Population Trends Research Articles

Abstract C024: MPLA+IFNg-activated tumor-associated macrophages alter fibroblast composition

Abstract In a previous study, we developed a strategy to reprogram tumor-associated macrophages (TAMs) and induce a collaborative innate-adaptive immune response by combining monophosphoryl lipid A (MPLA) with IFNγ. However, we also observed downregulation of extracellular matrix (ECM)-associated genes in MPLA+IFNγ-treated mammary tumors, indicating that the combination treatment impacts the tumor microenvironment beyond just the immune cells. In this study, we investigated how MPLA+IFNg treatment modulates the tumor ECM, with a particular focus on fibroblasts-the major ECM-producing cells. Using scRNA-seq to profile mammary carcinomas, we identified six macrophage populations (C1q+, Ccr2+, Spp1+, Lyz+, mt+ and ki67+ TAMs) and two fibroblast populations (Cd34+ and a-SMA+ fibroblasts) in MMTV-PyMT tumor. MPLA+IFNγ treatment increased the numbers and percentages of Lyz+ TAMs and Cd34+ fibroblasts, while the numbers and percentages of Spp1+ TAMs and α-SMA+ fibroblasts were decreased by the treatment. Thus, MPLA+IFNγ treatment induced significant changes in both macrophage and fibroblast populations. Further analysis revealed an unusual gene expression pattern in Lyz+ TAMs. Mgst1 and Gng12 expression was detected in Lyz+ TAMs at levels comparable to those in fibroblasts, despite these genes typically being expressed in fibroblasts but not in macrophages of normal human tissues. However, to our surprise, MPLA+IFNγ treatment did not significantly increase Mgst1 and Gng12 expression of mono-cultured TAMs or bone marrow-derived macrophages, suggesting that these genes were not directly upregulated by MPLA+IFNγ treatment. Instead, the Mgst1 and Gng12 transcripts may have originated from engulfed fibroblasts. In addition, following MPLA+IFNγ treatment, more iNOS+ macrophages (which we previously identified as tumoricidal macrophages) were found in very close proximity to α-SMA+ fibroblasts. To directly test whether MPLA+IFNg-treated TAMs kill and engulf fibroblasts, we performed ex vivo co-cultures of TAMs and fibroblasts. Following MPLA+IFNγ treatment, TAMs effectively killed and engulfed the fibroblasts, whereas minimal fibroblast engulfment was observed in the control co-cultures. Our data suggest that tumoricidal MPLA+IFNγ-treated TAMs can regulate the ECM of tumors by targeting and eliminating the major ECM-producing cells, the fibroblasts. Ongoing studies are determining the functional consequences of the TAM-mediated regulation of fibroblasts and ECM composition. Citation Format: Lijuan Sun, Bodu Liu, Yixin Zhao, Mikala Egeblad. MPLA+IFNg-activated tumor-associated macrophages alter fibroblast composition [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C024.

