Opportunities for new research using the post-2001 ONS Longitudinal Study

The addition of 2001 Census data to the ONS Longitudinal Study extends the range of research topics that this unique data resource can support. Census questions on religion, care-giving and self-rated health that were asked for the first time in 2001 and the repetition of 1991 questions on limiting long-standing illness and ethnicity raise opportunities for new longitudinal investigation in these areas. This article describes how new 2001 methodologies including data imputation, the One Number Census and de jure enumeration affect the LS database. The support service for existing and prospective LS users is described.     

Status of an invading mainland jackrabbit on Cerralvo island, Gulf of California

We report the first observations of the black-tailed jackrabbit ( Lepus californicus ) on Cerralvo Island, Baja California Sur, Mexico. Evidence suggests a self-sustaining population. Analysis of available records indicates no previous record of Lepus on the island. Introduction of the jackrabbit to the island appears to have occurred between 1960 and 1991.     

Stability and change in ethnic groups in England and Wales

The Office for National Statistics (ONS) Longitudinal Study (LS) is an exceptional resource for exploring dynamic processes in individuals' lives for a representative sample of the population of England and Wales and across a thirty year period, including how those processes vary by ethnic group. However, analyses tend to assume a certain stability in the meaning of the ethnic group being studied: the insights into ethnic group differentiation are premised on the fact that the group has the same meaning over time. Here we show how the LS allows us to challenge such notions of group stability. This has practical implications for the ways we measure and conceive of Britain's minority ethnic groups. We illustrate this point with two examples: one exploring the change in ethnic group identification by the same individuals between 1991 and 2001, and the second exploring how loss to follow up is differentially experienced according to ethnic group. We provide some suggestions on the implications of this ethnic group instability for other research.     

NHE3 phosphorylation via PKCη marks the polarity and orientation of directionally migrating cells

Endogenous electric fields (EF) may provide an overriding cue for directional cell migration during wound closure. Perceiving a constant direction requires active sodium-hydrogen exchanger (pNHE3) at the leading edge of HEK 293 cells but its activation mechanism is not yet fully understood. Because protein kinase C (PKC) is required in electrotaxis, we asked whether NHE3 is activated by PKC during wound healing. Using pharmacological (pseudosubstrate and edelfosine) inhibition, we showed that inhibition of PKCη isoform impairs directional cell migration in HEK 293 cells in the presence of a persistent directional cue (0.25–0.3 V/mm of EF for 2 h). Further, we found that pNHE3 forms complexes with both PKCη and ?-tubulin, suggesting that these molecules may regulate the microtubule-organizing center. In addition, cellular pNHE3 content was reduced significantly when PKCη was inhibited during directional cell migration. Taken together, these data suggest that PKCη-dependent phosphorylation of NHE3 and the formation of pNHE3/PKCη/?-tubulin complexes at the leading edge of the cell are required for directional cell migration in an EF.     

BAP1 loss defines a new class of renal cell carcinoma

The molecular pathogenesis of renal cell carcinoma (RCC) is poorly understood. Whole-genome and exome sequencing followed by innovative tumorgraft analyses (to accurately determine mutant allele ratios) identified several putative two-hit tumor suppressor genes, including BAP1. The BAP1 protein, a nuclear deubiquitinase, is inactivated in 15% of clear cell RCCs. BAP1 cofractionates with and binds to HCF-1 in tumorgrafts. Mutations disrupting the HCF-1 binding motif impair BAP1-mediated suppression of cell proliferation but not deubiquitination of monoubiquitinated histone 2A lysine 119 (H2AK119ub1). BAP1 loss sensitizes RCC cells in vitro to genotoxic stress. Notably, mutations in BAP1 and PBRM1 anticorrelate in tumors (P = 3 × 10(-5)), and combined loss of BAP1 and PBRM1 in a few RCCs was associated with rhabdoid features (q = 0.0007). BAP1 and PBRM1 regulate seemingly different gene expression programs, and BAP1 loss was associated with high tumor grade (q = 0.0005). Our results establish the foundation for an integrated pathological and molecular genetic classification of RCC, paving the way for subtype-specific treatments exploiting genetic vulnerabilities.