Neural stem cells (NSCs), capable of ischemia‐homing, regeneration, and differentiation, exert strong therapeutic potentials in treating ischemic stroke, but the curative effect is limited in the ...harsh microenvironment of ischemic regions rich in reactive oxygen species (ROS). Gene transfection to make NSCs overexpress brain‐derived neurotrophic factor (BDNF) can enhance their therapeutic efficacy; however, viral vectors must be used because current nonviral vectors are unable to efficiently transfect NSCs. The first polymeric vector, ROS‐responsive charge‐reversal poly(2‐acryloyl)ethyl(p‐boronic acid benzyl)diethylammonium bromide (B‐PDEA), is shown here, that mediates efficient gene transfection of NSCs and greatly enhances their therapeutics in ischemic stroke treatment. The cationic B‐PDEA/DNA polyplexes can effectively transfect NSCs; in the cytosol, the B‐PDEA is oxidized by intracellular ROS into negatively charged polyacrylic acid, quickly releasing the BDNF plasmids for efficient transcription and secreting a high level of BDNF. After i.v. injection in ischemic stroke mice, the transfected NSCs (BDNF‐NSCs) can home to ischemic regions as efficiently as the pristine NSCs but more efficiently produce BDNF, leading to significantly augmented BDNF levels, which in turn enhances the mouse survival rate to 60%, from 0% (nontreated mice) or ≈20% (NSC‐treated mice), and enables more rapid and superior functional reconstruction.
The first nonviral gene carrier, reactive‐oxygen‐species‐responsive charge‐reversal poly(2‐acryloyl)‐ethyl(p‐boronic acid benzyl)diethylammonium bromide (B‐PDEA), is shown to mediate efficient gene transfection to neural stem cells (NSCs). When BDNF gene plasmids are used, the transfected NSCs homing to the ischemic regions increase animal survival and reconstruct functions.
In large-scale nuclear and particle physics experiments, there is a high demand for high precision clock distribution and synchronization. In this paper, the design and testing of a high precision ...clock distribution and synchronization system for the CSR External Target Experiment (CEE) is presented. To achieve high synchronization precision, a dedicated high-quality clock distribution network is designed, while the timestamp synchronization is achieved over the existing trigger link in CEE with a customized protocol in order to simplify the system structure. Automatic metastability elimination and real-time monitoring of both the timestamps on the front end nodes and the clock electronics status are also implemented. The test results indicate that the period jitter of the clock network is better than 4 ps rms, and all the expected functionalities have been achieved successfully.
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Gene engineered mesenchymal stem cells (MSCs) have been proposed as promising tools for their various applications in biomedicine. Nevertheless, the lack of an effective and safe way ...to genetically modify these stem cells is still a major obstacle in the current studies. Herein, we designed novel magnetic complexes by assembling cationized pullulan derivatives with magnetic iron oxide nanoparticles for delivering target genes to MSCs. Results showed that this complexes achieved effective gene expression with the assistance of external magnetic field, and resisted the adverse effect induced by serum proteins on the gene delivery. Moreover, neither significant cytotoxicity nor the interference on the osteogenic differentiation to MSCs were observed after magnetofection. Further studies revealed that this effective and serum resistant gene transfection was partly due to the accelerated and enhanced intracellular uptake process driven by external magnetic field. To conclude, the current study presented a novel option for genetic modification of MSCs in an effective, relatively safe and serum compatible way.
Background： Subthalarnic nucleus deep brain stimulation （STN DBS） is effective against advanced Parkinson＇s disease （PD）, allowing dramatic improvement of Parkinsonism, in addition to a significant ...reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China. Meihods： Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson＇s Disease Rating Scale Part Ⅲ （UPDRS Ill）, Parkinson＇s Disease Questionnatire-39, Parkinson＇s Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures. Resulis： In the ＂oft＂ state （off medication）, DBS improved UPDRS Ill scores by 35.87% in 5 years, compared with preoperative baseline （P 〈 0.001 ）. In the ＂on＂ state （on medication）, motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% （P 〈 0.001 ） from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years （by 52.96%, P 〈 0.001 ）. The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 Its, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively. Conclusions： STN DBS is an effective intervention for PD, although with other studies, patients in our study required lower voltage and associated with a slightly diminished efficacy after 5 years. Compared medication for satisfactory symptom control.