Abstract C008: New insights from a novel mouse model of synovial sarcoma

Abstract Mouse models are the basis of preclinical and translational research in solid tumors. Multiple methods exist to induce tumor formation in mice, including genetically engineered mouse models, chemotoxic agents, injection of tumor cells, and xenograft approaches. Synovial sarcoma, a rare highly malignant soft-tissue tumor, poses a serious threat to patients due to its aggressive nature and associated high rates of mortality and morbidity. This disease's underlying cause and development remain poorly comprehended, and existing treatment approaches have yielded unsatisfactory outcomes. In the last two decades, numerous effective animal models of soft tissue sarcoma (STS) have been created, primarily utilizing genetically engineered mice and zebrafish, however long latency of tumor development for several months in these models creates a barrier for practical in-vivo experiments for drug testing or manipulating the cellular composition of the tumor microenvironment. In studying cancer immunotherapy, it is important to consider aspects of antitumor immune responses and to produce a model that mimics the complexity of the immune system We have generated a new mouse model of synovial sarcoma of exceptionally fast tumor development. Intramuscular delivery of Cre recombinase protein in mice which drives conditional knockdown in PTEN, stabilization of β-catenin, and formation of fusion oncogenes of SS18-SSX2 was sufficient to initiate high-grade synovial sarcomas with myofibroblastic differentiation in 3 weeks. As immunotherapy is increasingly applied to sarcomas, our mouse model will serve as a great tool for preclinical data. Flow cytometry-based analysis of peripheral blood shows significant changes in immune cell populations as early as five days after Tat-Cre injection and continues throughout the development of synovial sarcoma. These results suggest a significant systemic phenotypic alteration of circulating immune cells, which may impact other major organs in this genetic mouse model of synovial sarcoma. Single- cell RNA sequencing of the CD45+ leukocytes in the tumor microenvironment reveals subsets that may promote tumor progression. Our work promises to significantly enhance our understanding of the pathogenesis of this disease and establish a reliable preclinical platform for devising and assessing therapeutic interventions. Citation Format: Hesham Mohei, Donn Van Deren, Irene S. Molina, Malay Haldar. New insights from a novel mouse model of synovial sarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C008.

Abstract A011: Assessing pro-tumorigenicity of the aging microenvironment in a murine ovarian cancer model

Abstract Over 70% of high-grade serous ovarian cancer (HGSOC) patients are diagnosed after age 55 and the average patient who succumbs to HGSOC is 70 years old. Despite this, the majority of ovarian cancer studies, and cancer studies generally, utilize young mice that are more representative of human children. This approach overlooks age as a variable, despite its status as a top risk factor for cancer. Our preliminary studies reveal tumor burden and disease severity is significantly higher in aged mice compared to young animals. We have developed an epithelial cell line derived from C57BL/6 oviducts and used CRISPR-Cas9 genome editing to establish tumorigenic lines for syngeneic studies. One line harbors Trp53, Pten, and Brca2 deletions, is tumorigenic, and can be serially passaged in vitro. When injected intraperitoneally (IP) into 8-week and 56-week-old mice, equating to approximately 10- and 45-year-old humans respectively, a stark increase in tumor mass was evident in aged mice. Furthermore, the aged mice succumbed to disease at a faster rate after inoculation than the young group, where all mice succumbed to disease within 1-month of IP injection compared to some young mice surviving up to 3 months after injection. These findings, combined with epidemiologic data, suggest a metastatic driver in the aged microenvironment that facilitates worsened ovarian cancer progression. We are investigating two factors that change with age, (1) a suppressed immune system and (2) age-related changes to adipose tissue, as possible mechanisms driving this difference. Histologic analysis of tumors from each cohort showed decreased cleaved caspase-3 in aged tumors, indicating a reduction in tumor cell killing in older animals. Characterization of the pre-cancerous, tumor-naive microenvironment via flow cytometry and cytokine array have revealed that aged mice microenvironment is highly inflamed and features changes in immune populations and inflammatory states. Meanwhile, total RNA-sequencing of tumors harvested from aged and young mice showed minimal changes, but DEGs point to possible roles of fat transport and metabolism in these aged tumors, indicated by upregulated CD36 and lipoprotein lipase. Follow-up ex vivo experiments had demonstrated increased adhesion and proliferation of the previously described murine cancer cells to fat pads when cultured in vitro. When assessing tumor-naive fat depots, aged adipose tissue is comprised of significantly larger adipocytes and the omentum, a common secondary site of ovarian cancer and fatty organ, was found to have increased phospholipid content in older animals. Both findings point to a change in metabolic function in aged mice. Our preliminary findings indicate an important role of the aged microenvironment in driving enhanced diseases progression in older individuals and identifying the mechanisms behind this phenotype are critical; an improved understanding of how age affects HGSOC progression could enable the development of treatment strategies to prevent cancer cells from establishing in the peritoneum. Citation Format: Katherine A. Cummins, Ronny Drapkin. Assessing pro-tumorigenicity of the aging microenvironment in a murine ovarian cancer model [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A011.

