Interconnected Roles Research Articles

Distinct functions and transcriptional signatures in orally induced regulatory T cell populations

Oral administration of antigen induces regulatory T cells (Treg) that can not only control local immune responses in the small intestine, but also traffic to the central immune system to deliver systemic suppression. Employing murine models of the inherited bleeding disorder hemophilia, we find that oral antigen administration induces three CD4+ Treg subsets, namely FoxP3+LAP-, FoxP3+LAP+, and FoxP3-LAP+. These T cells act in concert to suppress systemic antibody production induced by therapeutic protein administration. Whilst both FoxP3+LAP+ and FoxP3-LAP+ CD4+ T cells express membrane-bound TGF-β (latency associated peptide, LAP), phenotypic, functional, and single cell transcriptomic analyses reveal distinct characteristics in the two subsets. As judged by an increase in IL-2Rα and TCR signaling, elevated expression of co-inhibitory receptor molecules and upregulation of the TGFβ and IL-10 signaling pathways, FoxP3+LAP+ cells are an activated form of FoxP3+LAP- Treg. Whereas FoxP3-LAP+ cells express low levels of genes involved in TCR signaling or co-stimulation, engagement of the AP-1 complex members Jun/Fos and Atf3 is most prominent, consistent with potent IL-10 production. Single cell transcriptomic analysis further reveals that engagement of the Jun/Fos transcription factors is requisite for mediating TGFβ expression. This can occur via an Il2ra dependent or independent process in FoxP3+LAP+ or FoxP3-LAP+ cells respectively. Surprisingly, both FoxP3+LAP+ and FoxP3-LAP+ cells potently suppress and induce FoxP3 expression in CD4+ conventional T cells. In this process, FoxP3-LAP+ cells may themselves convert to FoxP3+ Treg. We conclude that orally induced suppression is dependent on multiple regulatory cell types with complementary and interconnected roles.

Palynological Evidence From the Altai Mountains for the Links Between the Asian Westerly Jet Streams and Monsoon System During the Holocene

AbstractThe Asian westerly jet streams in the upper troposphere play a pivotal role in shaping precipitation patterns, sustaining the diverse but fragile ecosystems in arid Central Asia. Despite their significance, the evolution history of these jet streams and their synergistic effects with the monsoon systems on regional climate change in Asia during the Holocene remain poorly understood. To address this gap, we present a continuous pollen record since 8.6 cal ka BP from Lake Shuang in the Altai Mountains. The first two principal components of the pollen data are employed to track regional changes in vegetation, summer moisture, and winter temperature. Meanwhile, the pollen data and the TraCE‐21ka simulation results were compared to reveal the dynamic mechanism of regional climate change. Results indicate a humid phase spanning the interval ∼8 to 5 cal ka BP in this region, which broadly coincides with the intensification of the Indian Summer Monsoon. This temporal correlation is potentially linked to the poleward shift of the Asian jet, as suggested by simulation results. Furthermore, our data show a consistent winter warming trend throughout the Holocene, indicated by changes in the dominant tree pollen taxa and a reduction of cold‐resistant‐taxa. This trend is associated with the weakening of the East Asian Winter Monsoon, influenced by increasing winter solar insolation and atmospheric CO2 concentration. Overall, our research provides strong paleoclimatological evidence highlighting the interconnected meteorological roles of the Asian jet and monsoon systems in shaping regional climates.

Streptomyces at the Heart of Several Sectors to Support Practical and Sustainable Applications: A Review

This article emphasizes the various contributions of actinobacteria to the well-being of human life on our planet. Agrarian virtues begin with the substitution of chemical fertilizers with bio-fertilizing microorganisms which have a versatile potential for the benefit of soil and plants by playing complementary and interconnected roles. Thus, these microorganisms improve soil health through bioremediation phenomena and the elimination of several non-beneficial microorganisms. In agriculture, these microorganisms can be added to compost as inoculants to speed up the composting process and provide an additional source of beneficial microorganisms for the compost-treated soil. Streptomyces and other actinobacteria can also be used as biotechnological sources of herbicides and insecticides. In the medical and therapeutic sectors, this paper emphasizes the potential of actinobacteria, in particular Streptomyces species, in the production of antibiotics, antioxidant, and anticancer agents, opening up avenues for the creation of molecules with high benefits. In biotechnology, these totipotent microorganisms produce enzymes widely used in several industries, generating considerable revenue. Sporadic data accumulated on these types of microorganisms opens up many new avenues for exploiting these natural biocatalytic resources. Papers published in the last decade have exploded the amount of information that can be put to practical use. To maximize the value of these microorganisms, it would be advisable to create common threads between the themes that bring together the areas of expertise where these microorganisms could potentially be exploited. This bibliographical synthesis is a contribution to the development of a targeted database.

