Many volatile compounds secreted by bacteria play an important role in the interactions of microorganisms, can inhibit the growth of phytopathogenic bacteria and fungi, can suppress or stimulate ...plant growth and serve as infochemicals presenting a new type of interspecies communication. In this work, we investigated the effect of total pools of volatile substances and individual volatile organic compounds (VOCs) synthesized by the rhizosphere bacteria
Pseudomonas chlororaphis
449 and
Serratia plymuthica
IC1270, the soil-borne strain
P. fluorescens
B-4117 and the spoiled meat isolate
S. proteamaculans
94 on
Arabidopsis thaliana
plants. We showed that total gas mixtures secreted by these strains during their growth on Luria-Bertani agar inhibited
A. thaliana
growth. Hydrogen cyanide synthesis was unnecessary for the growth suppression. A decrease in the inhibition level was observed for the strain
P. chlororaphis
449 with a mutation in the
gacS
gene, while inactivation of the
rpoS
gene had no effect. Individual VOCs synthesized by these bacteria (1-indecene, ketones 2-nonanone, 2-heptanone, 2-undecanone, and dimethyl disulfide) inhibited the growth of plants or killed them. Older
A. thaliana
seedlings were more resistant to VOCs than younger seedlings. The results indicated that the ability of some volatiles emitted by the rhizosphere and soil bacteria to inhibit plant growth should be considered when assessing the potential of such bacteria for the biocontrol of plant diseases.
Graphic Abstract
In experimental models of glioblastoma multiforme (GBM), irradiation (IR) induces local expression of the chemokine CXCL12/SDF-1, which promotes tumour recurrence. The role of CXCR7, the ...high-affinity receptor for CXCL12, in the tumour's response to IR has not been addressed.
We tested CXCR7 inhibitors for their effects on tumour growth and/or animal survival post IR in three rodent GBM models. We used immunohistochemistry to determine where CXCR7 protein is expressed in the tumours and in human GBM samples. We used neurosphere formation assays with human GBM xenografts to determine whether CXCR7 is required for cancer stem cell (CSC) activity in vitro.
CXCR7 was detected on tumour cells and/or tumour-associated vasculature in the rodent models and in human GBM. In human GBM, CXCR7 expression increased with glioma grade and was spatially associated with CXCL12 and CXCL11/I-TAC. In the rodent GBM models, pharmacological inhibition of CXCR7 post IR caused tumour regression, blocked tumour recurrence, and/or substantially prolonged survival. CXCR7 expression levels on human GBM xenograft cells correlated with neurosphere-forming activity, and a CXCR7 inhibitor blocked sphere formation by sorted CSCs.
These results indicate that CXCR7 inhibitors could block GBM tumour recurrence after IR, perhaps by interfering with CSCs.
Cytotoxic activity of T- and NK-cells can be efficiently retargeted against cancer cells using chimeric antigen receptors (CARs) and rTCRs. In the context of solid cancers, use of armored CAR T- and ...NK cells secreting additional anti-cancer molecules such as cytokines, chemokines, antibodies, BiTEs, inverted cytokine receptors, and checkpoint inhibitors, appears particularly promising, as this may help overcome immunosuppressive tumor microenvironment, attract bystander immune cells, and boost CAR T/NK-cell persistence. Placing the expression of such molecules under the transcriptional control downstream of CAR-mediated T/NK-cell activation offers the advantage of targeted delivery, high local concentration, and reduced toxicity. Several canonic DNA sequences that are known to function as activation-inducible promoters in human T and B cells have been described to date and typically encompass the multimers of NFkB and NFAT binding sites. However, relatively little is known about the DNA sequences that may function as activation-driven switches in the context of NK cells. We set out to compare the functionality of several activation-inducible promoters in primary human T cells, as well as in NK cell lines NK-92 and YT.
Lentiviral constructs were engineered to express two fluorescent reporters: mCherry under 4xNFAT, 2xNFkB, 5xNFkB, 10xNFkB, 30xNFkB promoters, as well as two variants of the CD69 promoter, and copGFP under the strong constitutive promoter of the human EF1a gene. Pseudotyped lentiviral particles obtained using these constructs were transduced into primary human T cells and NK-92 and YT cell lines expressing a CAR specific for PSMA. The transgenic cells obtained were activated by CD3/CD28 beads (T cells) or via a CAR (CAR-NK cell lines). Promoter activity before and after activation was assayed using FACS analysis.
In T cells, the CD69 promoter encompassing CNS1 and CNS2 regions displayed the highest signal/noise ratio. Intriguingly, in the context of CAR-YT cell line neither of the seven promoters tested displayed acceptable activation profile. In CAR-NK-92 cells, the largest fold activation (which was modest) was achieved with the 10xNFkB and 30xNFkB promoters, however its expression was clearly leaky in "resting" non-activated cells.
