Abiotic stresses severely affect plant growth and productivity. To cope with abiotic stresses, plants have evolved tolerance mechanisms that are tightly regulated by reprogramming transcription ...factors (TFs). APETALA2/ethylene-responsive factor (AP2/ERF) transcription factors are known to play an important role in various abiotic stresses. However, our understanding of the molecular mechanisms remains incomplete. In this study, we identified the role of OsERF83, a member of the AP2/ERF transcription factor family, in response to drought stress. OsERF83 is a transcription factor localized to the nucleus and induced in response to various abiotic stresses, such as drought and abscisic acid (ABA). Overexpression of OsERF83 in transgenic plants (OsERF83OX) significantly increased drought tolerance, with higher photochemical efficiency in rice. OsERF83OX was also associated with growth retardation, with reduced grain yields under normal growth conditions. OsERF83 is predominantly expressed in the vascular tissue of all organs. Transcriptome analysis revealed that OsERF83 regulates drought response genes, which are related to the transporter (OsNPF8.10, OsNPF8.17, OsLH1), lignin biosynthesis (OsLAC17, OsLAC10, CAD8D), terpenoid synthesis (OsTPS33, OsTPS14, OsTPS3), cytochrome P450 family (Oscyp71Z4, CYP76M10), and abiotic stress-related genes (OsSAP, OsLEA14, PCC13-62). OsERF83 also up-regulates biotic stress-associated genes, including PATHOGENESIS-RELATED PROTEIN (PR), WALL-ASSOCIATED KINASE (WAK), CELLULOSE SYNTHASE-LIKE PROTEIN E1 (CslE1), and LYSM RECEPTOR-LIKE KINASE (RLK) genes. Our results provide new insight into the multiple roles of OsERF83 in the cross-talk between abiotic and biotic stress signaling pathways.
In this research, we report highly sensitive and specific sandwich-type SPR-based biosensor for the detection H5Nx whole viruses. A few of aptamers, for the first time, were successfully screened and ...characterized for whole avian influenza (AI) viruses, H5Nx, by using Multi-GO-SELEX method. The affinities of the aptamers developed in this study were ranged from 8×104 to 1×104EID50/ml, and the aptamers IF22, IF23 were found to be specific to H5N1 and H5N8, respectively. In addition, some flexible aptamers IF20, IF15, and IF10 were found to bind to the H5N1 and H5N2, H5N1 and H5N8, or H5N1, H5N2, and H5N8, respectively. Moreover, aptamers IF10 and IF22 were found to bind H5N1 virus simultaneously and confirmed to bind the different site of the same H5N1 whole virus. Therefore, this pair of aptamers, IF10 and IF22, were successfully applied to develop the sandwich-type SPR-based biosensor assay which is rapid, accurate for the detection of AI whole virus from H5N1-infected feces samples. The minimum detectible concentration of H5N1 whole virus was found to be 200 EID50/ml with this sandwich-type detection using the aptamer pair obtained in this study. In addition, the sensitivity of this biosensor was successfully enhanced by using the signal amplification with the secondary aptamer conjugated with gold nanoparticles.
•Few of aptamers were successfully screened and characterized for whole viruses, H5Nx.•A pair of aptamer IF10 and IF22 was found to bind H5N1 virus simultaneously and confirmed to bind the different site of the H5N1 whole virus.•This pair of aptamers were successfully applied to develop the sandwich-type SPR-based biosensor for detection of H5N1 whole virus.•The LOD of SPR-based biosensor was found to be 200 EID50/ml H5N1.
Zinc is an important trace metal in immune systems, and zinc transporters are involved in many immune responses. Recent advances have revealed the structural and biochemical bases for zinc transport ...across the cell membrane, with clinical implications for the regulation of zinc homeostasis in immune cells like dendritic cells, T cells, B cells, and mast cells. In this review, we discuss the function, structure, and transport aspects of two major mammalian zinc transporter types, importers and exporters. First, Zrt-/Irt-like proteins (ZIPs) mediate the zinc influx from the extracellular or luminal side into the cytoplasm. There are 14 ZIP family members in humans. They form a homo- or heterodimer with 8 transmembrane domains and extra-/intracellular domains of various lengths. Several ZIP members show specific extracellular domains composed of two subdomains, a helix-rich domain and proline-alanine-leucine (PAL) motif-containing domain. Second, ZnT (zinc transporter) was initially identified in early studies of zinc biology; it mediates zinc efflux as a counterpart of ZIPs in zinc homeostasis. Ten family members have been identified. They show a unique architecture characterized by a Y-shaped conformation and a large cytoplasmic domain. A precise, comprehensive understanding of the structures and transport mechanisms of ZIP and ZnT in combination with mice experiments would provide promising drug targets as well as a basis for identifying other transporters with therapeutic potential.
