Molecular mechanism of specific DNA sequence recognition by NRF1.

Nuclear respiratory factor 1 (NRF1) regulates the expression of genes that are vital for mitochondrial biogenesis, respiration, and various other cellular processes. While NRF1 has been reported to bind specifically to GC-rich promoters as a homodimer, the precise molecular mechanism governing its recognition of target gene promoters has remained elusive. To unravel the recognition mechanism, we have determined the crystal structure of the NRF1 homodimer bound to an ATGCGCATGCGCAT dsDNA. In this complex, NRF1 utilizes a flexible linker to connect its dimerization domain (DD) and DNA binding domain (DBD). This configuration allows one NRF1 monomer to adopt a U-turn conformation, facilitating the homodimer to specifically bind to the two TGCGC motifs in the GCGCATGCGC consensus sequence from opposite directions. Strikingly, while the NRF1 DBD alone could also bind to the half-site (TGCGC) DNA of the consensus sequence, the cooperativity between DD and DBD is essential for the binding of the intact GCGCATGCGC sequence and the transcriptional activity of NRF1. Taken together, our results elucidate the molecular mechanism by which NRF1 recognizes specific DNA sequences in the promoters to regulate gene expression.

Fine structure and assembly pattern of a minimal myophage Pam3.

The myophage possesses a contractile tail that penetrates its host cell envelope. Except for investigations on the bacteriophage T4 with a rather complicated structure, the assembly pattern and tail contraction mechanism of myophage remain largely unknown. Here, we present the fine structure of a freshwater Myoviridae cyanophage Pam3, which has an icosahedral capsid of ~680 Å in diameter, connected via a three-section neck to an 840-Å-long contractile tail, ending with a three-module baseplate composed of only six protein components. This simplified baseplate consists of a central hub-spike surrounded by six wedge heterotriplexes, to which twelve tail fibers are covalently attached via disulfide bonds in alternating upward and downward configurations. In vitro reduction assays revealed a putative redox-dependent mechanism of baseplate assembly and tail sheath contraction. These findings establish a minimal myophage that might become a user-friendly chassis phage in synthetic biology.

Structural basis for specific DNA sequence motif recognition by the TFAP2 transcription factors.

The TFAP2 family regulates gene expression during differentiation, development, and organogenesis, and includes five homologs in humans. They all possess a highly conserved DNA binding domain (DBD) followed by a helix-span-helix (HSH) domain. The DBD-HSH tandem domain specifically binds to a GCC(N3)GGC consensus sequence, but the precise recognition mechanisms remain unclear. Here, we found that TFAP2 preferred binding to the GCC(N3)GGC sequence, and the pseudo-palindromic GCC and GGC motifs and the length of the central spacer between the two motifs determined their binding specificity. Structural studies revealed that the two flat amphipathic α-helical HSH domains of TFAP2A stacked with each other to form a dimer via hydrophobic interactions, while the stabilized loops from both DBD domains inserted into two neighboring major grooves of the DNA duplex to form base-specific interactions. This specific DNA binding mechanism controlled the length of the central spacer and determined the DNA sequence specificity of TFAP2. Mutations of the TFAP2 proteins are implicated in various diseases. We illustrated that reduction or disruption of the DNA binding ability of the TFAP2 proteins is the primary cause of TFAP2 mutation-associated diseases. Thus, our findings also offer valuable insights into the pathogenesis of disease-associated mutations in TFAP2 proteins.

Induced pluripotent stem cell-derived extracellular vesicles overexpressing SFPQ protect retinal Müller cells against hypoxia-induced injury.