Turning catalytically active pores into active pumps.

We develop a semi-analytical model of self-diffusioosmotic transport in active pores, which includes advective transport and the inverse chemical reaction that consumes solute. In previous work [Antunes et al., Phys. Rev. Lett. 129, 188003 (2022)], we have demonstrated the existence of a spontaneous symmetry breaking in fore-aft symmetric pores that enables them to function as a micropump. We now show that this pumping transition is controlled by three timescales. Two timescales characterize advective and diffusive transport. The third timescale corresponds to how long a solute molecule resides in the pore before being consumed. Introducing asymmetry to the pore (either via the shape or the catalytic coating) reveals a second type of advection-enabled transition. In asymmetric pores, the flow rate exhibits discontinuous jumps and hysteresis loops upon tuning the parameters that control the asymmetry. This work demonstrates the interconnected roles of shape and catalytic patterning in the dynamics of active pores and shows how to design a pump for optimum performance.

Response to “Serving in the Household and the Imagination: The Brontës, Alcott and the Interconnected Roles of a Neglected ‘Transatlantic’ Female Figure,” by Paula Guimarães

Response to “Serving in the Household and the Imagination: The Brontës, Alcott and the Interconnected Roles of a Neglected ‘Transatlantic’ Female Figure,” by Paula Guimarães

Serving in the Household and the Imagination: The Brontës, Alcott, and the Interconnected Roles of a Neglected “Transatlantic” Female Figure

Tabitha Aykroyd, Martha Brown, Nancy and Sarah Garrs were just a few of the very many girls and women working as domestic servants in early Victorian Britain. The main purpose of this article is to analyze the precise context and conditions in which they were employed in Haworth Parsonage, where the Brontë sisters lived for most of their lives (1820–1855), and the influence that they had on the well-being of this famous family and on the imagination and literary activity of the sisters. Aspects connected with the following will be explored and problematized: the value and respect that the Brontës attributed to or showed these domestic laborers and their work, including sharing in their tasks and duties; brief but useful connections of these figures with the sisters’ own professional activities as middle-class women (namely, when serving as teachers and governesses themselves); and also comparison with some relevant literary representations of the figure and role of the “female servant” in the Brontës’ novels. A complementary purpose is of a more transatlantic nature: to compare their earlier British domestic context with Louisa May Alcott’s later American one, and their literary representations of the female servant with Alcott’s own extensive treatment of that neglected figure in some of her fictional works. The justification for this comparison does not lie so much in the known influence that the works written by the Brontës, in particular Charlotte’s, had on Alcott, but more in their sharing of very similar concerns as regards this topic, in spite of very specific (transatlantic) differences that can be revealing of their respective attitude towards servitude.

SIRT5 Activation and Inorganic Phosphate Binding Reduce Cancer Cell Vitality by Modulating Autophagy/Mitophagy and ROS.

Cancer cells show increased glutamine consumption. The glutaminase (GLS) enzyme controls a limiting step in glutamine catabolism. Breast tumors, especially the triple-negative subtype, have a high expression of GLS. Our recent study demonstrated that GLS activity and ammonia production are inhibited by sirtuin 5 (SIRT5). We developed MC3138, a selective SIRT5 activator. Treatment with MC3138 mimicked the deacetylation effect mediated by SIRT5 overexpression. Moreover, GLS activity was regulated by inorganic phosphate (Pi). Considering the interconnected roles of GLS, SIRT5 and Pi in cancer growth, our hypothesis is that activation of SIRT5 and reduction in Pi could represent a valid antitumoral strategy. Treating cells with MC3138 and lanthanum acetate, a Pi chelator, decreased cell viability and clonogenicity. We also observed a modulation of MAP1LC3B and ULK1 with MC3138 and lanthanum acetate. Interestingly, inhibition of the mitophagy marker BNIP3 was observed only in the presence of MC3138. Autophagy and mitophagy modulation were accompanied by an increase in cytosolic and mitochondrial reactive oxygen species (ROS). In conclusion, our results show how SIRT5 activation and/or Pi binding can represent a valid strategy to inhibit cell proliferation by reducing glutamine metabolism and mitophagy, leading to a deleterious accumulation of ROS.