This study investigated the impact of topography and vegetation on distribution of rare earth elements（REEs）in calcareous soils using methods of single extraction and mass balance calculation. The ...purposes of the study were to set a basis for further research on the biogeochemical REE cycle and to provide references for soil–water conservation and REE-containing fertilizer amendments. The results show a generally flat Post-Archean Average Australian Shale—normalized REE pattern for the studied calcareous soils. REE enrichment varied widely. The proportion of acidsoluble phases of heavy REEs was higher than that of light REEs. From top to bottom of the studied hills, dominant REE sources transitioned from limestone in-situ weathering to input from REE-containing phases（e.g., clay minerals,amorphous iron, REE-containing fluids）. Our results indicate that the REE content of calcareous soils is mainly controlled by slope aspect, while the enrichment degree of REEs is related to geomorphological position and vegetation type.Furthermore, the proportion of acid-soluble phases of REEs is mainly controlled by geomorphological position.
In this study, we characterized the miR482 family in cotton using existing small RNA datasets and the recently released draft genome sequence of Gossypium raimondii, a diploid cotton species whose ...progenitor is the putative contributor of the Dt (representing the D genome of tetraploid) genome of the cultivated tetraploid cotton species G. hirsutum and G. barbadense. Of the three ghr-miR482 members reported in G. hirsutum, ghr-miR482a has no homolog in G. raimondii, ghr-miR482b and ghr-miR482c each has a single homolog in G. raimondii. Gra-miR482d has five homologous loci (gra-miR482d, f-i) in G. raimondii and also exists in G. hirsutum (ghr-miR482d). A variant, miR482.2 that is a homolog of miR2118 in other species, is produced from several GHR-MIR482 loci in G. hirsutum. Approximately 12% of the G. raimondii NBS-LRR genes were predicted targets of various members of the gra-miR482 family. Based on the rationale that the regulatory relationship between miR482 and NBS-LRR genes will be conserved in G. raimondii and G. hirsutum, we investigated this relationship using G. hirsutum miR482 and G. raimondii NBS-LRR genes, which are not currently available in G. hirsutum. Ghr-miR482/miR482.2-mediated cleavage was confirmed for three of the four NBS-LRR genes analysed. As in tomato, miR482-mediated cleavage of NBS-LRR genes triggered production of phased secondary small RNAs in cotton. In seedlings of the susceptible cultivar Sicot71 (G. hirsutum) infected with the fungal pathogen Verticillium dahliae, the expression levels of ghr-miR482b/miR482b.2, ghr-miR482c and ghr-miR482d.2 were down-regulated, and several NBS-LRR targets of ghr-miR482c and ghr-miR482d were up-regulated. These results imply that, like tomato plants infected with viruses or bacteria, cotton plants are able to induce expression of NBS-LRR defence genes by suppression of the miRNA-mediated gene silencing pathway upon fungal pathogen attack.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The genetic diversity and phenotypic variability of crop agronomic traits is valued by breeders for their benefits in crop breeding but are limited for most target traits. The rice Waxy (Wx) gene ...(LOC_Os06g04200) encodes granule‐bound starch synthase I (GBSSI), which determines the amylose content (AC) of endosperm by controlling amylose synthesis. The number of altered bases in each line (coloured in red) is indicated by the letter S followed by a number. (c) A structural model of Wxb constructed using the PROTEIN DATA BANK server; mutated residues contributing to the changes of AC are shown as spheres and are coloured (P124 in apricot, R125 in blue, R158 in red violet, G159 in white, V160 in green, D161 in red, T178 in orange and Y191 in purple). (d) Analysis of potential off‐target sites in the seven T1 edited lines. To determine the effect of these mutations on AC, we measured the apparent amylose contents (AACs) of grains from the seven mutant lines (Wxm5‐Wxm11), NIP (Wxb) and a 'soft rice' control Nangeng9108 (NG9108) (Wxmp) (Figure 1e).