Splicing factor proline/glutamine-rich (SFPQ) is expressed in induced pluripotent stem cells (iPSCs), which are reported to orchestrate hypoxic injury responses and release extracellular vesicles (EVs). Therefore, this study sought to explore the role of iPSC-derived EVs carrying SFPQ in hypoxia-induced injury to retinal Müller cells. We induced oxygen-glucose deprivation/reoxygenation (OGD/R) in Müller cells. SFPQ was overexpressed or knocked down in iPSCs, from which EVs were extracted. Müller cells were co-cultured with EVs, and the results indicated that SFPQ protein was transferred into retinal Müller cells by iPSC-derived EVs. We identified an interaction of SFPQ with HDAC1 in retinal Müller cells. Specifically, SFPQ recruited HDAC1 to downregulate HIF-2α by regulating its acetylation. The in vitro studies suggested that iPSC-derived EVs, SFPQ or HDAC1 overexpression, or HIF-2α silencing diminished cell injury and apoptosis but elevated proliferation in retinal Müller cells. The in vivo studies indicated that iPSC-derived EVs containing SFPQ curtailed apoptosis of retinal Müller cells, thus alleviating retinal ischemia/reperfusion (I/R) injury of rat model. Taken together, iPSC-derived EVs containing SFPQ upregulated HDAC1 to attenuate OGD/R-induced Müller cell injury via downregulation of HIF-2α.

Catalytic Ozonation of Polluter Benzene from -20 to >50 °C with High Conversion Efficiency and Selectivity on Mullite YMn2O5.

Catalytic decomposition of aromatic polluters at room temperature represents a green route for air purification but is currently challenged by the difficulty of generating reactive oxygen species (ROS) on catalysts. Herein, we develop a mullite catalyst YMn2O5 (YMO) with dual active sites of Mn3+ and Mn4+ and use ozone to produce a highly reactive O* upon YMO. Such a strong oxidant species on YMO shows complete removal of benzene from -20 to >50 °C with a high COx selectivity (>90%) through the generated reactive species O* on the catalyst surface (60 000 mL g-1 h-1). Although the accumulation of water and intermediates gradually lowers the reaction rate after 8 h at 25 °C, a simple treatment by ozone purging or drying in the ambient environment regenerates the catalyst. Importantly, when the temperature increases to 50 °C, the catalytic performance remains 100% conversion without any degradation for 30 h. Experiments and theoretical calculations show that such a superior performance stems from the unique coordination environment, which ensures high generation of ROS and adsorption of aromatics. Mullite's catalytic ozonation degradation of total volatile organic compounds (TVOC) is applied in a home-developed air cleaner, resulting in high efficiency of benzene removal. This work provides insights into the design of catalysts to decompose highly stable organic polluters.

Ozone Decomposition below Room Temperature Using Mn-based Mullite YMn2O5.

A super-low-temperature ozone decomposition is realized without energy consumption on a ternary oxide catalyst mullite YMn2O5 for the first time. The YMn2O5 oxide catalyzed ozone decomposition from a low temperature of -40 °C with 29% conversion (reaction rate: 1534.2 µmol g-1 h-1) and quickly reached 100% (5459.5 µmol g-1 h-1) when warmed up to -5 °C. The superior low-temperature performance over YMn2O5 could surpass that of the reported ozone decomposition catalysts. The structure and element valence characterizations confirmed that YMn2O5 remained the same after 100 h of room-temperature reaction, indicating excellent durability of the catalyst. O2-TPD (O2-temperature-programmed desorption) showed that the active sites are the Mn3+ sites bonded with singly coordinated oxygen on the surface. Combined with in situ Raman measurements and density functional theory calculations, we found that the ozone decomposition reaction on YMn2O5 showed a barrier of only 0.29 eV, following the Eley-Rideal (E-R) mechanism with a rate-limiting step of intermediate O22- desorption. The low barrier minimizes the accumulation of intermediate products and realizes the fast O3 decomposition even at super-low temperatures. Fundamentally, the moderate Mn-O bonding strength in the low-symmetry ternary oxides is crucial to produce singly coordinated active species on the surface responsible for the efficient ozone degradation at low temperatures.

