Multiple Populations Research Articles

A data-driven typology of emotion regulation profiles.

Typologies serve to organize knowledge and advance theory for many scientific disciplines, including more recently in the social and behavioral sciences. To date, however, no typology exists to categorize an individual's use of emotion regulation strategies. This is surprising given that emotion regulation skills are used daily and that deficits in this area are robustly linked with mental health symptoms. Here, we attempted to identify and validate a working typology of emotion regulation across six samples (collectively comprised of 1,492 participants from multiple populations) by using a combination of computational techniques, psychometric models, and growth curve modeling. We uncovered evidence for three types of regulators: a type that infrequently uses emotion regulation strategies (Lo), a type that uses them frequently but indiscriminately (Hi), and a third type that selectively uses some (cognitive reappraisal and situation selection), but not other (expressive suppression), emotion regulation strategies frequently (Mix). Results showed that membership in the Hi and Mix types is associated with better mental health, with the Mix type being the most adaptive of the three. These differences were stable over time and across different samples. These results carry important implications for both our basic understanding of emotion regulation behavior and for informing future interventions aimed at improving mental health. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Abstract 67: Predicting colorectal patient prognoses by functional characterisation of heterogeneous cell types and their spatial interaction using a new technique: Whole slide imaging mass cytometry

Abstract Immunotherapies stimulate T cell function in the tumor microenvironment (TME). CD3+ and CD8+ T cell infiltration can predict disease recurrence in colorectal cancer (CRC) patients and has been validated as Immunoscore® (IS). The TME comprises multiple heterogeneous populations of immune cells, including T cells and cancer-associated fibroblasts (CAFs); CRC tumors are also morphologically diverse. Standard BioTools™ (SBI) has developed a novel whole slide Imaging Mass Cytometry™ technique that allows complete analysis of cell population heterogeneity in the TME using >40 markers. We hypothesised there are multiple heterogeneous subtypes of CAFs within CRC tumors and that they modulate T cell infiltration and patient outcome. In collaboration with SBI, we studied a cohort of CRC patients stratified based on T cell infiltrate and disease recurrence. We identified multiple CAF populations that interact with tumor-infiltrating T cell populations. Slides from 10 CRC patients with high or low CD3+CD8+ T cell infiltrate (IS) were stained with a panel encompassing markers for CAF and T cell heterogeneity, function, and metabolism. Slides were imaged using the Hyperion XTi™ Imaging System at SBI. Using a scan mode called Preview Mode, the whole slide was imaged in minutes to identify CAF and T cell phenotypic regions of interest. Next, the same slide was imaged at 1 μm resolution using Cell Mode (CM). Finally, for each sample, an additional serial section was imaged using a slightly lower resolution called Tissue Mode (TM). TM allowed us to image the samples in several hours instead of days while capturing the full heterogeneity of the entire tissue sample. We used clustering to identify phenotype clusters and neighbourhood analysis to study spatial enrichment. We also compared results between CM and TM. We report: Identification of heterogeneous CAF subtypes in CRC patients with high or low IS; determination of CAF populations that spatially interact with T cells in patients with high or low IS; and examination of consistent spatial interactions between CAF and T cells in CRC, and whether these interactions differ in patients with high or low IS. TM revealed several heterogeneous cellular populations that differed between patients with high or low IS; importantly, low IS tumors had more podoplanin+αSMA+ CAF populations and fewer podoplanin+αSMA- cell populations compared with high IS tumors. High IS tumors had more PD-1+CD8+ T cells compared with low IS tumors; these PD-1+CD8+ T cells spatially interacted with podoplanin+αSMA- CAF populations in high IS tumors. CAF-PD-1+CD8+ T cell interactions were absent from low IS tumors. Thus, CAF-PD-1+CD8+ T cell interactions are important in CRC patients with high IS, and these cellular interactions require further investigation. Citation Format: Rory M. Costello, Sonya Fenton, Helen McGuire, Liang Lim, David Howell, Qanber Raza, Jyh Yun Chwee, Roslyn Kemp. Predicting colorectal patient prognoses by functional characterisation of heterogeneous cell types and their spatial interaction using a new technique: Whole slide imaging mass cytometry [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 67.