Genomic Single Nucleotide Polymorphism (SNP) markers and mitochondrial haplotypes illuminate the origins of Crown-of-Thorns Starfish (Acanthaster solaris) outbreaks in the South China Sea.

Outbreaks of the coral predator Crown-of-Thorns Starfish (CoTS) pose a severe threat to coral reefs in the Indo-Pacific Ocean. In 2018, the South China Sea (SCS) experienced significant CoTS outbreaks, leading to extensive coral mortality across the Xisha, Zhongsha, Dongsha, and Nansha Islands, severely impacting the coral reef ecosystem. To explore the origins of these outbreaks, we conducted a comprehensive genomic analysis using data from genomic single nucleotide polymorphism sites (SNPs) and mitochondrial haplotypes. Our analysis reveals that CoTS populations in the SCS, which exhibit moderate genetic diversity and may have undergone positive selection or population expansion. There was limited genetic differentiation among CoTS populations from XS, ZS, and NS groups. Especially between the XS and ZS groups, there was almost no genetic differentiation. The populations from XS, ZS, and NS groups have strong genetic connections with populations in Vietnam and the Philippines. There was high gene flow from Vietnam to the Xisha Islands and from the Philippines to the Nansha Islands, suggesting that the CoTS populations in these regions primarily originate from these neighboring countries. The comprehensive analyses of SNP and mitochondrial genomes have provided valuable insights into the population genetics of CoTS. This research has generated significant genomic resources and facilitated important studies on the genetics of the CoTS species. By identifying potential source populations and understanding the genetic basis of their spread, managers can develop more effective conservation strategies to protect vulnerable coral reef ecosystems in the SCS.

Decomposing Future Exposure from Increasing Flood Risk and Forecast Population Changes Across Shared Socioeconomic Pathways (SSPs) in the United States

Extreme weather events, like flooding, are expected to become more severe due to climate change and increasingly impact populations across the US. Adding to this challenge, populations have concurrently settled in risky areas that were previously thought to have low, or no, exposure. Objective: This research seeks to understand the unique contribution of population growth and climate change as independent components of future risk levels in the US. To do so, future population level forecasts are coupled with future flood projections along all five Shared Socioeconomic Pathways (SSPs) at the block group level across the US. The results indicate that, across the five SSPs, the most increase in exposure will occur in SSP5 (+470,719), and the least will occur in SSP 3 (+57,189). By decomposing the contributions from flood and population growth, we find that the population growth-induced effect contributed to an increase in the population exposure for all of the SSPs except for SSP3. This research, and these results, provide a foundation for understanding future risks of flood exposure in an isolated framework and lay the groundwork for the development and integration of planning, adaptation, and mitigation efforts that may be used to address the growing risk of flooding in the context of the population forecasts provided here.

Bioplastic’s Valorisation by Anaerobic Co-Digestion with WWTP Mixed Sludge

Bioplastics are designed to degrade at the end of their lifecycle, but effective management of their end-of-life phase and integration into existing organic waste management systems remain significant challenges. Some bioplastics decompose under anaerobic conditions, with the anaerobic digestion (AD) process being a potential solution for their disposal. AD is a promising technology for valorising organic wastes, enabling biomethane production, reducing carbon footprints, and promoting product circularity. This study focuses on evaluating the continuous co-digestion of bioplastics with mixed sludge from an urban wastewater treatment plant (WWTP). Polyhydroxybutyrate (PHB) was the selected bioplastic, as various studies have reported its high and rapid degradation under anaerobic mesophilic conditions. PHB’s biodegradability under typical WWTP anaerobic digestion conditions (35 °C, 20-day retention time) was assessed in batch tests and the results indicate that PHB degradation ranged from 68 to 75%, depending on particle size. To further explore the potential of AD for PHB valorisation, the feasibility of anaerobic co-digestion of PHB with WWTP sludge was tested on a continuous laboratory scale using two digesters: a conventional digester (CSTR) and an anaerobic membrane bioreactor (AnMBR). The results indicated complete degradation of PHB, which led to higher biomethanisation percentages in both digesters, rising from 58% to 70% in the AnMBR and from 44% to 72% in the CSTR. The notable increase observed in the CSTR was attributed to changes in microbial populations that improved sludge biodegradability.