Unlike in T cells, the robust activation-driven inducible expression of genetic cassettes in NK cells requires unbiased genome-wide identification of promoter sequences.
The area of research presented in the article are digital platforms. The platform approach, the platform economy, which primarily ensures the interaction of market participants, is gaining an ...increasing number of participants and is becoming more widespread in various industries: from trade to the hotel business and education.
The article analyses the impact of the platform approach on the business model of the organization, namely, on the ability to create consumer value and deliver it to its customers, using the advantages of this approach. The ongoing transformation is more based on information technology, human capital, analytical decision-making tools, and business process flexibility. The paper also analyses the experience related to the implementation of the platforms in various countries and organizations.
The study gives a possible business model of a platform organization and a University that has implemented platform solutions. The authors note that the mistakes made during the implementation of the platform are mostly due to the human factor: employees may not be ready for changes or are not technically educated enough. The indifference of managers also plays a role, because the risks arising from this are neutralized worse than others. To reduce the risks, the authors defined the directions of further research.
The paper presents the vegetation thematic classification of the Burla banded pine forest carried on using "Canopus-V" remote sensing data and the supervised classification technique by a spectral ...angle mapper. Areas of selected elements have been assessed: 1. Pine forests, 2. Birch forests; 3. Meadows; 4. Anthropogenic objects (roads, etc.); 5. Agricultural lands; 6. Water objects. Sites of anthropogenic disturbed forests are identified according to remote sensing data. The results show that the data obtained in the classification by a spectral angle can be used to compile geobotanical maps, but due to low spectral resolution of Canopus-V satellite data, it is not always possible to classify individual objects validlys.
Volatile compounds emitted by bacteria can play a significant role in interacting with microorganisms, plants, and other organisms. In this work, we studied the effect of total gaseous mixtures of ...organic as well as inorganic volatile compounds (VCs) and individual pure volatile organic compounds (VOCs: ketones 2-nonanone, 2-heptanone, 2-undecanone, a sulfur-containing compound dimethyl disulfide) synthesized by the rhizosphere
Pseudomonas chlororaphis
449 and
Serratia plymuthica
IC1270 strains, the soil-borne strain
P. fluorescens
B-4117, and the spoiled meat isolate
S. proteamaculans
94 strain on
Arabidopsis thaliana
plants (on growth and germination of seeds). We demonstrated that total mixtures of volatile compounds emitted by these strains grown on Luria–Bertani agar, Tryptone Soya Agar, and Potato Dextrose Agar media inhibited the
A. thaliana
growth. When studied bacteria grew on Murashige and Skoog (MS) agar medium, volatile mixtures produced by bacteria could stimulate the growth of plants. Volatile compounds of bacteria slowed down the germination of plant seeds; in the presence of volatile mixtures of
P. fluorescens
B-4117, the seeds did not germinate. Of the individual VOCs, 2-heptanone had the most potent inhibitory effect on seed germination. We also showed that the tested VOCs did not cause oxidative stress in
Escherichia coli
cells using specific
lux
-biosensors. VOCs reduced the expression of the
lux
operon from the promoters of the
kat
G,
oxy
S, and
sox
S genes (whose products involved in the protection of cells from oxidative stress) caused by the action of hydrogen peroxide and paraquat, respectively.
Wortmannin has been shown to be an efficient radiosensitizer. Since wortmannin is able to inhibit DNA-dependent protein kinase (DNA-PK) and double-strand break (DSB) rejoining, it is believed that ...its mechanism of radiation sensitization is through the inhibition of DNA-PK-mediated repair of DSBs. However, since wortmannin is not a specific inhibitor, the possibility that other kinases are inhibited and thereby may contribute to radiosensitization cannot be ruled out. Here we present data confirming the radiosensitizing effect of wortmannin on cells of different cell lines. In the same range of wortmannin concentrations, survival after exposure to ionizing radiation correlated well with DSB rejoining and the induction of micronuclei, suggesting that the inhibition of the processing of DSBs is involved in the sensitizing effect. Pretreatment with wortmannin enhanced the radiosensitivity of ataxia telangiectasia (AT) cells, thereby precluding the participation of ATM protein in the radiation sensitization by wortmannin. At the same time, irradiated DNA-PK-deficient cells were not significantly affected by pretreatment with wortmannin. These observations support a likely mechanism; that is, wortmannin sensitizes cells to radiation through inhibition of the DNA-PK-mediated rejoining of DSBs.
The transmission problem describing a steady-state temperature distribution in a plane consisting of two half-planes occupied by different materials with exponential internal thermal conductivities ...with a single finite crack along the interface is considered. The compatibility conditions for the boundary functions are formulated under which the problem has a unique classical solution. Closed-form representations of the classical solution are found. The weak solution to the problem is studied without making additional assumptions, and asymptotic expansions are constructed for the weak solution and its first derivatives near the ends of the crack.
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