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.

Movement and Perceptual Strategies to Intercept Virtual Sound Sources

To intercept a moving object, one needs to be in the right place at the right time. In order to do this, it is necessary to pick up and use perceptual information that specifies the time to arrival of an object at an interception point. In the present study, we examined the ability to intercept a laterally moving virtual sound object by controlling the displacement of a sliding handle and tested whether and how the interaural time difference (ITD) could be the main source of perceptual information for successfully intercepting the virtual object. The results revealed that in order to accomplish the task, one might need to vary the duration of the movement, control the hand velocity and time to reach the peak velocity (speed coupling), while the adjustment of movement initiation did not facilitate performance. Furthermore, the overall performance was more successful when subjects employed a time-to-contact (tau) coupling strategy. This result shows that prospective information is available in sound for guiding goal-directed actions.

Mutant p53 expression in fallopian tube epithelium drives cell migration

Ovarian cancer is the fifth leading cause of cancer death among US women. Evidence supports the hypothesis that high-grade serous ovarian cancers (HGSC) may originate in the distal end of the fallopian tube. Although a heterogeneous disease, 96% of HGSC contain mutations in p53. In addition, the "p53 signature," or overexpression of p53 protein (usually associated with mutation), is a potential precursor lesion of fallopian tube derived HGSC suggesting an essential role for p53 mutation in early serous tumorigenesis. To further clarify p53-mutation dependent effects on cells, murine oviductal epithelial cells (MOE) were stably transfected with a construct encoding for the R273H DNA binding domain mutation in p53, the most common mutation in HGSC. Mutation in p53 was not sufficient to transform MOE cells but did significantly increase cell migration. A similar p53 mutation in murine ovarian surface epithelium (MOSE), another potential progenitor cell for serous cancer, was not sufficient to transform the cells nor change migration suggesting tissue specific effects of p53 mutation. Microarray data confirmed expression changes of pro-migratory genes in p53(R273H) MOE compared to parental cells, which could be reversed by suppressing Slug expression. Combining p53(R273H) with KRAS(G12V) activation caused transformation of MOE into high-grade sarcomatoid carcinoma when xenografted into nude mice. Elucidating the specific role of p53(R273H) in the fallopian tube will improve understanding of changes at the earliest stage of transformation. This information can help develop chemopreventative strategies to prevent the accumulation of additional mutations and reverse progression of the "p53 signature" thereby, improving survival rates.

A new microtubule-targeting compound PBOX-15 inhibits T-cell migration via post-translational modifications of tubulin

The ordered, directional migration of T-lymphocytes is a key process during immune surveillance, immune response, and development. A novel series of pyrrolo-1,5-benzoxazepines have been shown to potently induce apoptosis in variety of human chemotherapy resistant cancer cell lines, indicating their potential in the treatment of both solid tumors and tumors derived from the hemopoietic system. Pyrrolobenzoxazepine 4-acetoxy-5-(1-naphtyl)naphtho[2,3-b]pyrrolo[1,2-d][1,4]-oxazepine (PBOX-15) has been shown to depolymerize tubulin in vitro and in the MCF7 breast cancer cell line. We hypothesized that this may suggest a role for this compound in modulating integrin-induced T-cell migration, which is largely dependent on the microtubule dynamics. Experiments were performed using human T lymphoma cell line Hut78 and peripheral blood T-lymphocytes isolated from healthy donors. We observed that human T-lymphocytes exposed to PBOX-15 have severely impaired ability to polarize and migrate in response to the triggering stimulus generated via cross-linking of integrin lymphocyte function associated antigen-1 receptor. Here, we show that PBOX-15 can dramatically impair microtubule network via destabilization of tubulin resulting in complete loss of the motile phenotype of T-cells. We demonstrate that PBOX-15 inhibitory mechanisms involve decreased tubulin polymerization and its post-translational modifications. Novel microtubule-targeting effects of PBOX-15 can possibly open new horizons in the treatment of overactive inflammatory conditions as well as cancer and cancer metastatic spreading.

Interleukin-8 is associated with proliferation, migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models

Interleukin-8 (IL-8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Overexpression of IL-8 has been detected in many human tumors, including colorectal cancer (CRC), and is associated with poor prognosis. The goal of our study was to determine the role of IL-8 overexpression in CRC cells in vitro and in vivo. We stably transfected the IL-8 cDNA into two human colon cancer cell lines, HCT116 and Caco2, and selected IL-8-secreting transfectants. Real-time RT-PCR confirmed that IL-8 mRNA was overexpressed in IL-8 transfectants with 45- to 85-fold higher than parental cells. The IL-8-transfected clones secreted 19- to 28-fold more IL-8 protein than control and parental cells as detected by ELISA. The IL-8 transfectants demonstrated increased cellular proliferation, cell migration and invasion based on functional assays. Growth inhibition studies showed that IL-8 overexpression lead to a significant resistance to oxaliplatin (p < 0.0001). Inhibition of IL-8 overexpression with small interfering RNA reversed the observed increases in tumorigenic functions and oxaliplatin resistance, suggesting that IL-8 not only provides a proliferative advantage but also promotes the metastatic potential of colon cancer cells. Using a tumor xenograft model, IL-8-expressing cells formed significantly larger tumors than the control cells with increased microvessel density. Together, these findings indicate that overexpression of IL-8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL-8 to be an important therapeutic target in CRC.

