The authors argue that despite significant numbers of foreign workers present in the Russian labor market Russia remains unattractive for highly skilled foreign workers. The economic crisis the country has faced since 2014 has resulted in a further outflow of foreign nationals from OECD countries. So Russia has to look for employees among newcomers from the former Soviet states, the majority of whom come from Central Asia. Russian politics with regard to immigration is characterized by the collision between “geopolitical” and domestic policy rationales. On one hand, seeking to maximize its influence in the post-Soviet space Russia provides preferential conditions of employment for citizens of partner countries in the framework of the Eurasian Economic Union. On the other hand, the Kremlin is afraid to liberalize its approach to immigration and the integration of immigrants through fear of losing popularity among the electorate. The second substantial feature of Russian immigration politics is an extreme level of securitization of migration issues. The government considers these issues primarily through a policing lens. One cannot claim that the Russian state does not take any steps to liberalize “migratory regulation”; however, the effect of these measures is being vastly reduced by new restrictions. In addition, liberally designed laws do not bring the expected results due to the corrupt practices that pervade the whole of migration regulation.

Objectives: Female genital mutilation (FGM) is a significant public health problem. It is estimated around 14,700 women affected by FGM live in Switzerland, primarily among women with a history of migration. Our qualitative research investigated the sexual health of immigrant women living with FGM in Switzerland, describing their own perception of health, reproductive life and sexuality. Methods: We conducted semi-structured, in-depth interviews with a group of eight immigrant women of African origin living in Switzerland with Type III FGM (infibulation). Results: Seven of the women were from Somalia and one from Ivory Coast. All of the Somali women were mothers and married (two separated), and the Ivorian woman was a single mother. The women in our study reported a low level of sexual satisfaction and reproductive health. They affirmed their desire to improve, or at least change, their condition. Although they rarely talk with their husbands about sexual subject matter, they would like to include them more and improve dialogue. Conclusions: Specific socio-sexual management is recommended when caring for immigrant women living with FGM in order to respond to their specific health care needs. Multidisciplinary approaches may be able to offer more comprehensive health care, including facilitated communication to improve dialogue between women and health care professionals, and eventually between women and their husbands in discussing sexual matter.

Migrations are much more important than currently recognised, for explaining important patterns observed in the European archaeology record – according to this archaeology led model. At a high level, they explain the introduction of different farming, monument building, the spread of metalworking and patterns of trade and exchange. This paper presents an archaeogenetic model based on a strategic review of the Neolithic and Chalcolithic archaeology of Europe, alongside a review of recently published ancient DNA data. The model is archaeology led. It takes archaeology themes and proposes migratory events to explain them. Ancient DNA data and further archaeology evidence is then used to test these proposed migrations- to reject or refine them. The model introduces a new and more strategic way of looking at archaeological cultures - that updates early 20th century approaches to studying archaeology cultures, and integrates with the detailed ‘post processual’ studies of the late 20th Century. The model consists of seven maps – each showing multiple migration events – with key evidence to support each migration map. It proposes a new category of a ‘Black Sea’ related population that makes a major genetic contribution to the Middle Neolithic of Europe. The proposed migrations provide an explanation for the observed patterns of archaeology, for example: • multiple Neolithic migrations that introduced, farming and metalworking into Europe; • a major ‘Black Sea’ related ‘Middle Neolithic’ migration that carried advanced knowledge of astronomy that can be recognised in a variety of types of monument from the Neolithic through to Bronze Age Europe; and, • migrations of related cultures (‘supercultures’) that explain patterns of trade and exchange in Bronze Age western Europe. The model also provides ancient DNA and archaeology based support for the key aspects of Childe’s ‘dawn of civilisation’ in Europe and Egypt and Gimbutas’ ‘Old Europe’ and “three waves of migration from the Steppe”.

TTF1-NP(5,2′,4′-trihydroxy-6,7,5′-trimethoxyflavone nanoparticles), derived from the traditional Changbai Mountain medicinal plant Sorbaria sorbifolia (SS), has been showedits anti-cancer effect in various liver cancer cell types and tissues. The present study was designed to evaluate the antitumor mechanism of the TTF1-NP against HepG2 hepatoma cells and HepG2 cells-induced hepatocarcinoma (HCC) in nude mouse model. Here we demonstrated that TTF1-NP inhibits tube formation of HUVECs and HepG2 cell migration and invasion, and inhibits tumor growth in nude mice implanted with HepG2 cells through the downregulation of STAT3 protein and activation, along with VEGF, KDR, bFGF, MMP2 and MMP9 levels. We further revealed that TTF1-NP decreased the DNA-binding capacity of STAT3. Together our results provide a mechanism by which TTF1-NP suppresses cancer cell migration, invasion and angiogenesis through the action of STAT3 and suggests TTF1-NP as a potential therapy for hepatocellular cancer treatment.

The Evolutionary history and domestication of Camels are largely unexplored because of the lack of well dated early archaeological records. However, limited records suggest that domestication of Camels likely happened in the late second millennium BCE. Over the time, camels have helped human for their basic needs like meat, milk, wool, dung to long routes transportation. This multifaceted animal has helped the mankind to connect through continents and in trade majorly through the Silk route. In India, both dromedary and Bactrian camels are found and their habitat is entirely different from each other, dromedaries inhabit in hot deserts and Bactrians are found mostly in cold places (Nubra Valley, Ladakh). Fewer studies on Indian dromedaries have been conducted but no such studies are done on Bactrian camels. It is needed to study the genetics of Bactrian camels to find out their genetic affinity and evolutionary history with other Bactrians found in different parts of the world. Furthermore, parallel studies on humans and Bactrian camel are required to understand the co-evolution and migration pattern of humans during their dispersal in different time periods.

Sinulariolide, a natural product extracted from cultured-type soft coral Sinularia flexibilis, possesses bioactivity against the movement of several types of cancer cell. However, the molecular pathway of its effects on human bladder cancer remain poorly understood. Using a human bladder cancer cell line as an in vitro model, this study investigated the underlying mechanism of sinulariolide against cell migration/invasion in TSGH-8301 cells. We found that sinulariolide inhibited TSGH-8301 cell migration/invasion, and the effect was concentration-dependent. Furthermore, the protein expressions of matrix metalloproteinases (MMPs) MMP-2 and MMP-9, as well as urokinase, were significantly decreased after 24-h sinulariolide treatment. Meanwhile, the increased expressions of tissue inhibitors of metalloproteinases (TIMPs) TIMP-1 and TIMP-2 were in parallel with an increased concentration of sinulariolide. Finally, the expressions of several key phosphorylated proteins in the mTOR signaling pathway were also downregulated by sinulariolide treatment. Our results demonstrated that sinulariolide has significant effects against TSGH-8301 cell migration/invasion, and its effects were associated with decreased levels of MMP-2/-9 and urokinase expression, as well as increased TIMP-1/TIMP-2 expression. The inhibitory effects were mediated by reducing phosphorylation proteins of the PI3K, AKT and mTOR signaling pathway. The findings suggested that sinulariolide is a good candidate for advanced investigation with the aim of developing a new drug for the treatment of human bladder cancer.

Hepatocellular Carcinoma is one of the most predominant malignancies with high fatality rate and is rising at an alarming rate because it is quite resistant to radioand chemotherapy. The proliferation, migration and activation of endothelial cells are involved in tumor occurrence and development. Indirubin is the major active anti-tumor ingredient of a traditional Chinese herbal medicine. In this research, Td-ECs were derived from human umbilical vein endothelial cells (HUVECs) by treating HUVECs with the conditioned medium of human liver cancer cell line HepG2. The effects of indirubin on cell proliferation, migration, invasion and angiogenesis of Td-ECs were assessed. Indirubin significantly inhibited Td-EC cell proliferation in a dose- and time-dependent manner. Indirubin also inhibited Td-EC migration and angiogenesis. However, indirubin’s effects on HUVECs were weaker than on Td-ECs.

Enamel matrix derivative (EMD) is used for periodontal tissue regeneration therapy, and can induce mineralization in dental pulp cells (DPCs). We designed a synthetic peptide (SP) derived from the response of cells to EMD, and investigated the effect of the SP on potentiating osteogenesis in DPCs, which have a critical role of dental pulp homeostasis. DPCs were treated with 0, 10, 100, or 1000 ng/mL SP to determine its effect on cell proliferation, cell migration, cell differentiation, and mineralization. We then examined the molecular effects of the SP, focusing on changes in the mitogen-activated protein kinases (MAPK) signaling pathway in these cells. The SP significantly promoted DPC proliferation and migration. Cultures treated with the SP also showed an enhanced expression of markers of osteogenic differentiation and mineralization. The SP also induced the activation of MAPK signaling pathway components. These results suggest that our SP could promote the dental pulp tissue repair by hard tissue formation and the mineralization through activating MAPK signaling pathway. This study provides the first evidence that SP might be a new material for dental pulp tissue treatment.

Monarch butterflies are a species of conservation priority due to declining overwintering populations in both eastern and western North America. Declines in western overwintering monarchs—more than 99% since monitoring began—are especially acute. However, the degree to which the western monarch is a distinct biological entity is uncertain. In this review, we focus on phenotypic and genetic differentiation between eastern and western monarchs, with the goal of informing researchers and policy-makers who are interested in monarch conservation. Eastern and western monarchs occupy distinct environments and show some evidence for phenotypic differentiation—particularly for migration-associated traits—though population genetic and genomic studies suggest that they are genetically indistinguishable from one another. We suggest future studies that could improve our understanding of differences between eastern and western monarchs. We also discuss the concept of adaptive capacity in eastern and western monarchs as well as non-migratory populations outside of the monarch’s primary North American range.

Purpose: To investigate the effect of pigment dispersion on trabecular meshwork (TM) cells. Methods: Porcine TM cells from ab interno trabeculectomy specimens were exposed to pigment dispersion, then analyzed for changes in morphology, immunostaining, and ultrastructure. Their abilities to phagocytose, migrate, and contract were quantified. An expression microarray, using 23,937 probes, and a pathway analysis were performed. Results: TM cells readily phagocytosed pigment granules. Pigment induced stress fiber formation (pigment (P): 60.1 ± 0.3%, n = 10, control (C): 38.4 ± 2.5%, n = 11, P < 0.001) and contraction at 24 hours onward (P < 0.01). Phagocytosis declined (P: 68.7 ± 1.3%, C: 37.0 ± 1.1%, n = 3, P < 0.001) and migration was reduced after 6 hours (P: 28.0.1 ± 2.3, n = 12, C: 40.6 ± 3.3, n = 13, P < 0.01). Microarray analysis revealed that Rho, IGF-1, and TGFβ signaling cascades were central to these responses. Conclusions: TM cell exposure to pigment dispersion resulted in reduced phagocytosis and migration, as well as increased stress fiber formation and cell contraction. The Rho signaling pathway played a central and early role, suggesting that its inhibitors could be used as a specific intervention in treatment of pigmentary glaucoma.

Epithelial-mesenchymal transition (EMT) is a cellular biological process involved in migration of primary cancer cells to secondary sites facilitating metastasis. Besides, EMT also confers properties such as stemness, drug resistance and immune evasion which can aid a successful colonization at the distant site. EMT is not a binary process; recent evidence suggests that cells in partial EMT or hybrid E/M phenotype(s) can have enhanced stemness and drug resistance as compared to those undergoing a complete EMT. Moreover, partial EMT enables collective migration of cells as clusters of circulating tumor cells or emboli, further endorsing that cells in hybrid E/M phenotypes may be the ‘fittest’ for metastasis. Here, we review mechanisms and implications of hybrid E/M phenotypes, including their reported association with hypoxia. Hypoxia-driven activation of HIF-1α can drive EMT. In addition, cyclic hypoxia, as compared to acute or chronic hypoxia, shows the highest levels of active HIF-1α and can augment cancer aggressiveness to a greater extent, including enriching for a partial EMT phenotype. We also discuss how metastasis is influenced by hypoxia, partial EMT and collective cell migration, and call for a better understanding of interconnections among these mechanisms. We discuss the known regulators of hypoxia, hybrid EMT and collective cell migration and highlight the gaps which needs to be filled for connecting these three axes which will increase our understanding of dynamics of metastasis and help control it more effectively.

: Annona squamosa L. is an important medicinal plant used in traditional medicine for the treatment of various diseases. Different parts of A. squamosa L. have various therapeutic effects; however, the anticancer activity of the leaves has not yet been identified. In vitro, MTT, nuclear staining, and LDH assays were used to evaluate cell survival and proliferation in cells exposed to the extracts. The effect of the extracts on cell migration was investigated using a monolayer wound repair assay, and the apoptotic effects were evaluated using flow cytometry. A breast cancer model was used to study the effect of the extract on the tumor size, and the expression of different proliferative and apoptotic markers was evaluated by immunohistochemical analysis. At a concentration of 100 µg/mL, A. squamosa leaf extracts exerted strong antiproliferative and cytotoxic effects against various cell lines. The extracts reduced wound closure and strongly induced apoptosis. In vivo study, rats were sacrificed 24 h after the last injection, and tumor size, as well as the expression of proliferative and apoptotic markers, were observed to be greatly affected by treatment with the extracts. Therefore, A. squamosa leaf extract may be developed as a potential novel drug to treat breast cancer in the future

Anthropogenic change is associated with population growth, land use change, and changing economies. However, internal migration patterns and armed conflicts are also key drivers behind anthropogenic and demographic processes. To better understand this sort of change, we explore the spatial relationship between forced migration due to armed conflict and changing demographic factors in Colombia, a country which has a recent history of 7 million internal migrants. In addition, we use remote sensing, Google Earth Engine, as well as spatial statistical analyses of demographic data in order to measure anthropogenic change between 1984 and 2008; and we look into spatiotemporal relationships between both demographic and anthropogenic changes, which are caused by forced migration. We find, thus, that the latter is significantly and positively related to an increasing rural-urban kind of migration which originates in armed conflict, and results show that it is also negatively associated with interregional expulsion. Indeed, anthropogenic prints (term hereafter used to denote changes in nighttime satellite imagery) pertaining to different regions have had different sensitivities towards forced migration, and across different time periods. Finally we discuss how social and political phenomena such as Colombia’s armed conflict can have significant effects on the dynamics and motions of humans and territories in countries of the Global South.