Rodlike “POSS–bottlebrush block copolymers” (POSSBBCPs) containing crystalline polyhedral oligomeric silsesquioxane (POSS) pendants in A block and amorphous polymeric grafts in B block were utilized ...to create one-dimensional (1D) photonic crystals (PCs). 3-(12-(cis-5-Norbornene-exo-2,3-dicarboximido)dodecanoylamino)propylheptaisobutyl POSS (NB-A16-POSS, MA) and exo-5-norbornene-2-carbonyl-end poly(benzyl methacrylate) (NBPBzMA, MB) were employed in sequential ring-opening metathesis polymerization to afford poly3-(12-(cis-5-norbornene-exo-2,3-dicarboximido)dodecanoylamino)propylheptaisobutyl POSS-block-poly(exo-5-norbornene-2-carbonylate-graft-benzyl methacrylate)s, P(NB-A16-POSS)- b -P(NB- g -BzMA)s, with well-modulated block compositions (f A = 34, 50, and 67 wt %) and overall degrees of polymerization (DP = 323–939). The P(NB-A16-POSS)- b -P(NB- g -BzMA)s hierarchically self-assembled to form highly ordered 1D PC films with periodic lamellar arrays that can reflect visible light with particular wavelengths. Their reflectance bandwidths, reflectivities, and ranges of peak reflectance wavelnegth (λpeak) were largely dependent on the block composition. The 1D PC films based on lamellar P(NB-A16-POSS)- b -P(NB- g -BzMA)s demonstrated the capability of formaulation of λpeak as linear functions of initial polymerization parameter (M0/I0).
Lichens are symbiotic organisms which produce distinct secondary metabolic products. In the present study, we tested the cytotoxic activity of 17 lichen species against several human cancer cells and ...further investigated the molecular mechanisms underlying their anti-cancer activity. We found that among 17 lichens species, F. cucullata exhibited the most potent cytotoxicity in several human cancer cells. High performance liquid chromatography analysis revealed that the acetone extract of F. cucullata contains usnic acid, salazinic acid, Squamatic acid, Baeomycesic acid, d-protolichesterinic acid, and lichesterinic acid as subcomponents. MTT assay showed that cancer cell lines were more vulnerable to the cytotoxic effects of the extract than non-cancer cell lines. Furthermore, among the identified subcomponents, usnic acid treatment had a similar cytotoxic effect on cancer cell lines but with lower potency than the extract. At a lethal dose, treatment with the extract or with usnic acid greatly increased the apoptotic cell population and specifically activated the apoptotic signaling pathway; however, using sub-lethal doses, extract and usnic acid treatment decreased cancer cell motility and inhibited in vitro and in vivo tumorigenic potentials. In these cells, we observed significantly reduced levels of epithelial-mesenchymal transition (EMT) markers and phosphor-Akt, while phosphor-c-Jun and phosphor-ERK1/2 levels were only marginally affected. Overall, the anti-cancer activity of the extract is more potent than that of usnic acid alone. Taken together, F. cucullata and its subcomponent, usnic acid together with additional component, exert anti-cancer effects on human cancer cells through the induction of apoptosis and the inhibition of EMT.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inspired by the effectiveness of low-intensity ultrasound on tissue regeneration, we investigated the potential effect of short-term high-intensity ultrasound treatment for acceleration of wound ...healing in an in vitro wound model and dermal equivalent, both comprising human dermal fibroblasts. Short-term ultrasound of various amplitudes significantly increased the proliferation and migration of fibroblasts and subsequently increased the production of the extracellular matrix components fibronectin and collagen type I, both of which are important for wound healing and are secreted by fibroblasts. In addition, ultrasound treatment increased the contraction of a fibroblast-embedded three-dimensional collagen matrix, and the effect was synergistically increased in the presence of TGF-β. RNA-sequencing and bioinformatics analyses revealed changes in gene expression and p38 and ERK1/2 MAPK pathway activation in the ultrasound-stimulated fibroblasts. Our findings suggest that ultrasound as a mechanical stimulus can activate human dermal fibroblasts. Therefore, the activation of fibroblasts using ultrasound may improve the healing of various types of wounds and increase skin regeneration.