Exploiting Human Resource Requirements to Infer Human Movement Patterns for Use in Modelling Disease Transmission Systems: An Example from Eastern Province, Zambia

In this research, an agent-based model (ABM) was developed to generate human movement routes between homes and water resources in a rural setting, given commonly available geospatial datasets on population distribution, land cover and landscape resources. ABMs are an object-oriented computational approach to modelling a system, focusing on the interactions of autonomous agents, and aiming to assess the impact of these agents and their interactions on the system as a whole. An A* pathfinding algorithm was implemented to produce walking routes, given data on the terrain in the area. A* is an extension of Dijkstra's algorithm with an enhanced time performance through the use of heuristics. In this example, it was possible to impute daily activity movement patterns to the water resource for all villages in a 75 km long study transect across the Luangwa Valley, Zambia, and the simulated human movements were statistically similar to empirical observations on travel times to the water resource (Chi-squared, 95% confidence interval). This indicates that it is possible to produce realistic data regarding human movements without costly measurement as is commonly achieved, for example, through GPS, or retrospective or real-time diaries. The approach is transferable between different geographical locations, and the product can be useful in providing an insight into human movement patterns, and therefore has use in many human exposure-related applications, specifically epidemiological research in rural areas, where spatial heterogeneity in the disease landscape, and space-time proximity of individuals, can play a crucial role in disease spread.

Footprints in the sand: a persistent spatial impression of fishing in a mobile groundfish assemblage

Fishing is well known to curtail the size distribution of fish populations. This paper reports the discovery of small-scale spatial patterns in length appearing in several exploited species of Celtic Sea demersal 'groundfish'. These patterns match well with spatial distributions of fishing activity, estimated from vessel monitoring records taken over a period of 6 years, suggesting that this 'mobile' fish community retains a persistent impression of local-scale fishing pressure. An individual random-walk model of fish movement best matched these exploitation 'footprints' with individual movement rates set to <35 km per year. We propose that Celtic Sea groundfish may have surprisingly low movement rates for much of the year, such that fishing impact is spatially heterogeneous and related to local fishing intensity.

EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer

PURPOSE: EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumor initiation, neovascularization, and metastasis in a wide range of epithelial and mesenchymal cancers; however, its role in colorectal cancer recurrence and progression is unclear.

EXPERIMENTAL DESIGN: EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumors (N = 338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive colorectal cancer cell line models.

RESULTS: Colorectal tumors displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III colorectal cancer tissues, in both univariate and multivariate analyses. Preclinically, we found that EphA2 was highly expressed in KRASMT colorectal cancer cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines, and downregulation of EphA2 using RNAi or recombinant EFNA1 suppressed migration and invasion of KRASMT colorectal cancer cells.

CONCLUSIONS: These data show that EpHA2 is a poor prognostic marker in stage II/III colorectal cancer, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target. Clin Cancer Res; 22(1); 230-42. ©2015 AACR.

Step by step: reconstruction of terrestrial animal movement paths by dead-reckoning

BACKGROUND: Research on wild animal ecology is increasingly employing GPS telemetry in order to determine animal movement. However, GPS systems record position intermittently, providing no information on latent position or track tortuosity. High frequency GPS have high power requirements, which necessitates large batteries (often effectively precluding their use on small animals) or reduced deployment duration. Dead-reckoning is an alternative approach which has the potential to 'fill in the gaps' between less resolute forms of telemetry without incurring the power costs. However, although this method has been used in aquatic environments, no explicit demonstration of terrestrial dead-reckoning has been presented.

RESULTS: We perform a simple validation experiment to assess the rate of error accumulation in terrestrial dead-reckoning. In addition, examples of successful implementation of dead-reckoning are given using data from the domestic dog Canus lupus, horse Equus ferus, cow Bos taurus and wild badger Meles meles.

CONCLUSIONS: This study documents how terrestrial dead-reckoning can be undertaken, describing derivation of heading from tri-axial accelerometer and tri-axial magnetometer data, correction for hard and soft iron distortions on the magnetometer output, and presenting a novel correction procedure to marry dead-reckoned paths to ground-truthed positions. This study is the first explicit demonstration of terrestrial dead-reckoning, which provides a workable method of deriving the paths of animals on a step-by-step scale. The wider implications of this method for the understanding of animal movement ecology are discussed.

The Emerging Church Movement: A Sociological Assessment

With so many voices, groups, and organizations participating in the Emerging Church Movement (ECM), few are willing to “define” it, though authors have offered various definitions. Emerging Christians themselves do not offer systematic or coherent definitions, which contributes to frustration in isolating it as a coherent group – especially for sociologists who strive to define and categorize. In presenting our understanding of this movement, we categorize Emerging Christianity as an orientation rather than an identity, and focus on the diverse practices within what we describe as “pluralist congregations” (often called “gatherings,” “collectives” or “communities” by Emerging Christians themselves). This leads us to define the ECM as a creative, entrepreneurial religious movement that strives to achieve social legitimacy and spiritual vitality by actively disassociating from its roots in conservative, evangelical Christianity. Our findings are extensively developed in The Deconstructed Church: Understanding Emerging Christianity (Marti and Ganiel 2014).

Cross-border Movement of Patients in the EU: A Re-Appraisal

The national welfare state, so it seems, has come under attack by European integration. This article focuses on one facet of the welfare state, that is, health care and on one specific dimension, that is, cross-border movement of patients. The institution which has played a pivotal role in the development of the framework regulating the migration of patients is the European Court of Justice (ECJ). The Court’s activity in this sensitive area has not remained without critics. This was even more so since the Court invoked Treaty (primary) law which not only has made it difficult to overturn case law but also has left the legislator with very little room for manoeuvre in relation to any future (secondary) EU law. What is therefore of special interest in terms of legitimacy is the legal reasoning by which the Court has made its contribution to the development of this framework. This article is a re-appraisal of the legal development in this field.