Rapid changes in the range limits of scots pine 4000 years ago.

Paleoecological data provide estimates of response rates to past climate changes. Fossil Pinus sylvestris stumps in far northern Scotland demonstrate former presence of pine trees where conventional pollen evidence of pine forests is lacking. Radiocarbon, dendrochronological, and fine temporal-resolution palynological data show that pine forests were present for about four centuries some 4000 years ago; the forests expanded and then retreated rapidly some 70 to 80 kilometers. Despite the rapidity of this response to climate change, it occurred at rates slower by an order of magnitude than those necessary to maintain equilibrium with forecast climate changes attributed to the greenhouse effect.

July temperatures in europe from pollen data, 6000 years before present.

Mean July temperatures across Europe 6000 years before present were reconstructed from palynological data by the transfer function method. Reconstructed summer temperatures were warmer than those at present over most of Europe with the greatest heating, more than 2 degrees C, in the midcontinent and the far north. This pattern is explained by high summer insolation and a weak zonal insolation gradient 6000 years before present and the effective heating of the landmass relative to ocean and coastal areas. A strong land-sea pressure gradient may in turn have increased westerly air flow into southern Europe, which is consistent with cooler reconstructed summer temperatures in the Mediterranean region, and reduced the environmental lapse rate in the central European mountains.

PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme.

BACKGROUND: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. METHODS: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semiquantitative polymerase chain reaction, and DNA sequencing. All statistical tests were two-sided. RESULTS: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P =.033, P =.001, and P<.001, respectively), and mutation of p53 was statistically significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P =.002) and p53 (P =.012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performance score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of prolonged survival in patients with glioblastoma multiforme who were older than 60 years of age. CONCLUSION: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.

A novel region of deletion on chromosome 6q23.3 spanning less than 500 Kb in high grade invasive epithelial ovarian cancer.

Detailed deletion mapping of chromosome 6q sequences in invasive ovarian tumors have implicated several broad regions involving 6q14-16, 6q21-23, 6q25-26, and the telomeric portion in band 6q27 as regions of frequent loss in this malignancy. In order to define regions of loss involved in the development of ovarian cancer, we used 23 polymorphic markers on 6q to examine allelic loss in 25 high-grade, late stage ovarian tumors. Four non-overlapping deletion regions were observed: (1) at 6q21-22.3 (D6S301-D6S292); (2) within a 1 cM region at 23.2-23.3 between markers D6S978-D6S1637 (at D6S311); (3) at 6q26 (between markers D6S411-D6S1277) and (4) at 6q27 with the markers D6S297 and D6S193. The highest region of loss was observed with marker D6S311 (lost in 17 of 19 informative cases, 89%) in 6q23.3, followed by D6S977 and D6S1637 (71 and 55%, respectively). The average fractional allele loss in the high-grade tumors was around 35%. Previous reports have shown 6q27 as the region of most frequent loss in invasive ovarian cancer. However, our results indicate a novel region in 6q23.3 (spanning less than 500 Kb distance between the markers) with the highest loss, implicating this region of chromosome 6q to harbor a putative tumor suppressor gene involved in the development of invasive epithelial ovarian cancer.

Sequence, expression and function of an mRNA encoding a soluble form of the human interleukin-6 receptor (sIL-6R).

Soluble receptors have been shown to be potent immunomodulators of their respective ligands. Since IL-6 is a central growth factor for myeloma cells, an sIL-6R may modulate IL-6 activity. We have previously reported a novel IL-6R mRNA from myeloma cells that exhibits a 94-nt deletion of the entire transmembrane domain from codons 356 (G-TG) to 387 (AG-G). The transmembrane domain deletion results in a shift in the translational reading frame with the insertion of 10 new amino acids followed by a stop codon. Sequence analysis shows the ligand-binding domain of the sIL-6R to be identical to that of the membrane-bound IL-6R up to the transmembrane domain deletion. The sIL-6R cDNA was expressed in QT-6 fibroblasts and PA-1 ovarian cells using the expression vector pCDM8. Supernates were immunoprecipitated with anti-IL-6R antibody and cells transfected with the sIL-6R cDNA produced a single band with a molecular weight of 50-55 kDa. This molecular weight corresponds to the size of the sIL-6R protein observed in normal human urine. Supernates were collected from mock or sIL-6R transfected PA-1 cells after 48 hours and assayed for their ability to stimulate or suppress the growth of an IL-6 dependent cell line, ANBL-6. Soluble IL-6R alone had no effect on the growth of the ANBL-6 cells. However, the growth of ANBL-6 cells by sIL-6R was potentiated in the presence of IL-6 and could be blocked by anti-IL-6 antibody. The above results suggest that, in the presence of IL-6, sIL-6R associates with gp130 leading to signal transduction and cell growth.

