Initial Phase Research Articles

Using Geographically Weighted Models to Explore Temporal and Spatial Varying Impacts on Commute Trip Change Resulting from COVID-19

Using Geographically Weighted Models to Explore Temporal and Spatial Varying Impacts on Commute Trip Change Resulting from COVID-19

Functional enzyme analysis and metabolic regulation mechanism of the combined microflora LXB in the degradation of lignocellulose

Biodegradation of lignocellulosic biomass is a practical and effective method. A random combination of six isolates and two purchased strains was constructed to obtain LXB that exhibited a lignocellulose degradation rate of 36.4 % after 168 h. The Carbohydrate-Active enZYmes Database identified 1872 genes that were differentially expressed and involved in the degradation of lignocellulose in LXB. The cellulase- and hemicellulase- encoding genes were highly expressed, with the hemicellulase- encoding genes displaying the highest expression levels during the initial and peak phases of lignocellulose degradation. A considerable increase was observed in the expression of genes encoding versatile peroxidases and alcohol oxidases involved in lignin catabolism. LXB catalyses the breakdown of lignocellulose via six major pathways within the carbohydrate metabolic network. Catechol, discovered in the benzoate degradation pathway, is involved in lignin degradation. Furthermore, LXB can degrade harmful exogenous substances, thus contributing to the overall detoxification process.

A unique circ_0067716/EIF4A3 double-negative feedback loop impacts malignant transformation of human bronchial epithelial cells induced by benzo(a)pyrene

Benzo(a)pyrene as a pervasive environmental contaminant is characterized by its substantial genotoxicity, and epidemiological investigations have established a correlation between benzo(a)pyrene exposure and the susceptibility to human lung cancer. Notably, much research has focused on the link between epigenetic alterations and lung cancer induced by chemicals, although circRNAs are also emerging as relevant contributors to the carcinogenic process of benzo(a)pyrene. In this study, we identified circ_0067716 as being significantly upregulated in response to stress injury and downregulated during malignant transformation induced by benzo(a)pyrene-7,8-diol-9,10-epoxide (BPDE) in human bronchial epithelial cells. The observed differential expression of circ_0067716 in cells treated with BPDE for varying durations suggests a strong correlation between this circRNA and BPDE exposure. The tissue samples of lung cancer patients also suggest that a lower circ_0067716 expression is associated with BPDE-DNA adduct levels. Remarkably, we demonstrate that EIF4A3, located in the nucleus, interacts with the flanking sequences of circ_0067716 and inhibits its biogenesis. Conversely, circ_0067716 is capable of sequestering EIF4A3 in the cytoplasm, thereby preventing its translocation into the nucleus. EIF4A3 and circ_0067716 can form a double-negative feedback loop that could be affected by BPDE. During the initial phase of BPDE exposure, the expression of circ_0067716 was increased in response to stress injury, resulting in cell apoptosis through the involvement of miR-324-5p/DRAM1/BAX axis. Subsequently, as cellular adaptation progressed, long-term induction due to BPDE exposure led to an elevated EIF4A3 and a reduced circ_0067716 expression, which facilitated the proliferation of cells by stabilizing the PI3K/AKT pathway. Thus, our current study describes the effects of circ_0067716 on the genotoxicity and carcinogenesis induced by benzo(a)pyrene and puts forwards to the possible regulatory mechanism on the occurrence of smoking-related lung cancer, providing a unique insight based on epigenetics.

Auto-BCS: A Hybrid System for Real-Time Breast Cancer Screening from Pathological Images.

