Control Of Migration Research Articles

Optogenetic control of migration of contractile cells predicted by an active gel model

Cell crawling on flat substrates stems from intracellular flows of the actin cytoskeleton that are driven by both actin polymerization at the front and myosin contractility at the back. Optogenetics makes it experimentally possible to spatially control contraction and possibly cell migration too. Here we theoretically analyze this situation using a one-dimensional active gel model that reflects the property of myosin II to assemble into minifilaments. Our model predicts bistability between sessile and motile solutions when cell adhesion and contractility are sufficiently large and in balance. We show that one can switch between the different states at realistic parameter values via optogenetic activation or inhibition of contractility, in agreement with recent experiments performed for neutrophils in microchannels. We predict the required activation strengths and initiation times, compare the effects of local and global increases of myosin II levels, and show that actin polymerization alone can affect a switch in direction only at high strength.

Actin dynamics regulation by TTC7A/PI4KIIIα limits DNA damage and cell death under confinement

The actin cytoskeleton has a crucial role in the maintenance of the immune homeostasis by controlling various cellular processes, including cell migration. Mutations in TTC7A have been described as the cause of a primary immunodeficiency associated to different degrees of gut involvement and alterations in the actin cytoskeleton dynamics. This study investigates the impact of TTC7A deficiency in immune homeostasis. In particular, the role of the TTC7A/phosphatidylinositol 4 kinase type III α pathway in the control of leukocyte migration and actin dynamics. Microfabricated devices were leveraged to study cell migration and actin dynamics of murine and patient-derived leukocytes under confinement at the single-cell level. We show that TTC7A-deficient lymphocytes exhibit an altered cell migration and reduced capacity to deform through narrow gaps. Mechanistically, TTC7A-deficient phenotype resulted from impaired phosphoinositide signaling, leading to the downregulation of the phosphoinositide 3-kinase/AKT/RHOA regulatory axis and imbalanced actin cytoskeleton dynamics. TTC7A-associated phenotype resulted in impaired cell motility, accumulation of DNA damage, and increased cell death in dense 3-dimensional gels in the presence of chemokines. These results highlight a novel role of TTC7A as a critical regulator of lymphocyte migration. Impairment of this cellular function is likely to contribute to the pathophysiology underlying progressive immunodeficiency in patients.

Bioinformatics analysis of the clinicopathological and prognostic significance of BAG3 mRNA in gynecological cancers

BAG3 is a co-chaperone BAG family protein that plays important roles in protein homeostasis, cell survival, cell motility, and tumour metastasis. This study aimed to clarify the clinicopathological and prognostic implications of BAG3 mRNA expression in tumours. We performed bioinformatics analysis on BAG3 mRNA expression using TCGA, XIANTAO, UALCAN, and Kaplan-Meier plotter databases. BAG3 mRNA expression was downregulated in breast and endometrial cancers and positively correlated with favourable PAM50 subtyping in breast cancer，clinical stage and short overall survival in ovarian cancer and negatively correlated with T stage, clinical stage, and histological grade in cervical and endometrial cancers. The top BAG3-related pathways included ligand-receptor interactions and activity, DNA packaging and nucleosomes, hormonal responses, membrane regions, microdomains and rafts, and endosomes in breast cancer; ligand-receptor interactions, transmembrane transporters and channels, cell adhesion, and keratinisation in cervical cancer; ligand-receptor interactions, anion transmembrane transporters, lipoproteins, keratinisation, cell adhesion, and protein processing in endometrial cancer; metabolism of porphyrin, chlorophyll, pentose, uronic acid, ascorbate, and alternate and cell adhesion in ovarian cancer. BAG3 expression could represent a potential marker for carcinogenesis, histogenesis, aggressive behaviours, and prognosis in gynecological cancers. IMPACT STATEMENT What is already known on this subject? BAG3 regulates cell activity, autophagy, and resistance to apoptosis through multiple domains and plays an important role in tumour development. BAG3 positively regulates tumour cell invasion and migration in cervical and ovarian cancers. What do the results of this study add? BAG3 expression is closely associated with histogenesis, clinicopathology, and prognosis in gynecological cancers and is involved in signalling pathways associated with the control of cell proliferation, migration, invasion, and drug resistance in tumours. What are the implications of these findings for clinical practice and/or further research? Abnormal BAG3 expression can be employed as a possible marker of tumour development, invasion, and prognosis, providing new ideas for treating cancer.