Responses of butterflies to twentieth century climate warming: implications for future ranges.

We analyse distribution records for 51 British butterfly species to investigate altitudinal and latitudinal responses to twentieth century climate warming. Species with northern and/or montane distributions have disappeared from low elevation sites and colonized sites at higher elevations during the twentieth century, consistent with a climate explanation. We found no evidence for a systematic shift northwards across all species, even though 11 out of 46 southerly distributed species have expanded in the northern part of their distributions. For a subset of 35 species, we model the role of climate in limiting current European distributions and predict potential future distributions for the period 2070-2099. Most northerly distributed species will have little opportunity to expand northwards and will disappear from areas in the south, resulting in reduced range sizes. Southerly distributed species will have the potential to shift northwards, resulting in similar or increased range sizes. However, 30 out of 35 study species have failed to track recent climate changes because of lack of suitable habitat, so we revised our estimates accordingly for these species and predicted 65% and 24% declines in range sizes for northern and southern species, respectively. These revised estimates are likely to be more realistic predictions of future butterfly range sizes.

Monoclonal antibodies specific for peptide epitopes of the epidermal growth factor receptor's extracellular domain.

The ErbB tyrosine kinase receptor family plays an important role in normal cellular growth and differentiation. In addition, ErbB receptor family members are commonly amplified and overexpressed in various human neoplasms and tumor-derived cell lines, where it is believed that increased signalling as a result of receptor overexpression may play an important role in oncogenesis. Consequently, ErbB receptor family members are being investigated rigorously as potential biomarkers of cancer and as therapeutic targets in malignant tissues. Numerous studies now demonstrate the existence of "soluble" ErbB (sErbB) analogs in normal and cancerous tissues. These sErbB proteins embody the extracellular domain (ECD) of the receptor only; they are generated by either proteolytic cleavage or from truncated, alternatively spliced mRNA transcripts. Recently, we have identified an alternate transcript of the human c-erbB1 (Epidermal Growth Factor Receptor) proto-oncogene from placenta that encodes a sErbB1 protein of 60-kDa. This protein, p60 sErbB1, is glycosylated and secreted when expressed in transfected tissue culture cells in vitro. Although "soluble" receptor analogs may play important physiological roles in intercellular communication, tissue morphogenesis, tissue regeneration and repair, and embryogenesis by inhibiting or stimulating specific mitogenic and pattern forming signals, their mechanism of action has not been thoroughly elucidated. To further characterize sErbB1 expression in human tissues and cell lines and to better understand their role in carcinogenesis and normal development, we have generated monoclonal antibodies (MAbs) toward specific peptide epitopes of ErbB1 extracellular subdomains III and IV. These antibody reagents are described here and should be useful experimental, preparative, analytical, diagnostic, and therapeutic reagents for the study of sErbB1 molecules in normal development and cancer.

Performance appraisal--in the search for the Holy Grail.

Despite the enormous body of literature concerning Performance Appraisal, when all is said and done, more seems to have been said than done--at least done effectively. This article analyses the conceptual and methodological basis of performance appraisal, to disclose the complexity of this common management evaluation instrument. There is a concentration on methodology. This has been a purposeful approach since organisations have been, and are most concerned with the search for a sound methodology, akin to a search for the Holy Grail. Several common measurement tools are examined and it is finally concluded that there is no one best way to measure performance. A scheme that is methodologically sound and conceptually pure does not exist.