Impact of non-neuronal cells in Alzheimer's disease from a single-nucleus profiling perspective.

The role of non-neuronal cells has been relatively overlooked in Alzheimer's disease (AD) neuropathogenesis compared to neuronal cells since the first characterization of the disease. Genome wide-association studies (GWAS) performed in the last few decades have greatly contributed to highlighting the critical impact of non-neuronal cells in AD by uncovering major genetic risk factors that are found largely in these cell types. The recent development of single cell or single nucleus technologies has revolutionized the way we interrogate the transcriptomic and epigenetic profiles of neurons, microglia, astrocytes, oligodendrocytes, pericytes, and endothelial cells simultaneously in the same sample and in an individual manner. Here, we review the latest advances in single-cell/nucleus RNA sequencing and Assay for Transposase-Accessible Chromatin (ATAC) sequencing to more accurately understand the function of non-neuronal cells in AD. We conclude by giving an overview of what still needs to be achieved to better appreciate the interconnected roles of each cell type in the context of AD.

Angiotensin-Converting Enzyme 2 Activation Is Not a Common Feature of Angiotensin-Converting Enzyme Inhibitory Peptides.

Angiotensin-converting enzyme (ACE) catalyzes the formation of angiotensin II (Ang II), a vasoconstrictor, whereas its homologue ACE2 degrades Ang II into angiotensin (1-7) (Ang (1-7)), a vasodilator. Given the similarities in structure and their interconnected roles in the regulation of cardiovascular system, this study aims to investigate if ACE-inhibitory (ACEi) peptides can also activate ACE2. About 200 potent ACEi peptides were subjected to molecular docking, 20 peptides were selected for cell and in vitro enzymatic activity studies, and 5 peptides were fed orally to spontaneously hypertensive rats at a dose of 15 mg/kg body weight/day for 7 days. Peptides IKW and RIY showed significant antihypertensive activity with activated circulating/aortic ACE2, circulating Ang (1-7), and decreased Ang II levels. IQY reduced blood pressure, increased Ang (1-7) level, but did not affect ACE and ACE2. Peptides MAW and MRW did not affect blood pressure, ACE, and ACE2. Our study showed that ACE2 activation is not a common feature of ACEi peptides.

The effect of interconnectivity on stock returns during the Global Financial Crisis

This paper examines the role of interconnectivity in global stock markets during the Global Financial Crisis (GFC) using a comprehensive dataset of 8,827 firms traded in developed and emerging markets. Our contribution includes two key findings. We first use a difference-in-differences approach to show that stocks in countries with higher trade openness ex-ante to the GFC experienced lower average and annual cumulative returns of 9.08 p.p. and 36.32 p.p., respectively, compared to stocks traded in less exposed countries, one year after the crisis outbreak. Second, we employ complex network theory to analyze the role of network interconnectedness in our baseline results. To construct the network of interdependence between stock returns, we utilize a regularized Vector Autoregression Model, which enables us to overcome the limitations of commonly used correlation networks. Our findings suggest that while a firm’s high connectivity before the crisis can alleviate adverse shock effects resulting from export dependence, this effect may be weakened if the firm’s performance is closely linked to central firms.

International risk of food insecurity and mass mortality in a runaway global warming scenario

Climate and agriculture have played an interconnected role in the rise and fall of historical civilizations. Our modern food system, based on open-environment production and globalised supply chains, is vulnerable to a litany of abiotic and biotic stressors exacerbated by anthropogenic climate change. Despite this evidence, greenhouse gas emissions continue to rise. Current trajectories suggest global warming of ∼2.0–4.9 °C by 2100, however, a worst-case emissions scenario with rapid combustion of all available fossil fuels could cause a rise of ∼12 °C. Even if emissions decline, unprecedented atmospheric CO2-e concentrations risk triggering tipping points in climate system feedbacks that may see global warming exceed 8 °C. Yet, such speculative ‘runaway global warming’ has received minimal attention compared to mainstream low- to mid-range scenarios. This study builds on The Limits to Growth to provide new insights into the international risk of mass mortality due to food insecurity based on a higher-resolution illustration of World3’s ‘runaway global warming’ scenario (∼8–12 °C+). Our simulation indicates rapid decline in food production and unequal distribution of ∼6 billion deaths due to starvation by 2100. We highlight the importance of including high-resolution simulations of high-range global warming in climate change impact modelling to make well-informed decisions about climate change mitigation, resilience and adaptation.

