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Antimicrobial Resistance Dynamics in Poultry Environment and the Role of Insects as Vectors of Resistance
No full textThis study investigated the potential role of insects in the spread of antimicrobial resistance (AMR) within and around broiler-rearing facilities, specifically focusing on antimicrobial resistance genes (ARGs). By evaluating spatial patterns of AMR, defining the diversity and presence of ARGs, and analyzing the implications for animal and human health, we aimed to better understand AMR dynamics in broiler production environments. We employed multiple sampling techniques to collect insect and environmental samples. Shotgun sequencing was performed to examine the microbial communities and determine the presence of antimicrobial-resistant genes. Spatial variations in AMR and evaluation of elements influencing AMR dissemination were assessed by statistical analysis. Results from this research uncovered a diverse assortment of pathogens and AMR genes within the livestock environment, and highlighted insects as potential vectors for the transmission of resistant bacteria. Variations in AMR occurrence were found among the sampling sites, emphasizing the need for directed surveillance and intervention protocols. The findings of AMR in broiler farms indicated that antibiotic-resistant bacteria pose risks to food safety, human and animal health, and animal welfare, highlighting the necessity of dynamic management practices. Altogether, this study expands upon the understanding of AMR dynamics in broiler facility landscapes and showcases the significance of managing AMR in livestock environments to protect human and animal health. Additionally, our findings highlight the need for integrated management strategies considering the intricate interactions between microbes, arthropod vectors, livestock, and the environment in limiting the spread of AMR
"Trust to Us, the Union Men of the South": The 1866 Southern Loyalist Convention and the Fight for Reconstruction
No full textIn 1866, unconditional Unionists of the South, who had remained loyal to the United States during its civil war, convened in Philadelphia to express their displeasure with President Andrew Johnson. In their view, Johnson���s willful inaction enabled traitors rather than Unionists to continue dominating Southern politics in the aftermath of the war. If the Union defeated the Confederacy but its supporters remained in power, Unionists��� staunch devotion to the Union was rendered pointless. The 1866 Southern Loyalist Convention was the culmination of years of political struggles. Scholarly literature on Southern Unionists is extensive, yet historians have overlooked the significance of this convention. This thesis argues that the convention utilized a narrative of suffering that Southern Unionists employed consistently throughout the Civil War and Reconstruction. In various pamphlets published early in the crisis, Southern Unionists voiced their disapproval of secession and had articulated their perspectives on national affairs. By concentrating those disparate voices in a single location, the Southern Loyalist Convention amplified long standing whispers of Unionist dissatisfaction. Collectively, these broadsheets pointed to deep divisions among Unionists, generally involving disagreements about African American enfranchisement. Despite the internal divisions that ultimately prevented them from forming a powerful Unionist coalition, Southern Unionists were consistent in a few key ways. They insisted upon their undying support for the Union, demanded the implementation of their agenda, and constructed a powerful narrative of their own suffering. Their mutual misery, in fact, became the foundation upon which Unionists built relationships with each other at this convention. This thesis considers how the 1866 Convention contributed to a post-war narrative that historians have labeled the ���Won Cause��� memory of the war
Spinal Plasticity: Using Spinal Learning to Inform Maladaptive and Adaptive Effects of Nociceptive Input After Spinal Cord Injury
No full textThe traditional dogma of the spinal cord as a rigid conduit of information has been challenged in recent years. Evidence demonstrates that circuitry within the spinal cord can undergo adaptive and maladaptive plasticity particularly after spinal cord injury. Our work has focused on instrumental learning in the spinal cord along with the impact of nociceptive input after spinal cord injury. In this dissertation I explored how spinal cord injury affects plasticity. This work places particular emphasis on the impact of nociceptive input and factors that allow peripheral input to drive adaptive rather than maladaptive plasticity.
This dissertation explored spinal plasticity after injury in a complete thoracic (T2) transection in order to clarify the properties of the spinal cord itself. The first series of experiments show that the consequences of training vary with duration. These experiments also revealed two unexpected findings that motivated the following two chapters.