Breast cancer is recognized as a prominent cause of cancer-related mortality among women globally, emphasizing the critical need for early diagnosis resulting improvement in survival rates. Current breast cancer diagnostic procedures depend on manual assessments of pathological images by medical professionals. However, in remote or underserved regions, the scarcity of expert healthcare resources often compromised the diagnostic accuracy. Machine learning holds great promise for early detection, yet existing breast cancer screening algorithms are frequently characterized by significant computational demands, rendering them unsuitable for deployment on low-processing-power mobile devices. In this paper, a real-time automated system "Auto-BCS" is introduced that significantly enhances the efficiency of early breast cancer screening. The system is structured into three distinct phases. In the initial phase, images undergo a pre-processing stage aimed at noise reduction. Subsequently, feature extraction is carried out using a lightweight and optimized deep learning model followed by extreme gradient boosting classifier, strategically employed to optimize the overall performance and prevent overfitting in the deep learning model. The system's performance is gauged through essential metrics, including accuracy, precision, recall, F1 score, and inference time. Comparative evaluations against state-of-the-art algorithms affirm that Auto-BCS outperforms existing models, excelling in both efficiency and processing speed. Computational efficiency is prioritized by Auto-BCS, making it particularly adaptable to low-processing-power mobile devices. Comparative assessments confirm the superior performance of Auto-BCS, signifying its potential to advance breast cancer screening technology.

Role of beta-hydroxybutyrate measurement in the evaluation of plasma glucose concentrations in newborn infants

ObjectiveThe Glucose in Well Babies (GLOW) Study showed that there are two phases of low glucose concentrations in healthy newborn infants: an initial phase in which plasma concentrations of ketones...

A search for high-redshift direct-collapse black hole candidates in the PEARLS north ecliptic pole field

Direct-collapse black holes (DCBHs) of mass ∼104 − 105 M⊙ that form in HI-cooling halos in the early Universe are promising progenitors of the ≳109 M⊙ supermassive black holes that fuel observed z ≳ 7 quasars. Efficient accretion of the surrounding gas onto such DCBH seeds may render them sufficiently bright for detection with the JWST up to z ≈ 20. Additionally, the very steep and red spectral slope predicted across the ≈1 − 5 μm wavelength range of the JWST/NIRSpec instrument during their initial growth phase should make them photometrically identifiable up to very high redshifts. In this work, we present a search for such DCBH candidates across the 34 arcmin2 in the first two spokes of the JWST cycle-1 PEARLS survey of the north ecliptic pole time-domain field covering eight NIRCam filters down to a maximum depth of ∼29 AB mag. We identify two objects with spectral energy distributions consistent with theoretical DCBH models. However, we also note that even with data in eight NIRCam filters, objects of this type remain degenerate with dusty galaxies and obscured active galactic nuclei over a wide range of redshifts. Follow-up spectroscopy would be required to pin down the nature of these objects. Based on our sample of DCBH candidates and assumptions on the typical duration of the DCBH steep-slope state, we set a conservative upper limit of ≲5 × 10−4 comoving Mpc−3 (cMpc−3) on the comoving density of host halos capable of hosting DCBHs with spectral energy distributions similar to the theoretical models at z ≈ 6 − 14.

Navigating the Eco-Design Paradox: Criteria and Methods for Sustainable Eco-Innovation Assessment in Early Development Stages

This paper examines the growing importance of eco-innovation in aligning sustainability with technological development. It explores the ‘eco-design paradox’, which emphasizes the tension between the need for flexible design and the availability of data required for assessing environmental impacts during early innovation stages. This paradox presents a challenge: the lack of detailed data can have an impact on the ability to make sustainable optimal design decisions as designs are still fluid. The study investigates the essential sustainability aspects to be evaluated in the initial phases of innovation and explores the involvement of decision-makers and entrepreneurs in the sustainability assessment process. The paper uses a robust action research methodology to examine various eco-innovation diagnostic tools in collaboration with two French Institutes of Technology (FITs). A comparative analysis is conducted to assess these tools’ efficacity in evaluating several dimensions of sustainability, including environmental, social, and economic aspects. Our investigation identifies key criteria that are crucial for early-stage sustainability assessments, such as innovation description, systemic vision, functionality, and stakeholder involvement. The findings will guide policy makers, researchers, and practitioners in the field of eco-innovation by providing a comprehensive framework for evaluating and promoting sustainable innovations in their early stages. The insights from our findings show how important expert knowledge is in the eco-innovation diagnostic process. They also demonstrate the need for a more integrated approach to eco-innovation.