Abstract 1071: Circulation of rare events in the liquid biopsy for early detection of lung mass lesions

Abstract Lung cancer screening with low-dose CT scans (LDCT) has reduced mortality for patients with high-risk smoking histories. However, this method of screening remains imperfect. High rates of false positive scans expose patients to additional morbidity as they pursue subsequent diagnostic evaluation. Real-world application of screening LDCT remains low. Finally, current screening guidelines exclude those without smoking histories, a population which comprises up to a quarter of lung cancer patients. We sought to explore the utility of liquid biopsy (LBx) in lung cancer patients and its use in early cancer screening and diagnosis. Using the third generation High-Definition Single Cell Assay (HDSCA3.0) workflow, we analyzed 99 peripheral blood samples divided into three cohorts: Normal Donors (ND, n=50) who were healthy volunteers with no known pathology, Screening CT patients (CT, n=25) who underwent standard LDCT screening with resultant Lung-RADS 1-2, Biopsy patients (BX, n=24) who had abnormal CT scans requiring tissue biopsy. The ND group was used to characterize baseline epithelial, mesenchymal, endothelial, and immune cells, alongside acellular events (oncosomes). For the CT and BX patients, demographic information including age, gender, and average BMI was roughly equivalent, however average pack-years smoked differed owing to 10 (42%) patients in the BX group who had no prior smoking history. A total of 14 (58%) BX patients were diagnosed with primary lung cancer (BX+), of which 11(75%) were adenocarcinoma, 2 (19%) were squamous cell carcinoma and 1 (6%) was small cell. Across the cohorts we observed intra- and interpatient heterogeneity of rare events including multiple phenotypic rare cell populations and oncosomes. The comparison of the rare event enumerations between the ND, CT, BX+, and BX- cohorts revealed a greater incidence of total events, total rare cells and oncosomes, as well as specific cellular phenotypes in the CT and BX cohorts compared to the ND cohort. LBx analytes were detected at a significant elevation in the BX samples compared to the CT samples, but there was no significant difference between BX+ and BX- samples. The data supports the utility of the LBx in distinguishing patients with an alveolar mass lesion from those without, providing a mechanism for screening prior to LDCT to better inform clinical workup and avoid unnecessary radiation exposure and biopsy. Citation Format: Anya Shah, Karen Resnick, Jeremy Mason, Peter Kuhn, Jorge Nieva, Stephanie Shishido. Circulation of rare events in the liquid biopsy for early detection of lung mass lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1071.

The Status of Implementation Research in Exit and Post-Exit Human Trafficking Interventions in Sub-Saharan Africa

ABSTRACT Conservative estimates place the number of individuals affected by human trafficking in the sub-Saharan African region at close to nine million. While there has been growing attention paid to innovative prevalence estimation approaches, and development of evidence-based interventions in the region, literature examining how these interventions are adapted, implemented, and delivered across multiple sectors, populations, and geo-political settings remains nascent at best. This critical gap in implementation research stymies the scale-up of effective anti-trafficking approaches. The central aim of this scoping review is to contribute to the anti-trafficking knowledge base by describing the current state of implementation research in this region based on 12 identified peer-reviewed human trafficking studies in sub-Saharan Africa. While none of the retrieved studies focuses solely on the implementation of a human trafficking intervention, the studies identified and discussed the acceptability and cost impacts of their implementation efforts. We conclude that advancing trafficking knowledge and praxis would require the synergistic and concurrent pursuit of both implementation and intervention strategies.

Direct Fabrication of Glycoengineered Cells via Photoresponsive Thiol-ene Reaction.

Three-dimensional printing of cell constructs with high-cell density, shape fidelity, and heterogeneous cell populations is an important tool for investigating cell sociology in living tissues but remains challenging. Herein, we propose an artificial intercellular adhesion method using a photoresponsive chemical cue between a thiol-bearing polymer and a methacrylate-bearing cell membrane. This process provided cell fabrication containing 108 cells/mL, embedded multiple cell populations in one structure, and enabled millimeter-sized scaleup. Our approach allows for the artificial cell construction of complex structures and is a promising bioprinting strategy for engineering tissues that are structurally and physiologically relevant.

Investigating the Prevalence of Comorbidity in Multiple Sclerosis Clinical Trial Populations.