Factors influencing recruitment and retention: why RNs work in rural and remote area hospitals.

This study aimed to construct a demographic profile of registered nurses employed in three rural and three remote area hospitals in NSW. The study also identified factors that contributed to the nurses seeking their present positions, intending to remain in them or leave. Interviews were conducted with 52 registered nurses and all 158 nurses employed in the hospitals were subsequently surveyed using a questionnaire developed on the basis of the interviews. The major positive professional factors that nurses associated with their employment were: employers' recognition of the importance of continuing professional education, good relations with peers and job satisfaction. A liking for country life and a preference for raising their children in country towns were the RNs' main personal reasons for seeking and remaining in their employment. The major negative professional factors of employment were: poor attitudes of doctors and administrators, employers' lack of understanding of professional needs, inadequate backup, staff shortages and inadequate access to professional education. Concerns about their children's education and the cost of educating children away from home were the most commonly cited personal reasons for leaving, or intending to leave, employment.

The lessons of palaeoecology re-taught.

Terrestrial Ecosystems in Changing Environments by Herman H. Shugart Cambridge University Press (Cambridge Studies in Ecology), 1998. £75.00 hbk, £27.95 pbk (xiv+537 pages) ISBN 0 521 56342 9/0 521 56523 5.

Brucellosis in reindeer, Rangifer tarandus L., inoculated experimentally with Brucella suis, type 4.

An investigation of brucellosis caused by Brucella suis, type 4, in reindeer, Rangifer tarandus L., and other ungulates inoculated experimentally with virulent isolates was undertaken to observe the course of infection, follow titres of serum agglutins, and determine the extent to which intraspecific and interspecific transmission might occur among confined animals. Titres rose to maximum levels within 1 to 2 months following inoculation, decreased during the next 4 months, and persisted at low levels thereafter. Titres in uninoculated associates of these animals followed the same pattern, but at lower levels. Abortion occurred in reindeer that received large numbers of organisms; females receiving smaller numbers at an earlier stage of gestation produced normal fawns. Possible explanations for the holarctic distribution of B. suis, type 4, in reindeer are considered.

Ligand-independent dimerization of oncogenic v-erbB products involves covalent interactions.

Mutant v-erbB products of avian c-erbB1 have previously been used to correlate structural domains of the receptor encoded by this proto-oncogene with tissue-specific transformation potential. In these studies, deletion of the ligand-binding domain of the receptor has been shown to be required for transformation of erythroblasts, fibroblasts, and endothelial cells. It has, therefore, been postulated that deletion of this domain results in an allosteric change in the receptor analogous to the ligand-bound state of the epidermal growth factor receptor; i.e., it induces a receptor conformation that is constitutively active with respect to mitogenic signaling. While oncogenic v-erbB products have been shown to be expressed on the cell surface of both fibroblasts and erythroblasts, no comprehensive analysis of the oligomeric potential of these products has been conducted. Since the first event known to follow epidermal growth factor binding to its receptor is oligomerization, and receptor dimerization has been correlated with mitogenic signaling, we have carefully analyzed the ability of several v-erbB products to oligomerize in the three target cell types transformed by these oncogenes. In this report, we demonstrate the v-erbB products can efficiently homodimerize in all three target tissues, that this dimerization is ligand independent and occurs at the cell surface, and that there is no apparent correlation between v-erbB dimerization and transformation of avian fibroblasts. Furthermore, both oncogenic and nononcogenic v-erbB products can heterodimerize with the native c-erbB1 product in chicken embryo fibroblasts, suggesting that heterodimerization between v-erB and native c-erbB1 is not sufficient to result in c-erbB1-mediated sarcomagenesis.

Neurotensin is an autocrine trophic factor stimulated by androgen withdrawal in human prostate cancer.

