In the recent era, the increasing persistence of hazardous contaminants is badly affecting the globe in many ways. Due to high environmental contamination, almost every second species on earth facing ...the worst issue in their survival. Advances in newer remediation approaches may help enhance bioremediation's quality, while conventional procedures have failed to remove hazardous compounds from the environment. Chemical and physical waste cleanup approaches have been used in current circumstances; however, these methods are costly and harmful to the environment. Thus, there has been a rise in the use of bioremediation due to an increase in environmental contamination, which led to the development of genetically engineered microbes (GEMs). It is safer and more cost-effective to use engineered microorganisms rather than alternative methods. GEMs are created by introducing a stronger protein into bacteria through biotechnology or genetic engineering to enhance the desired trait. Biodegradation of oil spills, halobenzoates naphthalenes, toluenes, trichloroethylene, octanes, xylenes etc. has been accomplished using GEMs such bacteria, fungus, and algae. Biotechnologically induced microorganisms are more powerful than naturally occurring ones and may degrade contaminants faster because they can quickly adapt to new pollutants they encounter or co-metabolize. Genetic engineering is a worthy process that will benefit the environment and ultimately the health of our people.
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•Toxins are typically generated by anthropogenic activities into the environment.•The reduction of pollutants using various microbial techniques is addressed.•Strategy, and recommendation are summarized along with future prospects.
Cancer-associated fibroblasts (CAFs) found in primary and metastatic tumours are highly versatile, plastic and resilient cells that are actively involved in cancer progression through complex ...interactions with other cell types in the tumour microenvironment. As well as generating extracellular matrix components that contribute to the structure and function of the tumour stroma, CAFs undergo epigenetic changes to produce secreted factors, exosomes and metabolites that influence tumour angiogenesis, immunology and metabolism. Because of their putative pro-oncogenic functions, CAFs have long been considered an attractive therapeutic target; however, clinical trials of treatment strategies targeting CAFs have mostly ended in failure and, in some cases, accelerated cancer progression and resulted in inferior survival outcomes. Importantly, CAFs are heterogeneous cells and their characteristics and interactions with other cell types might change dynamically as cancers evolve. Studies involving single-cell RNA sequencing and novel mouse models have increased our understanding of CAF diversity, although the context-dependent roles of different CAF populations and their interchangeable plasticity remain largely unknown. Comprehensive characterization of the tumour-promoting and tumour-restraining activities of CAF subtypes, including how these complex bimodal functions evolve and are subjugated by neoplastic cells during cancer progression, might facilitate the development of novel diagnostic and therapeutic approaches. In this Review, the clinical relevance of CAFs is summarized with an emphasis on their value as prognosis factors and therapeutic targets.
Gene Drives on the Horizon National Academies of Sciences, Engineering, and Medicine; Division on Earth and Life Studies; Board on Life Sciences ...
06/2016
eBook
Odprti dostop
Research on gene drive systems is rapidly advancing. Many proposed applications of gene drive research aim to solve environmental and public health challenges, including the reduction of poverty and ...the burden of vector-borne diseases, such as malaria and dengue, which disproportionately impact low and middle income countries. However, due to their intrinsic qualities of rapid spread and irreversibility, gene drive systems raise many questions with respect to their safety relative to public and environmental health. Because gene drive systems are designed to alter the environments we share in ways that will be hard to anticipate and impossible to completely roll back, questions about the ethics surrounding use of this research are complex and will require very careful exploration.
Gene Drives on the Horizon outlines the state of knowledge relative to the science, ethics, public engagement, and risk assessment as they pertain to research directions of gene drive systems and governance of the research process. This report offers principles for responsible practices of gene drive research and related applications for use by investigators, their institutions, the research funders, and regulators.
