Summary
FtsZ is a tubulin‐like GTPase that polymerizes to initiate the process of cell division in bacteria. Heterocysts are terminally differentiated cells of filamentous cyanobacteria that have ...lost the capacity for cell division and in which the ftsZ gene is downregulated. However, mechanisms of FtsZ regulation during heterocyst differentiation have been scarcely investigated. The patD gene is NtcA dependent and involved in the optimization of heterocyst frequency in Anabaena sp. PCC 7120. Here, we report that the inactivation of patD caused the formation of multiple FtsZ‐rings in vegetative cells, cell enlargement, and the retention of peptidoglycan synthesis activity in heterocysts, whereas its ectopic expression resulted in aberrant FtsZ polymerization and cell division. PatD interacted with FtsZ, increased FtsZ precipitation in sedimentation assays, and promoted the formation of thick straight FtsZ bundles that differ from the toroidal aggregates formed by FtsZ alone. These results suggest that in the differentiating heterocysts, PatD interferes with the assembly of FtsZ. We propose that in Anabaena FtsZ is a bifunctional protein involved in both vegetative cell division and regulation of heterocyst differentiation. In the differentiating cells PatD‐FtsZ interactions appear to set an FtsZ activity that is insufficient for cell division but optimal to foster differentiation.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The coordination of carbon and nitrogen metabolism is essential for bacteria to adapt to nutritional variations in the environment, but the underlying mechanism remains poorly understood. In ...autotrophic cyanobacteria, high CO₂ levels favor the carboxylase activity of ribulose 1,5 bisphosphate carboxylase/oxygenase (RuBisCO) to produce 3-phosphoglycerate, whereas low CO₂ levels promote the oxygenase activity of RuBisCO, leading to 2-phosphoglycolate (2-PG) production. Thus, the 2-PG level is reversely correlated with that of 2-oxoglutarate (2-OG), which accumulates under a high carbon/nitrogen ratio and acts as a nitrogen-starvation signal. The LysR-type transcriptional repressor NAD(P)H dehydrogenase regulator (NdhR) controls the expression of genes related to carbon metabolism. Based on genetic and biochemical studies, we report here that 2-PG is an inducer of NdhR, while 2-OG is a corepressor, as found previously. Furthermore, structural analyses indicate that binding of 2-OG at the interface between the two regulatory domains (RD) allows the NdhR tetramer to adopt a repressor conformation, whereas 2-PG binding to an intradomain cleft of each RD triggers drastic conformational changes leading to the dissociation of NdhR from its target DNA. We further confirmed the effect of 2-PG or 2-OG levels on the transcription of the NdhR regulon. Together with previous findings, we propose that NdhR can sense 2-OG from the Krebs cycle and 2-PG from photorespiration, two key metabolites that function together as indicators of intracellular carbon/nitrogen status, thus representing a fine sensor for the coordination of carbon and nitrogen metabolism in cyanobacteria.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
c-di-GMP is a ubiquitous bacterial signal regulating various physiological process.
PCC 7120 (
) is a filamentous cyanobacterium able to form regularly-spaced heterocysts for nitrogen fixation, in ...response to combined-nitrogen deprivation in 24h.
possesses 16 genes encoding proteins for c-di-GMP metabolism, and their functions are poorly characterized, except
(
) whose deletion causes a decrease in heterocyst frequency 48h after nitrogen starvation. We demonstrated here that c-di-GMP levels increased significantly in
after combined-nitrogen starvation. By inactivating each of the 16 genes, we found that the deletion of
5 (
) led to an increase of heterocyst frequency 24h after nitrogen stepdown. A double mutant
had an additive effect over the single mutants in regulating heterocyst frequency, indicating that the two genes acted at different time points for heterocyst spacing. Biochemical and genetic data further showed that the functions of CdgSH and CdgS in the setup or maintenance of heterocyst frequency depended on their opposing effects on the intracellular levels of c-di-GMP. Finally, we demonstrated that heterocyst differentiation was completely inhibited when c-di-GMP levels became too high or too low. Together, these results indicate that the homeostasis of c-di-GMP level is important for heterocyst differentiation in
.
