Diverse phenotypes resulting from polyphosphate kinase gene (ppk1) inactivation in different strains of Helicobacter pylori

Connections among biochemical pathways should help buffer organisms against environmental stress and affect the pace and trajectory of genome evolution. To explore these ideas, we studied consequences of inactivating the gene for polyphosphate kinase 1 (ppk1) in strains of Helicobacter pylori, a genetically diverse gastric pathogen. The PPK1 enzyme catalyzes synthesis of inorganic polyphosphate (poly P), a reservoir of high-energy phosphate bonds with multiple roles. Prior analyses in less-fastidious microbes had implicated poly P in stress resistance, motility, and virulence. In our studies, ppk1 inactivation caused the expected near-complete absence of poly P (>250-fold decrease) but had phenotypic effects that differed markedly among unrelated strains: (i) poor initial growth on standard brain heart infusion agar (five of six strains tested); (ii) weakened colonization of mice (4 of 5 strains); (iii) reduced growth on Ham's F-12 agar, a nutritionally limiting medium (8 of 11 strains); (iv) heightened susceptibility to metronidazole (6 of 17 strains); and (v) decreased motility in soft agar (1 of 13 strains). Complementation tests confirmed that the lack of growth of one Δppk1 strain on F-12 agar and the inability to colonize mice of another were each due to ppk1 inactivation. Thus, the importance of ppk1 to H. pylori differed among strains and the phenotypes monitored. We suggest that quantitative interactions, as seen here, are common among genes that affect metabolic pathways and that H. pylori's high genetic diversity makes it well suited for studies of such interactions, their underlying mechanisms, and their evolutionary consequences

Mycobacterium tuberculosis Responds to Chloride and pH as Synergistic Cues to the Immune Status of its Host Cell

PubMed ID: 23592993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Helicobacter pylori Usurps Cell Polarity to Turn the Cell Surface into a Replicative Niche

Helicobacter pylori (Hp) intimately interacts with the gastric epithelial surface and translocates the virulence factor CagA into host cells in a contact-dependent manner. To study how Hp benefits from interacting with the cell surface, we developed live-cell microscopy methods to follow the fate of individual bacteria on the cell surface and find that Hp is able to replicate and form microcolonies directly over the intercellular junctions. On polarized epithelia, Hp is able to grow directly on the apical cell surface in conditions that do not support the growth of free-swimming bacteria. In contrast, mutants in CagA delivery are defective in colonization of the apical cell surface. Hp perturbs the polarized epithelium in a highly localized manner, since wild-type Hp does not rescue the growth defect of the CagA-deficient mutants upon co-infection. CagA's ability to disrupt host cell polarity is a key factor in enabling colonization of the apical cell surface by Hp, as disruption of the atypical protein kinase C/Par1b polarity pathway leads to rescue of the mutant growth defect during apical infection, and CagA-deficient mutants are able to colonize the polarized epithelium when given access to the basolateral cell surface. Our study establishes the cell surface as a replicative niche and the importance of CagA and its effects on host cell polarity for this purpose

Systematic review: Factors influencing creativity in the design discipline and assessment criteria

Using psychological instrument to measure creativity is getting popular in design research. However, unlike quantifying general creativity using divergent thinking, the complexity and interdisciplinarity of the design discipline have made it difficult to explore research on design creativity. Therefore, to better quantify and measure design creativity, 31 relevant studies were retrieved by Google Scholar and the University of London Common Research in this article. This study summarizes the factors that influence design creativity in different design disciplines, the rules for setting the internal dimensions, and the valid instruments for measuring design creativity. The factors affecting design creativity can be divided into internal factors (aesthetic, spatial ability, and ambiguity tolerance) and external factors (environment and visual stimulation). Among these factors, different instruments and evaluation criteria considerably impact the result, while the measurement of design creativity is still not mature enough. A single scale evaluation or creative task evaluation cannot comprehensively evaluate the design creativity, which consists of aesthetic, functional, and technical aspects. In addition, the reference value of ordinary creativity remains to be further discussed in design. Under some professional design fields, the effect of widely recognized factors closely related to creativity, such as divergent thinking, imagination, and personality, is insignificant

Mycobacterium tuberculosis response to cholesterol is integrated with environmental pH and potassium levels via a lipid metabolism regulator.