The second series identified a previously unknown effect of exposure to controllable
stimulation. An extended exposure to controllable stimulation altered how later stimulation is
interpreted, causing it to be read as adaptive (controllable) regardless of how it was presented.
This series also identified the anatomical locus of this shift and began to clarify its mechanistic
underpinnings.
The next series of experiments clarified the impact of proprioceptive signaling on the effects of uncontrollable noxious input. These experiments found that limb position modulates how nociceptive stimulation affects spinal cord plasticity. This series revealed that noxious stimulation only impairs plastic potential when applied while the hind limbs are extended.
The final set of experiments explored the role of ionic plasticity in spinal plasticity after injury. These experiments focused on the importance of the release of the GABAergic break on adaptive plasticity. They also identified pharmacological manipulations that can be used to manipulate ionic plasticity and, as a result, spinal plasticity. This suggests the potential of harnessing ionic plasticity to drive adaptive over maladaptive change.
Collectively, these experiments highlight the potential of harnessing plasticity after spinal cord injury for good. The studies show how the consequences of nociceptive stimulation vary with duration, order of presentation, limb position, and changes in GABA-dependent inhibition
How Likely Is a Repeat of the February 2021 Winter Storm Event in Texas, Really? An Impact-Driven Analysis of Compound Cold-Weather Variables in the Context of the Changing Climate
No full textThe extreme cold that led to the failure of the Texas electrical grid in February 2021 has been extensively analyzed in terms of both its likelihood and its predictability. Other authors have pointed out that the severity of its impact ��� power lost to 4.5 million households representing 10 million people for roughly 3 full days ��� is disproportionate to the severity of the cold. Because the return periods of individual extreme weather variables did not correlate with the extreme impacts experienced, we analyzed combinations of cold-weather variables known to affect residential heating demand, electrical generation, and fuel supply. We evaluated these combinations using cold-weather indices which include multiple variables and copulas which combine individual variables.
We weighted temperatures by the population of the metropolitan area in which they occurred to reflect their impact on the electrical grid and adjusted these temperatures to reflect the changing climate of Texas. We found that the conditions experienced at the time of failure, February 15th, 2021, at 2am Central Time, could reasonably be expected between every 3 and 18 years, with the most extreme combination being low temperatures and time spent at or below freezing. After scaling past temperatures to reflect a warming climate, this combination has been more extreme in Texas four or more times over the past 80 years than what was experienced when the electrical grid was not able to produce enough electricity to meet demand for it.
Cold-weather conditions were additionally analyzed over the locations where these generation resources and their fuel supply had the highest failure rates. We found significant differences in the likelihood of the February 2021 conditions both in individual variables and combinations.
Wind power was reduced by turbine icing and was unable to restart for over a week. Using freezing duration following icing conditions for most stations in a cluster resulted in return periods which seemed to align with the impacts of this storm, yet still resulted in the turbine icing component of this interconnected failure being the least likely aspect to occur again
Synthesis and Evaluation of Tribological Performance of Mxenes
No full textThis work addresses the challenges associated with the synthesis of MXene (acid etching) using an alternative method of molten salt etching and alteration of interfacial properties. This thesis is part of a thrust to develop acid free synthesis of MXenes at an industrial scale.
The initial part of the thesis is focused on the acid-free synthesis of MXenes via molten salt etching. Despite numerous prior reports of molten salt etching of MAX phases, few of these reports achieved water-dispersible MXene nanosheets and none for Nb-based MXenes. Here, we demonstrate the synthesis and aqueous dispersibility of Nb2CTz nanosheets via molten salt etching and utilizing a KOH wash to add hydroxyl surface groups. However, little is known about the oxidation of molten salt-etched MXenes compared to acid-etched MXenes. This work has indicated the slower oxidation behavior for MXenes etched by molten salts, which may be due to the decreased amount of oxygen-containing terminal groups.