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

BackgroundCommon respiratory illnesses, such as emphysema and chronic obstructive pulmonary disease, are characterized by connective tissue damage and remodeling. Two major fibers govern the mechanics of airway tissue: elastin enables stretch and permits airway recoil, while collagen prevents overextension with stiffer properties. Collagenase and elastase degradation treatments are common avenues for contrasting the role of collagen and elastin in healthy and diseased states; while previous lung studies of collagen and elastin have analyzed parenchymal strips in animal and human specimens, none have focused on the airways to date.MethodsSpecimens were extracted from the proximal and distal airways, namely the trachea, large bronchi, and small bronchi to facilitate evaluations of material heterogeneity, and subjected to biaxial planar loading in the circumferential and axial directions to assess airway anisotropy. Next, samples were subjected to collagenase and elastase enzymatic treatment and tensile tests were repeated. Airway tissue mechanical properties pre- and post-treatment were comprehensively characterized via measures of initial and ultimate moduli, strain transitions, maximum stress, hysteresis, energy loss, and viscoelasticity to gain insights regarding the specialized role of individual connective tissue fibers and network interactions.ResultsEnzymatic treatment demonstrated an increase in airway tissue compliance throughout loading and resulted in at least a 50% decrease in maximum stress overall. Strain transition values led to significant anisotropic manifestation post-treatment, where circumferential tissues transitioned at higher strains compared to axial counterparts. Hysteresis values and energy loss decreased after enzymatic treatment, where hysteresis reduced by almost half of the untreated value. Anisotropic ratios exhibited axially led stiffness at low strains which transitioned to circumferentially led stiffness when subjected to higher strains. Viscoelastic stress relaxation was found to be greater in the circumferential direction for bronchial airway regions compared to axial counterparts.ConclusionTargeted fiber treatment resulted in mechanical alterations across the loading range and interactions between elastin and collagen connective tissue networks was observed. Providing novel mechanical characterization of elastase and collagenase treated airways aids our understanding of individual and interconnected fiber roles, ultimately helping to establish a foundation for constructing constitutive models to represent various states and progressions of pulmonary disease.

Not so silent partners: Exploring the interconnected roles of entrepreneurs and their spouses

When launching their ventures, the majority of entrepreneurs are married. Yet, our understanding of the spousal influence on the entrepreneurial process remains limited. This is surprising considering the spouse represents one of the most influential figures in an individual's life. Through an inductive qualitative analysis of 18 spouse-entrepreneur pairs, we explore the interactive nature of venture-related roles between the spousal couple and how these spousal roles evolve over the course of the venture. Our study shows that the dynamic alignment between entrepreneurial roles and spousal roles allows the venture to progress through various stages of firm innovation, creation, and growth. Thus, our paper extends the broader literature on roles during the venturing process as we illuminate the “not-so-silent role” of spouses in entrepreneurship.

Abstract 1385: Oncogenic regulation of autophagy and DNA emission

Abstract Background: Cancer cells release higher levels of cell-free DNA (cfDNA) into the circulatory system than normal cells. However, the molecular mechanisms underlying the process of programmed DNA elimination remain poorly understood. Emerging evidence has indicated that oncogenes such as HRAS can be released through extracellular vesicles (EVs). Moreover, studies have shown an active mechanism of DNA emission through autophagy. Autophagy is an evolutionarily conserved process that degrades and recycles cytoplasmic materials such as organelles and proteins in the lysosomes. Interestingly, Microtubule-associated protein 1 light chain-3 (LC3B) is known to degrade nuclear lamina components in HRAS-induced cells, potentially producing a pool of cytoplasmic chromatin. Cytoplasmic chromatin is ultimately degraded in lysosomes or re-routed outside of the cells. The aim of our study was to evaluate the role of autophagy proteins in circulating tumor (ctDNA) and EV-associated DNA emission in cancer cell lines harboring oncogenes (RAS and BRAF) as this aspect of the process is relatively understudied. Methods: We have assessed protein and RNA expression of autophagy genes (LC3B, ATG5 and ATG7) in IEC-18 cells that have been transduced with the HRAS oncogene (RAS3 cells) and human colorectal cancer cell lines SW620 and HCT116 using RT-qPCR and western blot (WB). All conditions were compared to their respective control cells (IEC-18, CCD-841 CoN and CCD18-Co cells. To determine the role of LC3 in nuclear membrane degradation, we employed transmission electron microscopy (TEM). We have further validated the role of autophagy genes in EV-DNA emission by shRNA knockdown using shRNA against highly expressed autophagy genes, such as LC3B in RAS3 cells. EV-DNA was measured using droplet digital PCR (ddPCR). Results: To determine whether autophagy expels oncogenic DNA via EVs in KRAS-mutant CRC cells, we focused on the role of ATG5, LC3B and ATG7, as this aspect of the process is understudied. Our data shows higher LC3B and ATG7 expression in transformed RAS3 cells, compared to control cell lines (IEC18). Moreover, ATG5 is overexpressed in SW620 and HT29 colorectal cancer cells compared to control cell lines. LC3 is known to degrade the nuclear membrane in HRAS-activated cells. Indeed, we observed degradation of the nuclear membrane in RAS3 cells leading to the accumulation of cytosolic DNA shown by TEM. Furthermore, overexpression of LC3B in IEC18 cells using GFP-tagged LC3B resulted in increased EV emission. These findings suggest that the autophagy axis may contribute to oncogenic DNA emission via EVs. Lastly, shRNA knockdown of LC3 resulted in reduction of EV-DNA emission (ddPCR). Impact: EV biogenesis and autophagy pathways play pivotal and interconnected roles during DNA processing and extracellular emission. Therefore, understanding the detailed mechanisms is critical for biomarker discovery and potential therapeutic strategies targeting this process. Citation Format: Thupten Tsering, Kyle Dickinson, Laura Montermini, Janusz Rak, Julia Burnier. Oncogenic regulation of autophagy and DNA emission [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1385.