The Bosnian War and Refugee Policy: Crisis Management and Migration Control

Based on research in the United Nations high commissioner for refugees (UNHCR) archives in Geneva, this article aims to reflect, through an examination of UNHCR’s huge operation during the Bosnian war, on the major role played by the crisis paradigm in conflict management and related population movements, and on the construction and conceptualization over time of long-term forms of migration management. It analyses how the notion of “preventive protection” which emerges in the early 1990s illustrates a shift in the asylum regime, which concerns altogether the categories of its beneficiaries, the spaces, and the very nature of its application. The focus on humanitarian operations taking place as close as possible to the areas from which refugees are coming is at the origin of new patterns of emergency management which intend to contain and eventually hinder massive refugee flows and migration. This new approach of refugees flow was experimented during the Bosnian war; the UNHCR reflected on this experience and its learnings to build up long-term strategies for managing migration in a context of increased States’ hostility to the permanent welcoming of refugees. The continuity between wartime and peacetime for experimenting and enforcing new modes of migration management is emphasized, in order to show that the importance of the crisis paradigm symbolized by open conflicts and wars is thereafter used as a tool to manage migration flows in ordinary times.

Economic and mobility repercussions of the COVID-19 pandemic on the Chile–Bolivia border

This article analyzes how the pandemic caused by the coronavirus (COVID-19) has impacted international migration. In particular, we compare the mobility and economic repercussions faced by Bolivian and Venezuelan migrants. We conducted 16 semi-structured interviews with migrants who requested legal and social support and advice provided by the Open Assembly of Migrants and Pro-Migrants of Tarapacá, Chile (AMPRO), an organisation dedicated to defending migrant rights. The Bolivian interviewees worked in Chile before the pandemic in the city of Iquique (close to the Bolivian border). The Venezuelan interviewees are undocumented people in transit who entered Chile during the pandemic. Through this comparison, we describe the economic repercussions on the everyday life, mobility, and survival strategies of people in transit, transboundary workers, and migrants with transnational families, and reveal a realignment of Chile’s border regime that benefits post-pandemic capitalism. Furthermore, we clarify how the health restrictions implemented due to the pandemic have favoured the reconfiguration of the border regime imposed in Chile, through a racist immigration policy based on the control and management of migration, leading to a greater irregularization of migration.

Diaconia as the Art of the Possible: Diaconal Engagement for Roma Migrants in Oslo, Norway

Itinerant Roma migrants travelling from Eastern European countries have featured across the European Economic Area (EEA) since the European Union’s eastward expansions in 2004 and 2007. Being unskilled, many Roma migrants engage in casual work and street work such as playing music, selling magazines, collecting and recycling bottles and cans, and begging, making them conspicuously visible in countries with public welfare services and low poverty levels. Citizens of EEA countries can enter and stay legally in other countries in the EEA for up to three months, after which they must register as workers or jobseekers, and generally leave. It is well documented how the countries Roma citizens of EEA countries travel to have enacted migration control measures, often in the form of complex and fine-grained regulations, that exclude them from public welfare services. This is also true of the Nordic countries, such as Norway, where they coincide with universalistic welfare states aiming to cover everyone living in their territories with the same benefits and services. In the Nordic countries, as in other countries, service provision for Roma migrants is largely in the hands of non-governmental organisations, many of them diaconal organisations running emergency shelters, soup kitchens, and other humanitarian services to alleviate suffering for people at the margins of the welfare state. The diaconal organisations also engage in case work and advocacy work to ensure the realisation of the Roma migrants’ rights. Many of the organisations depend on public grants, making their relationship to the welfare state ambiguous. This article investigates Christian social practice in the form of diaconal engagement for Roma migrants in Oslo, Norway at the intersection of migration control, the universalistic welfare state, and the theological underpinnings of the organisations.