A significant portion of my thesis is focused on utilizing the MXene (acid etched and salt etched) for tribological applications as liquid or solid lubricants. Owing to the high thermal conductivity, electrical conductivity, and mechanical strength of Ti3C2Tz nanosheets, they seem to be a promising candidate as lubricant additives. In this work, we evaluate the performance of Ti3C2Tz as an additive to enhance the heat transfer, rheological properties, and tribological performance of oils. The improved properties (Thermal conductivity) and reduced fluidic drag in viscosity and friction lead to potential applications in (electrical) vehicles that will help attain improved fuel economy.
Although surface terminations (such as ���O, ���Cl, ���F, and ���OH) on MXene nanosheets strongly influence their functional properties, synthesis of MXenes with desired types and distribution of those terminations is still challenging. In my thesis, we demonstrated that thermal annealing helps remove much of the terminal groups of molten salt-etched multilayered (ML) Ti3C2Tz. In this work, the chloride terminations of molten salt-etched ML-Ti3C2Tz were removed via thermal annealing. This thermal annealing created some bare sites of high surface energy and reactivity that are available for further functionalization of Ti3C2Tz. Here, the annealed ML-Ti3C2Tz was re-functionalized by ���OH groups and 3-aminopropyl triethoxysilane (APTES)z, which were evaluated as a solid lubricant, exhibiting ���70.1 and 66.7% reduction in friction compared to a steel substrate, respectively. This enhanced performance is attributed to the improved interaction or adhesion of functionalized ML-Ti3C2Tz with the substrate material. This approach allows for the effective surface modification of MXenes and control of their functional properties.
The ability to control the d spacing of MXene has proved beneficial for energy storage applications such as batteries and supercapacitors, but no one has utilized this control of interlayer spacing for lubrication. In this work, we control the interlayer spacing between the ML-Ti3C2Tz MXene via chemical intercalation. In order to alter the d-spacing, we investigated several different-sized intercalating agents. The increase in the d-spacing of ML-Ti3C2TZ MXene resulted in a drop in electrical conductivity and friction coefficient. Specifically, the enlarged interlayer gap reduced electrical conductivity in the vacuum-filtered ML-Ti3C2Tz MXene films due to increased internal resistance. Additionally, the increased d-spacing or interlayer spacing of ML-Ti3C2Tz resulted in a reduction of the coefficient of friction. This decrease is attributed to the facilitated sliding of individual ML-Ti3C2Tz layers under applied shear forces or load, resulting from the weakened van der Waals interactions due to the increased interlayer spacing
Assessing Primate Eye Morphology
No full textEye morphology varies widely across primates with species exhibiting a range of eye colors and shapes, but we do not yet have a full understanding of what drives this diversity. We tested whether primate eye morphology is correlated with social factors, ecological factors, or both. We did so by examining the eye coloration and shape of 68 primate species (spanning great apes, lesser apes, prosimians, and African, Asian, and South American monkeys). We used modern methods of analyzing animal coloration that account for the specific visual system of each species. We found that primate eye coloration is correlated with both social and ecological factors. Primates with more discriminable gaze have larger social group sizes and canine size dimorphism. Primate eyes that have greater red chromaticity are associated with more open habitats. And, primates with more elongated eyes had larger body mass, lived in more open habitats, had larger group sizes, and lived closer to the equator. Our ancestral trait reconstruction suggested that the ancestral primate had moderately elongated eyes with brown irises and sclera. Our results suggest that both social and environmental factors have impacted the evolution of primate eye morphology
Evidence for Metabolism of Creatine by the Conceptus, Placenta, and Uterus for Production of ATP During Conceptus Development in Pigs