Small cell lung cancer (SCLC) is an exceptionally lethal malignancy for which more effective therapies are urgently needed. Several lines of evidence, from SCLC primary human tumours, patient-derived ...xenografts, cancer cell lines and genetically engineered mouse models, appear to be converging on a new model of SCLC subtypes defined by differential expression of four key transcription regulators: achaete-scute homologue 1 (ASCL1; also known as ASH1), neurogenic differentiation factor 1 (NeuroD1), yes-associated protein 1 (YAP1) and POU class 2 homeobox 3 (POU2F3). In this Perspectives article, we review and synthesize these recent lines of evidence and propose a working nomenclature for SCLC subtypes defined by relative expression of these four factors. Defining the unique therapeutic vulnerabilities of these subtypes of SCLC should help to focus and accelerate therapeutic research, leading to rationally targeted approaches that may ultimately improve clinical outcomes for patients with this disease.
Phenylketonuria (PKU) is a genetic disease that is characterized by an inability to metabolize phenylalanine (Phe), which can result in neurotoxicity. To provide a potential alternative to a ...protein-restricted diet, we engineered Escherichia coli Nissle to express genes encoding Phe-metabolizing enzymes in response to anoxic conditions in the mammalian gut. Administration of our synthetic strain, SYNB1618, to the Pah
PKU mouse model reduced blood Phe concentration by 38% compared with the control, independent of dietary protein intake. In healthy Cynomolgus monkeys, we found that SYNB1618 inhibited increases in serum Phe after an oral Phe dietary challenge. In mice and primates, Phe was converted to trans-cinnamate by SYNB1618, quantitatively metabolized by the host to hippurate and excreted in the urine, acting as a predictive biomarker for strain activity. SYNB1618 was detectable in murine or primate feces after a single oral dose, permitting the evaluation of pharmacodynamic properties. Our results define a strategy for translation of live bacterial therapeutics to treat metabolic disorders.
Does consensus messaging about contested science issues influence perceptions of consensus and/or personal beliefs? This question remains open, particularly for topics other than climate change and ...samples outside the United States. In a Spanish national sample (N = 5087), we use preregistered survey experiments to examine differential efficacy of variations in consensus messaging for vaccines and genetically modified organisms. We find that no variation of consensus messaging influences vaccine beliefs. For genetically modified organisms, about which misperceptions are particularly prevalent in our sample, we find that scientific consensus messaging increases perception of consensus and personal belief that genetically modified organisms are safe, and decreases support for a ban. Increasing degree of consensus did not have consistent effects. Although individual differences (e.g. a conspiratorial worldview) predict these genetically modified organism beliefs, they do not undercut consensus message effects. While we observe relatively modest effect sizes, consensus messaging may be able to improve the accuracy of beliefs about some contentious topics.
Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard ...to establish. We present a protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing all main subtypes of OC. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and interpatient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug-screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug-sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.
Bacillus licheniformis is a well-known platform strain for production of industrial enzymes. However, the development of genetically stable recombinant B. licheniformis for high-yield enzyme ...production is still laborious. Here, a pair of plasmids, pUB-MazF and pUB'-EX1, were firstly constructed. pUB-MazF is a thermosensitive, self-replicable plasmid. It was able to efficiently cure from the host cell through induced expression of an endoribonuclease MazF, which is lethal to the host cell. pUB'-EX1 is a nonreplicative and integrative plasmid. Its replication was dependent on the thermosensitive replicase produced by pUB-MazF. Transformation of pUB'-EX1 into the B. licheniformis BL-UBM harboring pUB-MazF resulted in both plasmids coexisting in the host cell. At an elevated temperature, and in the presence of isopropyl-1-thio-beta-d-galactopyranoside and kanamycin, curing of the pUB-MazF and multiple-copy integration of pUB'-EX1 occurred, simultaneously. Through this procedure, genetically stable recombinants integrated multiple copies of amyS, from Geobacillus stearothermophilus ATCC 31195 were facilely obtained. The genetic stability of the recombinants was verified by repeated subculturing and shaking flask fermentations. The production of alpha-amylase by recombinant BLiS-002, harboring five copies of amyS, in a 50-l bioreactor reached 50 753 U/ml after 72 hr fermentation. This strategy therefore has potential for production of other enzymes in B. licheniformis and for genetic modification of other Bacillus species. Keywords: Chromosomal integration, MazF, Bacillus licheniformis, Overexpression, alpha-Amylase
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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