Bacterial composition and cultural dynamics of microgreens-associated microbiota during selective enrichment for Listeria monocytogenes.

Widely-regarded as a so-called "superfood", microgreens have become an increasingly significant food crop from both nutritional and agricultural standpoints. However, similar to other produce commodities that are also cultivated using modernized indoor-farming methods, there have been mounting concerns over the potential risks of consuming microgreens contaminated by Listeria monocytogenes. To gain insights into the microbial properties of microgreens, this study characterized the bacterial composition of fresh microgreen retail products using amplicon sequencing of 16S rRNA genes. Dominated by Gammaproteobacteria, a total of 36 shared genera were identified as putative constituents of the microgreen core microbiome. By monitoring the dynamics of microgreen-borne bacteria undergoing a Listeria-selective cultural enrichment procedure, it was revealed that, regardless of the presence or absence of L. monocytogenes, off-target bacteria of the Klebsiella and Enterococcus genera were significantly enriched from microgreens by the primary enrichment step, with the secondary enrichment step continuing to promote the expansion of Enterococcus population. While Listeria was generally neither the most-enriched nor the dominant taxon in cultures sampled at different enrichment stages, significant enrichment of Lysinibacillus and Bacillus bacteria were detected in microgreens contaminated with L. monocytogenes, suggesting they could be co-enriched in competition with Listeria.

How to Count Parrots: Comparing the Performance of Point and Transect Counts for Surveying Tasman Parakeets (Cyanoramphus cookii)

Obtaining precise estimates of population size and trends through time is important for the effective management and conservation of threatened species. For parrots (Psittaciformes: Psittacidae), obtaining such estimates can be challenging, particularly for cryptic species that occur in low densities in complex and/or fragmented habitats. We used a statistical resampling approach with the aim to compare the reliability and precision of counts for the critically endangered Tasman parakeet (Cyanoramphus cookii) that were taken using two methods on Norfolk Island (Pacific Ocean), namely, fixed-point counts and line transect counts. The detections obtained during fixed-point counts had better estimated precision (0.274) than line transect counts (0.476). The fixed-point method was also more efficient, yielding 1.338 parakeet detections per count compared to the 0.642 parakeet detections per count obtained by the line transect method. Although Tasman parakeets can be detected by either of these methods, our research demonstrates that the fixed-point method is more precise and reliable. These findings can help prioritise resources for the long-term monitoring of recovering populations of this species and similar island species.

The Evolving Space of Emirati Women's Economic Participation

This conceptual paper discusses the contouring of the embryonic space in which Emirati women can enact economic agency. I examine this from three perspectives, namely, the workforce localisation policies, the government’s aspiration to establish itself as a force within the international political arena, and the country’s cultural landscape. These three factors represent the most powerful influences that determine Emirati women's experience of the workplace, and this paper explores their impact on the space that is evolving in which women can exercise their economic agency. The space available for Emirati women's economic participation is not prescribed; rather, it emerges as ever fluctuating and transforming as a consequence of the varying contextual dominance of one or other of these three potent influences. The UAE’s severe workforce imbalance, marked by 96% expatriates in the private sector and about 40% in the public sector, renders localising the workforce a key strategic objective. This fosters a route for women to find their place in the economy. The government’s goal to become a key player on the global stage and a beacon of Arab political power and diplomacy involves crafting a distinguished international image. A substantial component of achieving this goal is redressing the historic female disempowerment that is seen to characterise the region. Again, this ambition eases women's access to economic participation. The country’s cultural landscape, however, imposes certain constraints on women enacting economic agency. This landscape has altered exponentially since the affluence of the oil boom and many segments of the local population see positive aspects in Emirati women’s expanding economic capacities. Yet values which maintain that women are primarily domestic creatures survive and militate against full acceptance of women in the workforce. Additionally, this space is also keenly influenced and configured by myriad diverse collective and individual understandings of national development aspirations, cultural legacies, and new positionings of women. The contribution of this study is its analysis of how specific institutional and societal forces effect how gender can be done and undone in this geopolitical context in which women’s highly liminal economic agency is generating new conceptualisations of empowerment and freedoms.

