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The molecular and phenotypic irreversibility of mammalian cell differentiation was a fundamental principle of developmental biology at least until the 1980s, despite numerous reports dating back to the 1950s of the induction of pluripotency in amphibian cells by nuclear transfer (NT). Landmark reports in the 1980s and 1990s in sheep progressively challenged this dogmatic assumption; firstly, embryonic development of reconstructed embryos comprising whole (donor) blastomeres fused to enucleated oocytes, and famously, the cloning of Dolly from a terminally differentiated cell. Thus, the intrinsic ability of oocyte-derived factors to reverse the differentiated phenotype was confirmed. The concomitant elucidation of methods for human embryonic stem cell isolation and cultivation presented opportunities for therapeutic cell replacement strategies, particularly through NT of patient nuclei to enucleated oocytes for subsequent isolation of patient-specific (autologous), pluripotent cells from the resulting blastocysts. Associated logistical limitations of working with human oocytes, in addition to ethical and moral objections prompted exploration of alternative approaches to generate autologous stem cells for therapy, utilizing the full repertoire of factors characteristic of pluripotency, primarily through cell fusion and use of pluripotent cell extracts. Stunningly, in 2006, Japanese scientists described somatic cell reprogramming through delivery of four key factors (identified through a deductive approach from 24 candidate genes). Although less efficient than previous approaches, much of current stem cell research adopts this focused approach to cell reprogramming and (autologous) cell therapy. This chapter is a quasi-historical commentary of the various aforementioned approaches for the induction of pluripotency in lineage-committed cells, and introduces transcriptional and epigenetic changes occurring during reprogramming.
Assuntos
Blastocisto/citologia , Reprogramação Celular , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Células-Tronco Pluripotentes Induzidas/citologia , Anfíbios , Animais , Blastocisto/metabolismo , Técnicas de Cultura de Células , Diferenciação Celular/genética , Fusão Celular , Clonagem de Organismos/história , Desenvolvimento Embrionário , História do Século XX , História do Século XXI , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Técnicas de Transferência Nuclear/história , Oócitos/citologia , Oócitos/metabolismo , Ovinos , Transcrição GênicaRESUMO
Solar cells based on polycrystalline Cu(In,Ga)Se(2) absorber layers have yielded the highest conversion efficiency among all thin-film technologies, and the use of flexible polymer films as substrates offers several advantages in lowering manufacturing costs. However, given that conversion efficiency is crucial for cost-competitiveness, it is necessary to develop devices on flexible substrates that perform as well as those obtained on rigid substrates. Such comparable performance has not previously been achieved, primarily because polymer films require much lower substrate temperatures during absorber deposition, generally resulting in much lower efficiencies. Here we identify a strong composition gradient in the absorber layer as the main reason for inferior performance and show that, by adjusting it appropriately, very high efficiencies can be obtained. This implies that future manufacturing of highly efficient flexible solar cells could lower the cost of solar electricity and thus become a significant branch of the photovoltaic industry.
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Induced pluripotent stem cell (iPSC) technology is an emerging technique to reprogram somatic cells into iPSCs that have revolutionary benefits in the fields of drug discovery, cellular therapy, and personalized medicine. However, these applications are just the tip of an iceberg. Recently, iPSC technology has been shown to be useful in not only conserving the endangered species, but also the revival of extinct species. With increasing consumer reliance on animal products, combined with an ever-growing population, there is a necessity to develop alternative approaches to conventional farming practices. One such approach involves the development of domestic farm animal iPSCs. This approach provides several benefits in the form of reduced animal death, pasture degradation, water consumption, and greenhouse gas emissions. Hence, it is essentially an environmentally-friendly alternative to conventional farming. Additionally, this approach ensures decreased zoonotic outbreaks and a constant food supply. Here, we discuss the iPSC technology in the form of a "Frozen Ark", along with its potential impact on spreading awareness of factory farming, foodborne disease, and the ecological footprint of the meat industry.
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Fiber optic sensors (FOSs) based on the lossy mode resonance (LMR) technique have gained substantial attention from the scientific community. The LMR technique displays several important features over the conventional surface plasmon resonance (SPR) phenomenon, for planning extremely sensitive FOSs. Unlike SPR, which mainly utilizes the thin film of metals, a wide range of materials such as conducting metal oxides and polymers support LMR. The past several years have witnessed a remarkable development in the field of LMR-based fiber optic sensors; through this review, we have tried to summarize the overall development of LMR-based fiber optic sensors. This review article not only provides the fundamental understanding and detailed explanation of LMR generation but also sheds light on the setup/configuration required to excite the lossy modes. Several geometries explored in the literature so far have also been addressed. In addition, this review includes a survey of the different materials capable of supporting lossy modes and explores new possible LMR supporting materials and their potential applications in sensing.