Computational Analysis of Mechanical Properties in Polymeric Sandwich Composite Materials.

This article focuses on the computational analysis of sandwich composite materials based on polypropylene, polyester, glass, and cotton fibers. In the automotive components prepared from these fiber materials, the various components are used in different proportions. Through the manufacturing process, isotropic materials become somewhat anisotropic. Part of this article is aimed at obtaining input values of material characteristics for calculations using finite element analysis (FEM) and the comparison of experimental results with FEM-based material models created using the Digimat 2023.1 software. This article analyzes the modeling of two-phase as well as multiphase composite materials. This work focuses on calculations using FEM according to the test defined in the PR375 standard for loading the finished product in the luggage compartment of a car. The defined methodology enables the application of the FEM-based calculation directly to the product design in the initial phase of research. The construction and production of expensive prototypes and the subsequent production of automotive parts is replaced by computer-based simulation. This procedure makes it possible to simulate several optimization cycles over a relatively shorter time. From the results of computational simulations, it is clear that materials based on PP/PET/glass fibers show a much higher modulus of elasticity than materials created using cotton, i.e., materials of the PP/PET/cotton type. In order to achieve a high strength and stiffness, it is, therefore, appropriate to use glass fibers in the composite materials used for such applications.

Heterogeneous tunable III-V-on-silicon-nitride mode-locked laser emitting wide optical spectra

We demonstrate a III-V-on-silicon-nitride mode-locked laser through the heterogeneous integration of a semiconductor optical amplifier on a passive silicon-nitride cavity using the technique of micro-transfer printing. In the initial phase of our study, we focus on optimizing the lasing wavelength to be centered at 1550 nm. This optimization is achieved by conducting experiments with 27 mode-locked lasers, each incorporating optical amplifiers featuring distinct multiple-quantum-well photoluminescence values. Subsequently we present a comprehensive study investigating the behavior of the mode-locking regime when the electrical driving parameters are varied. Specifically, we explore the impact of the gain voltage and saturable absorber current on the locking stability of a tunable mode-locked laser. By manipulating these parameters, we demonstrate the precise control of the optical spectrum across a wide range of wavelengths spanning from 1530 to 1580 nm. Furthermore, we implement an optimization approach based on a Monte Carlo analysis aimed at enhancing the mode overlap within the gain region. This adjustment enables the achievement of a laser emitting a 23-nm-wide spectrum while maintaining a defined 10 dB bandwidth for a pulse repetition rate of 3 GHz.

DEVELOPMENT OF THE TECHNOLOGY OF CRANE-LESS LIFTING OF LONG-SPAN REINFORCED CONCRETE AND METAL COATINGS

Based on the analysis of well-known organizational-technological and structural-technical examples of crane-less lifting of long-span reinforced concrete and metal coatings of industrial and civil buildings, the goal was to develop a technological solution that would increase efficiency and shorten the duration of work on the construction of roofing structures. Taking into account the advantages and disadvantages of examples of the use of technologies of forced lifting of coatings by push-out methods, mechanized technological equipment for raising columns was developed, which consists of lifting modules and lifting fasteners. The lifting of the covering is carried out by leaning on the heads of the mounting columns, which are raised in the space between the paired design columns. In the process of increasing the load from the sections of the mounting columns, the support frames of the lifting modules and the lifting clamps take turns. According to the developed technological solution, in the initial phase, paired design columns are installed in the foundations by the method of free lifting with the help of cranes, and the construction and technological block of the covering is formed on low scaffolding. The support bars of the cover block are inserted into the space between the paired columns. Lifting modules and lifting fasteners are installed on the foundations, adjacent to the design columns. After completion of work on consolidation of the coating into a structural and technological unit, crane-less lifting of the coating to the design height is performed. For this, hydraulic lift cylinders raise the support frames and, fixed on them, the support bolts of the coating. Then the load from the coating is transferred to the lifting fasteners. At the next stage, the sections of the mounting columns are extended in the space between the columns. After lifting the covering to the design height with support on the mounting columns, the support bars of the covering are fixed on the heads of the design columns. Sections of mounting columns are dismantled. When using the developed technology, the lifting of the covering to a height of 34 m takes 1.8-2.0 shifts. At the same time, the dimensions of the construction site do not exceed the overall dimensions of the raised surface.