Locked in: Australia’s COVID-19 Border Closures and the Right to Leave

Abstract In March 2020, Australia became one of a handful of democratic states worldwide to adopt a blanket prohibition on the right of citizens to leave its territory, whether temporarily or permanently, in response to the COVID-19 pandemic. The International Health Regulations, which bind all members of the World Health Organization (‘WHO’), including Australia, provide an international legal framework to guide the public health response to the international spread of disease in a manner which respects human rights and fundamental freedoms. The right to freedom of movement in international human rights law is enshrined in the International Covenant on Civil and Political Rights (‘ICCPR’), which Australia ratified in 1990. Although states can place restrictions on freedom of movement to protect public health, they must be appropriate to achieve their protective function, the least intrusive instrument which might achieve the desired result, and proportionate to the interest to be protected. This article argues that in adopting sweeping restrictions on outbound travel, Australia re-purposed aspects of its migration control regime—ordinarily employed to externalise its international border and prevent people from entering the country—in order to prevent Australian citizens and permanent residents from leaving Australia. The outbound travel restrictions further bypassed an analysis of the intrusiveness and proportionality of the measures themselves, and shifted the burden onto individuals to request an exemption where the regulation of exit proved overly intrusive or disproportionate in their particular circumstances. In examining parliamentary transcripts, press statements by government officials, and recently revealed data regarding outbound travel exemptions, this article raises serious questions regarding the legality of the restrictions over time and their implementation in light of international law.

To Assess the Role of microRNA-451 in the Progression and Metastasis of Colorectal Cancer.

The study aimed to determine the expression of miR451 in colorectal cancer (CRC) subjects with CRC cells, and the role of miR451 in colorectal cancer cells. In October 2020, ATC purchased CRC and normal mucosal cell lines of CRC and implanted them in DMEM with 10% fetal serum. The suitability of the HT29 cell line is verified using the STR profile. In an incubator with 5% CO2, enlarged cells were placed at 37 °C. TCGA data was used to select the top 120 patients with a high voice and the lowest 120 patients with a low voice. Cells were collected and coated with Annexin V and PE according to the manufacturer's instructions after 24.0 h. After that, the cells were separated. Cells were also tested using flow cytometry. HCT-120 cells were transplanted into a concentration of 5×105/ml cells in 6-source plates. HCT120 cells in the experimental group were combined with miR451 mimics, miR451 inhibitors, or miR451 miR + SMAD4B for 12 h at 37 °C, and cells were collected 24 h later at 37 °C. The sample was injected with 5 ml of Annexin VFITC and PE. Compared with normal colorectal mucosal cells, CRC cell lines decreased miR451 expression levels (fetal human cells (FHC) and HCoEpiC). Then, the HCT120 cells were transfected with miR451 inhibitors, and 72 h after transfection, say of miR451 was normal. There was a significant decrease in cell function in the miR451mimic groups, but an increase when the miR451 was blocked. The proliferation of cancer cells was prevented and chemotherapy was effective when miR451 was overexpressed. The SMAD4 gene provides instructions for making a protein involved in transmitting chemical signals from the cell surface to the nucleus. The SMAD4B expression was tested by RT-qPCR and Western blotting after 72.0 h of transmission. The mRNA and protein expression of SMAD4B decreased significantly when miR451 was significantly higher than when inhibited, as revealed in the results of this study. Seventy-two hours after transplantation, mRNA levels and SMAD4B proteins were measured in HCT120 cells. In addition, the researchers in this study investigated whether miR451 was associated with SMAD4B-directed control of CRC growth and migration. It was found that SMAD4B is highly expressed in both CRC and para-cancer tissues while using the TCGA database to detect SMAD4B expression. Patients with CRC with SMAD4B have a severe prognosis. MiR451 is sensitive to depressive disorders by targeting SMAD4B, according to these studies. We found that miR451 inhibited cell growth and migration, made CRC cells more readily available in chemotherapy, and did so by targeting SMAD4B. The findings suggest that miR451 and its genetic predisposition, SMAD4B, may help predict the prognosis and course of cancer patients. Treatments that target the miR451/SMAD4B axis may be helpful to people with CRC.