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Liver cell types derived from induced pluripotent stem cells (iPSCs) share the potential to investigate development, toxicity, as well as genetic and infectious disease in ways currently limited by the availability of primary tissue. With the added advantage of patient specificity, which can play a role in all of these areas. Many iPSC differentiation protocols focus on 3 dimensional (3D) or organotypic differentiation, as these offer the advantage of more closely mimicking in vivo systems including; the formation of tissue like architecture and interactions/crosstalk between different cell types. Ultimately such models have the potential to be used clinically and either with or more aptly, in place of animal models. Along with the development of organotypic and micro-tissue models, there will be a need to co-develop imaging technologies to enable their visualization. A variety of liver models termed "organoids" have been reported in the literature ranging from simple spheres or cysts of a single cell type, usually hepatocytes, to those containing multiple cell types combined during the differentiation process such as hepatic stellate cells, endothelial cells, and mesenchymal cells, often leading to an improved hepatic phenotype. These allow specific functions or readouts to be examined such as drug metabolism, protein secretion or an improved phenotype, but because of their relative simplicity they lack the flexibility and general applicability of ex vivo tissue culture. In the liver field these are more often constructed rather than developed together organotypically as seen in other organoid models such as brain, kidney, lung and intestine. Having access to organotypic liver like surrogates containing multiple cell types with in vivo like interactions/architecture, would provide vastly improved models for disease, toxicity and drug development, combining disciplines such as microfluidic chip technology with organoids and ultimately paving the way to new therapies.
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Theoretical modeling of a surface plasmon resonance (SPR) based fiber optic sensor with a conducting metal oxide [indium tin oxide (ITO)] as the SPR active material is proposed. The theoretical analysis reveals that the proposed sensing probe can be utilized for sensing in the IR region, where most of the gases show their absorption regime. Comparison of sensitivity predicts that an ITO-layer-coated SPR-based fiber optic sensor is about 60% more sensitive than a gold-coated fiber optic sensor. The physical reasons behind sensitivity enhancement are provided. Apart from this, various advantageous features of the ITO over the noble metals, silver and gold, are addressed.
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A localized surface plasmon resonance based fiber optic sensor for refractive index sensing has been analyzed theoretically. The effects of size of the spherical metal nanoparticle as well as the light sources on the performance of the sensor have been studied rigorously. It is observed that a diffuse light source along with an intensity modulation method gives better performance in terms of sensing range. In addition, the use of a diffuse source makes the sensing device very cheap and compact, which is an important issue for the commercial applications. The refractive index range of the sensor is larger than the ranges reported for various types of fiber optic sensors utilizing intensity modulation.
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Nanog has an important role in pluripotency induction in bovines and snow leopards. To examine whether it was required for wild felids globally, we examined the induction of pluripotency in felids from Asia (Bengal tiger, Panthera tigris), Africa (serval, Leptailurus serval), and the Americas (jaguar, Panthera onca). Dermal fibroblasts were transduced with genes encoding the human transcription factors OCT4, SOX2, KLF4, and cMYC with or without NANOG. Both four- and five-factor induction resulted in colony formation at day 3 in all three species tested; however, we were not able to maintain colonies that were generated without NANOG beyond passage (P) 7. Five-factor induced pluripotent stem cell (iPSC) colonies from wild cats were expanded in vitro on feeder layers and were positive for alkaline phosphatase and protein expression of OCT-4, NANOG, and stage-specific embryonic antigen-4 at P4 and P14. Reverse-transcription polymerase chain reaction confirmed that all five human transgenes were transcribed at P4; however, OCT4, SOX2, and NANOG transgenes were silenced by P14. Endogenous OCT4 and NANOG transcripts were detected at P4 and P14 in all cell lines confirming successful reprogramming. At P14, the iPSCs from all three species remained euploid and differentiated in vivo and in vitro into derivatives of the three germ layers. This study describes an effective method for inducing pluripotency in three endangered wild cats from across the globe and confirms Nanog as an essential factor in the reprogramming event. Efficient production of iPSC from endangered felids creates a unique opportunity for species preservation through gamete production, nuclear transfer, embryo complementation, and future novel technologies.