Self-assembling peptide P11-4 is amphiphilic and pH-triggered with demonstrated effectivity repairing early carious lesions in enamel. However, P11-4 effects on dentin biomineralization and repair remain unexplored. Thus, cytocompatibility and effectiveness of P11-4 inducing mineralization and migration of odontoblast-like cells (MDPC-23) were investigated. MDPC-23 were seeded in contact with P11-4(0.5µg/ml and 1µg/ml), Dentin Matrix Protein 1 (DMP1 0.5µg/ml and 1 µg/ml) or Calcium hydroxide (Ca(OH)2 100µg/ml) solutions. Cytotoxicity was verified using MTT (n=6/group). Mineralization was tested using Alizarin Red (n=4/group). Cell migration was assessed by light microscopy (n=2/group). MTT and Alizarin Red data were compared using Krus-kal-Wallis and Mann-Whitney (α=0.05). P11-4 (0.5µg/ml and 1µg/ml) and DMP1 (0.5µg/ml and 1µg/ml) presented the highest cytocompatibility; Ca(OH)2 presented the lowest. DMP1 1µg/ml exhibited the highest mineralization ability, with no difference to P11-4 1µg/ml. Ca(OH)2 presented lower values than DMP1 1µg/ml (p<0.05), but similar to P11-4 1µg/ml. P11-4 and DMP1 at 0.5 µg/ml showed induced less mineralization than P11-4 and DMP1 at 1µg/ml (p<0.05), with no difference to Ca(OH)2. All materials stimulated cell migration, however, lower concentrations of DMP1 and P11-4 provided better results. P11-4 is cytocompatible, induces mineralization and MDPC-23 migration like DMP1. P11-4 could be an alternative for dentin mineralization and tooth repair.

The worldwide number of migrants has had a rapid increase during the last fifteen years. Despite the extensive research studies that elucidate the increase in migrants' recipient countries, we know little about the relationship between the climate factors and human mobility in the countries of origin. Hence, this study focuses on the effects of weather and the propensity of individuals to leave a territory by measuring the importance of rain precipitation or the lack of it in one of the critical food corridors of Central America, formed by El Salvador, Honduras, and Guatemala. To study the mobility process, we develop a stochastic frontier model; the main result shows a greater propensity to migrate when there is a significant drought event in the place of origin. Some other factors that motivate people to leave their homeland are the effect of other climate events measured through the control system (ENSO), homicide levels, economic performance, and exchange rate. The findings allow differentiating between drought and excess precipitation on a population and mobility to other territories. In addition, these results permit us to derive observable implications of the different effects of flooding and drought and create public policies of prevention, mitigation, and resilience.

Dispersal represents a key life-history trait with several implications for the fitness of organisms, population dynamics and resilience, local adaptation, meta-population dynamics, range shifting and biological invasions. Plastic and evolutionary changes of dispersal traits have been intensively studied over the past decades in entomology, in particular in wing-dimorphic insects for which literature reviews are available. Importantly, dispersal polymorphism also exists in wing-monomorphic and wingless insects, and except for butterflies, fewer syntheses are available. In this perspective, by integrating the very last research in the fast moving field of insect dispersal ecology, this review article provides an overview of our current knowledge of dispersal polymorphism in insects. After having provided a definition of the main terms characterising insects’ movements, some of the most often used experimental methodologies for the separation of dispersers and residents in wing-monomorphic and wingless insects are presented. The existing knowledge on the morphological and life-history trait differences between resident and disperser phenotypes is then synthetized. The fourth part examines the effects of range expansion on dispersal traits and performance, in particular for insects from range edges and invasion fronts. Finally, some research perspectives are proposed in the last part of the review.

The Epithelial- Mesenchymal Transition (EMT) is a biological phenomenon associated with explicit phenotypic and molecular changes in cellular traits. Unlike the earlier-held popular belief of it being a binary process, EMT is now thought of as a landscape including diverse hybrid E/M phenotypes manifested by varying degrees of the transition. These hybrid cells can co-express both epithelial and mesenchymal markers and/or functional traits, and can possess the property of collective cell migration, enhanced tumor-initiating ability, and immune/targeted therapy-evasive features, all of which are often associated with worse patient outcomes. These characteristics of the hybrid E/M cells have led to a surge in studies that map their biophysical and biochemical hallmarks that can be helpful in exploiting their therapeutic vulnerabilities. This review discusses recent advances made in investigating hybrid E/M phenotype(s) from diverse biophysical and biochemical aspects by integrating live cell-imaging, cellular morphology quantification and mathematical modeling, and highlights a set of questions that remain unanswered about the dynamics of hybrid E/M states.

Many cellular functions important for tumor initiation and progression are mediated by members of the integrin family, a diverse family of cell adhesion receptors. With recent studies emphasising on the role of the tumor microenvironment (TME) in tumor initiation and progression, it is not surprising that a lot of attention is being given to integrins. Several integrins are under trial with many demonstrating appealing activity in patients with different cancers. A deeper knowledge of the functions of integrins within the tumor microenvironment is still required, and might lead to better inhibitors being discovered. Integrin expression is commonly dysregulated in many tumors with integrins playing key roles in signaling as well as promotion of tumor cell invasion and migration. This review report new data on the differential expression of integrins within solid tumors using two publicly available resources: The Cancer Genomic Atlas (TCGA) and Gene Expression Profiling Interactive Analysis (GEPIA). In this analysis, I investigated the expression of integrin alpha 2 (ITGα2), ITGα3, ITGβ4 and ITGβ6 in tumor tissues versus adjacent normal tissues. This analysis showed that integrins were differentially expressed in cervical squamous cell carcinoma (CESC), head and neck squamous cell carcinoma (HNSC), esophageal carcinoma (ESCA) and lung adenocarcinoma (LUAD). This analysis showed that ITGα2 and ITGβ6 expression are upregulated in CESC and ESCA, ITGα3 is upregulated in HNSC and ESCA whilst ITGβ4 is highly expressed in CESC, HNSC, ESCA and LUAD tumor tissues compared to adjacent normal tissues. Integrins also play a major role in adhesion of circulating tumor cells to new sites and the resulting formation of secondary tumors. Furthermore, integrins have demonstrated the ability to promoting stem cell-like properties in tumor cells as well as drug resistance. Anti-integrin therapies rely heavily on the doses or concentrations used as these determine whether the drugs act as antagonists or as integrin agonists. This review offers the latest synthesis in terms of current knowledge of integrins functions within the tumor microenvironment and potential targets for different cancers.

Background: Mental health is a growing concern worldwide. It is not well understood whether Nepali workers, including international labour migrants from Nepal, are at higher risk of developing mental health problems. The purpose of our study is to determine the prevalence of and examine the risks factors for depression among returnee migrants and non-migrant working male adults in Nepal. Methods: A cross-sectional survey of a probability-based sample of 725 participants was conducted in February 2020. The sample was comprised of two groups based on migration status: returning migrants and non-migrants. Logistic regression was applied to investigate factors associated with symptoms depression.Results: The overall prevalence of depression was 10.1%. However, the prevalence of depression was lower (7%) among returnee migrants compared to non-migrants (13.7%). Participants in the lower income group were more at risk of depression (OR=5.38, 95% CI: 1.96-14.78) than those in the higher income group. Similarly, Buddhists and Christians were more likely to be depressed (OR=2.17, 95% CI: 1.02-4.64) than Hindus. Interestingly, participants having more than two children had a higher prevalence of depression (OR=5.14, 95% CI: 1.22-21.63) compared with those having no children. Unmarried participants were more likely to be depressed (OR=4.05, 95%, CI:1.10-14.93) than those who were married. Conclusion: The working Nepali adult male population in Nepal, including returning migrants, is at risk of depression, but this risk is lower in those in the higher income group, returnee migrants, married, Hindus and those with no children. This study highlights the need to monitor and develop national policies to ensure the mental health of Nepali male adult population, including returnee migrants.

Health of migrant is a widely studied topic. It has been argued that migrant health may deteriorate over time. Though migrants are ‘a hard to reach’ population in survey data, this paper builds on a unique dataset provided by Médecins du Monde from five countries. We study self perceived health (SPH) in connection with socio-economic and demographic factors and length of stay. Results show different results for men and women. Asylum seekers compared to other documented migrants have a worse health. Migrants with better living conditions tend to be in better health. Employment and stable accommodation has a positive effect on SPH. Women from poorer countries have a better physical SPH after 3 months of residing in the host country. This paper contributes widely to knowledge of health of migrants. Contrarily to other evidence, health of migrants tends to improve for some migrants.

The active layer thickness (ALT) is affected by local soil material and surface vegetation coverage in Tibetan plateau permafrost region. The human activities and engineering construction along the Qinghai-Tibet Highway (QTH) destroyed the surface vegetation coverage, which have seriously influenced the ALT and heat exchange balance. Meanwhile, the changes of the detailed internal structure in the active layer will affect the stability of engineering infrastructure. Ground-penetrating radar (GPR) was used to detect the ALT in the permafrost region. However, researches on the detailed structure of the active layer and spatial variation information of ALT are rare, the main reason given for this is that the lack of advanced imaging techniques to enhance the GPR images. In this paper, the researchers focus on solving this problem by applying the reverse time migration (RTM) method to GPR field data acquired in the Beiluhe region. Analyses of the results led to conclusions as follows: a) The RTM algorithm is proved to be accurate for imaging the characteristics of the active layer through the dielectric constant model obtained by common midpoint and GPR data velocity analysis. b) The result of RTM profiles show the loose structure and graben-like fine internal structure. Combining with drill data and soil materials information, the researchers deduce the graben-like structure might be coarse gravel layer, which may be related to subgrade settlements in some local area. c) The 2D contour maps not only show the spatial variation feature of ALT at two sides of the highway, but also can compensate the defect of the research for single 2D survey line. The ALT is about 0.6~0.8 m in most areas, and about 0.8~0.9 m near the highway at west side of the QTH on the 2D contour maps. From the RTM interpretation profile, the closer to the plash, the deeper thawed active layer. The detailed internal structure of the active layer and 2D contour maps of ALT have great significance for the study of fine internal structure and the characteristic of ALT spatial variation in the Tibetan plateau under the background of climatic change.

Parkinson’s disease (PD) is a slowly progressing neurodegenerative disorder that is coupled to both widespread protein aggregation and to loss of substantia nigra dopamine (DA) neurons, resulting in a wide variety of motor and non-motor signs and symptoms. Recent findings suggest that the PD process is triggered several years before there is sufficient degeneration of DA neurons to cause onset of overt motor symptoms. According to this concept, the number of DA neurons present in the substantia nigra at birth could influence the time from the molecular triggering event until the clinical diagnosis with lower number of neurons at birth increasing the risk to develop the disease. Conversely, the risk for diagnosis would be reduced if the number of DA neurons is high at birth. In this commentary, we discuss the genetic and epigenetic factors that might influence the number of nigral DA neurons that each individual is born with and how these may be linked to PD risk.

Angiogenesis, the sprout and growth of new blood vessels from existing vasculature, is an important process of tumor development for the supply of oxygen and nutrition to cancer cells. Endothelial cell is a critical player in angiogenic process by modulating cell proliferation, cell motility, and cell morphology in the response to pro-angiogenic factors and environments provided by tumor and cancer cells. Recent in vivo and in vitro studies have revealed that gap junction of endothelial cells also participates in the promotion of angiogenesis. Pro-angiogenic factors modulate gap junction function and connexins expression in endothelial cells, whereas endothelial connexins involve in angiogenic tube formation and cell migration of endothelial cells via both gap junction channel function dependent or independent mechanisms. In particular, connexin might have the potential to regulate cell mechanics such as cell morphology, cell migration, and cellular stiffness that are dynamically changed during angiogenic processes. Here, we review the implication for endothelial gap junction and cellular mechanics in vascular angiogenesis.

Investigation into geological storage of CO2 is underway at the Technology Development Plant (TDP) at Hontomín (Burgos, Spain), the only current onshore injection site in the European Union. The storage reservoir is a deep saline aquifer located within Low Jurassic Formations (Lias and Dogger), formed by fractured carbonates with low matrix permeability. Understanding the processes involved in CO2 migration within this kind of low-primary permeability carbonates influenced by fractures and faults is key to ensure safe operation and reliable plume prediction. During the hydraulic characterization tests, 2300 tons of liquid CO2 and 14000 m3 of synthetic brine were co-injected on site in various sequences to characterize the pressure response of the seal-storage pair [de Dios et al, 2017] The injection tests were analyzed with a compositional dual media model which accounts for both temperature effects (as the CO2 is liquid at the bottom of the wellbore) and multiphase flow hysteresis (to effectively simulate the alternating brine and CO2 injection tests that were performed). The pressure and temperature responses of the storage formation were history-matched mainly through the petrophysical characteristics of the fracture network [Le Gallo et al, 2017]. The dynamic characterization of the fracture network dominates the CO2 migration while the matrix does not appear to significantly contribute to the storage capacity. This initial modeling approach was improved using the characterization workflow developed within the European FP7 CO2ReMove project for sandstone fractured reservoirs [Ringrose et al., 2011; Deflandre et al., 2011]. Fractured reservoirs are challenging to handle because of their high level of heterogeneity that conditions the reservoir behaviour during the injection. In particular, natural fractures have a significant impact on well performance [Ray et al, 2012]. Furthermore, the understanding of the processes involved in CO2 migration within relatively low-permeability storage influenced by fractures and faults is essential for enabling safe storage operation [Iding and Ringrose, 2010]. As part of the European H2020 ENOS project, the site geological model is updated by integration of the recently acquired data such as the image log interpretations from injection and observation wells. The geological model is generated through the analysis and integration of data including borehole images and well test data. Following a methodology developed for naturally fractured hydrocarbon reservoirs [Ray et al., 2012], the image log analysis identified two sets of diffuse fractures. A Discrete Fracture Network [Bourbiaux et al., 2005] was built around both wells which encompass the caprock, storage and underburden formations. The fracture characteristics of the two sets of diffuse fractures, such as orientations, densities and conductivities, are calibrated upon the interpretation of the injection tests [Le Gallo et al, 2017]. For each facies, the DFN characteristics were then upscaled and propagated to the full-field reservoir simulation model as 3D fracture properties (fracture porosity, fracture permeability and equivalent block size).

