Synchronizing terrestrial and marine records of environmental change across the Eocene–Oligocene transition

Records of terrestrial environmental change indicate that continental cooling and/or aridification may have predated the greenhouse–icehouse climate shift at the Eocene–Oligocene transition (EOT) by ca. 600 kyr. In North America, marine-terrestrial environmental change asynchronicity is inferred from a direct comparison between the astronomically tuned marine EOT record and published 40Ar/39Ar geochronology of volcanic tuffs from the White River Group (WRG) sampled at Flagstaff Rim (Wyoming) and Toadstool Geologic Park (Nebraska), which are type sections for the Chadronian and Orellan North American Land Mammal Ages. We present a new age-model for the WRG, underpinned by high-precision 206Pb/238U zircon dates from 15 volcanic tuffs, including six tuffs previously dated using the 40Ar/39Ar technique. Weighted mean zircon 206Pb/238U dates from this study are up to 1.0 Myr younger than published anorthoclase and biotite 40Ar/39Ar data (calibrated relative to Fish Canyon sanidine at 28.201 Ma). Giving consideration to the complexities, strengths, and limitations associated with both the 40Ar/39Ar and 206Pb/238U datasets, our interpretation is that the recalculated 40Ar/39Ar dates are anomalously old, and the 206Pb/238U (zircon) dates more accurately constrain deposition. 206Pb/238U calibrated age–depth models were developed in order to facilitate a robust intercomparison between marine and terrestrial archives of environmental change, and indicate that: (i) early Orellan (terrestrial) cooling recorded at Toadstool Geologic Park was synchronous with the onset of early Oligocene Antarctic glaciation and (ii) the last appearance datums of key Chadronian mammal taxa are diachronous by ca. 0.7 Myr between central Wyoming and NW Nebraska

El bosque petrificado Piedra Chamana

The Piedra Chamana Fossil Forest, near the village of Sexi in central Cajamarca, records the vegetation of the South American tropics 39 million years ago, early in the New World tropical forests history and before the rise of the present-day Andes. In this fossil forest, notable discoveries have included the mangrove genus Avicennia, a genus of emergent forest trees (Cynometra), and the second dipterocarp known from the New World. The significance of the fossils rests on the unique circumstances of preservation, the detailed reconstruction of the forest and environment that is possible based on the plant fossils and ancient soils, and the importance of this record for the study of climate change. Sites like the fossil forest are particularly vulnerable to disturbance and loss of the fossil resources. Ongoing monitoring shows that human activities and erosion are having serious effects and, conservation measures are urgently needed. The importance of the fossils for science, the beauty of this area of the Andes, and the potential of the site for education and tourism justify recognition of the fossil forest at an international level. The lowland tropical forest represented by the fossils is very different from the diverse broad-leaf sclerophyllous forest or woodland now growing in the area. Soil loss and erosion of the soft, porous volcanic substrate when the vegetation cover is disturbed poses a threat to both the native biota and the fossils. The conservation measures needed at the fossil site would have multiple benefits for the ecology of the region.El Bosque Petrificado Piedra Chamana, cerca del pueblo de Sexi en Cajamarca, registra la vegetación de los trópicos de Sudamérica de hace 39 millones de años, la que existió en los inicios de la historia de los bosques tropicales del Nuevo Mundo y antes del levantamiento de los Andes. En este bosque, descubrimientos notables incluyen el manglar del género Avicennia, un género de árboles forestales emergentes (Cynometra), y el segundo dipterocarp conocido del Nuevo Mundo. La importancia de los fósiles se basa en sus circunstancias únicas de preservación, es así como fósiles de plantas y suelos antiguos permiten la reconstrucción detallada del bosque y el medio ambiente en que existieron, contribuyendo con el conocimiento del cambio climático. Los sitios como este bosque fósil son muy vulnerables al disturbio y pérdida de los recursos fósiles. El monitoreo muestra que las actividades humanas y la erosión están teniendo efectos serios y que son necesarias medidas urgentes para su conservación. La importancia de los fósiles para la ciencia, la belleza de esta área de los Andes, y el potencial para la educación y turismo justifican el reconocimiento del Bosque Petrificado Piedra Chamana a nivel internacional. El bosque tropical representado por los fósiles es muy diferente del bosque diverso esclerófilo de hoja ancha que se encuentra actualmente en el sitio. La pérdida del suelo y la erosión del substrato suave y poroso por alteración de la cubierta vegetal son una amenaza para la biota nativa y los fósiles. Por lo tanto, las medidas de conservación necesarias para proteger los fósiles tendrían múltiples beneficios para la ecología del área

Controls on Soft Tissue and Cellular Preservation in Late Eocene and Oligocene Vertebrate Fossils from the White River and Arikaree Groups of Nebraska, South Dakota, and Wyoming