EGFR-mutant lung adenocarcinomas (LUAD) display diverse clinical trajectories and are characterized by rapid but short-lived responses to EGFR tyrosine kinase inhibitors (TKIs). Through sequencing of ...79 spatially distinct regions from 16 early stage tumors, we show that despite low mutation burdens, EGFR-mutant Asian LUADs unexpectedly exhibit a complex genomic landscape with frequent and early whole-genome doubling, aneuploidy, and high clonal diversity. Multiple truncal alterations, including TP53 mutations and loss of CDKN2A and RB1, converge on cell cycle dysregulation, with late sector-specific high-amplitude amplifications and deletions that potentially beget drug resistant clones. We highlight the association between genomic architecture and clinical phenotypes, such as co-occurring truncal drivers and primary TKI resistance. Through comparative analysis with published smoking-related LUAD, we postulate that the high intra-tumor heterogeneity observed in Asian EGFR-mutant LUAD may be contributed by an early dominant driver, genomic instability, and low background mutation rates.
The filamentous, multicellular cyanobacterium
sp. PCC 7120 (
) is a prokaryotic model for the study of cell differentiation and cell-cell interactions. Upon combined-nitrogen deprivation,
forms a ...particular cell type, heterocyst, for aerobic nitrogen fixation. Heterocysts are semiregularly spaced among vegetative cells. Heterocyst differentiation is coupled to cell division, but the underlying mechanism remains unclear. This mechanism could be mediated by the putative protease HetF, which is a divisome component and is necessary for heterocyst differentiation. In this study, by suppressor screening, we identified PatU3, as a negative regulator acting downstream of HetF for cell division and heterocyst development. The inactivation of
restored the capacity of cell division and heterocyst differentiation in the Δ
mutant, and overexpression of
inhibited both processes in the wild-type background. We demonstrated that PatU3 was a specific substrate of the protease activity of HetF. Consequently, PatU3 accumulated in the
-deficient mutant, which was responsible for the resultant mutant phenotype. The cleavage site of PatU3 by HetF was mapped after the Arg117 residue, whose mutation made PatU3 resistant to HetF processing, and mimicked the effect of
deletion. Our results provided evidence that HetF regulated cell division and heterocyst differentiation by controlling the inhibitory effects of PatU3. This proteolytic pathway constituted a mechanism for the coordination between cell division and differentiation in a prokaryotic model used for studies on developmental biology and multicellularity.
The steel industry is one of the pillar industries in China. The physical and mental health of steel workers is related to the development of China's steel industry. Steel workers have long been ...working in shifts, high temperatures, noise, highly stressed, and first-line environments. These occupational related factors have an impact on the health of steel workers. At present, the existing hypertension risk scoring models do not include occupational related factors, so they are not applicable to the risk score of hypertension in steel workers. It is necessary to establish a risk scoring model for hypertension in steel workers. In this study, the learning vector quantization (LVQ) neural network algorithm and the Fisher-SVM coupling algorithm are applied to estimate the hypertension risk of steel workers, and the microscopic laws of the "tailing" phenomenon of the two algorithms are analyzed by means of graphics analysis, which can describe the influence trend of sample size change in different intervals on the classification effect. The results show that the classification accuracy of the algorithm depends on the size of the sample space. When the sample size <inline-formula> <tex-math notation="LaTeX">n \le 30~\ast </tex-math></inline-formula> (<inline-formula> <tex-math notation="LaTeX">k + 1 </tex-math></inline-formula>), the Fisher-SVM coupling intelligent algorithm is more applicable. Because its average accuracy rate is 90.00%, the average accuracy of the LVQ algorithm is only 63.34%. When the sample size is <inline-formula> <tex-math notation="LaTeX">n>30~\ast </tex-math></inline-formula> (<inline-formula> <tex-math notation="LaTeX">k + 1 </tex-math></inline-formula>), the LVQ algorithm is more applicable. Because its average accuracy rate is 93.33%, the average accuracy of the Fisher-SVM coupling intelligent algorithm is only 76.67%. The sample size of this paper is 4422, and the prediction of LVQ neural network model is more accurate. Therefore, based on the relative importance of each risk factor obtained by this model and to establish a steel worker hypertension risk rating scale, the score greater than 18 is considered as the high risk, 12-18 is considered as the medium risk, and less than 12 is considered as the low risk. Through the example's verification, the accuracy rate of the scale is 90.50% and the effect is very good. It shows that the established scoring system can effectively assess the risk of hypertension in steel workers and provide an effective basis for primary prevention of hypertension in steel workers.
Solid-state nanochannels have attracted considerable attention for their similar ion transport properties to biological ion channels. The construction of porous ion channels with good stability at ...the submicro/micrometer scale is very beneficial to develop large-area ion channel devices. In this manuscript, based on
in-situ
thermal crosslinking of a small organic molecule containing triphenylamine and styrene groups, we construct a heterogeneous membrane with asymmetrical charge and wettability on cylindrical anodic aluminum oxide (AAO) channels (
D
319 nm). This heterogeneous membrane has typical ion current rectification characteristics with a high rectification ratio of 36.9 and good stability. This work provides an effective strategy for the construction of submicrochannel heterogeneous membranes and also broadens the application range of bionic ion channels.