Longitudinal Follow-up Reveals Peripheral Immunological Changes Upon Tick Bite in a-Gal-Sensitized Individuals.

α-Gal syndrome is characterized by specific IgE (sIgE) antibodies to the carbohydrate galactose-α-1,3-galactose (α-Gal) and delayed onset of allergic symptoms after ingestion of mammalian meat. While tick bites are assumed to mediate sensitization, the immune response to tick bites has not yet been investigated. To investigate the peripheral immune response to tick bites in humans over time. In a longitudinal cohort study, immunological reactions associated with tick bites (Ixodes species) were analyzed within 1 day (V1), 2 weeks (V2), 1 month (V3), and 3 months (V4) after the occurrence of a bite. sIgE, sIgG, and sIgG subclass levels, as well as 10 cytokines, were quantified. Deep immune phenotyping was performed using mass cytometry. A total of 4 controls and 10 patients were bitten by a tick and followed up over 3 months. None of the controls developed sIgE to α-Gal, and sIgE increased in all patients from V1 until V2/V3, as did IL-8 levels. We noted a significant increase in CD19+ B cells and B-cell subpopulations, as well as a decrease in γδ CD56+ T cells in patients between V0 and V1. At V1, frequencies of plasmacytoid dendritic cells (pDCs) and γδ CD56+ T cells were lower in patients than in controls. Our study provides evidence of significant changes in several immune cell populations in α-Gal sensitized patients, along with increased levels of IL-8 and sIgE. This is the first exploratory study to investigate longitudinal peripheral immune profiles in patients and controls bitten by ticks.

Climate variability and worldwide migration: Current evidence and future projections

Abstract The literature linking climatic drivers and migration is growing, but there is still limited evidence and substantial uncertainty regarding future bilateral flows driven by climate stress on a global scale. The aim of this paper is to fill this gap by projecting changes in the flows of international migrants from medium-term population and climate change projections. We employ a bilateral gravity equation for emigration rates controlling for decadal weather averages of temperature, precipitation, droughts, and extreme precipitation in the origin countries. We use the parameter estimates of the gravity equation to estimate global, regional, and country-by-country emigration flows for several combinations of socio-economic development and climate change. Results indicate that global emigration flows are projected to increase to around 110 million in 2060 for SSP1 and RCP 4.5 and SSP5 and RCP 4.5; to 135 million for SSP5 and RCP 8.5; to 163 million for SSP3 and RCP 4.5. We report that changes in emigration flows are largely due to population growth in the origin countries.

Climatic factors, but not geographic distance, promote genetic structure and differentiation of Cleistogenes squarrosa (Trin.) Keng populations

Climate can shape plant genetic diversity and genetic structure, and genetic diversity and genetic structure can reflect the adaptation of plants to climate change. We used rbcl and trnL-trnF sequences to analyze the genetic diversity and genetic structure of C. squarrosa under the influence of different environmental factors in Inner Mongolia grassland. The results showed that the genetic diversity of this species was low. (The trnL-trnF sequences have higher genetic diversity than rbcl sequences.) C. squarrosa had low genetic diversity compared to other prairie plants, but had a more pronounced genetic structure. The haplotype network diagram of the combined sequences could be divided into two categories, and the results of the NJ, MP, and ML trees also showed that the haplotypes were divided into two branches. The results of genetic structure analysis showed that that the populations located in the desert steppe fall into exactly one cluster, and the populations located in the typical steppe fall into exactly another cluster. The neutrality tests were all negative and the mismatch distribution also showed a single peak across the population, suggesting that C. squarrosa had undergone population expansion and was well adapted to the local environment. The results of the mantel test showed that climate had a greater influence on the genetic distance of C. squarrosa, with annual precipitation having a higher influence than mean annual temperature. This study provided basic genetic information on the genetic structure of C. squarrosa and contributes to the study of genetic adaptation mechanisms in grassland plants.

