Highlights► A wide variety of bioreporter and biosensor assays for arsenic detection exists. ► Assay detection limits are mostly in the range of 10–50 μg As per L and below. ► New focus is on reporter integration into microdevices for more optimal detection. ► A number of case studies show realistic field applicability of bioreporter assays. 相似文献
Highlights► Comparing biofuel crops is exceedingly difficult using conventional measurement methods. ► The PETRO approach quantitatively compares biological matter in terms of energy and carbon. ► Tracking carbon flux from air to liquid fuel compares all biofuel crop yields on a common basis. ► Reporting energy yields (GJ ha−1 y−1) and carbon flux (MgC ha−1 y−1) enables regional comparison. 相似文献
Screening of a 65,536-member one-bead-one-compound (OBOC) combinatorial library of glycopeptide dendrimers of structure ((βGal)n + 1X8X7X6X5)2DapX4X3X2X1(β-Gal)m (βGal = β-galactosyl-thiopropionic acid, X8–1 = variable amino acids, Dap = l-2,3-diaminopropionic acid, n, m = 0, or 1 if X8 = Lys resp. X1 = Lys) for binding of Jurkat cells to the library beads in cell culture, resynthesis and testing lead to the identification of dendrimer J1 (βGal-Gly-Arg-His-Ala)2Dap-Thr-Arg-His-Asp-CysNH2 and related analogues as delivery vehicles. Cell targeting is evidenced by FACS with fluorescein conjugates such as J1F. The colchicine conjugate J1C is cytotoxic with LD50 = 1.5 μM. The β-galactoside groups are necessary for activity, as evidenced by the absence of cell-binding and cytotoxicity in the non-galactosylated, acetylated analogue AcJ1F and AcJ1C, respectively. The pentagalactosylated dendrimer J4 βGal4(Lys-Arg-His-Leu)2Dap-Thr-Tyr-His-Lys(βGal)-Cys) selectively labels Jurkat cell as the fluorescein derivative J4F, but its colchicine conjugate J4C lacks cytotoxicity. Tubulin binding assays show that the colchicine dendrimer conjugates do not bind to tubulin, implying intracellular degradation of the dendrimers releasing the active drug.
Highlights► The application of Pichia pastoris for biopharmaceutical production is described. ► Synthetic biology approaches and perspectives to improve production are reviewed. ► Glycoengineering efforts to produce humanized, uniform glycoproteins are covered. ► The design and application of synthetic promoter variants are highlighted. ► The molecular toolbox available for synthetic biology in P. pastoris is discussed. 相似文献
(a) Cells are taken from their culture media, mounted on grids or in capillaries, and cryopreserved. Tomographic data are collected in a soft X-ray microscope with the cells maintained at cryogenic temperature. (b) A single slice through a 3D tomographic reconstruction of an HT1080 fibrosarcoma cell. The slice comprises tomographic reconstructions from two adjacent fields of view computationally stitched together. (c) 3D volume rendering of the tomographic reconstruction shown in (b) after segmentation guided by linear absorption coefficients (LAC) and organelle morphology. Key: Red; Nucleus, Turquoise; Mitochondria, Blue; Lipids, Gray; cell membrane. Scale bar = 1.5 μm.
Identification of neuropsychiatric CNVs. A) Schematic of a deletion and duplication. B) Example of a locus enriched for deletions in cases. C) Number of risk CNVs implicated in published studies of neuropsychiatric disorders. The number of cases included in each study is shown on the x axis, and larger points represent studies with more control samples (see Table 1 for further details). SCZ = schizophrenia, ASD = autism spectrum disorder, ID = intellectual disability, MDD = major depressive disorder, ADHD = attention-deficit hyperactivity disorder, TS = Tourette syndrome, OCD = obsessive compulsive disorder, BD = bipolar disorder.
Highlights► Individual DNA molecules hundreds of kbp long may be stretched and visualized by optical microscopy. ► An optical barcode is generated by fluorescent labeling of short sequence motifs along the stretched DNA. ► Optical maps complement DNA sequencing for gap closing, finishing, validation and de novo assembly of genomes. ► Genome structural variations not accessible to sequencing or DNA arrays may be directly visualized. ► Epigenetic marks such as DNA methylation and DNA binding proteins may also be mapped on single genomic fragments. 相似文献
A library of benzimidazole derivatives 1–20 were synthesized, and studied for their α-chymotrypsin (α-CT) inhibitory activity in vitro. Kinetics and molecular docking studies were performed to identify the type of inhibition. Compound 1 was found to be a good inhibitor of α-chymotrypsin enzyme (IC50 = 14.8 ± 0.1 μM, Ki = 16.4 μM), when compared with standard chymostatin (IC50 = 5.7 ± 0.13 μM). Compounds 2–8, 15, 17, and 18 showed significant inhibitory activities. All the inhibitors were found to be competitive inhibitors, except compound 17, which was a mixed type inhibitor. The substituents (R) in para and ortho positions of phenyl ring B, apparently played a key role in the inhibitory potential of the series. Compounds 1–20 were also studied for their cytotoxicity profile by using 3T3 mouse fibroblast cells and compounds 3, 5, 6, 8, 12–14, 16, 17, 19, and 20 were found to be cytotoxic. Molecular docking was performed on the most active members of the series in comparison to the standard compound, chymostatin, to identify the most likely binding modes. The compounds reported here can serve as templates for further studies for new inhibitors of α-chymotrypsin and other chymotrypsin-like serine proteases enzymes.