Previous studies on microtaphonomy have identified multiple types of organic microstructures in fossil vertebrates from a variety of time periods and past environmental settings. This study investigates potential taphonomic, paleoenvironmental, and paleoclimatic controls on soft tissue and cellular preservation in fossil bone. To this end, fifteen vertebrate fossils were studied: eight fossils collected from the Oligocene Sharps Formation of the Arikaree Group in Badlands National Park, South Dakota, and seven fossils from formations in the underlying White River Group, including the Oligocene Brule Formation of Badlands National Park, and the Eocene Chadron Formation of Flagstaff Rim, Wyoming; Toadstool Geologic Park, Nebraska; and Badlands National Park, South Dakota. A portion of each fossil was demineralized to identify any organic microstructures preserved within the fossils. We investigated several factors which may have influenced cellular/soft tissue decay and/or preservation pathways, including taxonomic identity, paleoclimatic conditions, depositional environment, and general diagenetic history (as interpreted through thin section analysis). Soft tissue microstructures were preserved in all fossil samples, and cellular structures morphologically consistent with osteocytes were recovered from 11 of the 15 fossil specimens. Preservation of these microstructures was found to be independent of taxonomy, paleoclimate regime, apatite crystallinity, depositional environment, and general diagenetic history, indicating that biogeochemical reactions operating within microenvironments within skeletal tissues, such as within individual osteocyte lacunae or Haversian canals, may exert stronger controls on soft tissue and biomolecular decay or stabilization than external environmental (or climatic) conditions

Prevention Research Centers: Contributions to Updating the Public Health Workforce Through Training

Because public health is a continually evolving field, it is essential to provide ample training opportunities for public health professionals. As a natural outgrowth of the Centers for Disease Control and Prevention\u27s Prevention Research Centers Program, training courses of many types have been developed for public health practitioners working in the field. This article describes three of the Prevention Research Center training program offerings: Evidence-Based Public Health, Physical Activity and Public Health for Practitioners, and Social Marketing. These courses illustrate the commitment of the Prevention Research Centers Program to helping create a better trained public health workforce, thereby enhancing the likelihood of improving public health

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

Identification of six new susceptibility loci for invasive epithelial ovarian cancer

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers

A Study of the Influence of Sex on Genome Wide Methylation

Sex differences in methylation status have been observed in specific gene-disease studies and healthy methylation variation studies, but little work has been done to study the impact of sex on methylation at the genome wide locus-to-locus level or to determine methods for accounting for sex in genomic association studies. In this study we investigate the genomic sex effect on saliva DNA methylation of 197 subjects (54 females) using 20,493 CpG sites. Three methods, two-sample T-test, principle component analysis and independent component analysis, all successfully identify sex influences. The results show that sex not only influences the methylation of genes in the X chromosome but also in autosomes. 580 autosomal sites show strong differences between males and females. They are found to be highly involved in eight functional groups, including DNA transcription, RNA splicing, membrane, etc. Equally important is that we identify some methylation sites associated with not only sex, but also other phenotypes (age, smoking and drinking level, and cancer). Verification was done through an independent blood cell DNA methylation data (1298 CpG sites from a cancer panel array). The same genomic site-specific influence pattern and potential confounding effects with cancer were observed. The overlapping rate of identified sex affected genes between saliva and blood cell is 81% for X chromosome, and 8% for autosomes. Therefore, correction for sex is necessary. We propose a simple correction method based on independent component analysis, which is a data driven method and accommodates sample differences. Comparison before and after the correction suggests that the method is able to effectively remove the potentially confounding effects of sex, and leave other phenotypes untouched. As such, our method is able to disentangle the sex influence on a genome wide level, and paves the way to achieve more accurate association analyses in genome wide methylation studies

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A&gt;T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Evaluation of polygenic risk scores for breast and ovarian cancer risk prediction in BRCA1 and BRCA2 mutation carriers

Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 x 10(53)). In BRCA2 carriers, the strongest association with BC risk was seen for the overall BC PRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 x 10(-20)). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management

Pregnancy-related factors and the risk of breast carcinoma in situ and invasive breast cancer among postmenopausal women in the California Teachers Study cohort

Abstract Introduction Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the natural history of breast cancer development remain unclear. Methods Among 52,464 postmenopausal women participating in the California Teachers Study (CTS), 624 were diagnosed with breast carcinoma in situ (CIS) and 2,828 with invasive breast cancer between 1995 and 2007. Multivariable Cox proportional hazards regression methods were used to estimate relative risks associated with parity, age at first full-term pregnancy, breastfeeding, nausea or vomiting during pregnancy, and preeclampsia. Results Compared with never-pregnant women, an increasing number of full-term pregnancies was associated with greater risk reduction for both breast CIS and invasive breast cancer (both P trend &lt; 0.01). Women having four or more full-term pregnancies had a 31% lower breast CIS risk (RR = 0.69, 95% CI = 0.51 to 0.93) and 18% lower invasive breast cancer risk (RR = 0.82, 95% CI = 0.72 to 0.94). Parous women whose first full-term pregnancy occurred at age 35 years or later had a 118% greater risk for breast CIS (RR = 2.18, 95% CI = 1.36 to 3.49) and 27% greater risk for invasive breast cancer (RR = 1.27, 95% CI = 0.99 to 1.65) than those whose first full-term pregnancy occurred before age 21 years. Furthermore, parity was negatively associated with the risk of estrogen receptor-positive (ER+) or ER+/progesterone receptor-positive (PR+) while age at first full-term pregnancy was positively associated with the risk of ER+ or ER+/PR+ invasive breast cancer. Neither of these factors was statistically significantly associated with the risk of ER-negative (ER-) or ER-/PR- invasive breast cancer, tests for heterogeneity between subtypes did not reach statistical significance. No clear associations were detected for other pregnancy-related factors. Conclusions These results provide some epidemiologic evidence that parity and age at first full-term pregnancy are involved in the development of breast cancer among postmenopausal women. The role of these factors in risk of in situ versus invasive, and hormone receptor-positive versus -negative breast cancer merits further exploration