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351.
Alexey E. Machulkin Dmitry A. Skvortsov Yan A. Ivanenkov Anton P. Ber Mikhail V. Kavalchuk Anastasia V. Aladinskaya Anastasia A. Uspenskaya Radik R. Shafikov Ekaterina A. Plotnikova Raisa I. Yakubovskaya Ekaterina A. Nimenko Nikolay U. Zyk Elena K. Beloglazkina Nikolay V. Zyk Victor E Koteliansky Alexander G. Majouga 《Bioorganic & medicinal chemistry letters》2019,29(16):2229-2235
Prostate cancer (PC) is the second most commonly occurring cancer in men. Conventional chemotherapy has wide variety of disadvantages such as high systemic toxicity and low selectivity. Targeted drug delivery is a promising approach to decrease side effects of therapy. Prostate specific membrane antigen (PSMA) is overexpressed in prostate cancer cells while low level of expression is observed in normal cells. In this study we describe the development of Glu-urea-Lys based PSMA-targeting conjugates with paclitaxel. A series of new PSMA targeting conjugates with paclitaxel was designed and synthesized. The cytotoxicity of conjugates was evaluated against prostate (LNCaP, 22Rv1 and PC-3) and non-prostate (Hek293T, VA13, A549 and MCF-7) cell lines. The most promising conjugate 21 was examined in vivo using 22Rv1 xenograft mice model. It demonstrated good efficiency comparable with paclitaxel, while reduced toxicity. 3D molecular docking study was also performed to understand underlying mechanism of binding and further optimization of the linker substructure and conjugates structure for improving the target affinity. These conjugates may be useful for further design of novel PSMA targeting delivery systems for PC. 相似文献
352.
Vicuna Requesens Deborah Gonzalez Romero Maria Elena Devaiah Shivakumar P. Chang Yeun-Kyung Flory Ashley Streatfield Stephen Ring Rebecca Phillips Cassie Hood Nathan C. Marbaniang Cyrus Dean Howard John A. Hood Elizabeth E. 《Transgenic research》2019,28(5-6):537-547
Transgenic Research - Expression of recombinant proteins in plants is a technology for producing vaccines, pharmaceuticals and industrial enzymes. For the past several years, we have produced... 相似文献
353.
Domenico Rau Maria L. Murgia Monica Rodriguez Elena Bitocchi Elisa Bellucci Davide Fois Diego Albani Laura Nanni Tania Gioia Debora Santo Luca Marcolungo Massimo Delledonne Giovanna Attene Roberto Papa 《The Plant journal : for cell and molecular biology》2019,97(4):693-714
The complete or partial loss of shattering ability occurred independently during the domestication of several crops. Therefore, the study of this trait can provide an understanding of the link between phenotypic and molecular convergent evolution. The genetic dissection of ‘pod shattering’ in Phaseolus vulgaris is achieved here using a population of introgression lines and next‐generation sequencing techniques. The ‘occurrence’ of the indehiscent phenotype (indehiscent versus dehiscent) depends on a major locus on chromosome 5. Furthermore, at least two additional genes are associated with the ‘level’ of shattering (number of shattering pods per plant: low versus high) and the ‘mode’ of shattering (non‐twisting versus twisting pods), with all of these loci contributing to the phenotype by epistatic interactions. Comparative mapping indicates that the major gene identified on common bean chromosome 5 corresponds to one of the four quantitative trait loci for pod shattering in Vigna unguiculata. None of the loci identified comprised genes that are homologs of the known shattering genes in Glycine max. Therefore, although convergent domestication can be determined by mutations at orthologous loci, this was only partially true for P. vulgaris and V. unguiculata, which are two phylogenetically closely related crop species, and this was not the case for the more distant P. vulgaris and G. max. Conversely, comparative mapping suggests that the convergent evolution of the indehiscent phenotype arose through mutations in different genes from the same underlying gene networks that are involved in secondary cell‐wall biosynthesis and lignin deposition patterning at the pod level. 相似文献
354.
Olga A. Romanova Timur H. Tenchurin Tatiana S. Demina Elena V. Sytina Alexey D. Shepelev Stanislav G. Rudyak Olga I. Klein Sergey V. Krasheninnikov Elizaveta I. Safronova Roman A. Kamyshinsky Vissarion G. Mamagulashvili Tatiana A. Akopova Sergey N. Chvalun Andrey A. Panteleyev 《Cell proliferation》2019,52(3)
355.
María Aranguren‐Gassis Colin T. Kremer Christopher A. Klausmeier Elena Litchman 《Ecology letters》2019,22(11):1860-1869
Ongoing climate change is shifting species distributions and increasing extinction risks globally. It is generally thought that large population sizes and short generation times of marine phytoplankton may allow them to adapt rapidly to global change, including warming, thus limiting losses of biodiversity and ecosystem function. Here, we show that a marine diatom survives high, previously lethal, temperatures after adapting to above‐optimal temperatures under nitrogen (N)‐replete conditions. N limitation, however, precludes thermal adaptation, leaving the diatom vulnerable to high temperatures. A trade‐off between high‐temperature tolerance and increased N requirements may explain why N limitation inhibited adaptation. Because oceanic N limitation is common and likely to intensify in the future, the assumption that phytoplankton will readily adapt to rising temperatures may need to be reevaluated. 相似文献
356.