Provisional by design. Frontex data infrastructures and the Europeanization of migration and border control

ABSTRACT Data infrastructures for the Frontex joint operations are often only temporary and thus in need of being built up and removed easily, adjustable to changing constellations of security actors, and adaptable to new situations. They need to work through flaws, gaps, and inconsistencies. Still, they fabricate data used for the re-identification of migrants, police investigations, situational pictures, or risk analysis and lead to the intensification of security practices of Frontex. This is accomplished by data infrastructures that are provisional by design. People and forms are used as provisional gateway to interconnect various installed bases of national police and coast guard authorities, informal communication channels and ‘other’ entry fields proliferate around partially standardized classification systems, and ongoing coordination and repair tame and validate the proliferation of data. With this, the data infrastructure of joint border operations hints to a mode of Europeanization that is neither supranational nor intergovernmental. Instead of centralized administrations or fully integrated information systems, it aims for partial harmonization through interconnecting loosely information systems and institutional ecologies of national and EU agencies alike. This causes issues of accountability and requires an analysis that takes the mundane socio-technical conditions of knowledge production into account.

‘They don’t make us feel like we are seen’

This contribution is based on my master’s dissertation and ethnographic fieldwork conducted in Thessaloniki, Greece, where I have explored the experiences of people-on-the-move with harms and injustices resulting from the EU and Greece’s migration control practices. Through storytelling by my research participants and by taking a social harm-based approach I have recognised and identified different types of harm, and I have attempted to construct a bridge between the more abstract EU and Greek migration control policies and the micro-level harms these have caused for people-on-the-move.

The Gendered Necropolitics of Migration Control in a French Postcolonial Periphery

This article examines the postcolonial politics of migration control in Mayotte, an overseas French department, and argues that these bear necropolitical consequences. It sheds light on the gendered dimension of this necropolitical power by focusing on the life and border-crossing experiences of undocumented Comorian women. Entrenched barriers to the regularization of their administrative status endanger their access to healthcare and degrade the conditions for life long-term. The constant risk of arrest and massive forced removals furthermore engender dangerous border crossings, each instance exposing the passengers to the risk of death. The article also foregrounds that these necropolitics are exacerbated as a result of the postcolonial conundrum in which Mahoran elites find themselves, with the increasing support of Black and Muslim elites for the French far-right political party.

Arbitrary Detention of Mexican Citizens by Mexican Immigration Authorities

On 3 September 2015, Mexican immigration authorities detained four Indigenous Tzeltal Mexicans who were travelling by bus to the northern state of Sonora. Despite identifying themselves as Mexican citizens, the authorities considered their documents false, and they were detained for nine days until their identities were certified. The Mexican State took four years to acknowledge publicly and apologise for this arbitrary detention. Similarly, in 2017, a 39‑year‑old man born in Oaxaca, living in the streets of Puebla after being deported by the United States Government, was detained for being ‘identified’ as a Salvadorian citizen by Mexican authorities. However, it would be a mistake to consider these cases an exception or anomaly in the Mexican Transit Control Regime. Drawing on statistical and archival information from 2010 to 2020, as well as semi-structured interviews conducted in 2021, in this article, we examine the arbitrary detention of Mexican citizens by Mexican immigration authorities. We highlight the multiple rights violated, question how these detentions have been framed in the official discourse and examine the outcome of these detentions. Our analysis sheds light on the racialisation of migration control in Mexico.

