is a severe threat to human health as a frequently multidrug-resistant hospital-acquired pathogen. Part of the danger from this bacterium comes from its genome plasticity and ability to evolve ...quickly by taking up and recombining external DNA into its own genome in a process called natural competence for transformation. This mode of horizontal gene transfer is one of the major ways that bacteria can acquire new antimicrobial resistances and toxic traits. Because these processes in
are not well studied, we herein characterized new aspects of natural transformability in this species that include the species' competence window. We uncovered a strong correlation with a growth phase-dependent synthesis of a type IV pilus (TFP), which constitutes the central part of competence-induced DNA uptake machinery. We used bacterial genetics and microscopy to demonstrate that the TFP is essential for the natural transformability and surface motility of
, whereas pilus-unrelated proteins of the DNA uptake complex do not affect the motility phenotype. Furthermore, TFP biogenesis and assembly is subject to input from two regulatory systems that are homologous to
, namely, the PilSR two-component system and the Pil-Chp chemosensory system. We demonstrated that these systems affect not only the piliation status of cells but also their ability to take up DNA for transformation. Importantly, we report on discrepancies between TFP biogenesis and natural transformability within the same genus by comparing data for our work on
to data reported for
, the latter of which served for decades as a model for natural competence.
Rapid bacterial evolution has alarming negative impacts on animal and human health which can occur when pathogens acquire antimicrobial resistance traits. As a major cause of antibiotic-resistant opportunistic infections,
is a high-priority health threat which has motivated renewed interest in studying how this pathogen acquires new, dangerous traits. In this study, we deciphered a specific time window in which these bacteria can acquire new DNA and correlated that with its ability to produce the external appendages that contribute to the DNA acquisition process. These cell appendages function doubly for motility on surfaces and for DNA uptake. Collectively, we showed that
is similar in its TFP production to
, though it differs from the well-studied species
.
In this study, subsidies are classified into government subsidies beforehand (GSB) and government subsidies afterwards (GSA). We examine the impacts of GSB and GSA on the financial performance of ...Chinese enterprises of New Energy Vehicle (NEV). Analyzing a dataset of Chinese NEV firms' financial performance from 2013 to 2017 with panel regression models, we demonstrate that the two forms of government subsidies have different impacts on New Energy Vehicle enterprises' performance. Specifically, we find a positive U-shaped relationship between GSB and financial performance and an inverted one between GSA and financial performance. We further investigate the moderating role of intelligent transformation in the relationships between government subsidies and NEV enterprises’ performance. Our empirical analysis suggests that intelligent transformation can improve the efficiency of GSA and weaken the negative effects of excessive GSA. These results highlight the importance of intelligent transformation for NEV enterprises, providing policy makers with new insights into NEV subsidy policies.
•Two forms of government subsidies have different impacts on New Energy Vehicle enterprises.•A U-shaped relation between government subsidies beforehand and financial performance.•Intelligent transformation moderates the relationship between government subsidies afterwards and financial performance.
•Increases in Ti content increase critical cooling rate.•Quenched microstructures progress from massive to acicular and banded martensites.•Acicular martensite forms directly from γ-phase: ...γ → α′a.•Transition to banded martensite may occur when γ0 intervenes: γ → γ0 → α′b.•Quenched alloys are ductile, supersaturated, and amenable to age hardening.
The effect of Ti content on phase transformations, microstructures, and mechanical properties of U-Ti alloys are described for alloys containing 0.3 wt.% to 2.0 wt.%Ti. Rapid cooling is required to overcome diffusional decomposition of γ-phase and facilitate diffusionless transformation to supersaturated variants of α-phase. Critical cooling rate increases with increasing Ti content, opposite to the trend observed in U-Mo and U-Nb alloys. This difference occurs because the martensite transformation temperatures in these relatively dilute U-Ti alloys are above the knee of the C-curve for diffusional decomposition, unlike those in the more concentrated U-Mo and U-Nb alloys. In these U-Ti alloys critical cooling rate depends on the amount of undercooling required to reach Ms, which increases with increasing Ti content, and the time for diffusional decomposition to occur just above Ms, which decreases with increasing Ti content. The net result is that higher cooling rates are required as Ti content increases. Full quenching results in diffusionless transformation of γ-phase to supersaturated variants of α-phase. Very dilute alloys transform via a γ → β → αm sequence of massive transformations. Martensitic γ → α′a transformation begins at ∼0.4%Ti, and 100% α′a microstructures are obtained from ∼0.65% to ∼1.4% Ti. A transition to banded α′b martensite occurs at ∼1.5%Ti. Evidence suggests that the α′a to α′b transition may occur when the cubic γ-phase first transforms to tetragonal γ°, which in turn transforms to orthorhombic α′b via the sequence γ → γ° → α′b. Fully quenched alloys exhibit moderate strengths and ductilities, and their supersaturation with Ti makes them amenable to subsequent age hardening. Subcritical quenching typically results in two-phase microstructures with lower ductilities and near-zero Ti-supersaturation, eliminating the possibility of subsequent age hardening.
