Macrophage migration inhibitory factor (MIF) expression in human malignant gliomas contributes to immune escape and tumour progression

Macrophage migration inhibitory factor (MIF), which inhibits apoptosis and promotes angiogenesis, is expressed in cancers suppressing immune surveillance. Its biological role in human glioblastoma is, however, only poorly understood. We examined in-vivo expression of MIF in 166 gliomas and 23 normal control brains by immunohistochemistry. MIF immunoreactivity was enhanced in neoplastic astrocytes in WHO grade II glioma and increased significantly in higher tumour grades (III-IV). MIF expression was further assessed in 12 glioma cell lines in vitro. Quantitative RT-PCR showed that MIF mRNA expression was elevated up to 800-fold in malignant glioma cells compared with normal brain. This translated into high protein levels as assessed by immunoblotting of total cell lysates and by ELISA-based measurement of secreted MIF. Wild-type p53-retaining glioma cell lines expressed higher levels of MIF, which may be connected with the previously described role of MIF as a negative regulator of wild-type p53 signalling in tumour cells. Stable knockdown of MIF by shRNA in glioma cells significantly increased tumour cell susceptibility towards NK cell-mediated cytotoxicity. Furthermore, supernatant from mock-transfected cells, but not from MIF knockdown cells, induced downregulation of the activating immune receptor NKG2D on NK and CD8+ T cells. We thus propose that human glioma cell-derived MIF contributes to the immune escape of malignant gliomas by counteracting NK and cytotoxic T-cell-mediated tumour immune surveillance. Considering its further cell-intrinsic and extrinsic tumour-promoting effects and the availability of small molecule inhibitors, MIF seems to be a promising candidate for future glioma therapy.

Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D

The proinflammatory cytokine macrophage migration inhibitory factor (MIF) stimulates tumor cell proliferation, migration, and metastasis; promotes tumor angiogenesis; suppresses p53-mediated apoptosis; and inhibits antitumor immunity by largely unknown mechanisms. We here describe an overexpression of MIF in ovarian cancer that correlates with malignancy and the presence of ascites. Functionally, we find that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells. Together with the additional tumorigenic properties of MIF, this finding provides a rationale for novel small-molecule inhibitors of MIF to be used for the treatment of MIF-secreting cancers.

"...and they won land among the Picts by friendly treaty or the sword": How a re-examination of early historical sources and an analysis of early medieval settlement in north Co. Antrim confirms the validity of traditional accounts of Dál Riatic migration to Scotland from Ulster

Much recent scholarship has been critical of the concept of a Dál Riatic migration to, or colonisation of, Argyll. Scepticism of the accuracy of the early medieval accounts of this population movement, arguing that these are late amendments to early sources, coupled with an apparent lack of archaeological evidence for such a migration have led to its rejection. It is argued here, however, that this rejection has been based on too narrow a reading of historical sources and that there are several early accounts which, while differing in detail, agree on one point of substance, that the origin of Scottish Dál Riata lies in Ireland. Also, the use of archaeological evidence to suggest no migration to Argyll by the Dál Riata is flawed, misunderstanding the nature of early migrations and how they might be archaeologically identified, and it's proposed that there is actually quite a lot of evidence for migration to Argyll by the Dál Riata, in the form of settlement and artefactural evidence, but that it is to be found in Ireland through the mechanism of counterstream migration, rather than in Scotland.

KIF2A silencing inhibits the proliferation and migration of breast cancer cells and correlates with unfavorable prognosis in breast cancer

Background: Kinesin family member 2a (KIF2A), a type of motor protein found in eukaryotic cells, is associated with development and progression of various human cancers. The role of KIF2A during breast cancer tumorigenesis and progression was studied.

Methods: Immunohistochemical staining, real time RT-PCR and western blot were used to examine the expression of KIF2A in cancer tissues and adjacent normal tissues from breast cancer patients. Patients' survival in relation to KIF2A expression was estimated using the Kaplan-Meier survival and multivariate analysis. Breast cancer cell line, MDA-MB-231 was used to study the proliferation, migration and invasion of cells following KIF2A-siRNA transfection.