Bone marrow derived adult human mesenchymal stem cells (hMSCs) possess therapeutic qualities that enable them to enhance wound repair. However, the mechanisms by which this occurs remains poorly understood. Basic mechanisms may include the directed migration of delivered cells to target sites and/or the production and release of soluble factors that act at a distance. Allogeneic and even xenogeneic cells may effectively participate in wound repair. Labeled hMSCs were delivered to full-thickness skin wounds that were created in immunologically competent mice. The delivery occurred on day 3 post-wounding using two different carriers; one which released cells and one which retained cells. The fates of the delivered cells were tracked for up to 25 days. During this period, released cells migrated as a tight cohort deep into the wound to reach the subdermal vascular plexus. Simultaneously, enhanced formation of granulation tissue was evident. This migration of hMSCs was not essential in that enhanced granulation tissue formation and wound contraction occurred when cells were retained in the carrier matrix. This provided further evidence for the release of therapeutic factors by hMSCs to sites of injury.

A recent study from our lab revealed that inhibition of cyclooxygenase-2 exclusively reduces the level of PGE2 amongst the prostanoids and hamper the normal development of several structures, strikingly the cranial vault, in chick embryos. In order to unearth the mechanism behind the deviant development of cranial features, the expression pattern of various factors that are known to influence the cranial neural crest cell (CNCC) migration were checked in chick embryo after inhibiting the COX-2 activity using etoricoxib. The compromised level of cell adhesion molecules and their upstream regulators, namely CDH1, CDH2, MSX1, and TGF-β, observed in the etoricoxib treated embryos indicate that COX-2, through its downstream effector PGE2, regulates the expression of these factors perhaps to aid the migration of CNCC. The histological features and levels of FoxD3 as well as PCNA further consolidates the role of COX-2 in migration and survival of CNCC in developing embryo. The results of the current study indicate that the COX-2 plays a pivotal role in orchestrating the proliferation and migration of CNCC during embryonic development of chick.

The assessment of caprock integrity for underground storage of CO2 and/or enhanced oil recovery (EOR) systems is a multiscale endeavor. Caprock sealing behavior depends on coupled processes that operate over a broad range of length and time scales including nanoscale heterogeneity in capillary and wettability properties to depositional heterogeneity that is basin wide. Larger-scale sedimentary architecture, fractures, and faults can govern properties of potential “seal-bypass” systems that may be difficult to assess. We present a multiscale investigation of geologic sealing integrity of the caprock system that overlies the Morrow B sandstone reservoir, Farnsworth Unit, Texas, USA. The Morrow B sandstone is the target geologic unit for an on-going combined CO2 storage–EOR project by the Southwest Regional Partnership on Carbon Sequestration (SWP). Methods and/or data encompass small-to-large scales, including: petrography using electron and optical microscopy; mercury porosimetry; core examinations of sedimentary architecture and fractures; well logs; a suite of geomechanical testing; and a noble gas profile through sealing lithologies into the reservoir, as preserved from fresh core. The combined data set allows a comprehensive examination of sealing quality by scale, by primary features that control sealing behavior, and an assessment of sealing behavior over geologic time.

Historical legacy of Eastern European and Balkans’ health systems was mutually interdependent and shaped by local socioeconomic circumstances. Three distinctive systems of risk sharing and health financing to develop since the late XIX century were the Bismarck, Beveridge, and Semashko systems. Modern day healthcare systems in these countries are challenged by population ageing, accelerated innovation in medical technology, growing purchasing power and rising demand for healthcare services. Supply side changes contribute to demand side efficiency bottlenecks in financing, driving the costs of the already expensive medical care up. All of the nations have a large share of citizens experiencing difficulty with affordability and access to medical care, particularly in rural and remote areas. Network of Health technology assessment agencies have mushroomed over the past three decades. Principles of health economics theory and cost-effective resource allocation are slowly gaining ground in governing authorities’ mindset and decision-making process. For many years to come, pharmaceuticals and medical services will remain dependent on out-of-pocket spending. Currently accelerating and spreading 4.0 Industrial Revolution, together with the Belt and Road Initiative, are likely to substantially impact the further economic development of this vast region. Post-Pandemic ‘Green’ Recovery strategies adopted by many of the Eastern European governments shall also make this transition towards sustainable development more difficult and challenging given the large dependency of all these economies upon traditional carbon fuels.

Individual users' payment behaviors have changed. The diffusion of mobile devices makes people suitable for proximity mobile payment (PMP) services without the need for traditional payment. Existing mobile payment literature mainly focuses on users' adoption and continuous usage behavior, nevertheless, switching behavior on payment received little attention, especially focusing on why users switch from traditional payment to PMP. Thus, the objective of the current research is to investigate factors influencing users’ traditional payment - PMP switching to comprehend how these factors shape users’ switching intentions. We developed a traditional payment - PMP transition model based on the push-pull-mooring framework derived from migration theory. This research adopted a structural equation modeling analysis on 311 valid data. The findings indicate that a push factor drives users away from traditional payment in terms of dissatisfaction. The pull factors, including perceived substitutability and perceived usefulness, attract users to PMP. Furthermore, in terms of perceived technical compatibility, a positive mooring factor facilitates users' switching to PMP. The negative mooring factor, in terms of perceived risk, hinder users' switching intention. However, another pull factor - perceived ease of use, failed to influence switching intention significantly. This study found some distinctions between mobile payment switching and mobile payment adoption. These findings provide pivotal insights for mobile payment service providers.

Objective: Pancreatic carcinoma (PANC) is one of the important aggressive cancers, with deficiency in effective therapeutics. Studies have unveiled that miR-139-5p expression is significantly downregulated in other types of cancers. However, the functions and mechanisms of miR-139-5p in PANC remain unclear. Methods: Bioinformatic analysis was performed to analyze the differentially expressed genes in the TCGA database. PANC cell line with overexpressed miR-139-5p and Solute Carrier Family 7, Member 11 (SLC7A11) was established, and has been used to detect cell proliferation, migration, invasion and colony formation in PANC. Subsequently, bioinformatic analysis and luciferase assay were performed to confirm that SLC7A11 was a target gene of miR-139-5p. Xenograft mouse model was used to investigate the role of miR-139-5p in PANC tumorigenicity. Results: Through bioinformatic analysis, miR-139-5p was predicted to regulate phosphatidylinositol signaling pathway by targeting SLC7A11. MiR-139-5p was found to be lowly expressed in PANC tissues, while SLC7A11 was highly expressed. Low expression of miR-139-5p and high expression of SLC7A11 were positively associated with poor clinical outcomes. PANC cell proliferation, migration, and invasion could be inhibited by miR-139-5p overexpression and could be promoted by SLC7A11 overexpression. MiR-139-5p could regulate the protein expression level of PI3K and Akt associated with phosphatidylinositol signaling pathway could be by inhibiting the expression of SLC7A11. MiR-139-5p overexpression could suppress PANC tumor growth and the expression of SLC7A11, p-PI3K, p-Akt in tumor tissues. Therefore, the inhibiting effect of miR-139-5p to PANC cell proliferation, invasion and migration, at least, was partly due to its inhibiting effect on SLC7A11 expression. Conclusion: These results demonstrated a novel role of miR-139-5p/SLC7A11 in PANC and provided potential prognostic predictors for PANC patients.

Although the migration of hepatic stellate cells (HSCs) is important for hepatic fibrosis, the regulation of HSC migration is poorly understood. Interestingly, transforming growth factor (TGF)-β1 induces monocyte migration to sites of injury or inflammation in the early phase but inhibits cell migration in the late phase. In this study, we investigated the role of RhoA signaling in TGF-β1-induced HSC migration. We found that TGF-β1 increased the protein and mRNA levels of α-SMA and collagen type I in HSC-T6 cells. The level of RhoA-GTP in TGF-β1-stimulated cells was significantly higher than that in control cells. Moreover, cofilin phosphorylation and F-actin formation was more strongly detected in TGF-β1-stimulated cells than in control cells. Additionally, TGF-β1 induced the activation of NF-κB and the expression of extracellular matrix proteins and several cytokines in HSC-T6 cells. The active form of Rap1 (Rap1 V12) suppressed RhoA-GTP levels, whereas the dominant negative form of Rap1 (Rap1 N17) augmented RhoA-GTP levels. Therefore, we confirmed that Rap1 regulates RhoA activation in TGF-β1-stimulated HSC-T6 cells. These findings suggest that TGF-β1 regulates Rap1, resulting in RhoA suppression, NF-κB activation and F-actin formation during the migration of HSCs.

Urbanization is a global phenomenon and as the economies are shifting from rural based subsistence to services based, the net flow of migration is inevitable. Unfortunately, In India, migration is very poorly understood. India is next to China in production of bricks, accounting for nearly 13% of global annual bricks’ production. The condition of brick-kiln workers is pitiable, especially due to poor care available. They are exposed to health hazards such as various communicable diseases, sexually transmitted diseases and occupational health hazards. The diseases such as respiratory problems, allergies, gastrointestinal ailments and malnutrition are frequent in these populations. This paper reflects upon various policies that exist for the welfare of unorganised sector but do these workers qualify for these benefits? This paper provides empirical basis for paradigm shift for policy formulation to provide safety nets for migrant population and have better urban planning for future.

Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from Olea europaea. Anticancer effect of uvaol, a natural triterpene, has been scarcely studied. The aim of this study was to understand the anticancer mechanism of uvaol in HepG2 cell line. Cytotoxicity results showed a selectivity effect of uvaol with higher influence in HepG2 than WRL68 cells used as control. Uvaol presented anti-migratory capacity in HepG2, supported by the morphological changes and higher HSP-60 expression. This compound also induced arrest in G0/G1 phase and an increase in apoptosis rate. These results are supported by decreased Bcl-2 expression and down-regulation of AKT/PI3K signaling pathway. A reduction in reactive oxygen species levels in HepG2 cells was observed. Altogether, results showed anti-proliferative and pro-apoptotic effect of uvaol on hepatocellular carcinoma, constituting an interesting challenge in the development of new treatments against this type of cancer.

Extracellular vesicles (EVs) effectively suppress neuroinflammation and induce neuroprotective effects in different disease models. However, the mechanisms by which EVs regulate neuroinflammatory response of microglia remain largely unexplored. Here, we addressed this issue by testing the action of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on immortalized human microglial cells. We found that EVs induced a rapid increase in intracellular Ca2+ and promoted a significant ATP release in microglial after 20 min of treatment. Boyden chamber assays revealed that EVs promoted microglial migration by 20 %. Pharmacological inhibition of different subtypes of purinergic receptors demonstrated that EVs activated microglial migration preferentially through the P2X4R pathway. Proximity ligation and co-immunoprecipitation assays revealed that EVs promote association between milk fat globule-epidermal growth factor-factor VIII (MFG-E8) and P2X4 receptor proteins. Furthermore, pharmacological inhibition of αVβ3/αVβ5 integrin suppressed EV -induced cell migration and formation of lipid rafts in microglia. These results demonstrate that EVs promote microglial motility through P2X4 R/ MFG-E8 – dependent mechanisms. Our findings provide novel insights into the molecular mechanisms through which EVs target human microglia that may be exploited for the development of new therapeutic strategies targeting disease associated neuroinflammation.

Caribbean SIDS are among the most vulnerable to climate change which will have a disproportionate impact on local environments and economies. Whilst there is a growing literature on how Caribbean SIDS can adapt to become more resilient a question that has received little attention is with regard to migration as an unplanned response. It is recognised that events such as hurricanes and flooding can lead to internal relocation in the short term but societal responses to droughts through migration have not generally been investigated. This paper seeks to address this by considering the case of the island of Carriacou, part of the state of Grenada. Carriacou with its small population, limited land area and local economy, historically based on agriculture has had a high degree of migration. This is in part a response to limited economic opportunities. Environmental stress manifest through limited water availability, inappropriate land management and social conditions is likely to be exacerbated by climate change and variability. Resultant increases in the frequency and intensity of droughts, in the absence of proactive interventions, are likely to result in non-linear migration, both to Grenada itself and beyond.

This paper contains a concise overview of the deployment of scattered solar power plants in Poland, mainly from the perspective of their communication networks, and how the recent development of the Polish 4G networks has a very positive impact for the performance of the whole monitoring system (production control and video-surveillance), with a special emphasis on video-analytics, due to its higher bandwidth demand. All the information will be shown from the point of view of the solar photovoltaics developer I+D Energías, and therefore it constitutes a real user’s experience.

The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selective targeting and choosing the critical cancer surface biomarker are essential for targeted treatments to work. The folic acid receptor alpha (FRalpha) has gained popularity as a potential target in triple-negative breast cancer (TNBC). We have previously reported on a functionalized folic acid (FA)-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the essential features for efficient “smart” DDS. This biocompatible DDS self-assembles in a pH-dependent manner, providing stimuli-responsive, active targeting, extended-release of hydrophobic chemotherapeutic agents, and can effectively penetrate the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased spheroid volume, revealing a previously unknown mechanism of action. Upon further investigation, a size- and shape-dependent interaction FA-DABA-SMA with FR reduced the expression of p53, the product of the highly mutated TP53 gene, and additional oncogenic c-Myc and STAT3 proteins. Here, we investigated how this copolymer influences FR behavior and disrupting the receptor’s functions. Results indicate that FA-DABA-SMA increases FR expression levels in breast MDA MB-231 cancer cells and disrupting FR signaling by the reduction in HES1 and NOTCH1 protein expression levels. Also, FA-DABA-SMA induces apoptosis and further causes a change in the morphology of the MDA MB-231 cells, as well as significantly reduces their ability to migrate in a Scratch wound assay. Collectively, these findings provide a novel insight into the functionalized FA-DABA-SMA copolymer. The 350 kDa and 20 kDa copolymers actively target FRα to initialize internationalization. However, only the large size and sheet-shaped 350 kDa copolymers disrupt FRα signaling. The significance of these novel findings reveals the intracellular activity of the copolymer that is critically dependent on the size and structural shape. This report offers novel therapeutic insight into a dual mechanism of FA-DABA-SMA copolymer for its therapeutic potential for the treatment of cancer.