Characterizing Key Volatile Pollutants Emitted from Adhesives by Chemical Compositions, Odor Contributions and Health Risks.

As one of the major sources of volatile pollutants in indoor air, gaseous emissions from adhesives during interior decoration have attracted increasing concern. Identifying major volatile pollutants and the risk in adhesive gaseous emissions is of great significance, but remains rarely reported. In the present research, we assessed the major volatile pollutants emitted from white emulsion adhesive and silicone adhesive samples (n = 30) from three aspects: chemical composition, odor and health risk contributions. The results showed that a total of 21 volatile pollutants were detected. Significantly, xylene was the most concentrated compound from white emulsion adhesives, accounting for 45.51% of the total concentrations. Butanone oxime was the most concentrated compound in silicone adhesives, accounting for 69.86% of the total concentrations. The trends in odor concentration (evaluated by the odor activity value method) over time were well correlated with the total chemical concentrations. Xylene (58.00%) and butanone oxime (76.75%) showed the highest odor contribution, respectively. Moreover, from an integrated perspective of chemical emissions, odor and health risk contributions, xylene, ethylbenzene, ethyl acetate and benzene were identified as the key volatile pollutants emitted from the white emulsion adhesives, while butanone oxime, butanone, and ethanol were the key volatile pollutants emitted from the silicone adhesives. This study not only identified the key volatile pollutants but also provided characteristics of odor and health risks of gas emitted from adhesives.

Coordinating carbon and nitrogen metabolic signaling through the cyanobacterial global repressor NdhR.

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.

Crystal structure of a novel fold protein Gp72 from the freshwater cyanophage Mic1.

Cyanophages, widespread in aquatic systems, are a class of viruses that specifically infect cyanobacteria. Though they play important roles in modulating the homeostasis of cyanobacterial populations, little is known about the freshwater cyanophages, especially those hypothetical proteins of unknown function. Mic1 is a freshwater siphocyanophage isolated from the Lake Chaohu. It encodes three hypothetical proteins Gp65, Gp66, and Gp72, which share an identity of 61.6% to 83%. However, we find these three homologous proteins differ from each other in oligomeric state. Moreover, we solve the crystal structure of Gp72 at 2.3 Å, which represents a novel fold in the α + ß class. Structural analyses combined with redox assays enable us to propose a model of disulfide bond mediated oligomerization for Gp72. Altogether, these findings provide structural and biochemical basis for further investigations on the freshwater cyanophage Mic1.

NO is involved in H2-induced adventitious rooting in cucumber by regulating the expression and interaction of plasma membrane H+-ATPase and 14-3-3.

MAIN CONCLUSION: NO was involved in H2-induced adventitious rooting by regulating the protein and gene expressions of PM H+-ATPase and 14-3-3. Simultaneously, the interaction of PM H+-ATPase and 14-3-3 protein was also involved in this process. Hydrogen gas (H2) and nitric oxide (NO) have been shown to be involved in plant growth and development. The results in this study revealed that NO was involved in H2-induced adventitious root formation. Western blot (WB) analysis showed that the protein abundances of plasma membrane H+-ATPase (PM H+-ATPase) and 14-3-3 protein were increased after H2, NO, H2 plus NO treatments, whereas their protein abundances were down regulated when NO scavenger carboxy-2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTI O) was added. Moreover, the mRNA abundances of the HA3 and 14-3-3(7) gene as well as the activities of PM H+-ATPase (EC 3.6.1.35) and H+ pump were in full agreement with the changes of protein abundance. Phosphorylation of PM H+-ATPase and the interaction of PM H+-ATPase and 14-3-3 protein were detected by co-immunoprecipitation analysis. H2 and NO significantly up regulated the phosphorylation of PM H+-ATPase and the interaction of PM H+-ATPase and 14-3-3 protein. Conversely, the stimulation of PM H+-ATPase phosphorylation and protein interaction were significantly diminished by cPTIO. Protein interaction activator fusicoccin (FC) and inhibitor adenosine monophosphate (AMP) of PM H+-ATPase and 14-3-3 were used in this study, and the results showed that FC significantly increased the abundances of PM H+-ATPase and 14-3-3, while AMP showed opposite trends. We further proved the critical roles of PM H+-ATPase and 14-3-3 protein interaction in NO-H2-induced adventitious root formation. Taken together, our results suggested that NO might be involved in H2-induced adventitious rooting by regulating the expression and the interaction of PM H+-ATPase and 14-3-3 protein.