Community transformed? Exploring the interaction between online support and rural community life for people with acute mental health conditions

Since the onset of COVID-19, the benefits of online platforms to enhance rural service accessibility are more acknowledged. However, questions remain about the interconnected roles of geographical community and online digital communities in enhancing rural life – particularly for marginalised groups. In this study, we examine one Australian non-profit's online peer support forums as technology enabling transformed community experiences for rural people with mental health conditions. Interviews exploring forum use were conducted with 20 rural forum users in 2021. We found technology affordances were appropriated to target rural service and social interaction gaps, giving people resources used online, and also enabling coping in their geographical community. The study illustrates the benefits of understanding what rural people do with different technologies that can illuminate how apparently “one-size-fits-all” technologies can be appropriated to fill certain rural structural holes in social and service systems.

The Efforts of the Royal Thai Domestic Bureaucracy in an Effort to Protest against the Haze/Smog from Indonesia

This study aims to explain three determinant factors in influencing a country in making policies, especially the kingdom of Thailand. The three determinants of the considerations above have an interconnected role in influencing every consideration of policy makers to make decisions. Where in the domestic context, which consists of domestic politics, economic and military forces play a role together with the international context in shaping the direction of foreign policy. So that these three considerations do not stand separately because they influence each other in the policy-making process. The existence of deforestation and fires in Indonesia has caused significant problems. Because deforestation and forest fires are directly transboundary haze which makes Indonesia a smoke haze contributing country in the Southeast Asian region. Therefore, in relation to forest fires in Indonesia which have become an environmental issue, the Indonesian government also has a responsibility towards cross-border air pollution. Where in terms of international law, state responsibility is an obligation that must be carried out by a country to other countries. So that the Indonesian government in this case has responsibility for cross-border air pollution that occurs in Southeast Asia. The Indonesian government has also ratified ASEAN Agreement on Transboundary haze pollution (AATHP). Therefore, the Indonesian government is trying to solve this problem in a sustainable manner.

Keeping goods moving in the wake of a disaster: a qualitative study of intermodal transport

PurposeThis paper examines what facilitates the swift reconfiguration of freight movements across transport modes in the wake of a major disaster.Design/methodology/approachA qualitative research approach focussing on the New Zealand (NZ) domestic freight transport operations in the wake of the 2016 Kaikōura earthquake is used with data collected through 19 interviews with 27 informants. The interviews are thematically analysed by using the framework method.FindingsThe paper provides rich and detailed descriptions of the ability of a freight transport system to recover from a disaster through rapid modal shifts. This paper identifies nine factors enabling modular transport operations and highlights the critical role of physical, digital, operational and inter-organisational interconnectivity in the aftermath of a disaster.Originality/valueAlthough the management of freight disruptions has become a prevalent topic not only in industry and policy-making circles, but also in the academic literature, qualitative research focussing on the ability of commercial freight systems to adapt and recover from a disaster through rapid modal shifts is limited. This qualitative study sheds light on the mechanisms underlying the continuity of freight operations in the wake of a disaster and provides a comprehensive understanding of modular transport operations and the ability of freight systems to keep goods moving.