Comorbidity is common in multiple sclerosis (MS) with the most prevalent conditions being depression, anxiety, hypertension, and hyperlipidemia. Limited information regarding the representation of comorbidity status is available from phase III clinical trials in MS leading to concern about the potential underrepresentation of individuals with comorbidity in clinical trials. The objective was to estimate the prevalence of comorbidities in MS clinical trial populations. Individual-level data from multiple sponsors were requested for a 2-stage meta-analysis of phase III clinical trials of MS disease-modifying therapies. To ensure consistency of our approach across trials, we followed the Maelstrom retrospective harmonization guidelines. Chronic comorbidities at clinical trial enrollment recommended by the International Advisory Committee on Clinical Trials in MS were considered (depression, anxiety, hypertension, hyperlipidemia, migraine, diabetes, chronic lung disease). Additional comorbidities were also classified. Classification was based on medical history data. Individual comorbidities were summed and categorized as 0, 1, 2, or ≥3. We report the pooled prevalence (95% confidence interval [95% CI]) of comorbidity. The pooled prevalence and prevalence ratios across age, sex, race, disability level, and treatment were also reported. Heterogeneity was assessed using the I2 statistic. Seventeen trials involving 17,926 participants were included. Fourteen trials enrolled participants with relapsing MS (RMS) while 3 enrolled participants with progressive MS (PMS). The distributions of sex, age, and disability level were generally consistent within RMS and PMS trials. When pooled, almost half of trial participants (46.5%) had ≥1 comorbidity (1: 25.0%, 95% CI 23.0-27.0, I2 = 89.9; 2: 11.4% [9.3-14.0], I2 = 96.3; ≥3: 6.0% [4.2-8.4], I2 = 97.7). Depression (16.45% [12.96-20.88], I2 = 98.3) was the most prevalent comorbidity reported, followed by hypertension (10.16% [8.61-11.98], I2 = 93.2). Heterogeneity was high across trials. Older age and female participants were associated with increased number of comorbidities. Older individuals and male participants had a higher prevalence of hyperlipidemia, while older individuals and female participants had a higher prevalence of depression and anxiety. Individuals with comorbidities are included in clinical trials, although they may still be underrepresented compared with the general MS population. Given the comorbidity prevalence in the trial populations and studies suggesting an association of comorbidities with disease activity, comorbidity may influence outcomes in clinical trials.

Evidence of geographic variation in the non-signature whistle repertoires of two isolated populations of New Zealand common bottlenose dolphin

ABSTRACT Dolphins are social animals that depend on sound to communicate, navigate, and find food. The aim of our research was to describe dolphin whistle characteristics and compare whistles between two isolated populations of bottlenose dolphins in New Zealand. We focused on three aspects of dolphin bioacoustics (1) classification of whistles; (2) comparison of the whistles of two discrete bottlenose dolphin populations; and (3) comparison of whistles of dolphin populations from around the world. At Great Barrier Island, the most common type of whistle was upsweep followed by sine, while at Doubtful Sound, convex and sine whistles were the most common whistle types. Random Forest models discriminated between whistles from the two populations with an estimated accuracy of 90%. The key differences were whistle-type contour, duration, and end frequency. Linear Mixed models show that whistle acoustic parameters were influenced by location but not by group size or the presence of immatures. Whistle parameters of both populations fell within the range of multiple populations from around the world. This studyprovides a benchmark for future research into drivers of geographic variation in dolphin vocal communication.

Improved seizure liability detection by combining rat hippocampal brain slice electrophysiology with in vivo behavior observation following intracerebroventricular drug administration

An adverse effect of drug candidates, seizure is a serious issue in drug development. Improving evaluation systems for seizure liability is crucial for selecting good candidates. Firstly, in vitro electrophysiological measurement by a multielectrode array system in rat hippocampal brain slices was employed to confirm an increase in electrically evoked population spike (PS) area, the occurrence of multiple population spikes (MPSs), and thereby the seizure liability of five positive control chemicals: picrotoxin, 4-aminopyridine, pentylenetetrazole, penicillin G, and chlorpromazine. Aspirin, a negative control, did not affect PS area or generate MPSs. Furthermore, baclofen, an anticonvulsant drug, decreased PS area and inhibited the increase in PS area or occurrence of MPSs induced by picrotoxin. A comparative study of seizure liability among carbapenem antibiotics revealed that tienam > carbenin > omegacin and finibax. Despite leading to a strong decrease in PS area, physostigmine, cisplatin, and paroxetine still produced MPSs. Therefore, the increase in PS area or the occurrence of the MPS are considered significant evaluation parameters for seizure liability.In contrast, the in vitro electrophysiological measurement could not detect the seizure liability of diphenhydramine or fluvoxamine. A follow-up study of in vivo mouse behavioral change induced by intracerebroventricular administration of these drugs clearly detected convulsions. The in vitro electrophysiological study using hippocampal brain slices combined with in vivo behavior observation study of drug candidates administered by intracerebroventricular injection can implement to assess the seizure liability of even small amounts, especially in the early stages of drug development.