•miR-21 inactivates Twist1 via up-regulation of PDCD4.•miR-21 is involved in arsenite-induced epithelial–mesenchymal transition.•miR-21-mediated EMT promotes the migration and invasion of ...arsenite-transformed cells.
Arsenic is well established as a human carcinogen, but the molecular mechanisms leading to arsenic-induced carcinogenesis are complex and elusive. It is not been determined if the epithelial–mesenchymal transition (EMT) contributes to carcinogen-induced malignant transformation and subsequent tumor formation. We have found that, during the neoplastic transformation induced in human bronchial epithelial (HBE) cells by a low concentration (1.0μM) of arsenite, the cells undergo an EMT and show enhanced invasion and migration. With longer times for transformation of HBE cells, there was increased miR-21 expression. Further, during the transformation of HBE cells, inhibition of miR-21 with an miR-21 inhibitor increased levels of PDCD4, an inhibitor of neoplastic transformation; reduced Twist1, a transcription factor involved in cell differentiation; and inhibited cell invasion and migration. In addition, PDCD4 interacted with Twist1 and inhibited its expression function, which is involved in arsenite-induced EMT. Thus, miR-21, acting on PDCD4, which interacts with Twist1 and represses the expression of Twist1, contributes to the EMT induced by arsenite. These observations add to an understanding of the processes involved in arsenite-induced carcinogenesis.
DNA and histone methylation in gastric carcinogenesis Calcagno, Danielle Queiroz; Gigek, Carolina Oliveira; Chen, Elizabeth Suchi ...
World journal of gastroenterology : WJG,
02/2013, Volume:
19, Issue:
8
Journal Article
Open access
Epigenetic alterations contribute significantly to the development and progression of gastric cancer, one of the leading causes of cancer death worldwide. Epigenetics refers to the number of ...modifications of the chromatin structure that affect gene expression without altering the primary sequence of DNA, and these changes lead to transcriptional activation or silencing of the gene. Over the years, the study of epigenetic processes has increased, and novel therapeutic approaches that target DNA methylation and histone modifications have emerged. A greater understanding of epigenetics and the therapeutic potential of manipulating these processes is necessary for gastric cancer treatment. Here, we review recent research on the effects of aberrant DNA and histone methylation on the onset and progression of gastric tumors and the development of compounds that target enzymes that regulate the epigenome.
Recently emerged lead‐halide perovskite nanocrystals (PNCs) are promising optoelectronic material due to their easy solution processability, wide range of color tunability, as well as very high ...photoluminescence quantum yield. Despite their significant success in lab‐scale optoelectronic applications, the long‐term stability becomes the main issue, hindering them towards commercialization. The highly ionic nature of such lead‐halide structure makes them extremely unstable in water and air. But a very few groups have taken the advantage of such nature of the crystal structure for water‐triggered chemical transformation towards shape, composition, and morphology controlled stable and bright PNCs, which are otherwise difficult to obtain by typical direct approach. Furthermore, using polymer as an encapsulating layer for the PNCs, water‐soluble stable PNCs have been prepared. In this review, the recent progress on the water–hexane interface chemistry towards chemical transformation to produce several PNCs is described. Such method not only ensure to yield several shape‐controlled perovskites nanocrystals, but also formation of perovskites in aqueous phase that show promising application towards bio‐imaging.
Water‐triggered interfacial chemistry shows promising advantage for morphology, shape and composition control towards formation of new bio‐compatible perovskite nanocrystals. In this Review, the recent development of this unique approach at the water–hexane interface that may be extended to tailor not only CsPbX3 but also perovskite nanocrystals beyond this family is summarized.