Mathieu Santonja Anne Bousquet‐Mlou Stphane Greff Elena Ormeo Catherine Fernandez 《Ecology and evolution》2019,9(14):8201-8213
The Mediterranean region is recognized as a global biodiversity hotspot. However, over the last decades, the cessation of traditional farming in the north part of the Mediterranean basin has given way to strong afforestation leading to occurrence of abandoned agricultural lands colonized by pioneer expansionist species like Pinus halepensis. This pine species is known to synthesize a wide range of secondary metabolites, and previous studies have demonstrated strong allelopathic potentialities of its needle and root leachates. Pinus halepensis is also recognized to release significant amounts of volatile organic compounds (VOC) with potential allelopathic effects that have never been investigated. In this context, the objectives of the present study were to improve our knowledge about the VOC released from P. halepensis needles and roots, determine if these VOC affect the seed germination and root growth of two herbaceous target species (Lactuca sativa and Linum strictum), and evaluate if soil microorganisms modulate the potential allelopathic effects of these VOC. Thirty terpenes were detected from both, needle and root emissions with β‐caryophyllene as the major volatile. Numerous terpenes, such as β‐caryophyllene, δ‐terpinene, or α‐pinene, showed higher headspace concentrations according to the gradient green needles < senescent needles < needle litter. Seed germination and root growth of the two target species were mainly reduced in presence of P. halepensis VOC. In strong contrast with the trend reported with needle leachates in literature, we observed an increasing inhibitory effect of P. halepensis VOC with the progress of needle physiological stages (i.e., green needle < senescent needle < needle litter). Surprisingly, several inhibitory effects observed on filter paper were also found or even amplified when natural soil was used as a substrate, highlighting that soil microorganisms do not necessarily limit the negative effects of VOC released by P. halepensis on herbaceous target species. 相似文献
357.
358.
359.
Chen Wu Cecilia Deng Elena Hilario Nick W. Albert Declan Lafferty Ella R. P. Grierson Blue J. Plunkett Caitlin Elborough Ali Saei Catrin S. Günther Hilary Ireland Alan Yocca Patrick P. Edger Laura Jaakola Katja Karppinen Adrian Grande Ritva Kylli Veli-Pekka Lehtola Andrew C. Allan Richard V. Espley David Chagn 《Molecular ecology resources》2022,22(1):345-360
Bilberry (Vaccinium myrtillus L.) belongs to the Vaccinium genus, which includes blueberries (Vaccinium spp.) and cranberry (V. macrocarpon). Unlike its cultivated relatives, bilberry remains largely undomesticated, with berry harvesting almost entirely from the wild. As such, it represents an ideal target for genomic analysis, providing comparisons with the domesticated Vaccinium species. Bilberry is prized for its taste and health properties and has provided essential nutrition for Northern European indigenous populations. It contains high concentrations of phytonutrients, with perhaps the most important being the purple colored anthocyanins, found in both skin and flesh. Here, we present the first bilberry genome assembly, comprising 12 pseudochromosomes assembled using Oxford Nanopore (ONT) and Hi-C Technologies. The pseudochromosomes represent 96.6% complete BUSCO genes with an assessed LAI score of 16.3, showing a high conservation of synteny against the blueberry genome. Kmer analysis showed an unusual third peak, indicating the sequenced samples may have been from two individuals. The alternate alleles were purged so that the final assembly represents only one haplotype. A total of 36,404 genes were annotated after nearly 48% of the assembly was masked to remove repeats. To illustrate the genome quality, we describe the complex MYBA locus, and identify the key regulating MYB genes that determine anthocyanin production. The new bilberry genome builds on the genomic resources and knowledge of Vaccinium species, to help understand the genetics underpinning some of the quality attributes that breeding programs aspire to improve. The high conservation of synteny between bilberry and blueberry genomes means that comparative genome mapping can be applied to transfer knowledge about marker-trait association between these two species, as the loci involved in key characters are orthologous. 相似文献
360.
Cornelia Walther Martin Voigtmann Elena Bruna Ali Abusnina Anne-Luise Tscheließnig Michael Allmer Hermann Schuchnigg Cécile Brocard Alexandra Föttinger-Vacha Georg Klima 《Biotechnology progress》2022,38(3):e3249
The development of a biopharmaceutical production process usually occurs sequentially, and tedious optimization of each individual unit operation is very time-consuming. Here, the conditions established as optimal for one-step serve as input for the following step. Yet, this strategy does not consider potential interactions between a priori distant process steps and therefore cannot guarantee for optimal overall process performance. To overcome these limitations, we established a smart approach to develop and utilize integrated process models using machine learning techniques and genetic algorithms. We evaluated the application of the data-driven models to explore potential efficiency increases and compared them to a conventional development approach for one of our development products. First, we developed a data-driven integrated process model using gradient boosting machines and Gaussian processes as machine learning techniques and a genetic algorithm as recommendation engine for two downstream unit operations, namely solubilization and refolding. Through projection of the results into our large-scale facility, we predicted a twofold increase in productivity. Second, we extended the model to a three-step model by including the capture chromatography. Here, depending on the selected baseline-process chosen for comparison, we obtained between 50% and 100% increase in productivity. These data show the successful application of machine learning techniques and optimization algorithms for downstream process development. Finally, our results highlight the importance of considering integrated process models for the whole process chain, including all unit operations. 相似文献