The Gendered Necropolitics of Migration Control in a French Postcolonial Periphery

This article examines the postcolonial politics of migration control in Mayotte, an overseas French department, and argues that these bear necropolitical consequences. It sheds light on the gendered dimension of this necropolitical power by focusing on the life and border-crossing experiences of undocumented Comorian women. Entrenched barriers to the regularization of their administrative status endanger their access to healthcare and degrade the conditions for life long-term. The constant risk of arrest and massive forced removals furthermore engender dangerous border crossings, each instance exposing the passengers to the risk of death. The article also foregrounds that these necropolitics are exacerbated as a result of the postcolonial conundrum in which Mahoran elites find themselves, with the increasing support of Black and Muslim elites for the French far-right political party.

NSCLC patients with a changing T grade after operation may represent a special subset of tumor staging.

There is consensus that postoperative adjuvant therapy is not recommended in patients with stage 1a non-small cell lung cancer (NSCLC). Meanwhile, it is still controversial whether postoperative adjuvant chemotherapy is recommended for NSCLC patients with T2aN0M0 (stage 1b). In some patients with stage 1b NSCLC without pleural invasion, tumor diameter was measured between 3 and 4cm by preoperative imaging and less than 3cm by postoperative pathology specimens. TNM staging in such patients is both radiologic stage 1b and pathologic stage 1a. Thoracic surgeons are often confused about whether such patients with NSCLC will require subsequent treatment and how the survival prognosis for this group of patients will be. All data of radiographic TNM stage 1b patients who underwent radical R0 resection at the department of thoracic surgery, the First Affiliated Hospital of Soochow University between January 2013 and July 2017 were retrieved, and 208 patients were finally included in the study. Clinical data, including imaging data, pathology data, were obtained by reviewing the patients' electronic medical records. Disease-free survival (DFS) and overall survival (OS) were obtained by telephone interview. Statistical analysis was performed using SPSS (SPSS 26.0 for windows, SPSS). A total of 208 patients were included in this study, 61 patients with T-stage migration (observation group) and 147 patients without T-stage migration (control group). There were significant statistical differences between the two groups in terms of preoperative FEV1/FVC and tumor diameter (specimens, CT and 3-dimensional measurements). Logistic regression results showed that lower FEV1/FVC and smaller CT measurements would make the patient's T stage more likely to migrate. Bland-Altman plots showed that tumor length measured by imaging was significantly higher than that measured by pathological specimens. Taking DFS as the outcome, the survival curve of the observation group was significantly better than that of the control group. Similarly, there was a significant difference in OS between the two groups. For NSCLC patients whose preoperative imaging evaluation was stage 1b (tumor diameter more than 3cm, no main bronchus, pleura, no atelectasis), the presence of lung tissue with smaller tumor diameter and/or higher air content may indicate that the postoperative pathological staging may be changed to stage 1a (tumor diameter less than 3cm). These patients had better survival prognosis than those who did not undergo TNM stage change and were diagnosed with stage 1b non-small cell lung cancer before and after surgery.

Genetic Control of Avian Migration: Insights from Studies in Latitudinal Passerine Migrants.

Twice-a-year, large-scale movement of billions of birds across latitudinal gradients is one of the most fascinating behavioral phenomena seen among animals. These seasonal voyages in autumn southwards and in spring northwards occur within a discrete time window and, as part of an overall annual itinerary, involve close interaction of the endogenous rhythm at several levels with prevailing photoperiod and temperature. The overall success of seasonal migrations thus depends on their close coupling with the other annual sub-cycles, namely those of the breeding, post-breeding recovery, molt and non-migratory periods. There are striking alterations in the daily behavior and physiology with the onset and end of the migratory period, as shown by the phase inversions in behavioral (a diurnal passerine bird becomes nocturnal and flies at night) and neural activities. Interestingly, there are also differences in the behavior, physiology and regulatory strategies between autumn and spring (vernal) migrations. Concurrent molecular changes occur in regulatory (brain) and metabolic (liver, flight muscle) tissues, as shown in the expression of genes particularly associated with 24 h timekeeping, fat accumulation and the overall metabolism. Here, we present insights into the genetic basis of migratory behavior based on studies using both candidate and global gene expression approaches in passerine migrants, with special reference to Palearctic-Indian migratory blackheaded and redheaded buntings.