This paper draws on data from a representative city-wide household food security survey of Nairobi conducted in 2017 to examine the importance of food remitting to households in contemporary Nairobi. The next section of the paper provides an overview of urbanization and the rapid growth of Nairobi which has led to growing socio-economic inequality, precarious livelihoods for the majority, and growing food insecurity, as context for the more detailed empirical analysis of food security and food remittances that follows. It is followed by a description of the survey methodology and sections analyzing the differences between migrant and non-migrant households in Nairobi. Attention then turns to the phenomenon of food remitting, showing that over 50% of surveyed households in the city had received food remittances in the previous year. The paper then uses multivariate logistic regression to identify the relationship between Nairobi household characteristics and the probability of receiving food remittances from rural areas. The findings suggest that there are exceptions to the standard migration and poverty-driven explanatory model of the drivers of rural-urban food remitting and that greater attention should be paid to other motivations for maintaining rural-urban connectivity in Africa.

For its enthusiasts, the blockchain is an archivist's dream come true: an immutable historical record that is publicly accessible and immune from censorship. Proposals like Juried Protocol Galleries could enable bots to compute the provenance of digital artworks and their appearance in exhibitions and publications. Distributed file systems like IPFS claim to store creative works in a redundant, networked fashion outside the control of any single cloud provider. Projects designed to work with blockchains like Filecoin and Arweave propose a dedicated cryptocurrency as financial incentive to support the cost of governing and sustaining this "permaweb." As dreamy as this picture sounds, many of these promises depend on technologies that have yet to be sufficiently developed or adopted. Rather than forecast the future, we can separate the hype from the reality in the present day by examining a real-life example, namely the 2021 auction of Andy Warhol's digital art with NFTs. This essay will focus less on blockchain's general promise as a preservation medium and more on the particular case of the digital Warhols, which both in form and spirit would seem a perfect application of NFTs to preserve historically important works of digital art. Which promises of the crypto-dream of permanent access to digital heritage ring true for this case study, and which are overblown?

The implications of urban revitalization, gentrification, and residential migration have attracted widespread interest and ongoing debate among scholars across a range of disciplines. While a significant body of literature explores race and class interactions within urban gentrifying neighborhoods, few have examined the environments that await those displaced by this process. This study explores the social and political impact of urban gentrification and class stratification within the black community by examining responses of black middle class residents in Prince George’s County, MD to the growing in-migration of low-income and minority residents from Washington, DC. Drawing on data from the U.S. Census Bureau, a multi-neighborhood sample of ninety-five black middle class residents of Prince George’s County, and informal interviews with subject-area experts, this study explores how race and class shape residential decisions and their impact on residential mobility initiatives. Residents responded to a 26-item survey that covered demographic information, political and community engagement, and their attitudes and beliefs about the poor, changes in their community, and racial unity and responsibility. Findings from cross tabulations and binary logistic regression indicate that lower middle class residents are the most likely to resist in-migration by exiting their communities and/or voting against proposals to create affordable housing options. Core and upper middle class residents were the most likely to stay in their neighborhoods despite increases in low-income migration, to vote in support of policies to create affordable housing options and to believe their responsibility to poor blacks could include sharing residential space.

Currently, the design and construction of embankments of roads, railroads and hydraulic structures are based on regulatory documents developed 25-30 years ago. For the construction of granite massifs it is necessary to use sandy soils, the distribution of which in the Arctic zone of Siberia in the areas of construction is not more than 1.5%. In this case, the range of transport of sand in the alluvial area is 35 kilometers, in the rest of the area - an average of 60 kilometers. Large volumes of soil massifs require large amounts of transportation units, fuel consumption and are accompanied by large emissions of hydrocarbons into the atmosphere. Over the past 15 years, the authors have developed designs and technologies that significantly reduce the energy consumption during the construction of soil embankments. Combined structures are cages made of geosynthetic materials filled with unsuitable melted and frozen overmoistened clay and peaty soils. This allowed the use of soils within the construction sites and thereby reduce the range of transportation from 0.2 to 2.0 kilometers. As an example, when reducing the range of transportation from 25 km to 1 km, the energy consumption is reduced by a factor of 21. The use of geosynthetics made it possible to set the initial parameters of the water-heat regime control process, which increased the life cycle of the embankment from 2 to 5 times in comparison with traditional soil massifs and reduced the consumption of energy for repair and maintenance of linear transport structures. This article gives a theoretical substantiation of water-heat regime management, based on which new designs and technologies have been proposed and tested in Siberia in 2008-2013. The results of the tests confirm the theoretical research. Thus, the use of combined constructions of geosynthetics and inapplicable soils not only reduces the distance of transportation, but also reduces the volume of earthworks. It reduces the consumption of energy by 1.5-2 times.

The traditional bored pile technology has some arduous problems, such as the sediment at the pile tip, the mud skin along the pile shaft, and the stress release due to borehole construction. The post-grouted technology at the pile tip of bored pile has emerged because of demand. The grouting migration height (GMH) is of great significance to the strengthen and reinforcement of the pile foundation. This paper derives the calculation formula of the GMH based on the theory of the column hole expansion and Herschel-Bulkley model. The influence of relevant parameters on the GMH is discussed. Aiming at the problem of the grouting migration along the pile shaft in layered soils, the iterative calculation method of the GMH is proposed. The correctness of the GMH is verified by an engineering case, which can guide the engineering practice. The result shows that the GMH increases with the increase of the grouting pressure, the pile diameter and the thickness of the mud skin, and the grouting pressure is positively correlated with the GMH. The GMH decreases with the increase of the buried depth, the consistency coefficient and the rheological index. On this basis, the correctness of the GMH is verified by an engineering case.

We utilized all Spanish marriage records available at the municipality level from 2005-2007 to model spatial variations in intermarriage. We constructed a spatial regime zero inflated Poisson model and grouped-data probit model, with spatially lagged regressors, to predict the absolute and relative presence of intermarriage between Spaniards and migrants based on structural characteristics of the local marriage markets and their neighboring areas (i.e., relative group size, homogeneity of national origins, and sex ratio indicators). Our models do not assume collapsibility of the marriage market. Instead, they incorporate the local dimension of the marriage market and examine the association between intermarriage and structural variables at the spatial local level. The model also investigates intermarriage variation by size of place. The local characteristics of the marriage markets are robust indicators of both the absolute and relative importance of intermarriage, but their impact varies by size of municipality. The relative size of the migrant community positively impacts intermarriage. The homogeneity of the origins of migrants is negatively related to it. The impact of sex ratios in the migrant and native communities on intermarriage is not uniform across all municipalities and is not always related to more intermarriage.

This is a study of Political Economy on religion and migration management in the United States of America (USA). This paper offers a review of migrants-citizens relations in the USA, with attention to the pendulum effect, moving from integration policies (open doors and melting pot agenda) to official persecution (raids and deportations), with a high social opportunity cost. There has been a split between the State and civil society, causing civil disobedience and sanctuary network across the country. Also, it is paid attention to the American post-modern paradox, as a result of culture wars and identity politics that imply a violation of American constitutional principles (i.e. religious liberty, freedom of movement, to pursuit the happiness). Special attention is paid to the development of the Sanctuary Movement, as an ongoing example of the sociocultural upheaval bringing grassroots society into confrontation with powerful elites by promoting resistance and offering help to the needy, even if this results in sanctions. This movement was revitalized after the values crisis of 2008, but it has also been polarized between those who follow the traditional approach to socio-religious action in the form of peaceful civil disobedience, and those who follow the ideological anti-system and communitarian approach, which causes greater tension for the immigrants themselves

The nuclear factor-ĸB (NF-ĸB) transcriptional system is a major effector pathway involved in inflammatory responses. Previous studies found that a Gardenia decoction (GD) inhibited the expression of NF-κB in a lipopolysaccharide (LPS)-stimulated mouse intestinal injury model. Herein, we hypothesized that geniposide (GE), a component of Gardenia jasminoides Ellis, also exerts anti-inflammatory effects and inhibits NF-ĸB activity in LPS-induced intestinal epithelial cells (IEC-6). IEC-6 cells were stimulated with LPS, following which the effects of GE on NF-ĸB signaling in the IEC-6 cells were examined by western blotting to detect IĸB phosphorylation/degradation. The expression of NF-κB was determined by immunofluorescence assay (IFA). Enzyme-linked immunosorbent assay (ELISA) was used to detect the inhibitory effect of GE on the release of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) activated by LPS in IEC-6 cells. In addition, the migration ability of IEC-6 cells was observed by the scratch method. These results showed that GE dose-dependently downregulated levels of the proinflammatory cytokines TNF-α, IL-6 and IL-1β that had been upregulated by LPS and suppressed the phosphorylation of IĸB and NF-ĸB induced by LPS. Our findings indicated that GE could reduce LPS-induced NF-ĸB signaling and proinflammatory expression in IEC-6 cells and significantly enhance the migration of IEC-6 cells. Moreover, GE inhibited the expression of NF-κB, nuclear transfer, and transcriptional activity in IEC-6 cells. GE could block the synthesis of inflammatory factors of IEC-6 cells by inhibiting activation of the IĸB/NF-κB signaling pathway induced by LPS.

International migration is closely tied to demographic, socioeconomic, and environmental factors and their interaction with migration policies. Using a combination of a gravity econometric model and an overlapping generations model, we estimate the probability of bilateral migration among 160 countries in the period of 1960 to 2000 and use these findings to project international migration flows and their implication for income inequality within and between countries in the 21st century under five shared socioeconomic pathways (SSPs). Our results show that international migration not only increases the welfare in developing countries, but also closes the inequality gap within and between low-skilled and high-skilled labor in these countries. In most developed countries on the contrary, international migration increases the inequality gap and slightly reduces output. These changes are not uniform and vary significantly across countries depending on their population growth and human capital development trajectories. Overall, while migration is strongly affected by inequality between developed and developing countries, it has an ambiguous impact on inequality within and between countries.

We advance binational link-tracing sampling design, an innovative data collection methodology for sampling from transnational social fields, i.e., transnational networks embedding migrants and non-migrants. This paper shows the practical challenges of such a design, the representativeness of the samples and the qualities of the resulted networks. We performed 303 face-to-face structured interviews on sociodemographic variables, migration trajectories and personal networks of people living in a Romanian migration sending community (Dâmbovița) and in a migration receiving Spanish town (Castellón), simultaneously in both sites. Inter-connecting the personal networks, we built a multi-layered complex network structure embedding 4,855 nominated people, 5,477 directed ties (nominations) and 2,540 edges. Results indicate that the participants’ unique identification is a particularly difficult challenge, the representativeness of the data is not optimal (homophily on observed attributes was detected in the nomination patterns), and the relational and attribute data allow to explore the social organization of the Romanian migrant enclave in Castellón, as well as its connectivity to other places. Furthermore, we provide methodological suggestions for improving link-tracing sampling from transnational networks of migration. Our research contributes to the emerging efforts of applying social network analysis to the study of international migration.

Understanding cell migration is a key step to unravel many physiological phenomena and predict several pathologies, like cancer metastasis. In particular, mechanical confinement has been proved to be a key factor in the cellular migration strategy choice. As our insight in the field improves, new tools are needed in order to empower biologists’ analysis capabilities. In this framework, microfluidic devices have been used to engineer the mechanical stimuli and to investigate cellular migration response in a more controlled way. In this work, we will review the existing technologies employed in the realization of microfluidic cellular migration assays, namely soft lithography of PDMS and hydrogels and femtosecond laser micromachining. We will give an overview of the state of the art of these devices, focusing on the different geometrical configurations that have been exploited to study specific aspects of cellular migration. Our scope is to highlight the advantages and possibilities given by each approach and to envisage the future developments in in-vitro migration studies under mechanical confinement in microfluidic devices.

In the current natural environment, due to the complexity of the background and the high similarity of the color between immature green tomato and plant, the occlusion of the key organs (flower and fruit) by the leaves and stems will lead to low recognition rate and poor generalization of the detection model. Therefore, an improved tomato organ detection method based on convolutional neural network has been proposed in this paper. Based on the original Faster R-CNN algorithm, Resnet-50 with residual blocks was used to replace the traditional vgg16 feature extraction network, and K-means clustering method was used to adjust more appropriate anchor size than manual setting to improve detection accuracy. A variety of data augmentation techniques were used to train the network. The test results showed that compared with the traditional Faster R-CNN model, the mean average precision (mAP) of the optimal model was improved from 85.2% to 90.7%, the memory requirement decreased from 546.9MB to 115.9 MB, and the average detection time was shortened to 0.073S/sheet. As the performance greatly improved, the training model can be transplanted to the embedded system, which lays a theoretical foundation for the development of precise targeting pesticide application system and automatic picking device.