Detrusor Overactivity After Partial Bladder Outlet Obstruction Is Associated With High Urinary Adenosine Triphosphate Levels in Female Wistar Rats.

Bladder outlet obstruction (BOO) commonly causes detrusor overactivity (DO). In this study, a post hoc analysis of previous obtained data, we investigate if DO occurring in initial phases of BOO is associated with changes in urinary adenosine triphosphate (ATP) levels. Adult female Wistar rats were submitted to partial BOO (pBOO) or to sham obstruction. Cystometry was performed at 3 or 15 days after pBOO and saline voided was collected for ATP determination. Normality was tested using Shapiro-Wilk test. The mean frequency of voiding contractions (VCs) of the sham-operated animals at 15 days after surgery, plus or minus 3 standard deviations, was used to represent the normal range. Statistical analyses were performed using the chi-square and Mann-Whitney tests. DO was indicated by a VC frequency greater than or equal to 0.9 VCs/min. DO was observed in 63% of animals at 3 days and in 33% at 15 days following pBOO. ATP levels were significantly higher in rats with DO compared to those without DO. The DO phenotype, occurring in the initial phases of BOO, is associated with comparatively high urinary ATP levels.

Feasibility of Guided Internet-Based Cognitive Behavioral Therapy for Panic Disorder and Social Anxiety Disorder in Japan: Pilot Single-Arm Trial.

Cognitive behavioral therapy (CBT) is effective in treating anxiety disorders. Accessibility to CBT has been limited in Japan due to the shortage of therapists. While an open-source e-learning system can be used to create a simple internet-based cognitive behavioral therapy (ICBT) program, the safety and outpatient acceptance of this treatment approach have not been explored in Japan. The aim of this study was to investigate whether outpatients with anxiety disorders could accept and successfully complete the ICBT program with guidance by CBT therapists when implementing therapeutic modules and CBT tasks. Due to being in the initial phase of a novel treatment in Japan, this study was intended for verification with a small sample size. In total, 6 adults, including 4 male participants and 2 female participants, were enrolled in a single-arm trial. The intervention involved guided ICBT comprising 12 sessions, including CBT text, comprehension confirmation tests, and explanatory videos about cognitive behavioral models, accessible through a website. The therapist guided the participants in accessing the ICBT program and answering their questions using a chat tool. The primary outcome was anxiety severity assessed using the State-Trait Anxiety Inventory-Trait. Secondary outcomes included the Panic Disorder Severity Scale, Liebowitz Social Anxiety Scale (LSAS), Beck Anxiety Inventory (BAI), Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Working Alliance Inventory-Short Form (WAI-SF). Statistical analyses were performed using paired 2-tailed t tests to assess the changes in clinical symptoms. The total WAI-SF score at the final session was used to evaluate the therapeutic alliance. For statistical analyses, mean changes for total State-Trait Anxiety Inventory-Trait, BAI, Panic Disorder Severity Scale, LSAS, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 scores were analyzed using the paired 2-tailed t test. The 2-sided significance level for hypothesis testing was set at 5%, and 2-sided 95% CIs were calculated. Most participants diligently engaged with the ICBT program. No adverse events were reported. The mean total scores for the primary outcome decreased by 11.0 (SD 9.6) points (95% CI -22.2 to 0.20; Hedges g=0.95), but it was not statistically significant. The mean total scores for the secondary outcomes that assess clinical symptoms decreased, with a significant reduction observed in the BAI of 15.7 (SD 12.1) points (95% CI -28.4 to -3.0; P=.03; Hedges g=1.24). The mean total scores for PDSS and LSAS decreased significantly, by 12.0 (SD 4.24) points (95% CI -50.1 to 26.1; P=.16; Hedges g=1.79) and 32.4 (SD 11.1) points (95% CI -59.7 to -4.3; P=.04; Hedges g=1.38), respectively. Of the participants, 67% (n=4) showed treatment response, and 50% (n=3) achieved remission after the intervention. The therapeutic alliance, measured using the WAI-SF, was moderate. Guided ICBT may be feasible for the treatment of outpatients with panic disorder and social anxiety disorder in Japan. University Hospital Medical Information Network Clinical Trials Registry UMIN0000038118; https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000043439.

