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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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”.

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.

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 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.