Structures of an all-α protein running along the DNA major groove.

Despite over 3300 protein-DNA complex structures have been reported in the past decades, there remain some unknown recognition patterns between protein and target DNA. The silkgland-specific transcription factor FMBP-1 from the silkworm Bombyx mori contains a unique DNA-binding domain of four tandem STPRs, namely the score and three amino acid peptide repeats. Here we report three structures of this STPR domain (termed BmSTPR) in complex with DNA of various lengths. In the presence of target DNA, BmSTPR adopts a zig-zag structure of three or four tandem α-helices that run along the major groove of DNA. Structural analyses combined with binding assays indicate BmSTPR prefers the AT-rich sequences, with each α-helix covering a DNA sequence of 4 bp. The successive AT-rich DNAs adopt a wider major groove, which is in complementary in shape and size to the tandem α-helices of BmSTPR. Substitutions of DNA sequences and affinity comparison further prove that BmSTPR recognizes the major groove mainly via shape readout. Multiple-sequence alignment suggests this unique DNA-binding pattern should be highly conserved for the STPR domain containing proteins which are widespread in animals. Together, our findings provide structural insights into the specific interactions between a novel DNA-binding protein and a unique deformed B-DNA.

Characterization and prediction of odours from municipal sewage treatment plant.

One of the causes of public discomfort and complaint about odour in China is the nuisance odour, generated from the municipal sewage treatment plants. With the ability to be dispersed over a long distance, the odours can affect a large number of people. With the aim of identifying the compounds contributing the most to the overall odour emanating from municipal sewage treatment plant, and developing a prediction model for sensory odour concentration based on the compound odour activity value (OAV), odour samples from 2 days were collected at a municipal sewage treatment plant in Tianjin in the months of October and November 2013. Odour concentrations (OCs) were measured by the triangular odour bag method. Chemical components were quantified by gas chromatography-mass spectrometry. According to the analysis of odour emission characteristics, it was found that hydrogen sulfide and methyl mercaptan were the key odorants responsible for the overall odour. To understand the interrelationship of these two odorants, 10 groups of a binary mixture of hydrogen sulfide and methyl mercaptan, representing different levels of odour concentration and intensity, were prepared in the laboratory. OCs were regressed against OAV using multivariate linear regression. A statistically significant positive correlation was found between single-compound OAV and odour concentration (by both SPSS and Minitab software). Furthermore, the models were validated by field monitoring data, which showed the odour prediction concentration had a good fit to the measured concentration by using Minitab software. Lastly, the Austal 2000 model system was used for the simulation of the odour emission dispersion into the surrounding area. This study provides an effective way to predict the odour emission condition in municipal sewage treatment plant.

Structural Analysis of the Catalytic Mechanism and Substrate Specificity of Anabaena Alkaline Invertase InvA Reveals a Novel Glucosidase.