Anti-HBsAg IgY polyclonal antibodies potential as capture antibody for HBsAg Detection Kit development

Hepatitis B, affecting about 296 million globally, is a significant concern, with Indonesia ranking second in Southeast Asia for case numbers. The disease's latent initial phase, devoid of early symptoms upon hepatitis B virus (HBV) infection, highlights the demand for precise diagnostics. This research aimed to develop anti-HBsAg polyclonal antibodies (pAb) for application as capture agents within a sandwich enzyme-linked immunosorbent assay (ELISA). Chicken egg-derived IgY antibodies have advantages over mammalian ones due to simpler extraction and higher yield. In a study involving 21-week-old chickens, four intramuscular injections of 500 µg HBsAg antigen in Freund's adjuvant were administered at two-week intervals. Eggs as IgY source were collected daily and then IgY was isolated from eggyolk using polyethylene glycol (PEG) precipitation. The Bradford method was used to measure the total protein concentration, while the existence of IgY and pAb specific IgY against Anti-HBsAg was verified through SDS-PAGE and sandwich ELISA using HRP as a reporter, respectively. The resulting SDS-PAGE showed two distinct IgY bands: a 68 kDa heavy chain and a 23 kDa light chain. Using these anti-HBsAg IgY antibodies as capturing agents, the slightly elevation of IgY pAb against HBsAg level has been identified within the second week following the initial immunization. Subsequently, from the third to the eighth week, antibody levels escalated significantly, ranging from 2 to 13-fold higher than those observed in the second week. These findings suggest the potential use of IgY pAb as effective capture antibodies in sandwich ELISA for HBsAg antigen detection.

Influenza A virus hemagglutinin: from classical fusion inhibitors to proteolysis targeting chimera-based strategies in antiviral drug discovery

The influenza virus glycoprotein hemagglutinin (HA) participates in critical steps of the attachment of viral particles to the host cell membrane receptor and membrane fusion. Due to its crucial involvement in the initial phases of influenza A infections, HA emerges as a promising target in the search of novel drug-like candidates. Given its pivotal role in the early stages of influenza A infections, intense drug discovery efforts have been undertaken to target HA in the past decades. Drug discovery studies mainly rely on preventing the recognition of sialic acid units by the receptor binding site in the globular head (GH) domain, or the conformational rearrangement required for the fusion of viral and cell membranes. In this work, the aim is to summarize the progress made in HA-targeted development of small molecule fusion inhibitors. To this end, attention will primarily be focused on the analysis of the X-ray crystallographic structures of HA bound to fusion inhibitors. Furthermore, this study also aims to highlight the efforts made in exploiting the structural information in conjunction with molecular modeling techniques to discern the mechanism of action of the fusion inhibitors and to assist the design and interpretation of structure-activity relationships of novel lead compounds will be highlighted. The final section will be dedicated to elucidating novel and promising antiviral strategies proceeding from the transformation of known small molecule antivirals in proteolysis targeting chimera (PROTAC)-based targeted protein degradation. This knowledge will be valuable to assist the exploitation of classical and novel antiviral structure-based strategies, together with a deeper understanding of the mechanism of action and minimization of the impact of drug resistance.

A systematic approach to increase confidence in the diagnosis of muscle asymmetry

Asymmetry is one of the most widespread pathologies of the neuromuscular system. Depending on the composition of the same body from different types of muscles, as well as the fact that it does not seem so dangerous in the initial phases, the asymmetry is determined in clinical conditions, especially in severe phases. This requires long-term and sometimes painful treatment. The goal of the research is to detect the mentioned pathological condition at the initial stages. For this purpose, is designed a system that allows decision-making by applying several methods used to determine asymmetry.

