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Understanding the Functional Role of the Efflux Pump PecM and Defining the Transcription Factor PecS Regulon in Agrobacterium fabrum
No full textAgrobacterium fabrum, the causative agent of crown gall disease, infects a wide range of plants, causing significant damage worldwide. In the rhizosphere, it is exposed to a variety of biotic and abiotic stressors. The A. fabrum-encoded transcription factor PecS was previously shown to confer fitness in the rhizosphere. The gene encoding pecS is divergent to pecM, which encodes an efflux pump. The regulation of the pecS-pecM gene pair is under the control of PecS. The dissertation describes the identification of the substrate for A. fabrum PecM as well as physiologically relevant properties of both PecM and PecS.
The substrate of the efflux pump PecM was identified as the plant exudate 4-hydroxybenzaldehyde (4HBA), as evidenced in part by untargeted metabolomics which showed that pecM::Km cells in which pecM is disrupted accumulate 4HBA. 4HBA was able to selectively induce pecM expression. However, in vitro assays suggested that 4HBA is not a ligand for PecS, implying the presence of a different 4HBA-responsive transcription factor.
A notable feature of pecM::Km cells included resistance to oxidative stress. The pecM::Km cells were otherwise indistinguishable from WT cells with respect to colony morphology, growth in rich media, sensitivity to antibiotics and metal ions, biofilm formation, siderophore production, motility and chemotaxis. RNA sequencing and proteomics data showed that the list of differentially expressed genes (DEGs) and proteins (DEPs) in pecM::Km cells compared to WT was surprisingly long, given the limited number of identifiable phenotypes. These data suggest that the accumulation of 4HBA resulted in pecM::Km cells mounting an oxidative stress response and significant metabolic adjustments to compensate for the loss of the efflux pump, implying that PecM is important for maintaining cellular homeostasis.
By contrast, the disruption of pecS resulted in fewer DEGs and DEPs, with a remarkably poor correlation. A notable observation was the marked depletion of the aminopeptidase AmpS. The ampS was highly expressed, which means that reduced AmpS levels were achieved by post transcriptional regulation. The data also revealed that the PecS regulon is not conserved between species.
Taken together, this work points to the roles of both PecS and PecM in maintaining bacterial fitness in the rhizosphere
FASHION CONSUMERS RESPONSE TO FIRM, VICARIOUS, PRODUCT, AND SERVICE LEVEL GREENWASHING: A MULTI-GROUP STRUCTURAL EQUATION MODELING APPROACH
No full textTo address the research gap in systematic greenwashing research, this study is grounded in the Greenwashing Cycle Theory (GCT) proposal. GCT is a systematic and potentially sequential process spanning firm-level, vicarious-level, product-level, and service-level greenwashing, with executional-level greenwashing potentially present at any stage. Through the application of generational cohort theory, psychological contract theory, stimulus-organism theory, and the spillover phenomenon, a potential research gap has been identified, and a conceptual model has been developed to address related research questions. Four levels of greenwashing stimuli have been established, and 906 valid responses have been collected from the cloud research online platform. Two-way ANOVA test results indicated that different levels of greenwashing create diverse perceptions and interpretations among consumers. The interpretation of greenwashing varies across generations. Multi-group structural equation modeling results indicated that when greenwashing is interpreted as a higher-order internal belief (corporate hypocrisy), it leads to an extreme response from consumers. There is a difference in perception and interpretation of greenwashing. At each level of greenwashing perception, the consumer initiates offline NWOM, brand switching, and brand distance intention. A psychological contract exists between the luxury fashion consumer and the brand. Breaking this promise triggers such extreme responses. Consumers exhibit heightened reactivity to firm and service-level greenwashing within the fashion business. The spillover phenomenon of greenwashing has been observed at all levels of greenwashing, with a particular prominence in service and firm-level greenwashing. After experiencing one level of greenwashing within the luxury brand\u27s