Reconstruct recent multi-population migration history by using identical-by-descent sharing

Identical-by-descent (IBD) is a fundamental genomic characteristic in population genetics and has been widely used for population history reconstruction. However, limited by the nature of IBD, which could only capture the relationship between two individuals/haplotypes, existing IBD-based history inference is constrained to two populations. In this study, we propose a framework by leveraging IBD sharing in multi-population and develop a method, MatrixIBD, to reconstruct recent multi-population migration history. Specifically, we employ the structured coalescent theory to precisely model the genealogical process and then estimate the IBD sharing across multiple populations. Within our model, we establish a theoretical connection between migration history and IBD sharing. Our method is rigorously evaluated through simulations, revealing its remarkable accuracy and robustness. Furthermore, we apply MatrixIBD to Central and South Asia in the Human Genome Diversity Project and successfully reconstruct the recent migration history of three closely related populations in South Asia. By taking into account the IBD sharing across multiple populations simultaneously, MatrixIBD enables us to attain clearer and more comprehensive insights into the history of regions characterized by complex migration dynamics, providing a holistic perspective on intricate patterns embedded within the recent population migration history.

The structural properties of multiple populations in globular clusters: The instructive case of NGC 3201

All multiple population (MP) formation models in globular clusters (GCs) predict that second population (SP) stars form more centrally concentrated than the first population (FP). As dynamical evolution proceeds, spatial differences are progressively erased and only dynamically young clusters are expected to retain a partial memory of the initial structural differences. In recent years, this picture has been supported by observations of the MP radial distributions of both Galactic and extragalactic GCs. However, more recent observations have suggested that in some systems, FPs might actually form more centrally segregated, with NGC 3201 being one significant example of such a possibility. Here, we present a detailed morphological and kinematic characterization of the MPs in NGC 3201, based on a combination of photometric and astrometric data. We show that the distribution of the SP is clearly bimodal. Specifically, the SP is significantly more centrally concentrated than the FP within $ cluster’s half-mass radius. Beyond this point, the SP fraction increases again, likely due to asymmetries in the spatial distributions of the two populations. The central concentration of the SP observed in the central regions implies that it formed more centrally concentrated than the FP, even more so than what is observed in the present-day. This interpretation is supported by the key information provided by the MP kinematic properties. Indeed, we find that the FP is isotropic across all the sampled cluster extension, while the velocity distribution of the SP becomes radially anisotropic in the cluster’s outer regions, as expected for the dynamical evolution of SP stars formed more centrally concentrated than the FP. The combination of spatial and kinematic observations provide key insights into the dynamical properties of this cluster and lend further support to scenarios in which the SP forms more centrally concentrated than the FP.

Racial Perspectives on Facelifts: Evaluating Techniques and Outcomes Across Diverse Populations.

Facial aesthetic surgery is one of plastic and reconstructive surgery's most sought-after and evolving areas. The growing diversity in both local and worldwide populations compels us to reevaluate our previous approaches and underscores the significance of departing from a singular aesthetic standard. Thankfully, the historical practice of stereotypical racial profiling has become less prevalent in the literature. Regrettably, however, the comparative terminology persists, characterizing non-Caucasian races as deviating from the "norm," which typically refers to the White or Caucasian race. Additionally, there is a lack of contemporary literature comparing the distinctive considerations relevant to rhytidectomy across multiple racial populations. The aim of this study was to succinctly outline the current body of literature examining the impact of race on facial aging and rhytidectomy, laying the groundwork for subsequent discussion on the relationship between race and facial aesthetic surgery. A comprehensive literature review was conducted using PubMed (National Institutes of Health, Bethesda, MD), identifying all studies published before 2023 discussing facial aging and rhytidectomy, specifically in non-Caucasian patients. A total of 22 publications was identified. Asians were the most described group, with 12 publications, followed by Black/African with 5 and Hispanic/Latinx with 4. In today's context, the aesthetic surgeon must possess the knowledge and readiness to provide culturally sensitive, patient-centered care guided by subtle anatomical nuances, informed by anecdotal recommendations, and ultimately, aimed at effectively addressing aging concerns within diverse populations.