A submicrochannel heterogeneous membrane with asymmetric surface charge and wettability was constructed by
in-situ
thermal cross-linking polymerization on cylindrical AAO channels, and a typical ICR was presented by regulating the pH gradient.
Abstract
The bacterial ribonuclease RNase E plays a key role in RNA metabolism. Yet, with a large substrate spectrum and poor substrate specificity, its activity must be well controlled under ...different conditions. Only a few regulators of RNase E are known, limiting our understanding on posttranscriptional regulatory mechanisms in bacteria. Here we show that, RebA, a protein universally present in cyanobacteria, interacts with RNase E in the cyanobacterium Anabaena PCC 7120. Distinct from those known regulators of RNase E, RebA interacts with the catalytic region of RNase E, and suppresses the cleavage activities of RNase E for all tested substrates. Consistent with the inhibitory function of RebA on RNase E, depletion of RNase E and overproduction of RebA caused formation of elongated cells, whereas the absence of RebA and overproduction of RNase E resulted in a shorter-cell phenotype. We further showed that the morphological changes caused by altered levels of RNase E or RebA are dependent on their physical interaction. The action of RebA represents a new mechanism, potentially conserved in cyanobacteria, for RNase E regulation. Our findings provide insights into the regulation and the function of RNase E, and demonstrate the importance of balanced RNA metabolism in bacteria.
Graphical Abstract
Graphical Abstract
RNA turnover plays critical roles in the regulation of gene expression and allows cells to respond rapidly to environmental changes. In bacteria, the mechanisms of RNA turnover have been extensively ...studied in the models Escherichia coli and Bacillus subtilis, but not much is known in other bacteria. Cyanobacteria are a diverse group of photosynthetic organisms that have great potential for the sustainable production of valuable products using CO2 and solar energy. A better understanding of the regulation of RNA decay is important for both basic and applied studies of cyanobacteria. Genomic analysis shows that cyanobacteria have more than 10 ribonucleases and related proteins in common with E. coli and B. subtilis, and only a limited number of them have been experimentally investigated. In this review, we summarize the current knowledge about these RNA‐turnover‐related proteins in cyanobacteria. Although many of them are biochemically similar to their counterparts in E. coli and B. subtilis, they appear to have distinct cellular functions, suggesting a different mechanism of RNA turnover regulation in cyanobacteria. The identification of new players involved in the regulation of RNA turnover and the elucidation of their biological functions are among the future challenges in this field.
Near-infrared light (NIR) has the advantages of greater radiation depth, less tissue absorption and scattering, and lower risk, and the construction of a high-throughput NIR responsive membrane with ...ionic current rectification (ICR) characteristics in submicron or micron channels is of great significance for developing photoresponsive biosensors, and photoelectric and thermoelectric energy conversion in the future. In this paper, sulfhydryl- and carboxyl-terminated poly-
N
-isopropyl acrylamide with thermosensitivity is synthesized by a reversible addition-fragmentation chain transfer polymerization and ammonolysis reaction; it is further grafted at the base end of a polydopamine/Au nanoparticle-modified photothermal responsive heterogeneous membrane
via
a Au-S bond to achieve the thermosensitive polymer modification. After the asymmetric 808 nm NIR irradiation, the "on" or "off" status of a submicron channel can be realized stably and reversibly for the reversible phase transition of thermosensitive poly-
N
-isopropyl acrylamide under the photothermal effect of three polydopamine-Au layers. The conductance of the submicro-channel heterogeneous membrane with ICR characteristics increases at the asymmetric pH gradient, the rectification ratio maximally decreases by 11.4, and the photoresponsive current reaches 26.6 μA (0.1 mM KCl). At the same time, the ICR effect is also achieved at a high salt concentration of 1 M KCl and the photoresponsive current can reach 183.7 μA; the intensity of ICR and photoresponsive current can be effectively regulated by the power density, salt concentration and pH, and then the temperature-sensing switch with a NIR response is successfully constructed. This work provides a new way to improve the photoresponsive current and shows great potential in the fields of solar desalination and power generation.
A submicro-channel heterogeneous membrane with an 808 nm near-infrared light response is constructed as a temperature-sensing switch, showing a good ion current rectification effect and high photoresponsive current even at a high salt concentration.
PDF