greenwashing cycle, consumers are likely to form an overall evaluation of the brand. Not all manifestations of greenwashing will prompt knowledgeable consumers to escalate their responses to luxury brands. Some levels of greenwashing response are emotion-dominant rather than knowledge-dominant. The luxury fashion brand and the FTC should include firm, vicarious, product, and service-level greenwashing management in the manual to establish a systematic process for combating greenwashing. Luxury brands should exercise caution in their sustainability communication and presentation of tangible and intangible benefits within the fashion value chain. Potential theoretical and managerial implications were provided based on the research findings
Retrospective Study and Predictive Modeling of the Impact of Social Determinants of Health on Sepsis Outcomes
No full textSepsis, a life-threatening organ failure caused by the body’s abnormal and harmful response to an infection, remains a major global and national health challenge. In the United States, it contributes significantly to hospital mortality and imposes a substantial economic burden, with billions spent annually on treatment. Early diagnosis is difficult due to the nonspecific nature of sepsis symptoms, often leading to delays in care and poorer outcomes. As the incidence and severity of sepsis rise, identifying factors that influence outcomes is increasingly critical. Emerging research has shown that Social Determinants of Health (SDOH), including economic stability, education, neighborhood and built environment, social and community context, and access to health and healthcare, play a significant role in sepsis outcomes and may contribute to disparities in care.
This research aims to uncover how SDOH factors influence sepsis outcomes, including in-hospital mortality, 30-day readmission, and length of stay (LOS), and to evaluate the utility of predictive modeling that incorporates SDOH factors in identifying high-risk patients. The data included patient demographics, clinical data, community-level SDOH indicators, responses from an individual-level SDOH screening survey, and patient outcomes. Findings show that higher social vulnerability, as measured by the Social Vulnerability Index (SVI), and greater distance to urgent care facilities are significantly associated with increased LOS. Multivariate analysis further shows that this is more pronounced among male patients. Age was found to mediate the effect of SVI on sepsis outcomes by serving as a protective factor for mortality, LOS, and readmission. In contrast, chronic health conditions do not significantly mediate this relationship. Although the developed models demonstrated a limited ability to identify mortality and readmission cases accurately, Deep Neural Networks (DNNs) achieved superior performance, particularly in terms of F1 score, compared to Random Forest and Logistic Regression in the classification tasks.
This research makes several key contributions to the understanding of SDOH in sepsis care. It identifies geographic proximity to healthcare facilities as a novel and significant predictor of sepsis outcomes, particularly in-hospital mortality and LOS. The study also explores mediation analysis, revealing that age mediates the relationship between SDOH and sepsis outcomes. Furthermore, it explores the integration of community-level SDOH factors into machine learning models for sepsis outcome prediction, offering insights into how structural and spatial factors can enhance risk stratification in sepsis care
Shock Induced Droplet Aerobreakup for Newtonian and Non-Newtonian Fluids
Get PDFThis research investigates shock-induced aerodynamic breakup (aerobreakup) of fluids with different stress-strain behaviors. The central hypothesis is that shear stress from highspeed gas flow manifests differently depending on a fluid’s strain response, influencing droplet breakup morphology, fragment size distribution, and drag-induced acceleration. To test this, experiments and simulations were performed on μm–mm sized droplets of Newtonian (water) and shear-thinning fluids (nanofluids or xanthan gum). Two experimental setups were used: an open-ended shock tube and a closed conventional shock tube. In the openended setup, a normal shock impacts a stationary droplet held by an acoustic levitator. Droplet breakup and gas dynamics are visualized using high-speed back-illuminated and schlieren imaging. Breakup of water and nanofluids (TiO2 and Al2O3 dispersions) at shock speeds