ResearchPad - applied-biological-sciences https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Fibroblast rejuvenation by mechanical reprogramming and redifferentiation]]> https://www.researchpad.co/article/elastic_article_8266 Over the course of the aging process, fibroblasts lose contractility, leading to reduced connective-tissue stiffness. A promising therapeutic avenue for functional rejuvenation of connective tissue is reprogrammed fibroblast replacement, although major hurdles still remain. Toward this, we recently demonstrated that the laterally confined growth of fibroblasts on micropatterned substrates induces stem-cell-like spheroids. In this study, we embedded these partially reprogrammed spheroids in collagen-I matrices of varying densities, mimicking different three-dimensional (3D) tissue constraints. In response to such matrix constraints, these spheroids regained their fibroblastic properties and sprouted to form 3D connective-tissue networks. Interestingly, we found that these differentiated fibroblasts exhibit reduced DNA damage, enhanced cytoskeletal gene expression, and actomyosin contractility. In addition, the rejuvenated fibroblasts show increased matrix protein (fibronectin and laminin) deposition and collagen remodeling compared to the parental fibroblast tissue network. Furthermore, we show that the partially reprogrammed cells have comparatively open chromatin compaction states and may be more poised to redifferentiate into contractile fibroblasts in 3D-collagen matrix. Collectively, our results highlight efficient fibroblast rejuvenation through laterally confined reprogramming, which has important implications in regenerative medicine.

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<![CDATA[DNA origami protection and molecular interfacing through engineered sequence-defined peptoids]]> https://www.researchpad.co/article/N92aa6da2-9e9f-4fc4-94fc-67d2ecbad88b

Significance

DNA nanotechnology provides a structural toolkit for the fabrication of programmable DNA nano-constructs; however, their use in biomedical applications is challenging due the limited structural integrity in complex biological fluids. Here, we report a class of tailorable molecular coatings, peptoids, which can efficiently stabilize three-dimensional wireframed DNA constructs under a variety of biomedically relevant conditions, including magnesium-ion depletion and presence of degrading nuclease. Furthermore, we show that peptoid-coated DNA constructs offer a controllable anticancer drug release and an ability to display functional biomolecules on the DNA surfaces. Our study demonstrates an approach for building multifunctional and environmentally robust DNA-based molecular structures for nanomedicine and biosensing.

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<![CDATA[Pathway-guided analysis identifies Myc-dependent alternative pre-mRNA splicing in aggressive prostate cancers]]> https://www.researchpad.co/article/N5db096ad-d68c-4fe4-a612-07e8bd433378

Significance

Alternative pre-mRNA splicing is a regulated process that greatly diversifies gene products by changing the exons incorporated into mRNA. This process is dysregulated in cancers. Here, we studied exon usage in aggressive prostate cancers and linked exon incorporation decisions to cancer driver genes. Through computational and experimental studies, we found that a strong cancer driver gene, Myc, was linked to exon changes in genes that themselves regulate alternative splicing. These exons often encoded premature stop codons that would decrease gene expression, suggestive of a Myc-driven autoregulatory loop to help control levels of splicing regulatory proteins.

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<![CDATA[Apex structures enhance water drainage on leaves]]> https://www.researchpad.co/article/N45739587-47a2-46cb-8d42-3bf3f8e0c334

Significance

Liquid manipulation is of significance not only for industrial spraying and drainage facilities, but also for the survival of creatures. Plant leaves perform excellently in rainwater drainage and leaf drying at the apex to avoid damage. Here we demonstrate that apex structure enhances water shedding with high dripping frequencies and low retention volumes. Based on the understanding of the tiny apex structure in controlling water delivery at the plant leaf, the evolutionary law of leaf apex shape could be further revealed. The shape-controlled liquid manipulation mechanism would improve the microfluidic and drainage systems.

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<![CDATA[Controlled phage therapy by photothermal ablation of specific bacterial species using gold nanorods targeted by chimeric phages]]> https://www.researchpad.co/article/Nbd395e6f-a8ec-4b59-899c-449781b26b64

Significance

New methods for detecting and killing antibiotic-resistant, Gram-negative bacteria are of prime interest for a wide variety of applications. While phages have long been considered as potential antibacterial agents, many concerns about phage therapy stem from the fact that phages are replicating, evolvable entities whose biology is poorly understood in most cases. These concerns could be addressed by destroying the phage immediately upon use. We accomplish this by conjugating phages to gold nanorods, whose excitation by near-infrared light causes localized heating that essentially cooks nearby bacteria. Thus, the phages deliver gold nanorods to the targeted bacteria, and the nanorods destroy both bacteria and phages simultaneously. This strategy transforms phages from an evolving biological entity into a controlled, drug-like reagent.

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<![CDATA[Bioderivatization as a concept for renewable production of chemicals that are toxic or poorly soluble in the liquid phase]]> https://www.researchpad.co/article/N452ac20b-1773-4718-95a3-7517aea9b60a

Significance

Microorganisms can be rationally engineered to convert CO2 and H2O into chemicals, replacing those made from fossil fuels today. Sometimes such chemicals are poorly soluble in water or negatively affect the growth of the microorganism, resulting in cost-inefficient manufacturing. In nature, this problem is often solved by converting incompatible chemicals into those more compatible with the host and/or environment. Inspired by this, we propose a similar strategy for engineered biotechnology, whereby biochemical conversion inside the microorganism is followed by chemical reversal once outside. The principle was demonstrated with 1-octanol by implementing two different conversion methods in two different species, showing enhanced bioproduction in most cases. The approach may stimulate commercialization of sustainable and renewable production of chemicals.

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<![CDATA[A single combination gene therapy treats multiple age-related diseases]]> https://www.researchpad.co/article/N6bfe986c-49b7-4f1a-8d75-3c52678bcfae

Significance

Human and animal longevity is directly bound to their health span. While previous studies have provided evidence supporting this connection, therapeutic implementation of this knowledge has been limited. Traditionally, diseases are researched and treated individually, which ignores the interconnectedness of age-related conditions, necessitates multiple treatments with unrelated substances, and increases the accumulative risk of side effects. In this study, we address and overcome this deadlock by creating adeno-associated virus (AAV)-based antiaging gene therapies for simultaneous treatment of several age-related diseases. We demonstrate the modular and extensible nature of combination gene therapy by testing therapeutic AAV cocktails that confront multiple diseases in a single treatment. We observed that 1 treatment comprising 2 AAV gene therapies was efficacious against all 4 diseases.

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