Population trends of the Cape Parrot Poicephalus robustus in the Amatholes, Eastern Cape: trialling ground-based flock photography for demographic and health assessment

Globally, 60% of species in the order Psittaciformes are experiencing population declines. Understanding demographic and health trends in populations is vital for the prioritisation of limited conservation resources. The Cape Parrot Poicephalus robustus is a South African endemic forest species that is endangered by habitat degradation and Psittacine Beak and Feather Disease (PBFD). In the Amathole region of the Eastern Cape province, Cape Parrots gather in large numbers every autumn to feed at a particular orchard of Pecan trees Carya illinoinensis. This annual event is an opportunity for researchers to assess trends in a population that does not otherwise typically form large flocks. We used a novel, non-invasive method of flock photography analysis between 2017 and 2022 to assess the demographics and PBFD symptoms of the population. A mean of 439 ± SD 127 Cape Parrots visited the orchard on the peak day each year, with 1.2 males per female and 3 adults per juvenile overall. Proportions of juveniles fluctuated between extremes of 70% in 2019 and < 4% in 2020. PBFD symptoms increased markedly in the food-scarce year of 2019, with a gradual recovery seen in the years following. Roosting numbers were also tracked monthly from 2018 to 2022 to indicate local population fluctuations in the study area around Hogsback. An average of 112 ± SD 31 Cape Parrots roosted there, with roost counts notably higher from January to June, bolstered by newly-fledged juveniles prior to their dispersal. This study demonstrates the use of flock photographs as an effective, non-invasive tool to assess the demographics and health of an avian population.

Growth Simulation of Agriculturally Dominant Cities by Incorporating Multiple Drivers into a CA-based patch-generating Land Use Simulation Model: A Case Study in Siracusa, Italy

Abstract. Understanding the historical trajectory of land use and land cover (LULC) and predicting future alterations is essential to advancing the SDGs. Current researches on LULC in agriculture-dominated cities primarily focuses on the spatiotemporal pattern analysis of carbon storage changes, with relatively little attention given to LULC simulation studies. Moreover, most studies employing cellular automata (CA) models concentrate on urban centers, overlooking the specific sustainable development of agricultural cities. This paper selects Siracusa, Italy, as a case study, incorporating multiple drivers and constructing four development scenarios. The patch-generating land use simulation (PLUS) model is employed to predict the LULC for Siracusa by 2030 and to examine potential transformations under each scenario. Our findings show that 60% of the land in Siracusa is designated as cropland, predominantly situated in flat regions. Our simulation results reveal that urbanization and demographic growth are the main factors driving cropland conversion to urban areas. Different development scenarios exhibit significant variations in future land use structures; the cropland protection scenario emphasizes the stability and sustainability of agricultural development, whereas the economic development scenario highlights the substantial impact of urban and industrial expansion on agricultural land. These insights are instrumental for land use planning and policy-making in Siracusa and other agriculture-centric cities, providing a framework to guide urbanization while promoting agricultural sustainability.

Comparative genomics provides insights into adaptive evolution and demographics of bats.