near Mach 1 showed droplet flattening, liquid sheet formation, and atomization. The resulting mist expanded under the high-speed gas jet. Nanofluids exhibited delayed breakup due to higher viscosity and Ohnesorge number. Axisymmetric flow simulations captured gas dynamics and initial deformation. To study higher Mach number effects, a custom-built closed shock tube was used, reaching Mach 2.13 to 3.03 using helium and a vacuum-driven section. Droplets were generated via column breakup and imaged with high-speed cameras. Increasing Mach number led to transitions from bag to multi-bag to shear stripping and catastrophic breakup modes, consistent with higher Weber number. Quantitative image analysis showed increasing droplet centroid velocities with Mach number. Water droplets accelerated faster due to early misting, while xanthan gum accelerated more slowly due to viscoelastic ligament formation. Nanofluids broke up more rapidly at higher Mach numbers, likely due to lower surface tension. Deformation metrics showed increasing vertical elongation and reduced horizontal flattening with Mach number. Breakup initiation and total breakup times were modeled using the Wert and Hsiang models based on Weber and Ohnesorge numbers. These closed shock tube results confirm that fluid rheology and surface tension significantly influence breakup behavior and post-breakup droplet dynamics under highspeed aerodynamic loading
Investigating the Relationships Among Suspended Sediment Concentration, and Marsh Edge Erosion in Barataria Bay, LA
No full textBarataria Bay, Louisiana, USA exhibits a unique microtidal, wind-driven hydrodynamic climate where extensive levee infrastructure throughout Louisiana has starved Barataria Bay and similar interdistributary bays of the historic levels of terrigenous sediment import. This has contributed to extreme coastal wetland loss in Louisiana. This project seeks to understand how hydrodynamic and meteorological conditions are linked to sediments’ fate after erosion from the marsh edge. Specifically, this project seeks to differentiate the roles of wave resuspension and marsh edge erosion (MEE) in sediment dynamics in Barataria Bay. An acoustic wave and current profiler (AWAC) was used to capture hydrodynamic conditions, and the acoustic backscatter from the AWAC was used to quantify suspended sediment concentration (SSC). The wave parameters from the AWAC were then used to calculate bottom shear stress and estimate sediment resuspension. Additionally, Sentinel-2 imagery and the normalized difference turbidity index were used to quantify marsh edge erosion by identifying zones of high turbidity (ZHTs) originating from the marsh edge, and wind data was taken from the ERA5 reanalysis dataset. When wind speeds exceed 5 m/s a regime shift in the mechanism suspending sediment occurs. During quiescent conditions (wind speed \u3c 5 m/s), resuspension is low, and most SSC is likely due to advection from the Gulf Intracoastal Waterway and the mouth of the Mississippi River. When wind speed exceeds 5 m/s, both resuspension and the size of ZHTs scales with wind speed. This pattern is especially apparent in periods of northerly winds, while southerly winds do not exhibit the same regime shift. While ZHTs were intended as proxies for MEE, a quantitative link between ZHTs and MEE was unable to be established. Rather, ZHTs were visually traced to the marsh edge, and links between wind conditions and ZHTs were established. However, the significance of these relationships is limited due to the small number of images analyzed. This work demonstrates the way meteorological and hydrodynamic conditions lead to marsh edge erosion and sediment transport
Effects Of Staphylococcal Superantigen-Like Protein 11 (SSL11) On The Host Immune Response During Lung Infection
Get PDFStaphylococcus aureus (S. aureus) is an opportunistic pathogen that produces numerous immune evasion molecules that target various components of the host immune defense to cause infection. One of these is a family of virulence factors, Staphylococcal superantigen-like proteins (SSLs) with 14 members that exhibit host immune-evasion functions. SSL11 has been reported to inhibit neutrophil migration, preventing its recruitment to sites of infection. However, its role in vivo and effect on neutrophil phagocytosis have not been known. This thesis focuses on studying the effect of recombinant SSL11 protein in an in vivo S. aureus-induced pneumonia model and in vitro neutrophil phagocytosis. We hypothesize