International migrants comprised 14% of the UK population in 2020, but migrant health in the UK has rarely been studied at a population level using primary care electronic health records (EHRs). Given the difficulty of determining migration status using EHRs, this study developed a migration phenotype and assessed its validity. We developed a phenotyping algorithm using codes for country of birth, visa status, non-English main/first language and non-UK origin. It was applied to a Clinical Practice Research Datalink (CPRD) GOLD database of 16,071,111 primary care patients between 1997 and 2018. We compared the completeness and representativeness of the identified migrant population to Office for National Statistics (ONS) country of birth and 2011 census data by year, age, sex, geographic region of birth and ethnicity. Between 1997-2018, 403,768 migrants (2.51% of the CPRD GOLD population) were identified using the phenotype. 178,749 (1.11%) of these migrants were identified by codes indicating foreign country of birth or visa status, 216,731 (1.35%) a non-English main/first language, and 8,288 (0.05%) non-UK origin. The cohort was similarly distributed compared to ONS migration statistics in terms of sex and region of birth. Recording of migration improved from identifying approximately one-tenth of the expected proportion of migrants according to the ONS in 2004 to a quarter in 2018. Younger migrants were better represented than those aged 50 and over. The migration phenotype identified a large number of migrants and can be used to undertake large-scale migration health research in CPRD GOLD to inform healthcare policy, practice and action. While the cohort was representative of the UK migrant population in terms of sex and region of birth, migration status was under-recorded in earlier years and older ages, and future studies for these groups should therefore be interpreted with caution.

The neocortex is an exquisitely organized structure achieved through complex cellular processes from the generation of neural cells to their integration into cortical circuits after complex migration processes. During this long journey, neural cells need to stablish and release adhesive interactions through cell surface receptors known as cell adhesion molecules (CAMs). Several types of CAMs have been described regulating different aspects of neurodevelopment. Whereas some of them mediate interactions with the extracellular matrix, others allow contacts with additional cells. In this review, we will focus on the role of two important families of cell-cell adhesion molecules (C-CAMs), classical cadherins and nectins, as well as in their effectors, in the control of fundamental processes related with corticogenesis, with especial attention in the cooperative actions among the two families of C-CAMs.

Climate change-induced events amplify existing social, political, economic, infrastructural and environmental concerns in many Global South cities, and perhaps no city is more vulnerable than Bangladesh’s capital of Dhaka. Climate-induced rural-urban migration is a profound concern, and Dhaka’s political leaders have embraced technology-based innovation as a solution pathway. This article explores the societal impact of Dhaka’s innovation environment strategies for climate change adaptation and mitigation. Employing a case study qualitative methodology, our three findings expand knowledge about innovation-urban climate mitigation as understood by Dhaka-based entrepreneurs: First, the most effective innovations were not the most technologically advanced, but those with the highest degree of participant ownership. Second, gaps between recipient, corporate and governmental understandings of effective mitigation and adaptation harmed projects, and were driven by different definitions of risk and competing understandings of vulnerability. Third, even the most technical climate adaptation measures were inherently political in their application. We discuss how to better position urban climate innovation infrastructures in Bangladesh and beyond, including developing a better recognition of innovation lifecycles for urban climate adaptation and widening our definitions of ‘innovation’ to better incorporate more effective and inclusive climate adaptation solutions.

Ecklonia cava (E.cava) can alleviate vascular dysfunction in diseases associated with poor circulation. E. cava contains various polyphenols with different functions, but few studies have compared the effects of these polyphenols. Here, we comparatively investigated four major compounds present in an ethanoic extract of E. cava. These four major compounds were isolated and their effects were examined on monocyte-associated vascular inflammation and dysfunctions. Pyrogallol-phloroglucinol-6,6-bieckol (PPB) significantly inhibited monocyte migration in vitro by reducing levels of inflammatory macrophage differentiation and of its related molecular factors. In addition, PPB protected against monocyte-associated endothelial cell death by increasing the phosphorylations of PI3K-AKT and AMPK, decreasing caspase levels, and reducing monocyte-associated vascular smooth muscle cell proliferation and migration by decreasing the phosphorylations of ERK and AKT. The results of this study show that four compounds were effective for reduction of monocyte-associated vascular inflammation and dysfunctions, but PPB might be more useful for the treatment of vascular dysfunction in diseases associated with poor circulation.

Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine that contributes to the progression of several cancers. MIF overexpression has been reported in head and neck squamous cell carcinoma (HNSCC) patients. However, the exact role of MIF in HNSCC is not fully understood. Our aim was to evaluate the amount of secreted MIF and the role of MIF in the proliferation, cell cycle, and apoptosis in HNSCC cell lines. The MIF levels in conditioned media from human primary (HN18 and HN30) and metastatic (HN17 and HN31) HNSCC cell lines were evaluated using ELISA. The HNSCC cell lines were treated with recombinant MIF and its effect on proliferation, cell cycle, and apoptotic status was determined by MTT and flow cytometry, respectively. The HNSCC-secreted MIF concentration ranged from 49.33‒860 pg/ml. Exogenous MIF (25 ng/ml) significantly increased HN18, HN30, and HN31 cell proliferation. Moreover, MIF induced cell cycle progression and inhibited apoptosis in these cells. However, MIF did not affect growth or apoptosis in HN17 cell. In conclusion, the HNSCC cell lines were evaluated secrete MIF. Exogenous MIF promotes various effects on proliferation, cell cycle, and apoptosis in HNSCC cells.

Retinal pigment epithelial (RPE) cells are the major cell type in the epi- or sub-retinal membranes in the pathogenesis of proliferative vitreoretinopathy (PVR), which is a blinding fibrotic eye disease and still short of effective medicine. The purpose of this study is to demonstrate if Chalocomoracin (CMR), a novel purified compound from fungus-infected mulberry leaves, is able to inhibit vitreous-induced signaling events and cellular responses intrinsic to PVR. Our studies have revealed that the CMR IC50 for ARPE-19 cells is 35.5 μM at 72 hours, and that 5 μM CMR inhibits vitreous-induced Akt activation and p53 suppression; in addition we have discovered that this chemical effectively blocks vitreous-stimulated proliferation, migration and contraction of ARPE-19 cells, suggesting that CMR is a promising PVR prophylactic.

Changing mobility patterns combined with changes in the climate present challenges and opportunities for global health, requiring effective, relevant and humane policy responses. This study used data from a systematic literature review that examined the intersection between climate change, migration and health. The aim of the present study was to synthesize policy recommendations in the peer-reviewed literature, regarding this type of environmental migration with respect to health, to strengthen the evidence-base. Systematic searches were conducted in four academic databases (PubMed, Ovid Medline, Global Health and Scopus) and Google Scholar for empirical studies published between 1990 – 2020 that used any study design to investigate migration and health in the context of climate change. Studies underwent a two-stage protocol-based screening process and eligible studies were appraised for quality using a standardized mixed-methods tool. From the initial 2,425 hits, 68 articles were appraised for quality and included in the synthesis. Among the policy recommendations, six themes were discernible: (1) avoid the universal promotion of migration as an adaptive response to climate risk; (2) preserve cultural and social ties of mobile populations; (3) enable the participation of migrants in decision-making in sites of relocation and resettlement; (4) strengthen health systems and reduce barriers for migrant access to health care; (5) support and promote optimization of social determinants of migrant health; (6) integrate health into loss and damage assessments related to climate change. The results call for transformative policies that support the health and wellbeing of people engaging in, or affected by mobility responses, including those whose migration decisions and experiences are influenced by climate change, and to establish and develop inclusive migrant healthcare.

The effect of Alzheimer's disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. Alzheimer's disturbs the life of at least five million persons in the USA. CD4+ T cells could both exacerbate and reduce AD symptoms. Regulating CD4+ T cells homing to the leaky blood-brain barrier (BBB) constitutes a new hope for enhancing AD prognosis. Alzheimer's drugs such as Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne) and memantine are known to play an important part in regulating the neurotransmitters mechanisms. However, little is known about the effect of these drugs on CD4+ T cells homing. In this review, we focus on current and new drugs that could modulate CD4+ T cells interactions with the BBB in AD.

The intracellular calcium concentration ([Ca2+]i) modulation plays a key role in the regulation of cellular growth and survival in normal cells and failure of [Ca2+]i homeostasis is involved in tumor initiation and progression. Here we show that inhibition of Furin by its naturally occurring inhibitor the prodomain ppFurin in the MDA-MB-231 breast cancer cells resulted in enhanced SOCE through TRPC6 activation that associated reduced cells malignant phenotype. Expression of ppFurin in a stable manner in MDA-MB-231 and the melanoma MDA-MB-435 cell lines inhibits Furin activity as assessed by in vitro digestion assays. Accordingly, cell transfection experiments, revealed that the ppFurin-expressing cells are unable to process adequately the PC substrates proVEGF-C and proIGF-1R. Compared to MDA-MB-435 cells, expression of ppFurin in MDA-MB-231 significantly induces Ca2+ entry which is impaired by silencing of TRPC6 expression. Analysis of TRPC6 activation revealed its up-regulated tyrosine phosphorylation in ppFurin-expressing MDA-MB-231 cells. The expression of ppFurin in MDA-MB-231 cells reduced their viability and ability to migrate and enhanced their sensitization to the apoptosis inducer hydrogen peroxide. These findings suggest that Furin inhibition by ppFurin may be a useful strategy to interfere with Ca2+ mobilization leading to breast cancer cells malignant phenotype repression and reduction of their resistance to treatments.

Since the beginning of the 21st century, Romanian migrants have become one of the most significant national groups doing agricultural work in Spain, initially coming via a temporary migration program and later under several different modalities. However, despite their critical importance for the functioning of Europe’s largest agro-industry, the study of this long-term circular mobility is still underdeveloped in migration and agriculture literature. Thanks to extensive fieldwork carried out in the provinces of Huelva and Lleida in Spain and in the counties of Teleorman and Buzău in Romania, this paper has two main objectives: first, to identify some of the most common forms of mobility of these migrants and second, to discuss whether this industrial agriculture, hugely dependent on migrant work, is socially sustainable. The case of Romanian migrants in Spanish agriculture will serve to show how a critical sector for the EU and for the 2030 Agenda for Sustainable Development of the United Nations, operates on an unsustainable model based on precariousness and exploitation.

Glioblastomas (GBMs) are aggressive and invasive cancers of the brain, associated with high rates of tumor recurrence and poor patient outcomes despite initial treatment. Targeting cell migration is therefore of interest in highly invasive cancers such as GBMs, to prevent tumor dissemination and regrowth. One current aim of GBM research focusses on assessing anti-migratory properties of novel or repurposed inhibitors, including plant-based drugs which display anti-cancer properties. We investigated the potential anti-migratory activity of plant-based products with known cytotoxic effects in cancers, using a range of two-dimensional (2D) and three-dimensional (3D) migration and invasion assays as well as immunofluorescence microscopy to determine specific anti-migratory and phenotypic effects of three plant-derived compounds, Turmeric, Indigo and Magnolia bark, on established glioma cell lines. Migrastatic activity was observed in all three drugs, with Turmeric exerting the most inhibitory effect on GBM cell migration into scratches and from the spheroid edge at all timepoints investigated (p < 0.001). We also observed novel cytoskeletal phenotypes affecting actin and focal adhesion dynamics. By determining the migrastatic activity of Turmeric, Indigo and Magnolia on GBM cell migration, we demonstrate a potential role for Turmeric as a novel GBM anti-migratory therapeutic, in combination with the current standard of care, to prevent tumor recurrence and promote patient survival.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

Albanian migration has always reflected a family character, be that before 1945 when Albania was not yet completely isolated, as well as after 1990 when borders were reopened. This feature characterized all types of movement, internal or international, permanent or seasonal migration, return migration or transnational movements, and remigration. The role of the family has been very important in making decisions regarding migration and answering questions from why to how to migrate, from when to where, whom to ask for help or how to invest remittances. Based on the case study of a rural area in Northern Albania, The Administrative Unit of Dajç, this article explores in detail the roles of family and kinship on decisions regarding return migration, the re-adjustment process, remigration or transnational life. By exploring the role of the family context in remigration and vice-versa the article reflects that the family biography – including the lifestyle, plans for the future or expectations - has changed due to previous migration experiences or challenges and difficulties when returning to the home country. It demonstrates how individual decisions to migrate or to ‘return home’ are negotiated and supported within families making transnational life a family project. The article adopts a new approach in the Albanian Migration Studies which may be implied on broader areas for further research in the future.

The fluid seepage in local-saturated zone of subgrade promotes the migration of fine particles in the filler, resulting in the change of pore structure and morphology of the filler and the deformation of solid skeleton, which affects the fluid seepage characteristics. Repeatedly, the muddy interlayer, mud pumping and other diseases are finally formed. Based on the theory of two-phase seepage, the theory of porous media seepage, and the principle of effective stress in porous media, a two-phase fluid-solid coupling mathematical model in local-saturated zone of subgrade considering the effect of fine particles migration is established. The mathematical model is numerically calculated with the software COMSOL Multiphysics○R, the two-phase seepage characteristics and the deformation characteristics of the solid skeleton in local-saturated zone of the subgrade are studied. The research results show that due to the continuous erosion and migration of fine particles in local-saturated zone of the subgrade, the volume fraction of fine particles first increases then decreases and finally becomes stable with the increase of time. And the volume fraction of fine particles for the upper part of the subgrade is larger than that for the lower part of the subgrade. The porosity, the velocity of fluid, the velocity of fine particles, and the permeability show a trend of increasing first and then stabilizing with time; the pore water pressure has no significant changes with time. The vertical displacement increase first and then decrease slightly with the increase of time, and finally tend to be stable. For a filler with a larger initial volume fraction of fine particles, the maximum value of the volume fraction of fine particles caused by fluid seepage is larger, and the time required to reach the maximum value is shorter. It can be concluded that in actual engineering, the volume fraction of fine particles in the subgrade filler should be minimized on the premise that the filler gradation meets the requirements of the specification.

The majority of cellular responses to external stimuli are mediated by receptors such as G protein-coupled receptors (GPCRs) and systems including endoplasmic reticulum stress (ER stress). Since GPCR signalling is pivotal in numerous malignancies, they are widely targeted by a number of clinical drugs. Cancer cells often negatively modulate GPCRs in order to survive, proliferate and to disseminate. Similarly, numerous branches of the unfolded protein response (UPR) act as pro-survival mediators and are involved in promoting cancer progression via mechanisms such as epithelial to mesenchymal transition (EMT). However, there are a few proteins among these groups which impede deleterious effects by orchestrating the pro-apoptotic phenomenon and paving a therapeutic pathway. The present review exposes and discusses such critical mechanisms and some of the key processes involved in carcinogenesis.