Interrupted hot deformation tests were carried out to study the phase transformation behavior of Ti-10V-2Fe-3Al alloy during isothermal holding after deformation. The results show that post-dynamic ...transformation (post-DT) from α to β phase occurred first during isothermal holding and the meta-β phase retransformed to α phase after a long holding time. This phenomenon is quite different from α+β titanium alloys in which only reverse transformation (RT, βα) took place during isothermal holding. Microstructure evolution of β-matrix was also investigated and it was found that static recovery was the main softening mechanism. Furthermore, phase transformation has a great influence on the static softening and mechanical response of interrupted hot deformation. Due to the occurrence of post-DT, the yield strength of reloading pass reduced and became lower than the initial pass when the holding time exceeds 900 s. And significant static softening was achieved. The driving and opposing force for post-DT and RT were derived and compared based on thermodynamic analysis. Since the deformation and holding temperature is close to β-transus temperature, post-DT has a lower energy barrier which can be easily overcome by stored energy. This may explain why the phase transformation direction in Ti-10 V-2Fe-3Al alloy is opposite to that in α+β titanium alloys during isothermal holding.
•Post-dynamic transformation occurred before reverse transformation during holding.•Static softening mechanisms are static recovery and phase transformation.•The yield stress of reloading pass was smaller than that of the first pass.•The driving force of post-dynamic transformation was stored energy.
MicroRNAs (miRNAs) are a large family of small non-coding RNAs that negatively regulate protein-coding gene expression post-transcriptionally via base pairing between the 5' seed region of a miRNA ...and the 3' untranslated region (3'UTR) of a messenger RNA (mRNA). Recent evidence has supported the critical role that miRNAs play in many diseases including cancer. The miR-200 family consisting of 5 members (miR-200a, -200b, -200c, -141, -429) is an emerging miRNA family that has been shown to play crucial roles in cancer initiation and metastasis, and potentially be important for the diagnosis and treatment of cancer. While miR-200s were found to be critically involved in the metastatic colonization to the lungs in mouse mammary xenograft tumor models, a large number of studies demonstrated their strong suppressive effects on cell transformation, cancer cell proliferation, migration, invasion, tumor growth and metastasis. This review aims to discuss research findings about the role of the miR-200 family in cancer initiation, each step of cancer metastatic cascade, cancer diagnosis and treatment. A comprehensive summary of currently validated miR-200 targets is also presented. It is concluded that miR-200 family may serve as novel targets for the therapy of multiple types of cancer.
Under investigation in this paper is a (3+1)-dimensional nonlinear evolution equation, which was proposed and analyzed to study features and properties of nonlinear dynamics in higher dimensions. ...Using the Hirota bilinear method, we construct a bilinear Bäcklund transformation, which consists of four equations and involves six free parameters. With test function method and symbolic computation, three sets of lump–kink solutions and new types of interaction solutions are derived, and figures are presented to reveal the interaction behaviors. Setting constraints to the new interaction solution via the test function expressed by “polynomial-cos-cosh,” we simulate the periodic interaction phenomenon. Pfaffian solutions to the (3+1)-dimensional nonlinear evolution equation are obtained based on a set of linear partial differential conditions. According to our results, the diversity of solutions to the (3+1)-dimensional nonlinear evolution equation is revealed.
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase physiologically expressed by fetal neural cells. However, aberrantly expressed ALK is involved in the pathogenesis of diverse ...malignancies, including distinct types of lymphoma, lung carcinoma, and neuroblastoma. The aberrant ALK expression in nonneural cells results from chromosomal translocations that create novel fusion proteins. These protein hybrids compose the proximal part of a partner gene, including its promoter region, and the distal part of ALK, including the coding sequence for the entire kinase domain. ALK was first identified in a subset of T-cell lymphomas with anaplastic large cell lymphoma (ALCL) morphology (ALK+ ALCL), the vast majority of which harbor the well-characterized nucleophosmin (NPM)-ALK fusion protein. NPM-ALK co-opts several intracellular signal transduction pathways, foremost being the STAT3 pathway, normally activated by cytokines from the interleukin-2 (IL-2) family to promote cell proliferation and to inhibit apoptosis. Many genes and proteins modulated by NPM-ALK are also involved in evasion of antitumor immune response, protection from hypoxia, angiogenesis, DNA repair, cell migration and invasiveness, and cell metabolism. In addition, NPM-ALK uses epigenetic silencing mechanisms to downregulate tumor suppressor genes to maintain its own expression. Importantly, NPM-ALK is capable of transforming primary human CD4+ T cells into immortalized cell lines indistinguishable from patient-derived ALK+ ALCL. Preliminary clinical studies indicate that inhibition of NPM-ALK induces long-lasting complete remissions in a large subset of heavily pretreated adult patients and the vast majority of children with high-stage ALK+ ALCL. Combining ALK inhibition with other novel therapeutic modalities should prove even more effective.
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