Dilemmas of ‘biometric nationality’: migration control, biometric ID technology and political mobilisation of migrants in West Africa

ABSTRACT This article interrogates the use of biometric ID technology to facilitate political mobilisation of migrants for election purposes in West Africa. We contribute to the migration instrumentalisation (MI) debate by fishing out four structures that facilitate MI for election purposes, namely: regional migration regimes; state identity politics/policies; monetary inducement; and biometric ID technology. Based on a qualitative in-depth study of migrants from Chad, Niger, Benin, Cameroon and Togo in Nigeria, we reveal how biometric ID technology has been instrumentalised to delegitimise the state; and how migrants’ strategies/demand for political belonging – via ‘biometric nationality’ – intersect with elite manipulations.

Implementation of threshold- and memory-switching memristors based on electrochemical metallization in an identical ferroelectric electrolyte

The use of an identical electrolyte in electrochemical metallization (ECM)-based neuron and synaptic devices has not yet been achieved due to their different resistive-switching characteristics. Herein, we describe ECM devices comprising the same ferroelectric PbZr0.52Ti0.48O3 (PZT) electrolyte, which can sustain both neuron and synaptic behavior depending on the identity of the active electrode. The Ag/PZT/La0.8Sr0.2MnO3 (LSMO) threshold switching memristor shows abrupt and volatile resistive switching characteristics, which lead to neuron devices with stochastic integration-and-fire behavior, auto-recovery, and rapid operation. In contrast, the Ni/PZT/LSMO memory switching memristor exhibits gradual, non-volatile resistive switching behavior, which leads to synaptic devices with a high on/off ratio, low on-state current, low variability, and spike-timing-dependent plasticity (STDP). The divergent behavior of the ECM devices is attributed to greater control of cation migration through the ultrathin ferroelectric PZT. Thus, ECM devices with an identical ferroelectric electrolyte offer promise as essential building blocks in the construction of high-performance neuromorphic computing systems.

Narratives of displacement and poverty: the intersections of policy and the shared experience of the everyday

An extensive, and growing, global literature on the experience of people subject to migration control shows how state actions to “manage” migration and human mobility results in poverty and destitution. There is also a large body of evidence indicating how neo-liberal policy, alongside deeply embedded structures of privilege and inequality lead to the economic deprivation of fully entitled, “citizen” populations. Despite the commonality of disadvantage between these two groups—migrants and citizens—the parallels in experience of structures that create and maintain their impoverishment have rarely been explored. Close attention to the stories told by people with lived experience of poverty, as citizens or as migrants, challenges the normative assumptions about belonging and entitlement, deservingness and opportunity that underpin policy-making on both migration and social inequality. This essay argues that listening to, and engaging with, the stories of people in poverty is an important corrective to normative ideas about who can benefit from state support. Focusing on the UK, my aim is to explore the position of people subject to migration control alongside others living in poverty—marginalized and made precarious not by displacement but by deprivation, stigma and punitive welfare systems. Paying close attention to the stories people tell cuts through the official, normative positioning of people as outsiders whether as foreigners or as marginalized citizens. Stories thus reveal the technologies of power and oppression at work in everyday settings. Drawing on concepts including Butler's ideas of grievability and Mbembe's necropolitics I reflect on how welfare management systems and the “so-called” hostile environment, reduce the capacity of migrants and others to act as purposeful human beings. I hope to reveal the technologies of power and oppression at work in everyday settings and will argue that careful, attentive listening to human stories can challenge the imposition of normative discourses on the voiceless and encourage narratives that embrace complexity.

Precise temporal control of neuroblast migration through combined regulation and feedback of a Wnt receptor.