Adolescents often migrate unaccompanied by a caregiver, facing specific risks. Mentoring has been identified as a strategy with positive results for youth at risk. Its application with unaccompanied minors (UM) refugees and asylum seekers has gained momentum within EU countries receiving refugee citizens from the EU relocation program. Portugal hosts the fourth highest number of Middle East and North Africa UM refugees and asylum seekers among EU countries. Thus, it´s relevant to review strategies and intervention programs, focused on mentoring to inform future programs in Portugal supporting UM. This article aims to describe the use of mentoring strategies towards integrating UM refugees, and how this has been taking place in Portugal. This review has the potential to inform professionals, namely social education professionals involved in the Portuguese refugee relocation program and encourage the discussion about creating based mentoring-based programs for this target group.

The power of the river does not always work to the benefit of living things; rather, it has the ability to destroy human society and has negative effects on the environment. River Teesta has a prodigious significance on the riverine dweller and its changing precarious behaviour has repercussions on the lives of millions. Utilizing satellite images and 41 years of temporal analysis, the mapping of channel extraction and channel shifting has been demonstrated. Delineating the exact channel boundary is a laborious operation, but MNDWI technique is really valuable in this situation to produce valuable results. Descriptive statistics are used to analyze the Teesta River's active flow line migration trend and channel migration behaviour. A particular river's oscillating character over time has both beneficial and detrimental power, destroying important resources for environmental sustainability and human society while also providing fertile mother earth as a source of wealth. As a result, another goal of the current study was to determine how vulnerable riverine residents were. A livelihood vulnerability index (LVI) based on the riverine inhabitants' exposure, sensitivity, and capacity for adaptation was created. According to the findings, the river's erratic behaviour is putting the people who live beside it in danger. Therefore, it is vitally necessary to implement a capable management strategy to stop bank failure at the Teesta-Dharala confluence in order to save the riverine residents.

Cell migration is essential for physiological, pathological and biomedical processes such as, in embryogenesis, wound healing, immune response, cancer metastasis, tumour invasion and inflammation. In light of this, quantifying mechanical properties during the process of cell migration is of great interest in experimental sciences, yet few theoretical approaches in this direction have been studied. In this work, we propose a theoretical and computational approach based on the optimal control of geometric partial differential equations to estimate cell membrane forces associated with cell polarisation during migration. Specifically, cell membrane forces are inferred or estimated by fitting a mathematical model to a sequence of images, allowing us to capture dynamics of the cell migration. Our approach offers a robust and potentially accurate framework to compute geometric mechanical membrane forces associated with cell polarisation during migration and also yields geometric information of independent interest, we illustrate one such example that involves quantifying cell proliferation levels which are associated with cell division, cell fusion or cell death.

This study investigates the intricate relationship between Venezuelan migration and urban growth in Colombia from 2018 to 2021. The study employs remote sensing data and social network metrics to uncover migration patterns and their impact on urban expansion. The methodology consists of three stages. Firstly, nighttime satellite imagery is used to analyze year-over-year urban growth in Colombia. Secondly, social network data estimates Venezuelan migration, overcoming challenges of underreporting and informal border crossings. Lastly, an econometric analysis explores the quantitative link between Venezuelan migration and urban growth, integrating socioeconomic variables to address endogeneity. The findings reveal the complex interplay of Venezuelan migration, socioeconomic factors, and urban growth. The study outlines remote sensing analysis, introducing the Anthropogenic Footprint Expansion Index (AFEI) to quantify urban growth. Facebook API data estimates migration trends and explores socioeconomic impacts on urban expansion. The analysis uncovers migration, poverty, aging, and urban population proportion as key factors affecting Colombia's urban landscape. Furthermore, the research underscores how Venezuelan migration affected short-term urban expansion pre- and post-COVID-19. Migration had a notable effect before the pandemic, but this influence waned afterward. The study highlights migration's short-term nature and emphasizes age demographics' role in medium-term dynamics.

We previously reported that corneal fibroblasts within 3D fibrin matrices secrete, bind, and organize fibronectin into tracks that facilitate cell spreading and migration. Other cells use these fibronectin tracks as conduits, which leads to the development of an interconnected cell/fibronectin network. In this study, we investigate how cell induced reorganization of fibrin correlates with fibronectin track formation in response to two growth factors present during wound healing: PDGF BB, which stimulates cell spreading and migration; and TGFβ1, which stimulates cellular contraction and myofibroblast transformation. Both PDGF BB and TGF stimulated global fibrin matrix contraction (P < 0.005), however cell and matrix patterning were different. We found that during PDGF BB induced cell spreading, fibronectin was organized simultaneously with the generation of tractional forces at the leading edge of pseudopodia. Over time this led to the formation of an interconnected network consisting of cells, fibronectin and compacted fibrin tracks. Following culture in TGFβ1, cells were less motile, produced significant local fibrin reorganization, and formed fewer cellular connections as compared to PDGF BB (P < 0.005). Although bands of compacted fibrin tracks developed in between neighboring cells, fibronectin labeling was not generally present along these tracks, and the correlation between fibrin and fibronectin labeling was significantly less than that observed in PDGF BB (P < 0.001). Taken together, our results show that cell-induced ECM reorganization can occur independently from fibronectin patterning. Nonetheless, both events seem to be coordinated, as corneal fibroblasts in PDGF BB secrete and organize fibronectin as they preferentially spread along compacted fibrin tracks between cells, producing an interconnected network in which cells, fibronectin and compacted fibrin tracks are highly correlated. This mechanism of patterning could contribute to the formation of organized cellular networks that have been observed following corneal injury and refractive surgery.

Fluid flow and chemokine gradients play a large part in not only regulating homeostatic processes in the brain, but also in pathologic conditions by directing cell migration. Tumor cells in particular are superior at invading into the brain resulting in tumor recurrence. One mechanism that governs cellular invasion is autologous chemotaxis, whereby pericellular chemokine gradients form due to interstitial fluid flow (IFF) leading cells to migrate up the gradient. Glioma cells have been shown to specifically use CXCL12 to increase their invasion under heightened interstitial flow. Computational modeling of this gradient offers better insight into the extent of its development around single cells, yet very few conditions have been modelled. In this paper, a computational model is developed to investigate how a CXCL12 gradient may form around a tumor cell and what conditions are necessary to affect its formation. Through finite element analysis using COMSOL and coupled convection-diffusion/mass transport equations, we show that velocity (IFF magnitude) has the largest parametric effect on gradient formation, multidirectional fluid flow causes gradient formation in the direction of the resultant which is governed by IFF magnitude, common treatments and flow patterns have a spatiotemporal effect on pericellular gradients, exogenous background concentrations can abrogate the autologous effect depending on how close the cell is to the source, that there is a minimal distance away from the tumor border required for a single cell to establish an autologous gradient, and finally that the development of a gradient formation is highly dependent on specific cell morphology.

The origin of the man at the Earth is directly associated with the determination of directions of the flow distribution of the ancient man migration to adjacent territories. In such studies traditionally mainly landscape and climatological changes are considered. We suggest that along with the above factors, regional tectonic-geodynamic factors played a dominant role in the character of migration. The considered African-Levantine-Caucasian region is one of the most complex regions of the world, where collisional and spreading processes of geodynamics converge. First is determined an essential influence of the Akchagylian hydrospheric maximum (about 200 m above the mean sea level) limiting the ancient men migration from Africa to Eurasia. We propose that the Levantine Corridor emerged after the end of the Akchagylian transgression and landscape forming in the Eastern Mediterranean. This corridor location was formed by the movements between the Dead Sea Transform and the boundary of the carbonate platform of the Mesozoic Terrane Belt. Further landscape evolution was largely determined by the geodynamic behavior of the deep mantle rotating structure occurring below the central part of the region under study. All the mentioned events around and in the Levantine Corridor have been studied in detail on the basis of the combined geodynamic, paleogeographic, and paleomagnetic analyzes performed in northern Israel (Carmel uplift and Galilee plateau). Careful studies of the Evron quarry geological section indicate that it is a unique one for the dating of the marine and continental archaeological sequences and sheds light on the movement of the ancient man along the Levantine Corridor.

Oligosaccharides derived from λ-carrageenan (λ-COs) are gaining interest in the cancer field. They have been recently reported to regulate heparanase (HPSE) activity, a protumor enzyme involved in cancer cell migration and invasion, making them very promising molecules for new therapeutic applications. However, one of the specific features of commercial λ-carrageenan (λ-CARs) is that they are in fact heterogeneous mixtures of different CARs families, and are named according to the thickening purpose of the product which does not reflect the real com-position. Consequently, this can limit their use in a clinical grade. To address this issue, six commercial λ-CARs were compared for which differences in their physiochemical properties were shown. Then, a H2O2-assissed radical depolymerization was applied to each commercial source and the number and weight averaged molar masses (Mn and Mw) and sulfation degree (DS) of the λ-COs produced over time were determined. By adjusting the depolymerization time for each product, almost comparable λ-CO formulations could be obtained in term of molar masses and DS, that ranged within previously reported values suitable for anti-tumor proper-ties. However, when the anti-HPSE activity of these new λ-COs was screened, small changes that could not be attributed only to their small length or DS changes between them were found, suggesting a role of other features such as differences in the initial mixture composition. Further structural MS and NMR analysis revealed indeed qualitative and semi-quantitative differences between the molecular species, especially in the proportion of the anti-HPSE λ-type, other CARs types and adjuvants, but also showed that H2O2-based hydrolysis induced sugar degradation. Finally, when the effects of λ-COs were assessed in an in vitro migration cell-based model, they seemed more related to the proportion of other CAR types in the formulation than to their λ-type-dependent anti-HPSE activity.

For tropical forests to survive anthropogenic climate change, the trees that comprise them will need to tolerate the newly emerging conditions through adaptation or acclimation, or they can avoid climate change through range shifts and “species migrations”. In this review, we show that the rapid pace and extreme severity of modern climate change makes it extremely unlikely that tropical tree species can adapt (with some possible exceptions). We also show that while many tropical tree species are shifting their distributions to higher, cooler elevations, the rate of these migrations are mostly insufficient to offset ongoing changes in temperatures, especially in lowland tropical rainforests where thermal gradients are shallow or nonexistent. We argue that the best hope for tropical tree species to avoid becoming “committed to extinction” is acclimation. While several new methods are being developed to test for acclimation, we unfortunately still do not know if tropical tree species can acclimate or what factors may prevent or facilitate acclimation. Until these questions are answered, our ability to predict the fate of tropical species and tropical forests – and the many services that they provide to humanity – remains critically impaired.

The migratory life history of anadromous salmonids requires successful migration between nursery, feeding and spawning habitats. Smoltification is the major transformation anadromous salmonids undergo before migration to feeding areas and prepares juvenile fish for downstream migration and entry to seawater. We reviewed the effects of climate change on smolt ecology from growth of juveniles in freshwater to early post-smolts in sea. Shift in the suitable thermal conditions by climate change is causing Atlantic salmon to expand their range northwards, while in the southern edge of their distribution populations struggle with high temperatures and occasional droughts. Climatic conditions, particularly warmer temperatures, are affecting growth during freshwater phase in the river. Better growth in the northern latitudes leads to earlier smoltification. Thermal refuges, the areas of cooler water in the river, are especially important for salmonids impacted by climate change. Restoring and maintaining connectivity and suitable diverse mosaic habitat in rivers are important for survival and growth throughout the range. The start of the smolt migration has shifted earlier as a response to increasing water temperatures, which has led to concerns of mismatch with optimal conditions for post-smolts in the sea decreasing their survival. A wide smolt window allowing all migrating phenotypes from early to late migrant’s safe access to sea is important in changing environmental conditions. This is true also for regulated rivers, where flow regulation practices cause selection pressures on migrating salmonid phenotypes. Life history in freshwater affects also marine survival, and there is a need for better collaboration across life stages and habitats among researchers and managers to boost the smolt production in rivers.

Calcium-activated potassium channels (KCa) are the important participants in calcium signaling pathways due to their ability to be activated by increase of the intracellular free calcium concentration. KCa channels are involved in the regulation of various processes in the cells under normal, as well as pathophysiological conditions, including oncotransformation. Previously, with the use of patch-clamp method, we registered the KCa activity in the plasma membrane of human myeloid leukemia K562 cell line. Here, we performed the molecular and functional identification of KCa channels and have uncovered their role in proliferation, migration and invasion of K562 cells. Using a combined approach, we identified the functional activity of SK2, SK3 and IK channels in the plasma membrane of the cells. Selective SK and IK channel inhibitors, apamin and TRAM-34, reduced the proliferative, migratory and invasive capabilities of human myeloid leukemia cells. At the same time, the viability of K562 cells was not affected by KCa channel inhibitors. Our data imply that SK/IK channel inhibitors could be used to slow down the proliferation and spreading of leukemia cells that express functionally active KCa channels in the plasma membrane.

Globally, large numbers of adults remain unbanked and most of them live in rural areas of the Third World. The recent outbreak of the COVID-19 pandemic has shown us how inequalities in accessing financial services continue to affect us. However, financial inclusion has emerged as an effective tool to tackle socioeconomic ills and drive economic development. In fact, due to these modern technological developments, the number of studies in this area is very limited, especially in the context of developing economies. This study examines the impacts of migrant remittances on digital financial inclusion within households using the Migration and Remittance Household Survey in Bangladesh. To meet the research objectives of this study, a household survey was conducted and interviewed 2,165 households in 2022-2023 in Bangladesh. This study finds that the coefficient of remittance has a positive relationship with the probability of using mobile banking for a household's financial transactions. However, the use of ATM cards by households for financial transactions has not been significantly affected. The article concludes that remittance flows may enhance access to and use of digital financial inclusion by reducing some of the barriers and costs in Bangladesh, which can greatly contribute to the country's economic growth by creating and increasing a strong fund for investment.