We developed a methodology, inspired by the folding of proteins, for the precision synthesis of hairy polymer nanoparticles. High-molar mass and narrowly dispersed graft copolymers were synthesized ...by graft-through ring opening metathesis polymerization, to incorporate a designated number of side chains and dimerizable cinnamic acid groups. Intrachain photodimerization collapsed the backbone and arrested it into a compact globular conformation, resulting in hairy nanoparticles topologically equivalent to a core cross-linked star polymer. The single-chain collapse process translates the molecular information written on the 1D graft copolymer into the 3D globular polymer nanoparticle, like protein folding. Unprecedented control over structural parameters was achieved, including the length, number, and composition of the side chains as well as cross-linking density. Different side chains formed distinct subdomains in the sterically congested nanoparticle state and further self-assembled into micellar aggregates in a selective solvent. Both experimental observations and computational simulations indicated that preorganization of the side chains in the block sequence produces subdomains which primarily follow the backbone length scale, while random sequences showed side chain-dependent scaling. Polymer nanoparticles with discrete multiple subdomains were produced by folding of the ternary block graft copolymers. Drastic differences in the self-assembly behavior of ABC- and ACB-sequenced nanoparticles indicate that the spatial organization of subdomains can be achieved by sequence control.
In this study, a novel exploration method for centralized training and decentralized execution (CTDE)-based multi-agent reinforcement learning (MARL) is introduced. The method uses the concept of ...strangeness, which is determined by evaluating (1) the level of the unfamiliarity of the observations an agent encounters and (2) the level of the unfamiliarity of the entire state the agents visit. An exploration bonus, which is derived from the concept of strangeness, is combined with the extrinsic reward obtained from the environment to form a mixed reward, which is then used for training CTDE-based MARL algorithms. Additionally, a separate action-value function is also proposed to prevent the high exploration bonus from overwhelming the sensitivity to extrinsic rewards during MARL training. This separate function is used to design the behavioral policy for generating transitions. The proposed method is not much affected by stochastic transitions commonly observed in MARL tasks and improves the stability of CTDE-based MARL algorithms when used with an exploration method. By providing didactic examples and demonstrating the substantial performance improvement of our proposed exploration method in CTDE-based MARL algorithms, we illustrate the advantages of our approach. These evaluations highlight how our method outperforms state-of-the-art MARL baselines on challenging tasks within the StarCraft II micromanagement benchmark, underscoring its effectiveness in improving MARL.
Natural killer (NK) cells are lymphocytes that can directly destroy cancer cells. When NK cells are activated, CD56 and CD107a markers are able to recognize cancer cells and release perforin and ...granzyme B proteins that induce apoptosis in the targeted cells. In this study, we focused on the role of phytoncides in activating NK cells and promoting anticancer effects. We tested the effects of several phytoncide compounds on NK-92mi cells and demonstrated that α-pinene treatment exhibited higher anticancer effects, as observed by the increased levels of perforin, granzyme B, CD56 and CD107a. Furthermore, α-pinene treatment in NK-92mi cells increased NK cell cytotoxicity in two different cell lines, and immunoblot assays revealed that the ERK/AKT pathway is involved in NK cell cytotoxicity in response to phytoncides. Furthermore, CT-26 colon cancer cells were allografted subcutaneously into BALB/c mice, and α-pinene treatment then inhibited allografted tumor growth. Our findings demonstrate that α-pinene activates NK cells and increases NK cell cytotoxicity, suggesting it is a potential compound for cancer immunotherapy.
Aim
Bacteria naturally produce membrane vesicles (MVs), which have been shown to contribute to the spread of multi‐drug resistant bacteria (MDR) by delivering antibiotic‐resistant substances to ...antibiotic‐susceptible bacteria. Here, we aim to show that MVs from Gram‐positive bacteria are capable of transferring β‐lactam antibiotic‐resistant substances to antibiotic‐sensitive Gram‐negative bacteria.
Materials and Methods
MVs were collected from a methicillin‐resistant strain of Staphylococcus aureus (MRSA) and vesicle‐mediated fusion with antimicrobial‐sensitive Escherichia coli (RC85). It was performed by exposing the bacteria to the MVs to develop antimicrobial‐resistant E. coli (RC85‐T).
Results
The RC85‐T exhibited a higher resistance to β‐lactam antibiotics compared to the parent strain. Although the secretion rates of the MVs from RC85‐T and the parent strain were nearly equal, the β‐lactamase activity of the MVs from RC85‐T was 12‐times higher than that of MVs from the parent strain, based on equivalent protein concentrations. Moreover, MVs secreted by RC85‐T were able to protect β‐lactam‐susceptible E. coli from β‐lactam antibiotic‐induced growth inhibition in a dose‐dependent manner.
Conclusion
MVs play a role in transferring substances from Gram‐positive to Gram‐negative bacteria, shown by the release of MVs from RC85‐T that were able to protect β‐lactam‐susceptible bacteria from β‐lactam antibiotics.
Significance and impact of study
MVs are involved in the emergence of antibiotic‐resistant strains in a mixed bacterial culture, helping us to understand how the spread of multidrug‐resistant bacteria could be reduced.