Bats possess a range of distinctive characteristics, including flight, echolocation, impressive longevity, and the ability to harbor various zoonotic pathogens. Additionally, they account for the second-highest species diversity among mammalian orders, yet their phylogenetic relationships and demographic history remain underexplored. Here, we generated de novo assembled genomes for 17 bat species and two of their mammalian relatives (the Amur hedgehog and Chinese mole shrew), with 12 genomes reaching chromosome-level assembly. Comparative genomics and ChIP-seq assays identified newly gained genomic regions in bats potentially linked to the regulation of gene activity and expression. Notably, some antiviral infection related gene under positive selection exhibited the activity of suppressing cancer, evidencing the linkage between virus tolerance and cancer resistance in bats. By integrating published bat genome assemblies, phylogenetic reconstruction established the proximity of noctilionoid bats to vesper bats. Interestingly, we found two distinct patterns of ancient population dynamics in bats and population changes since the last-glacial maximum do not reflect species phylogenetic relationships. These findings enriched our understanding of adaptive mechanisms and demographic history of bats.

Transcriptomic profiling of backfat and muscle in Lijiang pigs with divergent body size across growth stages.

Backfat thickness is an important economic trait that affects pork quality and flavor. The Lijiang pig (LJP), a local breed in Yunnan province, China, exhibits variations in growth and body composition. However, the molecular basis for these variations is unclear. This study aimed to analyze transcriptome profiles of backfat at different growth stages in LJP with discrepant body size: two months (M2), four months, and six months. Firstly, we analyzed the gene expression differences and discovered a significantly highest number of differentially expressed genes (DEGs) at the M2 stage. Secondly, we identified four gene profiles with reverse expression trends in LJP populations with different body sizes, and the related genes mainly associated with immune response functionality. Thirdly, we observed a lower correlation in LJP with large body size at the M2 stage, with a specific enrichment of DEGs with high genetic differentiation related to neural activity. Finally, we correlated transcriptome profiles of muscle and backfat and discovered the lowest correlation at the M2 stage. Highly correlated genes exhibited more significant differences and were prominently enriched for immune response processes. This study unveils candidate genes linked to backfat growth in LJP, emphasizing the specificity of the early growth stage of backfat.

Abstract 4138617: Temporal and Regional Trends in Cardiovascular Mortality Associated with Parkinson's Disease from 1999 to 2020: A Retrospective Study in the United States

Introduction: Parkinson’s disease (PD) is a common neurodegenerative disorder, and existing evidence links it to cardiovascular (CVD) mortality. Research Question: Is the CVD-related mortality higher in PD patients compared to that in the general population? Goals: We aim to identify CVD-related mortality trends in patients with PD in the US stratified by age, sex, race, and region, and compare them to CVD-related mortality trends in the general population. Methods: Death certificates from the CDC-WONDER database were examined for adults aged ≥65 years. Crude rates (CR) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, and change in AAMR was estimated via annual percent change (APC) and the average annual percent change (AAPC) using Joinpoint regression. Results: From 1999 to 2020, a total of 138,151 CVD-related deaths occurred in individuals with PD. The AAMRs decreased moderately till 2002 (APC: -3.25), then sharply till 2014 (APC: -5.43), but increased thereafter till 2020 (APC: 1.77). Males had higher AAMR than females, and the AAPC for CVD-related deaths in PD differed significantly from those in the general population. NH Whites displayed the highest AAMR (16.14) while NH Blacks or African Americans displayed the lowest (9.65). Hispanics or Latinos showed an AAMR of 11.22, followed by NH Asians or Pacific Islanders (10.24) and NH American Indians or Alaska Natives (9.70). AAMRs also varied substantially by region (West: 16.64; Midwest: 16.40; Northeast: 15.59; South: 13.12). States with the highest AAMRs were Nebraska, California, and Oklahoma. Rural regions exhibited a higher AAMR (16.34) than Urban regions (14.88). The AAPC for CVD-related deaths in PD differed significantly from those in the West and in urban regions. Most deaths occurred at nursing homes or long-term care (43.85%). The adults aged ≥85 years exhibited an alarmingly high CR (53.04), and the AAPC differed significantly from the general population due to CVD. Conclusions: We observed overall decreasing trends in CVD-related deaths in adults with PD from 1999 to 2014, which increased thereafter till 2020. Highest mortality was exhibited by males and NH Whites, residents of the West and the Midwest, and adults ≥85 years.