OBJECTIVE： To investigate the effects of resveratrol （RV） in reprogramming mouse embryonic fibroblasts （MEFs） into induced pluripotent stem cells （iPSCs） and the related mechanism. METHODS： Primary ...MEFs were isolated from E13.5 embryos and used within three passages. Retroviruses expressing Sox2 and Oct4 were produced by transfecting GP2-293t cells with recombinant plasmids murine stern cell virus （MSCV）-Sox2 and MSCV-Oct4. Supernatants containing retroviruses were obtained after 48-hour transfection and MEFs were then infected. Different concentrations （0, 5, 10 and 20 IJmol/L） of RV were added to embryonic stem cell （ESC） medium to culture MEFs 48 h post-infection, iPSC clones emerged and were further cultured. Expression of pluripotent markers of iPSCs was identified by cell immunofluorescence and reverse transcription-polymerase chain reaction. Both cytotoxicity and cell proliferation were assayed by Western blot analysis after RV was added into ESC medium. The ultrastructure change of mitochondria was observed by electron microscopy. RESULTS： More than 2.9-fold and 1.3-fold increases in colony number were observed by treatment with RV at 5 and 10 pmol/L, respectively. The reprogramming efficiency was significantly decreased by treatment with 20 pmol/L RV. The proliferation effect on MEFs or MEFs infected by two factors Sox2/Oct4 （2 factors-MEFs, 2F-MEFs） was investigated after RV treatment. At 20 pmol/L RV, induced cell apoptosis and proliferation inhibition were more obvious than those of 5 and 10 IJmol/L treatments. Clones were selected from the 10 pmol/L RV-treated group and cultured. Green fluorescent protein expression from one typical clone was silenced one month later which expressed ESC-associated marker genes Gdf3, Nanog, Ecatl, Fgf4 and Foxd3. Electron transmission microscope showed obvious cavitations in mitochondria. The expression of hypoxia-inducible factor-la was up-regulated when 2F-MEFs were treated with RV compared to the control group. CONCLUSION： RV improved the efficiency of reprogramming 2F-MEFs into iPSCs at low and moderate concentrations （5 and 10 pmol/L）. The effect of 10 pmol/L RV on reprogramming was much greater than that of 5 pmol/L RV. However, high concentration of RV （20 pmol/L） led to more severe cavitations in mitochondria and caused cytotoxic effects. Taken together, these findinqs suqclest that RV mimics hypoxia in cells and promotes reprogramming at a low concentration.
Recent origination of circular RNAs in plants Chu, Qinjie; Ding, Yuwen; Xu, Xiaoxu ...
The New phytologist,
January 2022, 2022-01-00, 20220101, Letnik:
233, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Summary
Circular RNA (circRNA) is a kind of new regulatory RNA with diverse biological functions. Numerous circRNAs have been identified in many plant species; however, evolution of plant circRNAs ...remains largely unknown.
In this study, we assembled full‐length sequences of 6519 rice (Oryza sativa) circRNAs and analyzed their conservation in another 46 plant species based on comparison of sequences and expression patterns.
We found that, at the genomic level, 8.7% of the 6519 circRNAs were conserved in dicotyledonous plants and 49.1% in Oryza genus. Meanwhile, 57.8% of parental protein‐coding genes of the rice circRNAs originated recently after divergence of monocotyledonous plants, implying recent origin of the majority of rice circRNAs, a conclusion further supported by the results based on analysis of 4663 full‐length circRNAs in Arabidopsis thaliana. Accordingly, we proposed three models to address the origination of different types of circRNAs.
Taken together, the results obtained in this study provide new insights for the evolutionary dynamics of plant circRNAs and candidate circRNAs for further functional exploration.
Synchronization is the key part to ensure the high performance of grid-connected systems. Phase-locked loop (PLL) is one of the most popular synchronizations due to its simple implementation and ...robustness under certain grid variations. Particularly, in single-phase applications, PLL based on second-order generalized integrator (SOGI-PLL) is widely used because of its simple structure, certain filtering ability and frequency adaptability. The sensitivity of SOGI-PLL to the dc offset and low-order harmonics has been studied a lot in the literature and many solutions have been proposed. However, as more and more power electronic devices are integrated into the power grid recently, the grid condition becomes more complex. As a result, the nonlinear loop coupling phenomenon of SOGI-PLL is more severe and obvious and thus the performance of SOGI-PLL is degraded a lot, especially under the conditions of grid frequency variations and weak grid. A popular method is to use the frequency-fixed SOGI-PLL (FFSOGI-PLL) while how to eliminate the estimation error under frequency variations remain an important task. Though some scattered methods have been proposed, a simple yet effective strategy is still missing. Besides, it has been shown that the system stability margin will be reduced due to the negative-resistance behavior of PLL. However, the models derived in the current documents cannot accurately reveal the instabilities caused by the standard SOGI-PLL for missing the dynamics of the frequency feedback loop. Moreover, the PLL parameters are usually designed according to the PLL bandwidth to guarantee system stability under a weak grid. How to optimize the parameters is still unclear. In view of this, this article further summarizes and reviews the existing achievements of single-phase SOGI-PLL, and points out the problems to be solved and the development direction to improve the SOGI-PLL under more complex and non-ideal grid conditions.
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