Invertases catalyze the hydrolysis of sucrose to glucose and fructose, thereby playing a key role in primary metabolism and plant development. According to the optimum pH, invertases are classified into acid invertases (Ac-Invs) and alkaline/neutral invertases (A/N-Invs), which share no sequence homology. Compared with Ac-Invs that have been extensively studied, the structure and catalytic mechanism of A/N-Invs remain unknown. Here we report the crystal structures of Anabaena alkaline invertase InvA, which was proposed to be the ancestor of modern plant A/N-Invs. These structures are the first in the GH100 family. InvA exists as a hexamer in both crystal and solution. Each subunit consists of an (α/α)6 barrel core structure in addition to an insertion of three helices. A couple of structures in complex with the substrate or products enabled us to assign the subsites -1 and +1 specifically binding glucose and fructose, respectively. Structural comparison combined with enzymatic assays indicated that Asp-188 and Glu-414 are putative catalytic residues. Further analysis of the substrate binding pocket demonstrated that InvA possesses a stringent substrate specificity toward the α1,2-glycosidic bond of sucrose. Together, we suggest that InvA and homologs represent a novel family of glucosidases.

Diosmetin protects against ischemia/reperfusion-induced acute kidney injury in mice.

BACKGROUND: Renal ischemia/reperfusion (I/R)-induced acute kidney injury remains to be a troublesome condition in clinical practice. Although the exact molecular mechanisms underlying renal I/R injury are incompletely understood, the deleterious progress of renal I/R injury involves inflammation, apoptosis, and oxidative stress. Diosmetin is a member of the flavonoid glycosides family, which suppresses the inflammatory response and cellular apoptosis and enhances antioxidant activity. The purpose of this study was to investigate the protective effect of diosmetin on I/R-induced renal injury in mice. METHODS: Thirty BALB/c mice were randomly divided into five groups. Four groups of mice received diosmetin (0.25, 0.5, and 1 mg/kg) or vehicle (I/R group) before ischemia. Another group received vehicle without ischemia to serve as a negative control (sham-operated group). Twenty-four hours after reperfusion, serum and renal tissues were harvested to evaluate renal function and histopathologic features. In addition, the expression of inflammation-related proteins, apoptotic molecules, and antioxidant enzymes was analyzed. RESULTS: Compared with sham mice, the I/R group significantly exacerbated renal function and renal tube architecture and increased the inflammatory response and renal tubule apoptosis. Nevertheless, pretreatment with diosmetin reversed these changes. In addition, diosmetin treatment resulted in a marked increase in antioxidant protein expression compared with I/R mice. CONCLUSIONS: The renoprotective effects of diosmetin involved suppression of the nuclear factor-κB and mitochondrial apoptosis pathways, as well as activation of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 pathway. Diosmetin has significant potential as a therapeutic intervention to ameliorate renal injury after renal I/R.

Comparative analyses of secreted proteins from the phytopathogenic fungus Verticillium dahliae in response to nitrogen starvation.

The soilborne fungus Verticillium dahliae is the major pathogen that causes the verticillium wilt disease of plants, which leads to huge economic loss worldwide. At the early stage of infection, growth of the pathogen is subject to the nutrition stress of limited nitrogen. To investigate the secreted pathogenic proteins that play indispensable roles during invasion at this stage, we compared the profiles of secreted proteins of V. dahliae under nitrogen starvation and normal conditions by using in-gel and in-solution digestion combined with liquid chromatography-nano-electrospray ionization tandem mass spectrometry (LC-nanoESI-MS). In total, we identified 212 proteins from the supernatant of liquid medium, including 109 putative secreted proteins. Comparative analysis indicated that the expression of 76 proteins was induced, whereas that of 9 proteins was suppressed under nitrogen starvation. Notably, 24 proteins are constitutively expressed. Further bioinformatic exploration enabled us to classify the stress-induced proteins into seven functional groups: cell wall degradation (10.5%), reactive oxygen species (ROS) scavenging and stress response (11.8%), lipid effectors (5.3%), protein metabolism (21.1%), carbohydrate metabolism (15.8%), electron-proton transport and energy metabolism (14.5%), and other (21.0%). In addition, most stress-suppressed proteins are involved in the cell-wall remodeling. Taken together, our analyses provide insights into the pathogenesis of V. dahliae and might give hints for the development of novel strategy against the verticillium wilt disease.

