Project description:The nucleus contains diverse phase-separated condensates that compartmentalize and concentrate biomolecules with distinct physicochemical properties. Here we consider whether condensates concentrate small molecule cancer therapeutics such that their pharmacodynamic properties are altered. We found that antineoplastic drugs become concentrated in specific protein condensates in vitro and that this occurs through physicochemical properties independent of the drug target. This behavior was also observed in tumor cells, where drug partitioning influenced drug activity. Altering the properties of the condensate was found to impact the concentration and activity of drugs. These results suggest that selective partitioning and concentration of small molecules within condensates contributes to drug pharmacodynamics and that further understanding of this phenomenon may facilitate advances in disease therapy.
Project description:It has long been recognized that species occupy a specific ecological niche within their ecosystem. The ecological niche is defined as the number of conditions and resources that limit species distribution. Within their ecological niche, species do not exist in a single physiological state but in a number of states we call the Natural Operating Range. In this paper we link ecological niche theory to physiological ecology by measuring gene expression levels of collembolans exposed to various natural conditions. The soil-dwelling collembolan Folsomia candida was exposed to 26 natural soils with different soil characteristics (soil type, land use, practice, etc). The animals were exposed for two days and gene expression levels were measured. The main factor found to regulate gene expression was the soil type (sand or clay), in which 18.5% of the measured genes were differentially expressed. Gene Ontology analysis showed animals exposed to sandy soils experience general stress, affecting cell homeostasis and replication. Multivariate analysis linking soil chemical data to gene expression data revealed that soil fertility influences gene expression. Land-use and practice had less influence on gene expression; only forest soils showed a different expression pattern. A variation in gene expression variation analysis showed overall low variance in gene expression. The large difference in response to soil type was caused by the soil physicochemical properties where F. candida experiences clay soils and sandy soils as very different from each other. This collembolan prefers fertile soils with high organic matter content, as soil fertility was found to correlate with gene expression and animals exposed to sandy soils (which, in general, have lower organic matter content) experience more general stress. Finally, we conclude that there is no such thing as a fixed physiological state for animals in their ecological niche and the boundary between the ecological niche and a stressed state depends on the genes/pathways investigated.
Project description:To evaluate the biological effects at the transcriptional level of manufactured nanomaterials, we performed whole genome microarrays of rat alveolar macrophages (NR8383) exposed to multi-walled carbon nanotubes (MWCNTs) with different physicochemical properties.
Project description:To evaluate the biological effects at the transcriptional level of manufactured nanomaterials, whole genome microarray analysis of rat lungs intratracheally instilled with cellulose nanofibrils (CNFs) with different physicochemical properties or multi-walled carbon nanotubes (MWCNTs) were performed.
Project description:It has long been recognized that species occupy a specific ecological niche within their ecosystem. The ecological niche is defined as the number of conditions and resources that limit species distribution. Within their ecological niche, species do not exist in a single physiological state but in a number of states we call the Natural Operating Range. In this paper we link ecological niche theory to physiological ecology by measuring gene expression levels of collembolans exposed to various natural conditions. The soil-dwelling collembolan Folsomia candida was exposed to 26 natural soils with different soil characteristics (soil type, land use, practice, etc). The animals were exposed for two days and gene expression levels were measured. The main factor found to regulate gene expression was the soil type (sand or clay), in which 18.5% of the measured genes were differentially expressed. Gene Ontology analysis showed animals exposed to sandy soils experience general stress, affecting cell homeostasis and replication. Multivariate analysis linking soil chemical data to gene expression data revealed that soil fertility influences gene expression. Land-use and practice had less influence on gene expression; only forest soils showed a different expression pattern. A variation in gene expression variation analysis showed overall low variance in gene expression. The large difference in response to soil type was caused by the soil physicochemical properties where F. candida experiences clay soils and sandy soils as very different from each other. This collembolan prefers fertile soils with high organic matter content, as soil fertility was found to correlate with gene expression and animals exposed to sandy soils (which, in general, have lower organic matter content) experience more general stress. Finally, we conclude that there is no such thing as a fixed physiological state for animals in their ecological niche and the boundary between the ecological niche and a stressed state depends on the genes/pathways investigated. Test animals were exposed to 26 natural soils + 2 control soils. 4 biological replicates per soil containing 25 grams of soil and 30 23-day-old animals per replicate, RNA was isolated after two days of exposure. for the micro-array hybridization design we made use of an interwoven loop design. from the four replicates per soil two were labeled with Cy3 and 2 with Cy5. It was made sure that now two replicates of the same soil were ever hybridized against the same soil.