The apelinergic system includes a series of endogenous peptides apelin, ELABELA/TODDLER and their 7-transmembrane G-protein coupled apelin receptor (APJ, AGTRL-1, APLNR). The APJ receptor is an attractive therapeutic target because of its involvement in cardiovascular diseases and potentially other disorders including liver fibrosis, obesity, diabetes, and neuroprotection. To date, pharmacological characterization of the APJ receptor has been limited due to the lack of small molecule functional agonists or antagonists. Through focused screening we identified a drug-like small molecule agonist hit 1 with a functional EC50 value of 21.5 ± 5 μM and binding affinity (Ki) of 5.2 ± 0.5 μM. Initial structure–activity studies afforded compound 22 having a 27-fold enhancement in potency and the first sub-micromolar full agonist with an EC50 value of 800 ± 0.1 nM and Ki of 1.3 ± 0.3 μM. Preliminary SAR, synthetic methodology, and in vitro pharmacological characterization indicate this scaffold will serve as a favorable starting point for further refinement of APJ potency and selectivity.
Highlights► Microbial interactions in food fermentations are crucial for product functionality. ► Complex microbial consortia tolerate more variation in the environment. ► Knowledge of communities of fermenting microbes drives diversification of starter cultures. ► Use of complex starter cultures requires new propagation methodologies. ► Immobilised cell technology is a high potential solution for propagating complex cultures. 相似文献
Highlights► Targeting enzymes to organelles with highest precursor pool affects product yield. ► Targeting of nonendogenous enzymes to organelles is a useful tool for engineering. ► Identification of transporters is central for effective metabolic engineering. ► Advances in metabolomics of isolated organelles will impact engineering strategies. ► Future plant metabolic engineering will include introduction of entire pathways. 相似文献
Highlights► Highly variable and complex pathogens remain challenging vaccine targets. ► Systems biology and reverse vaccinology continue to foster success. ► New ways of presenting conserved, functionally critical epitopes hold promise. ► Adjuvant systems allow for enduring, native antigen presentation. ► An ideal vaccine provides synergy between innate, cellular, and humoral immunity. 相似文献
Highlights► Production of novel pharmaceutical and commodity chemicals. ► Protein and pathway engineering pave the way for product diversifications. ► ‘Omics’ data have helped assembly of pathways from different species. ► Recombination of enzymatic domains and site-directed mutagenesis. ► Tunable control of pathways for better production. 相似文献
Highlights► The exposure of bacteria to pollutants induces chemoattraction or chemorepellence. ► Pollutant chemoreceptors so far identified are present on plasmids. ► Chemotaxis increases pollutant bioavailability and enhances biodegradation rates. ► Chemotaxis may improve microbial inoculants designed just on catabolic potential. 相似文献
Highlights► Photocrosslinking provides insight into context-dependent interactions. ► Interactome dynamics can be determined by photocrosslinking. ► Use of photocrosslinkers defines specific interaction interfaces within large complexes. ► Crosslinking captures transient interaction complexes containing IDPs and glycoproteins. 相似文献
Highlights► Comparative genomics can help predict the function of unknown plant metabolic genes. ► Functional gene annotations are foundational to the construction of metabolic models. ► Models can simulate effects of genetic changes and thus guide metabolic engineering. ► Examples of comparative genomics facilitating gene discovery in plants are presented. 相似文献
Highlights► Development of prodrug-based self-assembled hydrogels as a new class of biomaterials. ► Design of prodrugs that can self-assemble to form hydrogels. ► These hydrogels overcome limitations such as low-drug loading and burst release of drugs. ► Locally injectable self-assembled hydrogels exhibit potential as effective therapeutics. 相似文献
Highlights► Factors that limit bacteriocin application in the food industry may be addressed in a number of ways. ► Conjugation is widely exploited to facilitate bacteriocin production by specific LAB. ► Genetic manipulation can generate LAB producing greater concentrations and bacteriocin numbers. ► Bioengineering can greatly increase LAB bacteriocin activity and inhibitory spectra. 相似文献