Beyond pathways: Accelerated flavonoids candidate identification and novel exploration of enzymatic properties using combined mapping populations of wheat.

Although forward-genetics-metabolomics methods such as mGWAS and mQTL have proven effective in providing myriad loci affecting metabolite contents, they are somehow constrained by their respective constitutional flaws such as the hidden population structure for GWAS and insufficient recombinant rate for QTL. Here, the combination of mGWAS and mQTL was performed, conveying an improved statistical power to investigate the flavonoid pathways in common wheat. A total of 941 and 289 loci were, respectively, generated from mGWAS and mQTL, within which 13 of them were co-mapped using both approaches. Subsequently, the mGWAS or mQTL outputs alone and their combination were, respectively, utilized to delineate the metabolic routes. Using this approach, we identified two MYB transcription factor encoding genes and five structural genes, and the flavonoid pathway in wheat was accordingly updated. Moreover, we have discovered some rare-activity-exhibiting flavonoid glycosyl- and methyl-transferases, which may possess unique biological significance, and harnessing these novel catalytic capabilities provides potentially new breeding directions. Collectively, we propose our survey illustrates that the forward-genetics-metabolomics approaches including multiple populations with high density markers could be more frequently applied for delineating metabolic pathways in common wheat, which will ultimately contribute to metabolomics-assisted wheat crop improvement.

Single-Cell Transcriptomic Profiling Identifies Molecular Phenotypes of Newborn Human Lung Cells.

While animal model studies have extensively defined the mechanisms controlling cell diversity in the developing mammalian lung, there exists a significant knowledge gap with regards to late-stage human lung development. The NHLBI Molecular Atlas of Lung Development Program (LungMAP) seeks to fill this gap by creating a structural, cellular and molecular atlas of the human and mouse lung. Transcriptomic profiling at the single-cell level created a cellular atlas of newborn human lungs. Frozen single-cell isolates obtained from two newborn human lungs from the LungMAP Human Tissue Core Biorepository, were captured, and library preparation was completed on the Chromium 10X system. Data was analyzed in Seurat, and cellular annotation was performed using the ToppGene functional analysis tool. Transcriptional interrogation of 5500 newborn human lung cells identified distinct clusters representing multiple populations of epithelial, endothelial, fibroblasts, pericytes, smooth muscle, immune cells and their gene signatures. Computational integration of data from newborn human cells and with 32,000 cells from postnatal days 1 through 10 mouse lungs generated by the LungMAP Cincinnati Research Center facilitated the identification of distinct cellular lineages among all the major cell types. Integration of the newborn human and mouse cellular transcriptomes also demonstrated cell type-specific differences in maturation states of newborn human lung cells. Specifically, newborn human lung matrix fibroblasts could be separated into those representative of younger cells (n = 393), or older cells (n = 158). Cells with each molecular profile were spatially resolved within newborn human lung tissue. This is the first comprehensive molecular map of the cellular landscape of neonatal human lung, including biomarkers for cells at distinct states of maturity.

Phenotypic correlations of carpal gland diverticular number with production traits and its genome-wide association analysis in multiple pig populations.

Pig carpal glands play crucial roles in territorial recognition, reproductive behavior, and information exchange; however, their effects on production traits and underlying genetic mechanisms remain unclear. In this study, 1028 pigs from six populations were counted for the carpal gland diverticular numbers (CGDNs) on the left (CGDNL) and right (CGDNR) legs, and their carcass and meat quality traits were assessed. The CGDNs were significantly different among the populations, and Licha Black pigs had a lower CGDN than the Bama Xiang breed. It was also significantly different between sexes, with males having more diverticula than females (p ≤ 0.0391). Moreover, the number was asymmetric, with CGDNR being significantly higher than CGDNL. Notably, CGDNs was significantly correlated with each other in phenotype and genetics and with 24-h pH, 24-h meat color score, 24-h marbling score, fat content, moisture content, sodium salt content, and saturated fatty acid content in phenotype. Furthermore, genome-wide association analyses identified seven SNPs in association with CGDNs at a 5% genome-wide significance level, all of which were located in a 1.78-Mb (35.347-37.129 Mb) region on chromosome 1. CNC10010837 and CNC10010840 were the top SNPs: both had an additive effect of 0.789 ± 0.120 on CGDNR with p = 8.31E-10. These findings provide important insights into the functions and underlying genetic mechanisms of swine carpal glands.