Characterization of the First Fungal Glycosyl Hydrolase Family 19 Chitinase (NbchiA) from Nosema bombycis (Nb).

Chitinases (EC 3.2.1.14), as one kind of glycosyl hydrolase, hydrolyze the ß-(1,4) linkages of chitin. According to the sequence similarity, chitinases can be divided into glycoside hydrolase family 18 and family 19. Here, a chitinase from Nosema bombycis (NbchiA) was cloned and purified by metal affinity chromatography and molecular exclusion chromatography. Sequence analysis indicated that NbchiA belongs to glycoside hydrolase family 19 class IV chitinase. The optimal pH and temperature of NbchiA are 7.0 and 40 °C, respectively. This purified chitinase showed high activity toward soluble substrates such as ethylene glycol chitin and soluble chitosan. The degradation of chitin oligosaccharides (GlcNAc)(2-5) detected by high-performance liquid chromatography showed that NbchiA hydrolyzed mainly the second glycosidic linkage from the reducing end of (GlcNAc)(3-5). On the basis of structure-based multiple-sequence alignment, Glu51 and Glu60 are believed to be the key catalytic residues. The site-directed mutation analysis revealed that the enzymatic activity was decreased upon mutation of Glu60, whereas mutation of Glu51 totally abolished the enzymatic activity. This is the first report of a GH19 chitinase in fungi and in Microsporidia.

Sex effect on insulin secretion and mitochondrial function in pancreatic beta cells of elderly Wistar rats.

AIMS/HYPOTHESIS: Glucose tolerance progressively declines with age, and there is a high prevalence of type 2 diabetes in the elderly people. Previous studies have reported the sex differences in risk for type 2 diabetes, especially in the elderly people, whereas reasons for these sex differences remain poorly understood. This study aims to evaluate the effect of sex on glucose-stimulated insulin secretion and mitochondrial function in pancreatic beta cells of Wistar rats. METHODS: 3-month-old and 18-month-old Wistar rats of both sexes were used. Insulin secretion of islets was analyzed by glucose-stimulated insulin secretion and islet perifusion assays; ATP content and oxygen consumption rate of islets were determined to evaluate the mitochondrial function. RESULTS: Insulin secretion of islets under high glucose conditions declined significantly with age in both sexes. Glucose-stimulated insulin secretion of elderly female groups was markedly higher than that of male groups under high glucose conditions. Importantly, islets from elderly female groups showed higher mitochondrial function compared with male counterparts, evidenced by higher ATP content and oxygen consumption rate under high glucose conditions. It was also noted that mitochondrial biogenesis of islets from elderly female rats was significant higher compared with male rats. There were notable increases in expression of genes involved in mitochondrial biogenesis in islets from elderly female rats compared with male rats. CONCLUSION: This study demonstrates a sex dimorphism in the age-associated impairment of pancreatic beta cell function in elderly rats, while the potential mechanism may be related to the sexual differences in mitochondrial biogenesis and function.

Structural insights into the cofactor-assisted substrate recognition of yeast methylglyoxal/isovaleraldehyde reductase Gre2.

Saccharomyces cerevisiae Gre2 (EC1.1.1.283) serves as a versatile enzyme that catalyzes the stereoselective reduction of a broad range of substrates including aliphatic and aromatic ketones, diketones, as well as aldehydes, using NADPH as the cofactor. Here we present the crystal structures of Gre2 from S. cerevisiae in an apo-form at 2.00Å and NADPH-complexed form at 2.40Å resolution. Gre2 forms a homodimer, each subunit of which contains an N-terminal Rossmann-fold domain and a variable C-terminal domain, which participates in substrate recognition. The induced fit upon binding to the cofactor NADPH makes the two domains shift toward each other, producing an interdomain cleft that better fits the substrate. Computational simulation combined with site-directed mutagenesis and enzymatic activity analysis enabled us to define a potential substrate-binding pocket that determines the stringent substrate stereoselectivity for catalysis.