Results: The expression of KIF2A in cancer tissues was higher than that in normal adjacent tissues from the same patient (P <0.05). KIF2A expression in cancer tissue with lymph node metastasis and HER2 positive cancer were higher than that in cancer tissue without (P <0.05). A negative correlation was found between KIF2A expression levels in breast cancer and the survival time of breast cancer patients (P <0.05). In addition, multivariate analysis indicated that KIF2A was an independent prognostic for outcome in breast cancer (OR: 16.55, 95% CI: 2.216-123.631, P = 0.006). The proliferation, migration and invasion of cancer cells in vitro were suppressed by KIF2A gene silencing (P <0.05).

Conclusions: KIF2A may play an important role in breast cancer progression and is potentially a novel predictive and prognostic marker for breast cancer.

Retirement Transition Migration: Implications for Rural Development

Recent literature suggests that the increasingly blurred relationship between paid employment and retirement facilitates a retirement transition period, a life course stage which may involve a change of residence. The role of pre-retirement mobility in the repopulation of rural areas has, however, received relatively little academic scrutiny from UK geographers. This article draws upon findings from a two-year study conducted in three UK case study areas. It examines the extent of pre-retirement age (aged 50-64) migration into rural communities and the impacts this type of movement has upon economic activity, social and community engagement and service provision. It is argued that while this under-researched group offers significant potential to support the social and economic sustainability of rural communities (at least in the short and medium term), there are notable regional variations which are likely to have important long term implications for rural communities as this cohort ages in situ.

Rural Migration, Agrarian Change and Institutional Dynamics: Perspectives from the Majority World

Overall, this special issue provides insights into the mutually constitutive ways in which rapid economic development associated with industrialisation drives institutional change, migration and mobility, and, finally, altered relationships between – and conceptions of – rural and urban. The following papers pose important conceptual, normative as well as practical, policy-relevant questions relating to the human consequences of these processes and point to the applications of population research – a central objective of this journal.

Patterns and processes of recent migration to Northern Ireland

This paper describes patterns and processes of recent migration in Northern Ireland. A conceptual approach is provided for spatial understandings of migration in new destinations, and the role of context is explored with regard to migration to a divided society. Recent migration to Northern Ireland is characterised and the geography of migrant residences evidenced in the 2011 Census is presented. Key patterns include the rural nature of migration in Northern Ireland, variation among migrant groups, and the spatial concentration of migrant communities. This exploration of spatial patterns is expanded on through a consideration of the processes of migration and diversification according to the themes of Finding Housing and Neighbourhood Interactions. In conclusion we explore the implications of the data presented, reflecting on spatial problems and spatial solutions in diversifying Northern Ireland.

After the Male Breadwinner Model? Childcare Services and the Division of Labor in European Countries

Fundamental reforms in childcare services appear to have eroded traditional
support to the male breadwinner model across European states. There has been a strong debate about the direction of these changes, and the ways in which childcare services can alter the division of labor and promote gender equality. This paper deals with these issues by using fuzzy set ideal-type analysis to assess the conformity of childcare service provisions in European economies to Fraser’s four ideal typical models: male breadwinner, caregiver parity, universal breadwinner, and universal caregiver. We find that there is resilience of traditional gender roles in the majority of European countries, while there are different variants of the universal breadwinner shaping different forms of childcare policies. The more equalitarian universal caregiver model maintains its utopian character.

Conductivity sensor technology application in steady state migration test

In this paper the current development of the steady state migration test was reviewed. Experiments were carried out for a series of concrete mixes with the steady state migration test in which conductivity sensor technology is applied. With the developed steady state migration test, conductivity in anolyte, loop current and temperature can be monitored in real time. The experimental results are conductive to understand the mechanism of chloride migration during both unsteady state and steady state. The conductivity of anolyte could be used to calculate the chloride concentration in anolyte and the theoretical correlation between them was explained. Over all, the developed steady state migration is an effective, convenient, well-defined in theory and plentiful with information method which could be used to determine the chloride diffusion coefficient of cementitious materials.