Remittances are essential to economies in mountainous regions that face massive labour migration due to limited income generation and employment opportunities. In 2021, the share of remittances to GDP in the top 10 mountainous economies in the world was over 20%. Nonetheless, most are characterized by relatively lower GDP per capita and high poverty levels. Drawing a comparison with other mountainous areas, Phuthadjthaba, an emerging mountainous and border city of South Africa with Lesotho, faces similar out-migration and inferior socio-economic parameters. A global systematic literature review on the impact of remittances on livelihoods specifically targeting mountainous areas is missing. We, therefore, interrogate the role remittances can play in Phuthadijthaba. To inform our intended research, we seek to draw lessons from evidence on how migration and remittances affect mountainous communities globally. Accordingly, we carry out a systematic literature review (SLR) based on an updated Preferred Reporting Item for Systematic Reviews and Meta-Analysis (PRISMA) 2020 statement supported by Bibliometric (co-word) Analysis (BA) in VOSViewer. We collected data from Scopus and Dimensions websites and drew 165 publications, of which only 88 were included after exclusion and inclusion assessments. PRISMA results show that Mountain Research and Development, King Russell, and Nepal is the most productive and cited journal, the most productive and cited author, and the most researched country, respectively. Bibliometric analysis on keyword co-occurrences reveals women, agriculture, labour migration, land management, forest, and poverty, to be the research hotspots. In light of these findings, we proffer important recommendations to future researchers and policymakers.

Climate change is one of the widely acknowledged challenges faced by international communities in the 21^st century. It poses challenges to fundamental elements of our understanding of appropriate goals for socioeconomic policies, such as the connection of prosperity, growth, equity and sustainable development. Human activities-induced climatic changes have been widely perceived as threatening criteria for the long-term resilience of societies and communities throughout the world. The United Nations Intergovernmental Panel on Climate Change (UNIPCC) reported that greenhouse gas (GHG) emissions due to human activities, such as the burning of fossil fuels for energy generation, is changing the climate of Earth. Despite contributing less towards the causes, poor citizens of developing countries bear a lot of its impacts. In particular, women and girls face a major impact and finally, they migrate due to the social gender division and scarcity of food. Studies on gender and climate change-induced migration are scarce. This study provides an overview of the induced impact of climate change on the livelihood, health and migration of women and girls. The aim of this study would significantly advance our understanding of the current inter-linkages between migration, displacement patterns and climate change impacts.

Our understanding of how microbiome signatures are modulated in wild fish populations remains poorly known and has, until now, mostly been inferred from studies in commercial and farmed fish populations. Here, we have studied for the first time changes in the skin and blood microbiomes of the Salmo trutta population of the volcanic Kerguelen archipelago located at the northern limit of the Antarctic Ocean. Kerguelen is a natural framework of population expansion and a likely situation under further climate change in distribution areas. Our results showed that S. trutta of Kerguelen has a microbiome signature distinct from those of salmonids of the Northern Hemisphere. Our study also revealed that the skin and blood microbiomes differ between sedentary and migratory S. trutta. While 18 phyla were shared between both groups of trout, independent of the compartment, six phyla were unique to migratory trout. Further analyses showed that microbiome signatures undergo significant site-specific variations that correlate, in some cases, to the peculiarity of specific ecosystems. Our study also revealed the presence of potential pathogens at particular sites and the impact of abiotic factors on the microbiome, most notably due to the volcanic nature of the environment. This study contributes to a better understanding of the factors that modulate the microbiome signatures of migratory and sedentary fish populations. It will also help better monitor climate change's impacts on the colonization process in the sub-Antarctic region.

Pancreatic ductal adenocarcinoma (PDAC) is mostly diagnosed at advanced or even metastasized stages limiting patient´s prognosis. Metastasis requires high tumor cell plasticity implying phenotypic switching in response to changing environments. Here, Epithelial-Mesenchymal-Transition (EMT), being associated with the gain of cancer stem cell (CSC) properties, and its reversion are important. Since it is poorly understood whether different CSC-phenotypes exist along the EMT-axis and how these impact malignancy-associated properties, we aimed to characterize CSC-populations of epithelial and mesenchymal PDAC cells. Single-cell cloning revealed CSC (Holoclone) and non-CSC (Paraclone) clones from the PDAC cell lines Panc1 and Panc89. Panc1 Holoclone cells showed a mesenchymal phenotype dominated by high expression of the stemness marker Nestin, while Panc89 Holoclone cells exhibited a SOX2-dominated epithelial phenotype. Panc89 Holoclone cells showed enhanced cell growth and self-renewal capacity but slow cluster-like invasion. Contrarily, Panc1 Holoclone cells showed slower cell growth and self-renewal ability but were highly invasive. Moreover, cell variants differentially responded to chemotherapy. In vivo, Panc1 and Panc89 cell variants significantly differed regarding number and size of metastases as well as organ manifestation leading to different survival outcomes. Overall, these data support the existence of different CSC-phenotypes along the EMT-axis in PDAC manifesting in different metastatic propensities.

CD4+ T cells orchestrate and regulate immunity within jawed vertebrates, yet our understanding of their evolution, development, and cellular physiology has only begun to be unearthed in the past few decades. Discoveries of genetic diseases that ablate this cellular population have provided insight into their critical functions while transcriptomics, proteomics, and highresolution microscopy have recently revealed new insights into CD4+ T cell anatomy and physiology. This article compiles historical, microscopic, and multi omics data which can be used as a reference atlas to dissect cellular physiology within these influential cells and further understand pathologies like HIV infection that inflict human CD4+ T cells.

The Eastern Himalayan Syntaxis (EHS), featured by an exceptionally intense compression orogeny and an extremely rapid surface erosion rate, stands out as a prime area for investigating surface processes and landscape evolution. Understanding the formation of the EHS holds significant importance in advancing our comprehension of the evolutionary dynamics within the Tibetan Plateau and the complex interplay between endogenic and exogenic geological processes. Currently, two models, namely the tectonic aneurysm and the syntaxis expansion model, have been proposed to explain the formation and evolution of this syntaxis. In this study, we employ a multi-disciplinary approach, integrating geomorphic indices such as slope, relief, Hypsometric Integral (HI), Normalized Channel Steepness (Ksn), River Slope-Basin Area Integration (χ), combined with erosion rates on long-medium-short term timescales obtained from thermochronology, cosmogenic nuclides 10Be and landslide disaster probability data. Our findings suggest a relatively high tectonic activity in the confluence of the Yigong and Parlung Rivers in the northern end of the syntaxis. Moreover, our data reveals that spatial variability of tectonic activity is the primary driver of regional geomorphologic features and the spatial-temporal characteristics of erosion observed in the EHS, with lithology and climatic precipitation playing a lesser role. Furthermore, the northwards migration of the EHS appears to elucidate the shift of tectonic activity and rapid erosion from the core of the syntaxis near the Namche Barwa towards the confluence of the Yigong and Parlung Rivers. This northwards migration of the EHS underscores the need for increased attention to the high geological hazard risk in the northern part of the EHS.

Venoms are a rich source of bioactive compounds, and among them is leberagin-C (Leb-C), a disintegrin-like protein derived from the venom Macrovipera lebetina transmediterrannea snakes. Leb-C has shown promising inhibitory effects on platelet aggregation. Previous studies have demonstrated that this SECD protein specifically targets α5β1, αvβ3 and αvβ6 integrins through a mimic mechanism of RGD disintegrins. In our current study, we focused on exploring the potential effects of Leb-C on metastatic breast cancer. Our findings revealed that Leb-C disrupted the adhesion, migration, and invasion capabilities of MDA-MB-231 breast cancer cells and its highly metastatic D3H2LN sub-population. Additionally, we observed significant suppression of adhesion, migration, and invasion of Human Umbilical Vein Endothelial Cells (HUVECs). Furthermore, Leb-C demonstrated a strong inhibitory effect on fibroblast growth factor 2-induced proliferation of HUVEC. We conducted in vivo experiments using nude mice and found that treatment with 2 µM of Leb-C resulted in a remarkable 73% reduction in D3H2LN xenograft tumor size. Additionally, quantification of intratumor microvessels revealed a 50 % reduction in tumor angiogenesis in xenograft after 21 days of twice-weekly treatment with 2 µM of Leb-C. Collectively, these findings suggest the potential utility of this dinsintegrin-like protein for inhibiting aggressive and resistant metastatic breast cancer.

Cancers of the brain and nervous system account for 1 in every 100 cancer diagnoses in the United States and about 0.3 million diagnoses globally, every year. Surgery, radiotherapy, and chemo-therapy constitute the standard of care. Despite advancements in diagnosis and treatment delivery, mortality rate for these cancers have remained steady for over three decades. Immunotherapy is an emerging fourth treatment modality which has been effective against several cancers but not brain cancers, such as glioblastoma, GBM. Here, we develop in vitro assays to quantify molecular readouts of cell death, cell migration and clonogenicity, and synopsize these as biophysical markers for the rapid evaluation of immune checkpoint inhibitors (ICI), durvalumab and pembrolizumab, alone and in combination with radiotherapy (radioimmunotherapy). We find different trends in their direct action on two GBM cell lines (T98G and U87), even in the absence of immune cells. Radiation alone, and pembrolizumab with radiation, both reduced (p < 0.05) cell-cell adhesion. This reduction suggests increased potential for local invasion. Our assays offer additional insights regarding ICIs, may enable evaluation of their potential efficacy, and could set the stage for pa-tient-specific radioimmunotherapy against brain cancers, engendering improved treatment out-comes.

The Hippo pathway plays crucial roles in governing various biological processes during tumorigenesis and metastasis. Within this pathway, upstream signaling stimuli activate a core kinase cascade, involving MST1/2 and LATS1/2, which subsequently phosphorylates and inhibits the transcriptional co-activators YAP and its paralog TAZ. This inhibition modulates the transcriptional regulation of downstream target genes, impacting cell proliferation, migration, and death. Despite the acknowledged significance of protein kinases in the Hippo pathway, the regulatory influence of protein phosphatases remains largely unexplored. In this study, we conducted the first gain-of-functional screen for protein tyrosine phosphatases (PTPs) regulating the Hippo pathway. Utilizing a LATS kinase biosensor (LATS-BS), a YAP/TAZ activity reporter (STBS-Luc), and a comprehensive PTP library, we identified numerous novel PTPs that play regulatory roles in the Hippo pathway. Subsequent experiments validated PTPN12, a master regulator of oncogenic receptor tyrosine kinases (RTKs), as a previously unrecognized negative regulator of the Hippo pathway effectors, oncogenic YAP/TAZ, influencing breast cancer cell proliferation and migration. In summary, our findings offer valuable insights into the roles of PTPs in the Hippo signaling pathway, significantly contributing to our understanding of breast cancer bi-ology and potential therapeutic strategies.

Ferruginol is a promising abietane-type antitumor diterpene able to induce apoptosis in SK-Mel-28 human malignant melanoma. We here aim to increase this activity by testing the effect of a small library of ferruginol analogues. After an screening of their antiproliferative activity (SRB staining) on SK-Mel-28 cells the analogue 18-aminoferruginol (GI50=10 µM) was further selected for mechanistic studies including effects on mitochondrial viability (MTT assay, IC50=10 µM p<0.0001), induction of apoptosis (DAPI staining, p<0.001), changes in cell morphology associated with the treatment (cell shrinkage and membrane blebbing), induction of caspase-3/7 activity (2.5x at 48h, 6.5x at 72h; p<0.0001), changes in the mitochondrial membrane potential (not significant), and effects on 2D cell migration and 3D cell invasion (modified Boyden assay, not significant). The results were compared to those of the parent molecule (ferruginol, GI50»50 µM) and paclitaxel (GI50=10 nM) as a reference drug. In conclusion, we demonstrate here that derivatization of ferruginol into 18-aminoferruginol increases its antiproliferative activity 5 times in SK-MEL-28 cells as well as changing the apoptotic mechanism of its parent molecule ferruginol from activation of caspases without depolarization of mitochondrial membrane.

Drainage divide is a dynamic feature that migrates in response to tectonic activity. The asymmetric uplift between two adjacent basins causes the divide migration from a slower to faster uplift area. Sado Island, Japan, has been affected by southeastward tilting uplift since ca. 300k years. Despite the faster uplift on the northwest, the main divides have existed on the southeast side of the geometric center of the island, with no other feature suggesting tectonic inversion of the tilting direction. In this study, we conducted a DEM-based investigation that focused on divide migration. A spectrum from very inactive to active divide migration in the northwest. Regardless of their position, actively migrating divides are comprehensible, but inactive divides located in a relatively slow uplift area remain unclear. We concluded that some divides slowed down owing to the local balance of erosion rates across the divides, not implying the balance between uplift and river erosion at the basin scale, reflecting disequilibrium in river longitudinal profiles. The main divides of Sado have presumably continued to slowly migrate toward the faster uplift area; however, they are most likely to have never overcome the moving geometric center owing to land expansion at the seacoast due to asymmetric uplift.

The notion that ‘Stock-G’ humpback whales off western South America are primarily deep oceanic migrators is poorly supported. We documented 66 land-based sightings from Pucusana, Lima Sur: 18 incidental (2002–2023) and 48 dedicated sightings during the northbound winter migration (June-July 2023), covering respectively 38 and 105 individual whales, despite a mean daily observer effort of only 58.7 min. Estimated distances from shore ranged 20–7,000 m (mean= 2,729 m) at depths 25–99 m, while 50% migrated at < 2,500 m (median) from shore. Several groups skirted the coastline from headland to headland. Of five southbound migrating groups, four included an adult with neonate; no northbound groups enclosed a neonate. Two cases of single juvenile/subadult whales moving multidirectionally and closely associated with large seabird feeding frenzies, were considered foraging also. In 2023, 94% of all northbound nearshore sightings occurred from 14 June-11 July, signalling the maximum threat period for interactions with coastal fisheries off metropolitan Lima. If migration is temporally and spatially predictable, effective mitigating measures should be feasible.