Enhanced liquidity of p62 droplets mediated by Smurf1 links Nrf2 activation and autophagy

BackgroundMacro-autophagy/Autophagy is an evolutionarily well-conserved recycling process to maintain the balance through precise spatiotemporal regulation. However, the regulatory mechanisms of biomolecular condensates by the key adaptor protein p62 via liquid-liquid phase separation (LLPS) remain obscure.ResultsIn this study, we showed that E3 ligase Smurf1 enhanced Nrf2 activation and promoted autophagy by increasing p62 phase separation capability. Specifically, the Smurf1/p62 interaction improved the formation and material exchange of liquid droplets compared with p62 single puncta. Additionally, Smurf1 promoted the competitive binding of p62 with Keap1 to increase Nrf2 nuclear translocation in p62 Ser349 phosphorylation-dependent manner. Mechanistically, overexpressed Smurf1 increased the activation of mTORC1 (mechanistic target of rapamycin complex 1), in turn leading to p62 Ser349 phosphorylation. Nrf2 activation increased the mRNA levels of Smurf1, p62, and NBR1, further promoting the droplet liquidity to enhance oxidative stress response. Importantly, we showed that Smurf1 maintained cellular homeostasis by promoting cargo degradation through the p62/LC3 autophagic pathway.ConclusionsThese findings revealed the complex interconnected role among Smurf1, p62/Nrf2/NBR1, and p62/LC3 axis in determining Nrf2 activation and subsequent clearance of condensates through LLPS mechanism.

An adaptive linear active disturbance rejection control method for HVDC transmission system

With the advantages of large transmission capacity, low losses, rapid and flexible power regulation, and the ability to achieve non-synchronous networking, High Voltage Direct Current transmission systems are playing an increasingly important role in long distance transmission and grid interconnection. However, under certain circumstances, such as disturbances in the DC transmission system and sudden load changes, the converter based on PI control in DC transmission system suffer from slow response speed and poor stability. In order to improve the stability of the system and the response speed of DC voltage, this paper proposes an adaptive linear active disturbance rejection control (A-LADRC) method. The method is based on the analysis of the relationship between key bandwidth parameters and output quantities in linear active disturbance rejection control and enables adaptive adjustment of the controller bandwidth parameters for fast regulation of the DC voltage and to improve the stability of the DC voltage in the event of disturbances. Finally, the proposed control method is validated by simulation, and the results show that the proposed control method can effectively improve the response speed and robustness of the DC voltage, which has good practical engineering value.

The Effects of Pregnancy on Amino Acid Levels and Nitrogen Disposition.

Limited data are available on the effects of pregnancy on the maternal metabolome. Therefore, the objective of this study was to use metabolomics analysis to determine pathways impacted by pregnancy followed by targeted confirmatory analysis to provide more powerful conclusions about metabolic alterations during pregnancy. Forty-seven pregnant women, 18-50 years of age were included in this study, with each subject serving as their own control. Plasma samples were collected between 25 and 28 weeks gestation and again ≥3 months postpartum for metabolomics analysis utilizing an HILIC/UHPLC/MS/MS assay with confirmatory targeted specific concentration analysis for 10 of the significantly altered amino acids utilizing an LC/MS assay. Principle component analysis (PCA) on metabolomics data clearly separated pregnant and postpartum groups and identified outliers in a preliminary assessment. Of the 980 metabolites recorded, 706 were determined to be significantly different between pregnancy and postpartum. Pathway analysis revealed three significantly impacted pathways, arginine biosynthesis (p = 2 × 10-5 and FDR = 1 × 10-3), valine, leucine, and isoleucine metabolism (p = 2 × 10-5 and FDR = 2 × 10-3), and xanthine metabolism (p = 4 × 10-5 and FDR = 4 × 10-3). Of these we focused analysis on arginine biosynthesis and branched-chain amino acid (BCAA) metabolism due to their clinical importance and interconnected roles in amino acid metabolism. In the confirmational analysis, 7 of 10 metabolites were confirmed as significant and all 10 confirmed the direction of change of concentrations observed in the metabolomics analysis. The data support an alteration in urea nitrogen disposition and amino acid metabolism during pregnancy. These changes could also impact endogenous nitric oxide production and contribute to diseases of pregnancy. This study provides evidence for changes in both the ammonia-urea nitrogen and the BCAA metabolism taking place during pregnancy.