The Well-Aligned Orbit of Wasp-84b: Evidence for Disk Migration of a Hot Jupiter

We report the sky-projected orbital obliquity (spin–orbit angle) of WASP-84 b, a 0.69MJup planet in an 8.52 day orbit around a G9V/K0V star, to be λ = −0.3 ± 1.7°. We obtain a true obliquity of ψ = 17.3 ± 7.7° from a measurement of the inclination of the stellar spin axis with respect to the sky plane. Due to the young age and the weak tidal forcing of the system, we suggest that the orbit of WASP-84b is unlikely to have both realigned and circularized from the misaligned and/or eccentric orbit likely to have arisen from high-eccentricity migration. Therefore we conclude that the planet probably migrated via interaction with the protoplanetary disk. This would make it the first “hot Jupiter” (P d < 10 ) to have been shown to have migrated via this pathway. Further, we argue that the distribution of obliquities for planets orbiting cool stars (Teff < 6250 K) suggests that high-eccentricity migration is an important pathway for the formation of short-orbit, giant planets.

Barriers to Subcontracted Labor Productivity in Urban Development Projects: An On-site Project Management Perspective

Considering the confined and complex nature of urban construction projects, labor productivity is one of the key factors attributing to project success. With the proliferation of sub-contracted labor, there is a necessity to consider the ramifications of this practice to the sector. This research aims to outline how project managers can optimise productivity levels of sub-contracted labor in urban construction projects, by addressing the barriers that most restrict these efficiency levels. A qualitative research approach is employed, incorporating semi-structured interviews based on three case studies from an urban context. The results are scrutinised using mind mapping software and accompanying analytical techniques. The findings from this research indicate that the effective on-site management of sub-contracted labor has a significant impact on the degree of success of an urban development project. The two core barriers to sub-contracted labor productivity are; 1) ineffective supervision of sub-contracted labor, and 2) lack of skilled sub-contracted labor. The implication of this research is that on-site project management play an integral role in the level of productivity achieved by sub-contracted labor in urban development projects. Therefore, on-site management situated in urban, confined construction sites, are encouraged to take heed of the findings herein and address the barriers documented. The value of this research is obtained through consideration of the critical factors; construction management professionals can mitigate such barriers, in order to optimise subcontracted labor productivity on-site.

Contemporary and 'messy' rural in-migration processes: Comparing counterurban and lateral rural migration.

This paper questions the ongoing dominant coverage given to counterurbanisation in the rural population literature. It is argued that this provides only a partial account of the true diversity of contemporary migration processes operating in rural areas and has the potential to fuse together different in-migration processes. Specifically, lateral rural migration has been under-researched to date. Using empirical data from a survey of 260 migrant households to 3 UK case study areas (in Scotland, Wales, and Northern Ireland), the significance of lateral rural migration is revealed and compared with counterurban migration and migrants. The last change of address shows that 59% relocated from an urban area (participating in a counterurban flow) whilst 41% moved from another rural location (lateral rural flow). The boundary between migration processes can, however, be blurred: Some moves are an example of both counterurbanisation and lateral rural flows. Incorporating lifetime migration histories data demonstrates the contemporary complexity and messiness of rural in-migration processes. For example, 26% of these migrant households only ever undertook a lateral rural move during their lifetime. For others, the direction of migration has changed numerous times and intertwined with each move are aspects of life course, return, and inter-regional migration. Comparing the survey characteristics and motivations of counterurban and lateral rural migrants, alongside interview material, highlights important similarities and differences. The paper concludes by calling on rural population geographers to more fully engage with the complexity, totality, and indeed messiness of contemporary rural in-migration processes.