Study on the flow characteristics of microscale copper inverse opal wick structures

Ultra-thin heat pipes are extensively used to address heat dissipation challenges in compact electronic devices with limited space. Research on new types of micro-porous wick is crucial for enhancing the heat transfer of ultra-thin heat pipes. The hydraulic transport properties of micro-porous wick structures are crucial factors for the applications. The inverse opal (IO) micro-porous metal structure has gained extensive attention for its ordered periodic arrangement and high porosity characteristics. In the paper, the copper inverse opal (CIO) and gradient CIO are fabricated by a template-assisted deposition method. Experimental measurements are conducted to study the fluid ascent process within the CIO structure. In addition, a face-centered cubic geometric model is established based on the structure information obtained by a scanning electron microscope (SEM). The calculation employs a porous media model and takes into account the resistance characteristics in the initial phase. The relative error between the simulation and experimental results is less than 7.7%. Furthermore, the fabricated gradient CIO structure is uniform and exhibits a higher permeability than single-pore CIO. The permeability of this gradient CIO is about 1.9–3.2 × 10−14 m2. Understanding the microscopic liquid transport process within CIO structures is of great importance in the selection and optimization of capillary wick structures.

Impact of composition and knitting methods of fiberglass grid on the progression of reflective crack in asphalt pavement

In the asphalt pavement with semi-rigid base, the shrinkage cracks initiating from base course often propagate upward to surface course to develops into reflective cracks. The fiberglass grid, as a woven geotextile, is widely used to retard the occurrence of reflective cracks in China, but the impacts of material composition and knitting methods of it on reflective cracks are still not clear. In this paper, two kinds of models, including a two-scale model of fiber bundle-fiberglass grids layer and a coupled thermo-mechanical model of pavement structure, are established. In the two-scale model, the elastic constants (ECs) of fiber bundle and fiberglass grids layer are calculated under different compositions and knitting methods and then assigned to the coupled thermo-mechanical model to estimate the fatigue lives at initiation phase (FL-IP) and propagation phase (FL-PP) of reflective cracks based on an estimation theory. Moreover, this study designs the laboratory tests to validate this estimation method of fatigue life. Then, based on the predicted fatigue life at different phases of crack progression, the sensitivity analysis is implemented to analyze the impacts of composition and knitting methods on the fatigue life. As a result, the recommendations on design and preparation of fiberglass grid are proposed. The results show that, in material composition, the glass fibers with high elastic modulus and volume fraction and the coating materials with high elastic modulus are beneficial to retarding the initiation and propagation of reflective cracks and in knitting methods, increasing density of fiber bundles parallel to the traffic direction and reducing braided angle also has positive effect. These results can be used to optimizing design and preparation of fiberglass grid to reduce the occurrence of reflective cracks in asphalt pavement.

Digital Renaissance in Education: Unveiling the Transformative Potential of Digitization in Educational Institutions

Abstract This paper examines the ongoing trend of digitization within educational institutions, analyzing the potential opportunities that lie ahead. As educational landscapes evolve, embracing digitization offers institutions a pathway to unlock a myriad of prospects. This research explores the current state of digitization in educational settings, highlighting the opportunities that arise from the integration of digital technologies. The driving forces behind significant changes in higher education include escalating operating costs, the emergence of micro and nano degrees, the surge in online learning, the influx of digitally-native students, and the overarching wave of digital transformation. Students are increasingly leveraging digital technologies to showcase a diverse array of tools, integrating structured learning environments into the fabric of higher education teaching. This research provides a comprehensive overview of digital transformation in higher education, evaluating the potential of digitalization and forecasting its prospects in the near future. Key concepts such as digital transformation, virtual reality (VR) technology, artificial intelligence (AI), and Technology, Entertainment, Design (TED) courses are examined as practical and indispensable elements shaping the future of education. Through a meticulous analysis, it becomes evident that digitalization marks only the initial phase in a broader process wherein institutions harness new technologies not merely to replicate old tasks but to redefine educational paradigms. Furthermore, the paper emphasizes that digital transformation necessitates the infusion of new management practices capable of harnessing the full potential of information and communication technologies (ICT). The journey towards the digital transformation of educational institutions involves a profound shift in mindset, encompassing innovative approaches to teaching, learning, and administration. As institutions embrace this transformative journey, they position themselves to create enhanced value for students and forge dynamic collaborations with partners in the evolving landscape of higher education.