After therapeutic hormone deprivation, prostate cancer cells often develop androgen-insensitive growth through mechanisms thus far undefined. Neuropeptides have been previously implicated as growth factors in some prostate cancers. Here, we demonstrate that androgen-sensitive LNCaP human prostate cancer cells produce and secrete neurotensin following androgen withdrawal. We show that while LNCaP cells express the neurotensin receptor, only androgen-deprived cells exhibit a growth response to exogenous neurotensin. We further demonstrate that androgen-stimulated cells may be refractory to exogenous neurotensin due to androgen induction of a metalloprotease active toward neurotensin. Thus, prostate cancer cells deprived of androgen develop an alternative autocrine growth mechanism involving neurotensin.

Standardisation of temperature observed by automatic weather stations.

Daily mean, maximum and minimum surface air temperature data were gathered from a network of automatic weather stations (AWS) within the Moor House National Nature Reserve in northern England. Five AWS were installed next to the official Environmental Change Network weather station at Moor House. Data were compared graphically and correction constants were calculated to adjust data from each AWS to the standard of the official station by optimising the concordance correlation coefficient. Each corrected station was re-located next to one of five in-situ stations in and around the reserve, allowing correction of all temperature sensors to a common standard. The mean error associated with measured daily mean, maximum and minimum temperature for each sensor does not exceed +/- 0.2 K. The procedure quantifies a source of systematic measurement error, improving the identification of spatial temperature differences between stations.

A pilot study of women's attitudes towards breast-conserving surgery with primary radiation therapy for breast cancer.

Breast-conserving surgery ("lumpectomy") with primary radiation therapy is gaining acceptance as an alternative to mastectomy for breast cancer. Currently, little is known about the specific immediate and long-range biopsychosocial effects of breast-conserving therapy as compared to more traditional mastectomy procedures. Physicians' speculations about the women who chose breast-conserving treatment as opposed to mastectomy seem to have been influenced by the scientific debate concerning the efficacy of this procedure. This study is a preliminary investigation of the attitudes and experiences of women receiving breast-saving therapy for carcinoma of the breast.

Losses of chromosomal arms 1p and 19q in the diagnosis of oligodendroglioma. A study of paraffin-embedded sections.

Comparative genomic hybridization (CGH), fluorescence in situ hybridization (FISH), polymerase chain reaction-based microsatellite analysis, and p53 sequencing were performed in paraffin-embedded material from 18 oligodendrogliomas and histologically similar astrocytomas. The study was undertaken because of evidence that concurrent loss of both the 1p and 19q chromosome arms is a specific marker for oligodendrogliomas. Of the six lesions with a review diagnosis of oligodendroglioma, all had the predicted loss of 1p and 19q seen by CGH, FISH, and polymerase chain reaction. Other lesions, including some considered oligodendroglioma or mixed glioma by the submitting institution, did not. There were no p53 mutations in any of the six oligodendrogliomas, whereas 5 of the 10 remaining, successfully studied cases did have p53 mutations. The results suggest that CGH and FISH performed on current or archival tissue can aid in classification of infiltrating gliomas such as oligodendrogliomas and astrocytomas. The results of the p53 studies are consistent with findings of previous investigations that such mutations are less common in oligodendrogliomas than they are in astrocytomas.

Rapid responses of British butterflies to opposing forces of climate and habitat change.

Habitat degradation and climate change are thought to be altering the distributions and abundances of animals and plants throughout the world, but their combined impacts have not been assessed for any species assemblage. Here we evaluated changes in the distribution sizes and abundances of 46 species of butterflies that approach their northern climatic range margins in Britain-where changes in climate and habitat are opposing forces. These insects might be expected to have responded positively to climate warming over the past 30 years, yet three-quarters of them declined: negative responses to habitat loss have outweighed positive responses to climate warming. Half of the species that were mobile and habitat generalists increased their distribution sites over this period (consistent with a climate explanation), whereas the other generalists and 89% of the habitat specialists declined in distribution size (consistent with habitat limitation). Changes in population abundances closely matched changes in distributions. The dual forces of habitat modification and climate change are likely to cause specialists to decline, leaving biological communities with reduced numbers of species and dominated by mobile and widespread habitat generalists.