Background: The scaffold protein tyrosine kinase substrate 4 (TKS4) undergoes tyrosine phos-phorylation by the epidermal growth factor receptor (EGFR) pathway via Src kinase. The TKS4 deficiency in humans is responsible for the manifestation of a genetic disorder known as Frank-Ter Haar syndrome (FTHS). Based on our earlier investigation, the absence of TKS4 triggers migration, invasion, and epithelial-mesenchymal transition (EMT)-like phenomena while concurrently suppressing cell proliferation in HCT116 colorectal carcinoma cells. This indicates that TKS4 may play a unique role in the progression of cancer. In this study, we demonstrated that the enhancer of zeste homolog 2 (EZH2) and the histone methyltransferase of polycomb repressive complex 2 (PRC2) are involved in the migration, invasion, and EMT-like changes in TKS4-deficient cells (KO). EZH2 is responsible for the maintenance of the trimethylated lysine 27 on histone H3 (H3K27me3). Methods: We performed the transcriptome sequencing, chromatin immunoprecipitation, protein and RNA quantitative studies, cell mobility, invasion, and proliferation studies combined with/without EZH2 activity inhibitor 3-deazanoplanocine (DZNep) Results: We detected an elevation of global H3K27me3 levels in the TKS4 KO cells, which could be reduced with treatment with DZNep, an EZH2 inhibitor. Inhibition of EZH2 activity reversed the phenotypic effects of the knockout of TKS4, reducing the migration speed and wound healing capacity of the cells as well as decreasing the invasion capacity, while the decrease in cell prolif-eration became stronger. In addition, inhibition of EZH2 activity also reversed most epithelial and mesenchymal markers. We investigated the wider impact of TKS4 deletion on the gene expression profile of colorectal cancer cells using transcriptome sequencing of wild-type and TKS4 knockout cells, particularly before and after treatment with DZNep. Additionally, we observed changes in the expression of several protein-coding genes and long non-coding RNAs that showed a recovery in expression levels following EZH2 inhibition. Conclusions: Our results indicate that the removal of TKS4 causes a notable disruption in the gene expression pattern, leading to the disruption of several signal transduction pathways. Inhibiting the activity of EZH2 can restore most of these transcriptomics and phenotypic effects.

In response to injury, vascular smooth muscle cells (VSMCs) of the arterial wall dedifferentiate into a proliferative and migratory phenotype, leading to intimal hyperplasia. The ERK1/2 pathway participates in cellular proliferation and migration while dual-specificity phosphatase 6 (DUSP6, also named MKP3) can dephosphorylate activated ERK1/2. We showed that DUSP6 was expressed in low baseline levels in normal arteries; however, arterial injury significantly increased DUSP6 levels in the vessel wall. Compared with wild-type mice, Dusp6-deficient mice had smaller neointima. In vitro, IL-1β induced DUSP6 expression and increased VSMC proliferation and migration. Lack of DUSP6 diminished IL-1β-induced VSMC proliferation and migration. DUSP6 deficiency did not affect IL-1β-stimulated ERK1/2 activation. Instead, ERK1/2 inhibitor U0126 prevented DUSP6 induction by IL-1beta, indicating that ERK1/2 functions upstream of DUSP6 to regulate DUSP6 expression in VSMCs rather than downstream as a DUSP6 substrate. IL-1β decreased levels of cell cycle inhibitor p27 and cell-cell adhesion molecule N-cadherin in VSMCs whereas lack of DUSP6 prevented their downregulation, revealing novel functions of DUSP6 in regulating these two molecules. Taken together, our results indicate that lack of DUSP6 attenuated neointima formation following arterial injury by reducing VSMC proliferation and migration, which were likely mediated via maintaining p27 and N-cadherin levels.

The main known function of Nudix hydrolase 2 (Nudt2) is to hydrolyze the secondary messenger diadenosine 5', 5’’’-p1, p4-tetraphosphate (Ap4A). In this study we examined the role of Nudt2 in breast carcinoma through its expression in the human invasion ductal carcinoma tissues, and its functions in human triple negative breast cancer (TNBC) cell lines. A significantly high expression of Nudt2 in the human invasion ductal carcinoma tissues was observed in our study. Knockdown of Nudt2 in TNBC cell lines showed a significant reduction in cellular proliferation via the Ki67 marker, accompanied by G0/G1 phase cell cycle arrest. A significant reduction in the migration and invasion of Nudt2 knockdown TNBC cell lines was also observed. The effect of Nudt2 knockdown in the TNBC cell lines on tumorigenicity and anchorage-independent growth was assessed, where significant reductions in the Nudt2 knockdown TNBC cell lines were found. It can therefore be concluded that Nudt2 plays a significant role in promoting TNBC growth.

As a fundamental, overall, and strategic issue facing human society, human migration is a key factor affecting the development of countries and cities given constantly changing population numbers. The fuzziness of the spatiotemporal attributes of human migration limits the pool of open-source data for human migration prediction, leading to a relative lag in human migration prediction algorithm research. This study expands the definition of human migration research, reviews the progress of research into human migration prediction, and classifies and compares human migration algorithms based on open-source data. It also explores the critical uncertainty factors restricting the development of human migration prediction. Given the effect of human migration prediction, in combination with artificial intelligence and big data technology, the paper concludes with specific suggestions and countermeasures aimed at enhancing human migration prediction research results to serve economic and social development and national strategy.

Cellular locomotion is required for survival, fertility, proper embryonic development, regeneration, and wound healing. Cell migration is a major component of metastasis, which accounts for two-thirds of all solid tumor deaths. While many studies have demonstrated increased energy requirements, metabolic rates, and migration of cancer cells compared to normal cells, few have systematically compared normal and cancer cell migration as well as energy requirements side by side. Thus, we investigated how non-malignant and malignant cells migrate utilizing several cell lines from the breast and lung. Initial screening was done in an unbiased high-throughput manner for the ability to migrate/invade on collagen and/or Matrigel. We unexpectedly observed that all the non-malignant lung cells moved significantly faster than cells derived from lung tumors regardless of growth media used. Given the paradigm-shifting nature of our discovery, we pursued possible mechanisms responsible. Neither mass, cell doubling, nor volume, accounted for the individual speed and track length of the normal cells. Non-malignant cells had higher levels of ATP at premigratory-wound induction stages. Meanwhile, cancer cells also increased ATP at premigratory-wound induction – but not to the levels of the normal cells, indicating the possibility for further therapeutic investigation.

In the year in which the world "stopped" due to the pandemic, many people didn't have that option and had to keep moving as the only alternative to survive. One of the main destinations in South America, during the quarantine measures established around the world, was Brazil, especially because of the crisis Venezuela went through in the second half of the 2010s. Throughout the research, we observed measures that were applied by the Brazilian government on the grounds of public health issues or cases of health risks related to COVID-19. An analysis of the first measures published by the Brazilian government reveals an effort to securitize borders, which at the same time restricted the government's responsibility to fulfil its role of protecting migrants in need.

This study posits that for appropriately explaining the complex charland (mid-channel island) processes and formulating policy and planning measures, a comprehensive understanding of the dynamic characteristics of the geomorphological, ecological, and human systems holistically is essential. This is also valid for the territorial and maritime areas of Bangladesh. The objectives of this study are: (i) to analyze the salient features and characteristics of the geomorphological and riparian systems of the Bengal Delta; (ii) to analyze the evolutionary discourse of the legal systems concerning eroded (diluvion) and accreted (alluvion) land in Bangladesh; and (iii) to assess characteristics of coping and adaptation strategies of the charland inhabitants. The findings reveal that the delta-building processes, characterized by the dynamic shifts of river channels, and erosion and accretion of charlands have made the land and water systems of the territory very dynamic and unstable – resulting in consistent displacement of settlers and serious deterioration of their socioeconomic status. The historical evolution of land laws and regulations concerning the accreted land favoured vested interests. As no effective institutional framework and structure presently exists in Bangladesh for resettlement planning, formulation of a comprehensive national resettlement policy is therefore urgently needed.

In a rapidly evolving global landscape characterized by increased international travel, migration, and ecological shifts, this study sheds light on the emergence of protozoal and helminthic infections targeting the central nervous system (CNS) within Europe. Despite being traditionally associated with tropical regions, these infections are progressively becoming more prevalent in non-endemic areas. By scrutinizing the inherent risks, potential outcomes, and attendant challenges, this study underscores the intricate interplay between diagnostic limitations, susceptibility of specific population subsets, and the profound influence of climate fluctuations. The contemporary interconnectedness of societies serves as a conduit for the introduction and establishment of these infections, warranting comprehensive assessment. This study emphasizes the pivotal role of heightened clinician vigilance, judicious public health interventions, and synergistic research collaborations to mitigate the potential consequences of these infections. Though rare, their profound impact on morbidity and mortality underscores the collective urgency required to safeguard the neurological well-being of the European populace. Through this multifaceted approach, Europe can effectively navigate the complex terrain posed by these emergent infections.

Protein O-GlcNAcylation has been associated with neurodegenerative diseases such as Alzheimer´s disease (AD). O-GlcNAcylation of Amyloid Precursor Protein (APP) regulates both the trafficking and the processing of the APP through the amyloidogenic pathway, resulting in the release and aggregation of the Aβ1-42 peptide. Microglia clear Aβ aggregates and dead cells to maintain brain homeostasis. Here, using LC-MS/MS we reveal that the Aβ1-42 peptide modifies the microglia O-GlcNAcome. We have identified 55 proteins, focusing our research on Galectin-1 protein, since it is a very versatile protein from a functional point of view. Combining biochemical with genetic approaches we demonstrate that Aβ1-42 peptide specifically targets Galectin-1S8 O-GlcNAcylation via OGT. In addition, this Gal-1-O-GlcNAcylated form, in turn, controls human microglia migration. Given the importance of microglia migration in the progression of AD, this study reports the relationship between Aβ1-42 peptide and Serine 8- O-GlcNAcylation of Galectin to drive microglial migration

Deficient wound healing is frequently observed in patients diagnosed with diabetes, a clinical complication that compromises mobility and leads to limb amputation, decreasing patient autonomy and family lifestyle. Fibroblasts are crucial for secreting the extracellular matrix to pave the wound site for endothelial and keratinocyte regeneration. The biosynthetic pathways for collagen production are one of the main components of the extracellular matrix, as the crosslinking of extracellular collagen fibers is intimately related to fibroblast redox homeostasis. In this study, human dermic fibroblasts were cultured with 1 mM sodium selenite (inorganic) and 1 mM of two selenium amino acids (organic), Se-cysteine and Se-methionine. This concentration was compatible with long-term exposure necessary for extracellular matrix production and allowed us to examine the impact of these three compounds on the state and response of the thiol-based HyPer biosensor expressed in the cytoplasm. In addition, the abundance of extracellular matrix and ultrastructural properties were evaluated by Picrus Sirius red staining and scanning electronic microscopy, respectively. We also evaluated whether these selenium compounds effectively ameliorated the perturbations induced by culturing fibroblasts at high glucose levels (25 mM) regarding cytoplasmic redox, extracellular matrix, and glycation on collagen fibers. Our results indicate that cytoplasm protein oxidation was sensitive to selenium compound supplementation. Selenium amino acids increased the sensitivity to protein oxidation, and only Se-cysteine increased the disulfide bond reduction in fibroblasts maintained in high glucose. Despite the lack of effect of selenium compounds on the glu-cose-induced increase in matrix fiber thickness, we found that endothelial migration improved in the matrix generated by high glucose-cultured fibroblasts.

Genetic discoveries related to Alzheimer’s disease and other dementias have been performed using either large cohorts of affected subjects or multiple individuals from the same pedigree, therefore disregarding mutations in the context of healthy groups. Moreover, a large portion of studies so far have been performed on individuals of European ancestry, with a remarkable lack of epidemiological and genomic data from underrepresented populations. The present study aims at scanning 70 single-point mutations on the APP gene in a publicly available genetic dataset including 2.504 healthy individuals from 26 populations, and analyzing their distribution. Moreover, after gametic phase reconstruction, a pairwise comparison of the segments surrounding the mutations was performed to reveal patterns of haplotype sharing that could point to specific cross-population and cross-ancestry admixture events. Eight mutations have been detected in the worldwide dataset, with several of them being specific for a single individual, population or macroarea. Patterns of segment sharing reflect recent historical events of migration and admixture possibly linked to colonization campaigns. These observations reveal the population dynamics of the considered APP mutations in worldwide human groups, and support the development of ancestry-informed screening practices for the improvement of precision and personalized approaches to neurodegeneration and dementias.

This study aimed to evaluate the proliferation and migration of fibroblast cells derived from chronic wounds and investigate the impact of low-level laser therapy (LLLT) on their growth and migration. A total of 60 dermal samples were obtained from three sites of chronic pressure ulcers and diabetic ulcers in 20 patients. Following collection in the operating room, the dermal samples were isolated using the procedure described by Freshney RI. Fibroblasts from the wound base (Site 1) exhibited a slow proliferation rate and a decrease in proliferative capacity. Fibroblasts from wound margins (Site 2) and adjacent healing skin (Site 3) could be successfully isolated and maintained for multiple generations without any morphological changes. Fibroblasts from chronic wounds at Sites 2 and 3 showed slower proliferation rates and reduced migration capabilities compared to normal dermal fibroblasts (control samples). The fibroblast cells were exposed to LLLT at different energy levels (2.5, 3, and 3.5 J/cm2). The laser-treated groups demonstrated a significantly higher increase in cell count compared to the control sample, with the highest increase observed at an energy level of 3 J/cm2. These findings suggest that LLLT at an energy level of 3 J/cm2 could effectively enhance fibroblast migration, indicating its potential as a therapeutic intervention for chronic wounds.