that SSL11 protein (SSL11/WT) reduces excessive inflammation by impairing neutrophil migration, thus offering protection during severe S. aureus-induced pneumonia from the damage caused by excess neutrophil, whereas mutated SSL11 (SSL11/RA), lacking the SLeX binding site required for leukocyte migration inhibition, will not have similar protection. Mice were infected with S. aureus (SA) by oropharyngeal aspiration with treatment of SSL11/WT or SSL11/RA. Co-treatment of SSL11/WT and S. aureus inoculum resulted in a greater bacterial load in the lungs compared to the control group with only S. aureus infection. In contrast, pretreatment of SSL11/WT before infection led to a reduction in S. aureus in the lungs of female mice at 24 and 48 hours. Bronchoalveolar lavage fluid (BALF) analysis in the SSL11/WT pretreatment group in female mice shows a pattern of decreased neutrophil, monocyte, and macrophage counts with reduced cytokine release of IL-6 and MCP-1. Assessment of neutrophil-mediated phagocytosis of S. aureus treated with SSL11 protein shows that all SSL11/WT and SSL11/RA treatment significantly lowers the S. aureus phagocytosis and killing inside the phagolysosome by neutrophil in an SLeX-independent manner. These results suggest SSL11/WT pretreatment has a pattern of decreased neutrophil recruitment to the site of infection but somehow enhances bacterial clearance in the lungs post-24 hours in female mice. Meanwhile, both forms of SSL11 decrease the phagocytosis by the neutrophils in vitro, which is beneficial for S. aureus as it facilitates its survival. Further study on the topic might provide a new target against S. aureus infections
Wildlife disease surveillance from village to peak: Trypanosome infections of mammals on Sulawesi revealed higher prevalence in intact montane forests
No full textZoonotic diseases, including those carried by mammalian hosts, pose a significant threat to human health worldwide and substantial investment in wildlife disease surveillance is aimed at identifying the risk of spillover from wildlife to human populations where they interact. However, host species diversity is highest in the most intact habitats away from human habitation and most of the potential host species within these habitats are unsampled for infections. This is particularly true in biodiverse tropical ecosystems where the prevalence and identity of infections are the least known. We screened for presence of trypanosomes in 2,335 specimens from 66 species of rodents and shrews sampled from 11 mountain areas on the tropical island of Sulawesi, Indonesia. Our sampling spanned from the edge of human occupation into the most intact forests available on the island with sampling elevations ranging from 220 to 2,700 m. The two most common Trypanosoma species we detected were a native species from the Theileri clade (19.0 % of samples) and an introduced species from the Lewisi clade (5.1 % of murid rodent samples). Both species were detected at all elevations, extending from village edges to mountain peaks, but both reached their highest prevalence above 2,000 m elevation in the most intact forest away from human habitation. If these patterns with trypanosome infections are typical of other zoonotic diseases, wildlife disease surveillance would need to shift resources to study host-pathogen dynamics in more remote ecosystems. Sampling focused on the breadth of biodiversity, such as collected by and housed in natural history collections, is needed to further our understanding of zoonotic diseases and their prevalence
Targeting bacterial transcription factors for infection control: opportunities and challenges
Get PDFThe rising threat of antibiotic resistance in pathogenic bacteria emphasizes the need for new therapeutic strategies. This review focuses on bacterial transcription factors (TFs), which play crucial roles in bacterial pathogenesis. We discuss the regulatory roles of these factors through examples, and we outline potential therapeutic strategies targeting bacterial TFs. Specifically, we discuss the use of small molecules to interfere with TF function and the development of transcription factor decoys, oligonucleotides that compete with promoters for TF binding. We also cover peptides that target the interaction between the bacterial TF and other factors, such as RNA polymerase, and the targeting of sigma factors. These strategies, while promising, come with challenges, from identifying targets to designing interventions, managing side effects, and accounting