Investigating black hole accretion disks as potential polluter sources for the formation of enriched stars in globular clusters

Accretion disks surrounding stellar mass black holes have been suggested as potential locations for the nucleosynthesis of light elements, which are our primary observational discriminant of multiple stellar populations within globular clusters. The population of enriched stars in globular clusters are enhanced in N Na and sometimes in Al and/or in K . In this study, our aim is to investigate the feasibility of initiating nucleosynthesis for these four elements in black hole accretion disks, considering various internal parameters such as the temperature of the gas and timescale of the accretion. To achieve this, we employed a 132-species reaction network. We used the slim disk model, suitable for the Super-Eddington mass accretion rate and for geometrically and optically thick disks. We explored the conditions related to the mass, mass accretion rate, viscosity, and radius of the black hole-accretion disk system that would allow for the creation of N Na Al and K before the gas is accreted onto the central object. This happens when the nucleosynthesis timescale is shorter than the viscous timescale. Our findings reveal that there is no region in the parameter space where the formation of Na can occur and only a very limited region where the formation of N Al and K is plausible. Specifically, this occurs for black holes with masses lower than 10 solar masses ($m<10 M_ with a preference toward even lower mass values ($m<1 M_ and extremely low viscosity parameters ($ $). Such values are highly unlikely based on current observations of stellar mass black holes. However, such low mass black holes could actually exist in the early universe, as so-called primordial black holes. In conclusion, our study suggests that the nucleosynthesis within black hole accretion disks of elements of interest for the multiple stellar populations, namely N Na Al and K is improbable, but not impossible, using the slim disk model. Future gravitational wave missions will help constrain the existence of tiny and light black holes.

Unraveling dystonia circuitry in rodent models using novel neuromodulation techniques

Dystonia is a network disorder presumed to result from abnormalities in multiple brain regions and in multiple cell populations. The specific pathomechanisms affecting the motor circuits in dystonia are, however, still largely unclear. Animal models for dystonia have long been used to advance our understanding on how specific brain regions and cell populations are involved in dystonia symptomatogenesis. Lesioning, pharmacological modulation and electrical stimulation paradigms were able to highlight that both the basal ganglia and the cerebellum are pathologically altered in these animal models for dystonia. Techniques such as optogenetics and chemogenetics now offer the opportunity for targeted modulation of brain regions and most importantly cell populations and circuits. This could not only allow for a better understanding of the dystonic brain, but potentially improve and expand treatment options. In hopes that the insights from these neuromodulation techniques will eventually translate into therapies, we aim to summarize and critically discuss the findings from different in vivo approaches used to dissect the network dysfunctions underlying dystonia.

The effect of genetic variants of SLC22A18 on proliferation, migration, and invasion of colon cancer cells

Solute carrier family (SLC) transporters are expressed in the digestive system and play important roles in maintaining physiological functions in the body. In addition, SLC transporters act as oncoproteins or tumor-suppressor proteins during the development, progression, and metastasis of various digestive system cancers. SLC22A18, a member of the SLC22 gene family, is an orphan transporter with an unknown endogenous substrate. Previous study revealed that SLC22A18 is downregulated in colorectal cancer tissues and that it acts as a suppressor in colorectal cancer, although the effects of SLC22A18 variants on colon cancer cell proliferation, migration, and invasion are unknown. Therefore, in this study, we identified SLC22A18 variants found in multiple populations by searching public databases and determined the in vitro effects of these missense variations on transporter expression and cancer progression. Our results indicated that three missense SLC22A18 variants—p.Ala6Thr, p.Arg12Gln, and p.Arg86His—had significantly lower cell expression than the wild type, possibly owing to intracellular degradation. Furthermore, these three variants caused significantly higher proliferation, migration, and invasion of colon cancer cells than the wild type. Our findings suggest that missense variants of SLC22A18 can potentially serve as biomarkers or prognostic tools that enable clinicians to predict colorectal cancer progression.