When belief becomes research: conspiracist communities on the social web

IntroductionThis article explores two QAnon subgroups that were not active during the initial phase of the movement but now epitomize how QAnon has capitalized on social media to reach more people. We examine these smaller communities through the lens of information literacy and other literacies to identify opportunities for librarians and educators.ResultsThe communities of conspiracy theorists explored here exhibit information behaviors distinct from the initial QAnon community, presenting opportunities for information professionals to employ new models of information literacy, metaliteracy, and other literacies to combat conspiracy ideation. Notable themes evidenced in both samples include an increasing religiosity affiliated with QAnon, affective states that promote conspiracy ideation, faulty hermeneutics and epistemologies, and specific literacy gaps.Methods and discussionWe must update our understanding of QAnon and its adherents' shifting priorities and behaviors. Through investigating these smaller subgroups, researchers and educators can address the evolution of the QAnon movement by teaching to literacy gaps and logical fallacies, and acknowledging the troubling emotions that undergird broader belief systems.

An atypical 3-ketoacyl ACP synthase III required for acyl homoserine lactone synthesis in Pseudomonas syringae pv. syringae B728a.

The last step of the initiation phase of fatty acid biosynthesis in most bacteria is catalyzed by the 3-ketoacyl-acyl carrier protein (ACP) synthase III (FabH). Pseudomonas syringae pv. syringae strain B728a encodes two FabH homologs, Psyr_3467 and Psyr_3830, which we designated PssFabH1 and PssFabH2, respectively. Here, we explored the roles of these two 3-ketoacyl-ACP synthase (KAS) III proteins. We found that PssFabH1 is similar to the Escherichia coli FabH in using acetyl-acetyl-coenzyme A (CoA ) as a substrate in vitro, whereas PssFabH2 uses acyl-CoAs (C4-C10) or acyl-ACPs (C6-C10). Mutant analysis showed that neither KAS III protein is essential for the de novo fatty acid synthesis and cell growth. Loss of PssFabH1 reduced the production of an acyl homoserine lactone (AHL) quorum-sensing signal, and this production was partially restored by overexpressing FabH homologs from other bacteria. AHL production was also restored by inhibiting fatty acid elongation and providing exogenous butyric acid. Deletion of PssFabH1 supports the redirection of acyl-ACP toward biosurfactant synthesis, which in turn enhances swarming motility. Our study revealed that PssFabH1 is an atypical KAS III protein that represents a new KAS III clade that functions in providing a critical fatty acid precursor, butyryl-ACP, for AHL synthesis.IMPORTANCEAcyl homoserine lactones (AHLs) are important quorum-sensing compounds in Gram-negative bacteria. Although their formation requires acylated acyl carrier proteins (ACPs), how the acylated intermediate is shunted from cellular fatty acid synthesis to AHL synthesis is not known. Here, we provide in vivo evidence that Pseudomonas syringae strain B728a uses the enzyme PssFabH1 to provide the critical fatty acid precursor butyryl-ACP for AHL synthesis. Loss of PssFabH1 reduces the diversion of butyryl-ACP to AHL, enabling the accumulation of acyl-ACP for synthesis of biosurfactants that contribute to bacterial swarming motility. We report that PssFabH1 and PssFabH2 each encode a 3-ketoacyl-acyl carrier protein synthase (KAS) III in P. syringae B728a. Whereas PssFabH2 is able to function in redirecting intermediates from β-oxidation to fatty acid synthesis, PssFabH1 is an atypical KAS III protein that represents a new KAS III clade based on its sequence, non-involvement in cell growth, and novel role in AHL synthesis.