for changing bacterial resistance patterns. We also delve into how Artificial Intelligence contributes to these efforts and how it may be exploited in the future, and we touch on the roles of multidisciplinary collaboration and policy to advance this research domain. Abbreviations: AI, artificial intelligence; CNN, convolutional neural networks; DTI: drug-target interaction; HTH, helix-turn-helix; IHF, integration host factor; LTTRs, LysR-type transcriptional regulators; MarR, multiple antibiotic resistance regulator; MRSA, methicillin resistant Staphylococcus aureus; MSA: multiple sequence alignment; NAP, nucleoid-associated protein; PROTACs, proteolysis targeting chimeras; RNAP, RNA polymerase; TF, transcription factor; TFD, transcription factor decoying; TFTRs, TetR-family transcriptional regulators; wHTH, winged helix-turn-helix
A glucocorticoid receptor antagonist affects corticosterone but not neophobia in wild-caught house sparrows (Passer domesticus)
No full textAvoidance of novel stimuli (neophobia) affects how wild animals interact with their environment and may partly determine whether animals persist in human-altered landscapes. The neuroendocrine mediators of neophobia are poorly understood, although past work demonstrated that experimentally reducing circulating corticosterone in wild-caught house sparrows (Passer domesticus) decreased neophobia toward novel objects placed near the food dish. In this experiment, we directly tested the role of one of the two types of corticosterone receptors, the glucocorticoid receptor (GR), in mediating neophobia in house sparrows by administering a GR antagonist (RU486, n = 10) or a vehicle control (peanut oil, n = 10) over 5 consecutive days and measuring responses to novel objects both pre- and post-treatment. We also measured baseline and stress-induced corticosterone in all sparrows on the final day of behavior trials. To better understand the effects of RU486 on corticosterone over time, in a separate group of sparrows (n = 12) we administered RU486 or vehicle over 5 days and took multiple blood samples to assess baseline and stress-induced corticosterone. Overall, we did not detect an effect of subcutaneous RU486 injections on neophobia behavior. However, we did find that RU486 injections significantly decreased stress-induced corticosterone levels starting 1 day post-injection and baseline corticosterone levels starting 6 days post-injection, compared to vehicle-injected controls. Our results suggest that GR is not involved in mediating neophobia behavior in house sparrows
FORENSIC SAMPLING USING NANOPARTICLE EXTRACTION AND VACUUM CAPTURE
No full textA forensic sampling system was developed for extraction of material from surfaces for off-line analysis by mass spectrometry. The system is composed of a pulsed valve and vacuum aspirated capture with a membrane filter. Particles are deposited on a surface that contains the analyte of interest and the pulsed valve displaces the particle and analyte mixture that is captured on the filter. The material is extracted from the filter and analyzed by mass spectrometry. The sampling system was utilized to capture from the surface of brick, paper, carpet, fabric (90:10 polyester cotton fabric) and glass. Gas chromatography/mass spectrometry (GC-MS) data verified recoveries of caffeine from the surfaces and the detection limit on glass was found to be less than 1 µg. The sampling system was also used to extract ignitable liquids in simulated arson studies. Porous, non-porous and functionalized nanoparticles were used as extraction particles for gasoline and diesel fuels. GC-MS confirmed the presence of ignitable liquid materials and statistical analysis was used to assess components in burned matrices. Using functionalized C18 particles and porous nanoparticles as extraction particles, gasoline traces were identified. The signal intensity was four times as intense when using functionalized C18 particles compared to porous nanoparticles suggesting a more selective capture of specific ignitable liquids with the C18 particles. A portable system was also developed that utilizes inexpensive components. The system utilizes an automobile fuel injection valve and a compressed air canister, and a portable vacuum for sampling. The system is powered by a 12v lead-acid battery. The prototype design was used to extract small molecules from several surfaces at recoveries comparable to the laboratory pulsed valve sampling and performed better than swab based sampling on porous surfaces