A stochastic filtering approach to recover strain images from quasi-static ultrasound elastography.

BACKGROUND: Model-based reconstruction algorithms have shown potentials over conventional strain-based methods in quasi-static elastographic image by using realistic finite element (FE) or bio-mechanical model constraints. However, it is still difficult to properly handle the discrepancies between the model constraint and ultrasound data, and the measurement noise. METHODS: In this paper, we explore the usage of Kalman filtering algorithm for the estimation of strain imaging in quasi-static ultrasound elastography. The proposed strategy formulates the displacement distribution through biomechanical models, and the ultrasound-derived measurements through observation equations. Through this filtering strategy, the discrepancies are quantitatively modelled as one Gaussian white noise, and the measurement noise of ultrasound data is modelled as another independent Gaussian white noise. The optimal estimation of kinematic functions, i.e. the full displacement and velocity field, are computed through this Kalman filter. Then the strain images can be easily calculated from the estimated displacement field. RESULTS: The accuracy and robustness of our proposed framework is first evaluated in synthetic data in controlled conditions, and the performance of this framework is then evaluated in the real data collected from elastography phantoms and patients with favourable results. CONCLUSIONS: The potential of our algorithm is to provide the distribution of mechanically meaningful strain under a proper biomechanical model constraint. We address the model-data discrepancy and measurement noise by introducing process noise and measurement noise in our framework, and then the mechanically meaningful strain is estimated through the Kalman filter in the minimum mean square error (MMSE) sense.

Profiling the interplay and coevolution of Microcystis aeruginosa and cyanosiphophage Mic1.

The cyanosiphophage Mic1 specifically infects the bloom-forming Microcystis aeruginosa FACHB 1339 from Lake Chaohu, China. Previous genomic analysis showed that its 92,627 bp double-stranded DNA genome consists of 98 putative open reading frames, 63% of which are of unknown function. Here, we investigated the transcriptome dynamics of Mic1 and its host using RNA sequencing. In the early, middle, and late phases of the 10 h lytic cycle, the Mic1 genes are sequentially expressed and could be further temporally grouped into two distinct clusters in each phase. Notably, six early genes, including gp49 that encodes a TnpB-like transposase, immediately reach the highest transcriptional level in half an hour, representing a pioneer cluster that rapidly regulates and redirects host metabolism toward the phage. An in-depth analysis of the host transcriptomic profile in response to Mic1 infection revealed significant upregulation of a polyketide synthase pathway and a type III-B CRISPR system, accompanied by moderate downregulation of the photosynthesis and key metabolism pathways. The constant increase of phage transcripts and relatively low replacement rate over the host transcripts indicated that Mic1 utilizes a unique strategy to gradually take over a small portion of host metabolism pathways after infection. In addition, genomic analysis of a less-infective Mic1 and a Mic1-resistant host strain further confirmed their dynamic interplay and coevolution via the frequent horizontal gene transfer. These findings provide insights into the mutual benefit and symbiosis of the highly polymorphic cyanobacteria M. aeruginosa and cyanophages. IMPORTANCE: The highly polymorphic Microcystis aeruginosa is one of the predominant bloom-forming cyanobacteria in eutrophic freshwater bodies and is infected by diverse and abundant cyanophages. The presence of a large number of defense systems in M. aeruginosa genome suggests a dynamic interplay and coevolution with the cyanophages. In this study, we investigated the temporal gene expression pattern of Mic1 after infection and the corresponding transcriptional responses of its host. Moreover, the identification of a less-infective Mic1 and a Mic1-resistant host strain provided the evolved genes in the phage-host coevolution during the multiple-generation cultivation in the laboratory. Our findings enrich the knowledge on the interplay and coevolution of M. aeruginosa and its cyanophages and lay the foundation for the future application of cyanophage as a potential eco-friendly and bio-safe agent in controlling the succession of harmful cyanobacterial blooms.