Design of Integrated Energy–Water Systems Using Automated Targeting Modeling Considering the Energy–Water–Carbon Nexus

The swift expansion of the global population and economy has spurred growing requirements for energy and water in recent decades. Inefficient energy and water consumption, however, has led to an increase in CO2 emissions. Hence, the socio-economic development of a country must consider the interconnections between energy, water and carbon, as there are mutual dependencies among these three elements. This work considers the nexus between energy, water and carbon in the design of integrated energy–water systems using a new automated targeting modeling (ATM) framework. ATM incorporates the advantages of the insight-based Pinch method and a mathematical programming approach to provide visual understanding for a thorough analysis of the problem while guaranteeing accurate solutions. Minimum targets of power and water based on the integrated network operation were established by the ATM, with corresponding carbon emissions. A specific goal of annual carbon emissions reduction was set as the constraint and the ATM optimized the capacities of the components in the system accordingly to achieve minimum overall cost. The application of ATM on an industrial plant case study shows that a target of 45% reduction in the carbon discharge amount was achieved by shifting to greener fuel in the energy system at a minimum overall cost increase of 0.45% only. The framework can assist users in meeting power and water loads in their plant while planning for the appropriate decarbonization efforts at the minimum possible cost.

Complete suspension culture of human induced pluripotent stem cells supplemented with suppressors of spontaneous differentiation

Human induced pluripotent stem cells (hiPSCs) are promising resources for producing various types of tissues in regenerative medicine; however, the improvement in a scalable culture system that can precisely control the cellular status of hiPSCs is needed. Utilizing suspension culture without microcarriers or special materials allows for massive production, automation, cost-effectiveness, and safety assurance in industrialized regenerative medicine. Here, we found that hiPSCs cultured in suspension conditions with continuous agitation without microcarriers or extracellular matrix components were more prone to spontaneous differentiation than those cultured in conventional adherent conditions. Adding PKCβ and Wnt signaling pathway inhibitors in the suspension conditions suppressed the spontaneous differentiation of hiPSCs into ectoderm and mesendoderm, respectively. In these conditions, we successfully completed the culture processes of hiPSCs, including the generation of hiPSCs from peripheral blood mononuclear cells with the expansion of bulk population and single-cell sorted clones, long-term culture with robust self-renewal characteristics, single-cell cloning, direct cryopreservation from suspension culture and their successful recovery, and efficient mass production of a clinical-grade hiPSC line. Our results demonstrate that precise control of the cellular status in suspension culture conditions paves the way for their stable and automated clinical application.

Complete suspension culture of human induced pluripotent stem cells supplemented with suppressors of spontaneous differentiation.

Human induced pluripotent stem cells (hiPSCs) are promising resources for producing various types of tissues in regenerative medicine; however, the improvement in a scalable culture system that can precisely control the cellular status of hiPSCs is needed. Utilizing suspension culture without microcarriers or special materials allows for massive production, automation, cost-effectiveness, and safety assurance in industrialized regenerative medicine. Here, we found that hiPSCs cultured in suspension conditions with continuous agitation without microcarriers or extracellular matrix components were more prone to spontaneous differentiation than those cultured in conventional adherent conditions. Adding PKCβ and Wnt signaling pathway inhibitors in the suspension conditions suppressed the spontaneous differentiation of hiPSCs into ectoderm and mesendoderm, respectively. In these conditions, we successfully completed the culture processes of hiPSCs, including the generation of hiPSCs from peripheral blood mononuclear cells with the expansion of bulk population and single-cell sorted clones, long-term culture with robust self-renewal characteristics, single-cell cloning, direct cryopreservation from suspension culture and their successful recovery, and efficient mass production of a clinical-grade hiPSC line. Our results demonstrate that precise control of the cellular status in suspension culture conditions paves the way for their stable and automated clinical application.