No full textDuring gestation in pigs, most embryonic mortality occurs during two gestational time points with high energy demands due to extensive cell proliferation and migration. Between Days 14 and 25, free-floating conceptuses (embryo/fetus and associated placental membranes) elongate and attach to the uterus. Between Days 50 and 70, the uterine-placental interface undergoes extensive folding and develops mature areolae to maximize support for development of the fetuses. We hypothesize that insufficient energy in the form of ATP in conceptuses and uterine tissue may contribute to conceptus loss in pigs. Creatine, an organic compound commonly stored in the muscle as phosphocreatine, can regenerate ATP through the creatine (Cr)-creatine kinase (CK)- phosphocreatine (PCr) pathway. However, the expression of factors involved in creatine metabolism has not been examined in conceptus and uterine tissues throughout gestation in pigs. In the present study, we performed real-time qPCR to quantify expression of mRNAs for enzymes and the creatine transporter involved in the creatine metabolic pathway in conceptus and uterine tissues from Days 10, 12, 15, 18, 20, 24, 30, 40, 60, and 90 of gestation. Results of qPCR analyses revealed increases in expression of AGAT, GAMT, CKM, CKB, and SLC6A8 mRNAs in conceptuses on Day 15, and a further increase in AGAT mRNA in the chorioallantois on Day 90 of gestation. Immunofluorescence staining of the uterine-placental interface from Days 15, 16, 20, and 25 corroborated qPCR results, with the expression of GAMT, CKM, and CKB proteins appearing to increase in conceptus Tr cells on Day 15. The presence of GAMT, CKB, and CKM proteins were confirmed with Western blot analyses. Levels of endometrial AGAT and CKM mRNAs increased on Day 15, CKB mRNA increased again on Day 30, and AGAT, GAMT, and SLC6A8 mRNAs increased significantly on Days 40, 60, and 90. Furthermore, HPLC analyses confirmed the presence of Cr and PCr metabolites in uterine luminal fluid, allantoic fluid, and amniotic fluid with significant increases in the uterine fluid and allantoic fluid on Days 11 and 40, respectively. Collectively, results of this study indicate that the Cr-CK-PCr pathway could establish sufficient energy stores to support cell proliferation and migration required for conceptus elongation, implantation, and remodeling of the uterine-placental interface during gestation in pigs
Impact of Immune Reactions and Crosslinking Chemistry on Hydrogel Properties and Performance
No full textHydrogels are hydrophilic, three-dimensional structures that can be synthesized from synthetic and natural polymers for use in various tissue engineering applications. Their efficacy, however, is heavily dependent on the immune reaction to the material used. Another feature of hydrogels is their tunability in physicochemical properties, which can be modulated based on the crosslinking chemistries used to synthesize the structure. While often treated as being interchangeable, recent evidence suggests crosslinking chemistry���s potential to significantly impact material properties. Here, we sought to investigate the implications of polymer immunogenicity and crosslinking chemistry on hydrogel design and application.
Our first goal was to investigate poly(ethylene glycol) (PEG), a synthetic polymer considered to be bioinert, and how sensitization to the polymer impacts tissue engineering efficacy. To this end, PEG-based microporous annealed particle (MAP) hydrogels were assembled in situ of critical-sized calvarial defects through bioorthogonal tetrazine click reactions, and bone formation and morphology was found to be significantly influenced by PEG sensitization. Next, a head-to-head comparison of annealing chemistry used during MAP hydrogel assembly was further characterized between tetrazine-norbornene click reactions and radically-mediated thiol-norbornene click reactions. Differences in materials properties, such as storage moduli and susceptibility to enzymatic degradation, emerged as a result of annealing chemistry and were further modulated with respect to TNCP concentration. We deduced tetrazine-norbornene click products (TNCPs) induce secondary interactions that contribute to these changes, but these distinctions were negligible when applied in vivo.