Project description:soil microbial community compositions in the three sites having different soil physicochemical properties and distinct regional climates
Project description:Because of severe abiotic limitations, Antarctic soils represent simplified ecosystems, where microorganisms are the principle drivers of nutrient cycling. This relative simplicity makes these ecosystems particularly vulnerable to perturbations, like global warming, and the Antarctic Peninsula is among the most rapidly warming regions on the planet. However, the consequences of the ongoing warming of Antarctica on microorganisms and the processes they mediate are unknown. Here, using 16S rRNA gene pyrosequencing and qPCR, we report a number of highly consistent changes in microbial community structure and abundance across very disparate sub-Antarctic and Antarctic environments following three years of experimental field warming (+ 0.5-2°C). Specifically, we found significant increases in the abundance of fungi and bacteria and in the Alphaproteobacteria-to-Acidobacteria ratio. These alterations were linked to a significant increase in soil respiration. Furthermore, the shifts toward generalist or opportunistic bacterial communities following warming weakened the linkage between bacterial diversity and functional diversity. Warming also increased the abundance of some organisms related to the N-cycle, detected as an increase in the relative abundance of nitrogenase genes via GeoChip microarray analyses. Our results demonstrate that soil microorganisms across a range of sub-Antarctic and Antarctic environments can respond consistently and rapidly to increasing temperatures, thereby potentially disrupting soil functioning.
Project description:<p><strong>BACKGROUND:</strong> The coevolution and interaction between plants and microorganisms have long been a subject of significant research interest. Dark septate endophytes (DSE) have garnered great attention in contemporary research due to their functional diversity, in vitro cultivation ability, and ability to establish symbiotic associations with host plants. In the present study, three DSE strains, namely <em>Acrocalymma vagum</em>, <em>Zopfiella marina</em>, and <em>Phoma herbarum</em>, which were obtained from the roots of <em>Astragalus membranaceus</em>, were introduced into maize plants through inoculation. We evaluated the effects of DSE inoculation on maize growth and root secretion activity through a multi omics methods, and proposed mechanisms for 'internal pathways' and 'external pathways'.</p><p><strong>RESULTS:</strong> The findings indicated that A. vagum exhibited superior growth-promoting ability on maize compared to <em>Z. marina</em> and <em>P. herbarum</em>.GO and KEGG enrichment analysis found that <em>A. vagum</em> inoculation resulted in significant enrichment of differentially expressed genes in annotation functions related to hormone regulation and lipid metabolism. A. vagum inoculation revealed that the gene pathways involved in plant hormone signaling and plant pathogen interactions play a crucial role in promoting host growth, and <em>A. vagum</em> inoculation group exhibited the highest number of differentially expressed genes, the most intricate protein-protein interaction (PPI) model, and the most pronounced relationship between differentially expressed genes. After the inoculation of <em>A.vagum</em>, the levels of salicylic acid, zeatin, and IAA in maize plants significantly increased. Additionally, the diversity and abundance of endophytic fungi, as well as the proportion of harmful bacteria and beneficial fungi, had significantly increased. Compared with <em>Z. marina</em> and <em>P. herbarum</em>, the net photosynthetic rate (Pn) and stomatal conductance (Gs) of <em>A.vagum</em> inoculated plants significantly increased. Inoculation with <em>A.vagum</em> could enhance the ability of corn roots to secrete lipids, sugars, and amino acids, resulted in a notable augmentation of beneficial bacteria and fungi, accompanied by a significant reduction in the proportion of harmful bacteria in the rhizosphere soil, such as <em>Fusarium solani</em> and <em>Fusarium lacertarum</em>, exhibited significant inhibition, whereas <em>Bacillus niabensis</em> and <em>Bacillus nealsonii</em> demonstrated enrichment trends. Soil pH, organic matter, available potassium content, acid phosphatase, alkaline phosphatase and urease activity exhibited significant increases following the inoculation of <em>A. vagum</em>. Variance decomposition and structural equation modeling (SEM) analysis indicated that the 'internal pathway', maize growth is mainly influenced by the interaction of endogenous hormones, endophytic microorganisms, and photosynthetic parameters, whereas within the 'external pathway', the interaction between soil microorganisms and soil physicochemical properties exerted a dominant influence. Compared with the <em>Z. marina</em> and <em>P. herbarum</em> inoculation, <em>A. vagum</em> inoculation showed a more significant impact on maize growth, both in terms of 'internal pathway' and 'external pathway', in terms of pathway level and quantity.</p><p><strong>CONCLUSIONS:</strong> These findings provide a new perspective for understanding the potential mechanisms of 'microbe-plant' interactions and also contribute to the exploration of targeted functional microorganisms that promote growth and stress resistance.</p>
Project description:To further development of our gene expression approach to assess the effects of manufactured nanomaterials at the transcriptional level, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish characterization of physicochemical properties of exfoliated graphene (EGr).
Project description:To assess the biological impact of cellulose nanofibrils (CNFs) at the transcriptional level, we conducted whole-genome microarray analyses on rat alveolar macrophages (NR8383) exposed to CNFs with varying physicochemical properties. The findings were compared with those from exposure to microcrystalline cellulose (MCC) and lipopolysaccharide (LPS).