Defining the Unseen: Population-Specific Markers for Astyanax mexicanus Blind Cavefish.

Astyanax mexicanus is an emerging model system used to study development, evolution, and behavior of multiple cavefish populations that have repeatedly evolved from conspecific surface fish. Although surface and cavefish live and breed in the laboratory, there are no rapid methods for distinguishing between different cavefish populations. We present 2 methods for genotyping fish for a total of 16 population-specific markers using methods that are easy and inexpensive to implement in a basic molecular biology laboratory. This resource will help researchers maintain independent stocks within the laboratory and distinguish between fish from different populations.

A3 INVESTIGATING MACROPHAGE-TISSUE CELL COMMUNICATION AXES IN THE GASTROINTESTINAL TRACT

Abstract Background The gastrointestinal tract boasts the highest concentration of macrophages (MPs) in the body, acting as vital immune sentinels that oversee tissue balance. Three distinct subsets of MPs, namely CCR2+, Tim4+, and CCR2,Tim4 double-negative (DN) MPs, populate distinct gut niches. Their functional specialization suggests unique interactions within their non-hematopoietic tissue microenvironments. Despite their crucial roles, the intricacies of these interactions remain elusive. One recently discovered interaction involves a communication axis between MPs and neurons within the muscularis layer of the gut. Here, neurons secrete Colony Stimulating Factor 1 (CSF1), a survival factor for MPs. These MPs reciprocate by producing Bone Morphogenetic Protein 2 (BMP2), assisting neurons in regulating gut motility. Aims Based on the aforementioned interaction, we hypothesize that BMP2, derived from tissue-resident MPs, might influence functions of other tissue niches, subsequently prompting survival of MP via CSF1 production. Our aims are twofold: (1) Identify the role of BMP2 in gut macrophages; (2) Identify BMP2-responsive CSF1-producing tissue cells within the gut. Methods To discern the roles of MP subsets, we developed a conditional knockout mouse model, targeting Bmp2 expression in MPs. We validated successful Bmp2 deletion(BMP2 KO) through quantitative polymerase chain reaction (qPCR) and an in-situ hybridization immunofluorescence assay (RNAscope). Subsequently, single cell RNA (scRNAseq) was performed, combining samples from both control and KO small intestines. This was done to further confirm BMP2 KO and to identify BMP2-responsive CSF1-producing cells. Flow cytometry was then used to characterize the intestinal MPs in control and KO mice. Results Tim4+ MPs emerged as the primary source of BMP2. Comprehensive analysis using qPCR, RNAscope, and scRNAseq validated the complete KO of BMP2 across all macrophage subsets. The loss of MP-produced BMP2 led to a disruption in MP development. Notably, a marked reduction in DN and Tim4+ MPs was observed following deletion of Bmp2 in MPs, emphasizing the critical role of BMP2-driven CSF1 in sustaining these subsets. CSF1 producing cells co-expressing the cognate BMP receptor in the gut, were predominantly non-hematopoietic tissue cells. Among these, distinct fibroblast populations emerged as a potent but not the sole source of CSF1. Conclusions Our work underscores the involvement of multiple tissue cell populations, revealing an intricate network of interactions that extends beyond fibroblasts. This study unveils the multifaceted nature of tissue-MP interactions and their critical roles in maintaining gut homeostasis. Disturbances of these pathways may pave the way for disease by altering tissue homeostasis. Funding Agencies NSERC

Forecasting high-dimensional functional time series: Application to sub-national age-specific mortality

We study the modeling and forecasting of high-dimensional functional time series (HDFTS), which can be cross-sectionally correlated and temporally dependent. We introduce a decomposition of the HDFTS into two distinct components: a deterministic component and a residual component that varies over time. The decomposition is derived through the estimation of two-way functional analysis of variance. A functional time series forecasting method, based on functional principal component analysis, is implemented to produce forecasts for the residual component. By combining the forecasts of the residual component with the deterministic component, we obtain forecast curves for multiple populations. We apply the model to age- and sex-specific mortality rates in the United States, France, and Japan, in which there are 51 states, 95 departments, and 47 prefectures, respectively. The proposed method is capable of delivering more accurate point and interval forecasts in forecasting multi-population mortality than several benchmark methods considered.