Successful colonization of the host requires Mycobacterium tuberculosis (Mtb) to sense and respond coordinately to disparate environmental cues during infection and adapt its physiology. However, how Mtb response to environmental cues and the availability of key carbon sources may be integrated is poorly understood. Here, by exploiting a reporter-based genetic screen, we have unexpectedly found that overexpression of transcription factors involved in Mtb lipid metabolism altered the dampening effect of low environmental potassium concentrations ([K+]) on the pH response of Mtb. Cholesterol is a major carbon source for Mtb during infection, and transcriptional analyses revealed that Mtb response to acidic pH was augmented in the presence of cholesterol and vice versa. Strikingly, deletion of the putative lipid regulator mce3R had little effect on Mtb transcriptional response to acidic pH or cholesterol individually, but resulted specifically in loss of cholesterol response augmentation in the simultaneous presence of acidic pH. Similarly, while mce3R deletion had little effect on Mtb response to low environmental [K+] alone, augmentation of the low [K+] response by the simultaneous presence of cholesterol was lost in the mutant. Finally, a mce3R deletion mutant was attenuated for growth in foamy macrophages and for colonization in a murine infection model that recapitulates caseous necrotic lesions and the presence of foamy macrophages. These findings reveal the critical coordination between Mtb response to environmental cues and cholesterol, a vital carbon source, and establishes Mce3R as a transcription factor that crucially serves to integrate these signals

Contrastive Triple Extraction with Generative Transformer

Triple extraction is an essential task in information extraction for natural language processing and knowledge graph construction. In this paper, we revisit the end-to-end triple extraction task for sequence generation. Since generative triple extraction may struggle to capture long-term dependencies and generate unfaithful triples, we introduce a novel model, contrastive triple extraction with a generative transformer. Specifically, we introduce a single shared transformer module for encoder-decoder-based generation. To generate faithful results, we propose a novel triplet contrastive training object. Moreover, we introduce two mechanisms to further improve model performance (i.e., batch-wise dynamic attention-masking and triple-wise calibration). Experimental results on three datasets (i.e., NYT, WebNLG, and MIE) show that our approach achieves better performance than that of baselines.Comment: Accepted by AAAI 202

Interbank complex network and liquidity creation: Evidence from European banks

Liquidity creation, as a core functions of banks, affects the stability of the financial system and economic development significantly. However, the existing literature has largely ignored the impact of complex interbank linkages on liquidity creation. This may distort the understanding of liquidity creation away from its essence to some extent in the context of an increasingly interconnected financial system. Using a sample of 1406 banks from 29 European countries during 2010–2021, we use a complex network to model the interbank market and study its impact on liquidity creation. Our results indicate that dominant borrowers in the network create less liquidity as a result of their more prudent liquidity management. Higher bank capital weakens this negative relationship due to its risk-absorbing capacity. Conversely, dominant lenders in the network create more liquidity because of their more optimistic expectations and more lax liquidity management. Higher non-interest income weakens this positive relationship because of the higher risk of non-traditional business, which requires banks to hold more precautionary liquidity. Moreover, we test for endogeneity and use the full sample to verify the robustness of our results

Learning to Ask for Data-Efficient Event Argument Extraction

Event argument extraction (EAE) is an important task for information extraction to discover specific argument roles. In this study, we cast EAE as a question-based cloze task and empirically analyze fixed discrete token template performance. As generating human-annotated question templates is often time-consuming and labor-intensive, we further propose a novel approach called "Learning to Ask," which can learn optimized question templates for EAE without human annotations. Experiments using the ACE-2005 dataset demonstrate that our method based on optimized questions achieves state-of-the-art performance in both the few-shot and supervised settings.Comment: work in progres

Ferroelectric polymer nanopillar arrays on flexible substrates by reverse nanoimprint lithography

With the increasing interest in deploying ferroelectric polymer in flexible electronics and electromechanics, high-throughput and low-cost fabrication of 3D ferroelectric polymer nanostructures on flexible substrates can be a significant basis for future research and applications. Here, we report that large arrays of ferroelectric polymer nanopillars can be prepared directly on soft, flexible substrates by using low-cost polydimethylsiloxane (PDMS) soft-mold reverse nanoimprint lithography at 135 °C and at pressures as low as 3 bar. The nanopillar arrays were highly uniform over large areas of at least 200 × 200 μm and had good crystallinity with nearly optimum (110) orientation. Furthermore, the method leaves little or no residual polymer layer, fully isolating the nanopillars to avoid cross-talk and, obviating the need for additional etching processes that arises with conventional low-contrast nanoimprinting. The ferroelectric properties of individual nanopillars were probed by piezoresponse force microscopy, which showed that they exhibited switchable and bi-stable polarization. In addition, the polarization hysteresis loops probed by pyroelectric measurements of the entire array showed that the nanopillar capacitor arrays had good ferroelectric switching characteristics, over areas of at least 1 mm × 1 mm