Next, we evaluated whether the modulatory effects of TNCP-induced interactions could be applied in polymer-based biomaterials other than PEG. Specifically, we applied various concentrations of TNCPs to a hyaluronic acid (HA)-based bulk hydrogel and observed tetrazine-mediated changes to material properties. We also were able to leverage these interactions to assemble a supramolecular HA hydrogel that demonstrated shear-thinning and self-healing behavior that suggest potential as an injectable material, which was assessed in vitro using a genetically engineered strain of bacteria. Finally, TNCP-induced secondary interaction were leveraged in development of a hydrogel platform where a mock therapeutic was directly conjugated onto the HA backbone. Retention of the conjugated molecule and minimal degradation of the platform was observed after one week
Impact of Astaxanthin Supplementation on Markers of Cardiometabolic Health and Tactical Performance Among Firefighters
No full textFirefighters are at risk for cardiovascular disease (CVD) due to increased oxidative stress, inflammation, and poor cardiorespiratory fitness (CRF). Astaxanthin (AX) possesses antioxidant/anti-inflammatory and purported ergogenic properties. This study examined the impact of 12 mg/d for four weeks of AX supplementation on markers of oxidative stress, inflammation, cardiometabolic health, cardiorespiratory fitness, and occupational performance in career firefighters. In a randomized, double-blinded, placebo-controlled, crossover fashion, 15 male career firefighters (34.5��7.4 years; 177.7��7.0 cm; 95.6��12.0 kg; 30.1��2.9 kg/m��; 11.03��6.85 years of service) ingested 12 mg/d of AX (AstaReal��, Burlington, NJ, USA) or placebo for four weeks while following a standardized resistance training program. After each treatment, testing sessions were completed to assess 1) blood cardiometabolic health, oxidative stress, and inflammatory and CRF parameters, and 2) salivary oxidative stress and inflammatory responses and tactical performance to fire suppressive activities. Data were analyzed using general linear model multivariate analysis with repeated measures (GLM). Clinical significance was assessed via mean changes from baseline (BL) with 95% confidence intervals (mean [LL, UL]). Analysis of mean changes from BL revealed AX lessened the inflammatory response to a cardiopulmonary exercise test. Additionally, the percent ventilatory anaerobic threshold (%VANT) was higher following AX compared to placebo (4.84 [0.27, 9.41] %, p<0.039, ����_p^2=0.114). Analysis of mean changes from BL revealed AX may lessen increases in IL-1��, cortisol, and UA response to fire suppressive activities. Cardiometabolic health markers were not affected in a statistically significant manner. These findings provide some evidence that AX supplementation may help mediate occupation-related inflammation and oxidative stress in response to high-intensity, short-duration exercise in firefighters. More research is warranted to determine if long-term supplementation can improve cardiometabolic risk in this population
Target Identification Using Single Cell RNA-Seq: Algorithms and Applications
No full textTarget identification is a crucial step in the drug development process, significantly affecting the success rate and efficiency of bringing new therapies to market. Recent advancements in single-cell RNA sequencing and computational tools have accelerated the identification and validation of therapeutic targets by enabling a deeper understanding of disease mechanisms at the cellular level. However, challenges such as inadequate understanding of the molecular basis of certain diseases and limitations in current single-cell data analysis methods, particularly in capturing gene regulatory relationships, continue to hinder the full exploitation of these technologies in precision medicine.
To this end, we aim to enhance target identification in scRNA-seq, crucial for unraveling cellular differentiation and disease mechanisms. Firstly, we develop ���scInTime���, a computational method that capitalizes on single-cell trajectory data and gene regulatory networks to accurately identify master regulators of cellular differentiation. This algorithm aims to overcome the existing challenges in mapping cell fate decisions, a critical step in advancing personalized medicine. Secondly, we propose to undertake an integrated scRNA-seq data analysis to investigate the association between pyroptosis and the severity of COVID-19. This research is expected to shed light on the immune response to SARS-CoV-2 and identify potential targets for therapeutic intervention. By focusing on the mechanisms underlying severe COVID-19 cases, we anticipate contributing to the global effort in combating the pandemic. Thirdly, we address metabolic diseases, specifically investigating the role of hepatocyte adenosine kinase in fat deposition and liver inflammation. Here, we aim to elucidate the molecular pathways that lead to excessive fat storage and inflammation in the liver, offering targets for the treatment of metabolic syndromes. Finally, we conduct a sex-based study on the role of RSPO3 in estrogen-mediated sex differences. Understanding the molecular bases of sex differences in diseases is critical for the development of gender-specific therapies and this study will contribute to that knowledge base.
Overall, our goal is to leverage scRNA-seq for precise target identification, addressing significant gaps in the understanding of cellular differentiation and disease. This thesis is designed to set the stage for a series of investigations that will collectively advance our knowledge in the field and lead to novel therapeutic strategies