Many developmental processes depend on precise temporal control of gene expression. We have previously established a theoretical framework for regulatory strategies that can govern such high temporal precision, but experimental validation of these predictions was still lacking. Here, we use the time-dependent expression of a Wnt receptor that controls neuroblast migration in C. elegans as a tractable system to study a robust, cell-intrinsic timing mechanism in vivo. Single molecule mRNA quantification showed that the expression of the receptor increases non-linearly, a dynamic that is predicted to enhance timing precision over an unregulated, linear increase in timekeeper abundance. We show that this upregulation depends on transcriptional activation, providing in vivo evidence for a model in which the timing of receptor expression is regulated through an accumulating activator that triggers expression when a specific threshold is reached. This timing mechanism acts across a cell division that occurs in the neuroblast lineage, and is influenced by the asymmetry of the division. Finally, we show that positive feedback of receptor expression through the canonical Wnt pathway enhances temporal precision. We conclude that robust cell-intrinsic timing can be achieved by combining regulation and feedback of the timekeeper gene.

Apelin Regulation of K-Cl Cotransport in Vascular Smooth Muscle Cells as a Potential Target for Cardiovascular Disease

Background/Aims: Apelin and its signaling through the G-protein coupled receptor (APJ, gene symbol APLNR) regulate cardiovascular function via two mechanisms: 1) By promoting nitric oxide (NO)-mediated vasodilation, impaired by oxidized low-density lipoproteins (oxLDL); and 2) By inducing cell proliferation via the phosphatidylinositol-3-kinase (PI3K)/protein kinase B/Akt pathway (PI3K/Akt) and mitogen activated protein kinase (MAPK) pathways. The potassium chloride cotransporter (KCC1,3,4; SLC12A4,6,7) controls cell volume, and regulates cardiovascular function through proliferation, migration, and blood pressure control. Importantly, KCC regulatory mechanisms and apelin/APJ signaling pathways overlap placing KCC as a potential target for apelin/APJ to elicit its cardioprotective effects. Therefore, apelin’s action on KCC activity was examined in contractile and synthetic rat aortic vascular smooth muscle cells (VSMCs). Methods: KCC activity was measured by atomic absorption spectrophotometry in chloride (Cl-) and Cl--free medium with sulfamate (Sf-) as Cl- replacement, and with rubidium (Rb+) as a potassium (K+) congener. The calculated difference between Rb+ transport in the presence of chloride (Cl-) and sulfamate (Sf-) is the Cl--dependent Rb+ influx (i.e., K-Cl cotransport activity). Apelin-13 (1 µM) was added either during flux (acute effect) and/or in the growth media (chronic effect) based on the experimental goals. KCC activity was characterized with respect to the VSMC phenotypes, in the presence or absence of apelin and corresponding inhibitors of the signaling pathways, oxLDL, and as a function of various physiological factors described below. Results: The APJ receptor was expressed in both contractile and synthetic VSMC phenotypes, the former also possessing the soluble guanylyl cyclase-coupled protein kinase G (PKG) receptor, critical for NO-mediated signaling. In general, KCC activity was higher in synthetic vs. contractile VSMCs, consistent with enhanced migration and proliferation in the former. In addition, apelin-mediated activation of KCC was modulated by extracellular sodium [Na+]o, osmolality, length of apelin treatment (acute or chronic) and VSMC phenotype (contractile vs synthetic). Based on selective inhibitors, apelin activated KCC through the (NO)/soluble guanylate cyclase (sGC)/protein kinase G (PKG) (NO/sGC/PKG)-, PI3K/Akt- and MAPK-dependent pathway(s). Furthermore, apelin rescued the inhibition of KCC by oxLDL. Altogether, results suggest apelin/APJ as an important modulator of KCC activity to sustain cell volume regulation and cardiovascular function. More recently, the apelinergic system has been proposed as a novel target for the treatment of Corona virus disease 2019 (COVID-19) and, given the significant overlap between the regulatory mechanisms of this system and KCC, and their role in cardiovascular disease (CVD), this study opens new avenues to identify potential targets for diverse implementation strategies. Conclusion: A better understanding of apelin effects on KCC will help design a novel therapeutic approach to treat atherosclerosis-linked cardiovascular diseases, including COVID-19-associated mortality.