the biomass, they contribute more than 90% of the genome sequences [1]. These viral sequences or ‘viromes’ encode viruses that populate the Earth’s oceans [2, 3] and terrestrial environments [4, 5], where their infections impact life across diverse ecological niches and scales [6, 7], including humans [8–10]. Most viruses
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Pericyte migration and proliferation are tightly synchronized to endothelial cell sprouting dynamics Integr. Biol. (IF 2.5) Pub Date : 2021-01-30 Laura Beth Payne, Jordan Darden, Ariana D Suarez-Martinez, Huaning Zhao, Alissa Hendricks, Caitlin Hartland, Diana Chong, Erich J Kushner, Walter L Murfee, John C Chappell
Pericytes are critical for microvascular stability and maintenance, among other important physiological functions, yet their involvement in vessel formation processes remains poorly understood. To gain insight into pericyte behaviors during vascular remodeling, we developed two complementary tissue explant models utilizing ‘double reporter’ animals with fluorescently-labeled pericytes and endothelial
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Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor Integr. Biol. (IF 2.5) Pub Date : 2021-01-27 Emann M Rabie, Sherry X Zhang, Andreas P Kourouklis, A Nihan Kilinc, Allison K Simi, Derek C Radisky, Joe Tien, Celeste M Nelson
Metastasis, the leading cause of mortality in cancer patients, depends upon the ability of cancer cells to invade into the extracellular matrix that surrounds the primary tumor and to escape into the vasculature. To investigate the features of the microenvironment that regulate invasion and escape, we generated solid microtumors of MDA-MB-231 human breast carcinoma cells within gels of type I collagen
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Growth of tumor emboli within a vessel model reveals dependence on the magnitude of mechanical constraint Integr. Biol. (IF 2.5) Pub Date : 2021-01-14 Jonathan Kulwatno, Jamie Gearhart, Xiangyu Gong, Nora Herzog, Matthew Getzin, Mihaela Skobe, Kristen L Mills
Tumor emboli—aggregates of tumor cells within vessels—pose a clinical challenge as they are associated with increased metastasis and tumor recurrence. When growing within a vessel, tumor emboli are subject to a unique mechanical constraint provided by the tubular geometry of the vessel. Current models of tumor emboli use unconstrained multicellular tumor spheroids, which neglect this mechanical interplay
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Novel in vitro microfluidic platform for osteocyte mechanotransduction studies Integr. Biol. (IF 2.5) Pub Date : 2021-01-08 Xu L, Song X, Carroll G, et al.
AbstractOsteocytes are the major mechanosensing cells in bone remodeling. Current in vitro bone mechanotransduction research use macroscale devices such as flow chambers; however, in vitro microfluidic devices provide an optimal tool to better understand this biological process with its flexible design, physiologically relevant dimensions and high-throughput capabilities. This project aims to design
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Tumor-macrophage crosstalk: how to listen Integr. Biol. (IF 2.5) Pub Date : 2020-11-19 Dey T.
AbstractThe tumor microenvironment contains many cellular components influencing tumor behaviors, such as metastasis, angiogenesis and chemo-resistance. Tumor-associated macrophages (TAMs) are one of such components that can also manipulate the overall prognosis and patient survival. Analysis of tumor-macrophage crosstalk is crucial as tumor cells can polarize circulatory monocytes into TAMs. Such
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Endothelial cell apicobasal polarity coordinates distinct responses to luminally versus abluminally delivered TNF-α in a microvascular mimetic Integr. Biol. (IF 2.5) Pub Date : 2020-11-09 Salminen A, Tithof J, Izhiman Y, et al.
AbstractEndothelial cells (ECs) are an active component of the immune system and interact directly with inflammatory cytokines. While ECs are known to be polarized cells, the potential role of apicobasal polarity in response to inflammatory mediators has been scarcely studied. Acute inflammation is vital in maintaining healthy tissue in response to infection; however, chronic inflammation can lead
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A bioengineered organotypic prostate model for the study of tumor microenvironment-induced immune cell activation Integr. Biol. (IF 2.5) Pub Date : 2020-10-09 Kerr S, Morgan M, Gillette A, et al.
AbstractThe prostate tumor microenvironment (TME) is strongly immunosuppressive; it is largely driven by alteration in cell phenotypes (i.e. tumor-associated macrophages and exhausted cytotoxic T cells) that result in pro-tumorigenic conditions and tumor growth. A greater understanding into how these altered immune cell phenotypes are developed and could potentially be reversed would provide important
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A novel two-layer-integrated microfluidic device for high-throughput yeast proteomic dynamics analysis at the single-cell level Integr. Biol. (IF 2.5) Pub Date : 2020-09-29 Kaiyue Chen, Nan Rong, Shujing Wang, Chunxiong Luo
Current microfluidic methods for studying multicell strains (e.g., m-types) with multienvironments (e.g., n-types) require large numbers of inlets/outlets (m*n), a complicated procedure or expensive machinery. Here, we developed a novel two-layer-integrated method to combine different PDMS microchannel layers with different functions into one chip by a PDMS through-hole array, which improved the design
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Functional analysis of BRCA1 RING domain variants: computationally derived structural data can improve upon experimental features for training predictive models Integr. Biol. (IF 2.5) Pub Date : 2020-09-28 Majid Masso
Advancements in the interpretation of variants of unknown significance are critical for improving clinical outcomes. In a recent study, massive parallel assays were used to experimentally quantify the effects of missense substitutions in the RING domain of BRCA1 on E3 ubiquitin ligase activity as well as BARD1 RING domain binding. These attributes were subsequently used for training a predictive model
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Tumor-on-a-chip platform to interrogate the role of macrophages in tumor progression. Integr. Biol. (IF 2.5) Pub Date : 2020-09-15 Ye Bi,Venktesh S Shirure,Ruiyang Liu,Cassandra Cunningham,Li Ding,J Mark Meacham,S Peter Goedegebuure,Steven C George,Ryan C Fields
Tumor-infiltrating leukocytes, in particular macrophages, play an important role in tumor behavior and clinical outcome. The spectrum of macrophage subtypes ranges from antitumor ‘M1’-type to protumor ‘M2’-type macrophages. Tumor-associated macrophages (TAMs) typically display phenotypic features of both M1 and M2, and the population distribution is thought to be dynamic and evolves as the tumor progresses
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Mechanical stretch sustains myofibroblast phenotype and function in microtissues through latent TGF-β1 activation. Integr. Biol. (IF 2.5) Pub Date : 2020-09-02 Matthew Walker,Michel Godin,Andrew E Pelling
Developing methods to study tissue mechanics and myofibroblast activation may lead to new targets for therapeutic treatments that are urgently needed for fibrotic disease. Microtissue arrays are a promising approach to conduct relatively high-throughput research into fibrosis as they recapitulate key biomechanical aspects of the disease through a relevant 3D extracellular environment. In early work
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Multi-phenotypic and bi-directional behavioral screening of zebrafish larvae. Integr. Biol. (IF 2.5) Pub Date : 2020-09-02 Arezoo Khalili,Ellen van Wijngaarden,Georg R Zoidl,Pouya Rezai
Multi-phenotypic screening of zebrafish larvae, such as monitoring the heart and tail activities, is important in biological assays. Microfluidic devices have been developed for zebrafish phenotypic assays, but simultaneous lateral–dorsal screening of the same larva in a single chip is yet to be achieved. We present a multi-phenotypic microfluidic device for monitoring of tail movement and heart rate