A Regional Multiple-Stressor Rank-Based Ecological Risk Assessment for the Fjord of Port Valdez,Alaska

We conducted an ecological risk assessment of the marine environment of Port Valdez, a fjord in south-central Alaska. Because the assessment was regional rather than site-specific and contained a large number of different stressors in a variety of environments, we required a nontraditional method to estimate risks. We created a Relative Risk Model to rank and sum individual risks numerically within each subarea, from each source, and to each habitat. Application of this model involved division of Port Valdez into 11 subareas containing specific ecological and anthropogenic structures and activities. Within each subarea, the stressor sources were analyzed to estimate exposure of receptors within habitats leading to effects relevant to the chosen assessment endpoints. The subareas were analyzed and compared to form a Port-wide perspective of ecological risk. Available chemical concentrations from sediment and mussels collected from the Port were compared to various toxicological benchmarks as a partial confirmation of the risk analysis. An estimation of the risk of polycyclic aromatic hydrocarbons (PAHs) to marine invertebrates indicated low risk. The municipal boat harbor had the highest estimate, which reflected our relative risk rankings. The Relative Risk Model approach appears robust and has potential for use in situations where multiple stressors are of concern and for assessments covering broad geographic areas. In the Port Valdez assessment the approach provided relative risk rankings for chemical and physical stressors from various sources. But data were available for confirmation of risk estimates only for the chemical stressors. The rankings are relative, and extrapolation beyond the scenario in which they were developed is not warranted. Uncertainty is large, and the numerical scores collapse a multidimensional space into a single value. Use of just the numerical score out of context is more valid than with other indexes. The value of the approach lies in the relative rankings and the accounting of the components of the relative risk score.     

Transient Marker System for Iterative Gene Targeting of a Prototrophic Fungus

Auxotrophic microorganisms are often used for genetic engineering, because their biosynthetic deficiency can be complemented by the transforming DNA and allows selection for transformants that have become prototrophic. However, when complementation is obtained by ectopic expression this may lead to unpredictable side effects on the phenotype and, consequently, misinterpretation of experimental data. There are various ways to overcome the problem of auxotrophy, but the most reliable is to restore the function of the defective biosynthetic gene at the native genomic locus. This can be done by either sexual crossing or further genetic engineering. For fungal species lacking a perfect state or situations in which gene targeting is generally cumbersome we have developed a concept that allows transient disruption of pyrG. When the gene is in the disrupted state, multiple rounds of gene targeting can be performed with the strain. Once the desired genome engineering is completed, pyrG function can be rapidly returned to wild type by a simple selection scheme.     

History of click-speaking populations of Africa inferred from mtDNA and Y chromosome genetic variation

Little is known about the history of click-speaking populations in Africa. Prior genetic studies revealed that the click-speaking Hadza of eastern Africa are as distantly related to click speakers of southern Africa as are most other African populations. The Sandawe, who currently live within 150 km of the Hadza, are the only other population in eastern Africa whose language has been classified as part of the Khoisan language family. Linguists disagree on whether there is any detectable relationship between the Hadza and Sandawe click languages. We characterized both mtDNA and Y chromosome variation of the Sandawe, Hadza, and neighboring Tanzanian populations. New genetic data show that the Sandawe and southern African click speakers share rare mtDNA and Y chromosome haplogroups; however, common ancestry of the 2 populations dates back >35,000 years. These data also indicate that common ancestry of the Hadza and Sandawe populations dates back >15,000 years. These findings suggest that at the time of the spread of agriculture and pastoralism, the click-speaking populations were already isolated from one another and are consistent with relatively deep linguistic divergence among the respective click languages.     

Design of an injectable in situ gelation biomaterials for vitreous substitute

To adapt the physical properties of living materials to their biological function, nature developed various types of polymers with outstanding physical behavior. One example is the vitreous body, which is important intraocular elements not only because of its optical and mechanical performances, but also due to its important role in the pathogenesis and treatment of conditions affecting adjacent tissues and eventually the whole eye. Here, we report a novel biocompatible material for injectable vitreous substitute, composed of thermosensitive amphiphilic polymer, which is capable of forming a transparent gel in the vitreous cavity. It is nontoxic, provides adequate support for the retina, and allows light to reach the sensory elements at the back of the eye. The amphiphilic polymer exhibits mechanical stability by assembling to form highly interconnected hydrophobic domains, which leads to the constitution of a network structure.     

Lack of autophagy in the hematopoietic system leads to loss of hematopoietic stem cell function and dysregulated myeloid proliferation

The regulated lysosomal degradation pathway of autophagy prevents cellular damage and thus protects from malignant transformation. Autophagy is also required for the maturation of various hematopoietic lineages, namely the erythroid and lymphoid ones, yet its role in adult hematopoietic stem cells (HSCs) remained unexplored. While normal HSCs sustain life-long hematopoiesis, malignant transformation of HSCs or early progenitors leads to leukemia. Mechanisms protecting HSCs from cellular damage are therefore essential to prevent hematopoietic malignancies. By conditionally deleting the essential autophagy gene Atg7 in the hematopoietic system, we found that autophagy is required for the maintenance of true HSCs and therefore also of downstream hematopoietic progenitors. Loss of autophagy in HSCs leads to the expansion of a progenitor cell population in the bone marrow, giving rise to a severe, invasive myeloproliferation, which strongly resembles human acute myeloid leukemia (AML).     

Effects of environmental factors on microbial induced calcium carbonate precipitation

Aims: To gain an understanding of the environmental factors that affect the growth of the bacterium Sporosarcina pasteurii, the metabolism of the bacterium and the calcium carbonate precipitation induced by this bacterium to optimally implement the biological treatment process, microbial induced calcium carbonate precipitation (MICP), in situ. Methods and Results: Soil column and batch tests were used to assess the effect of likely subsurface environmental factors on the MICP treatment process. Microbial growth and mineral precipitation were evaluated in freshwater and seawater. Environmental conditions that may influence the ureolytic activity of the bacteria, such as ammonium concentration and oxygen availability, as well as the ureolytic activities of viable and lysed cells were assessed. Treatment formulation and injection rate, as well as soil particle characteristics are other factors that were evaluated for impact on uniform induction of cementation within the soils. Conclusions: The results of the study presented herein indicate that the biological treatment process is equally robust over a wide range of soil types, concentrations of ammonium chloride and salinities ranging from distilled water to full seawater; on the time scale of an hour, it is not diminished by the absence of oxygen or lysis of cells containing the urease enzyme. Significance and Impact of Study: This study advances the biological treatment process MICP towards field implementation by addressing key environmental hurdles faced with during the upscaling process.     

Fish consumption measured during pregnancy and risk of cardiovascular diseases later in life: an observational prospective study

Previous studies have indicated a protective effect of long chain n-3 PUFAs against cardiovascular disease; however, the overall evidence remains uncertain, and there is a general lack of knowledge in the field of cardiovascular epidemiology in women. Therefore, the objective of this study was to explore the association between fish intake and cardiovascular disease among 7429 women from a prospective pregnancy cohort in Aarhus, Denmark, who were followed for 12-17 years. Exposure information derived from a questionnaire sent to the women in gestation week 16, and daily fish consumption was quantified based on assumptions of standard portion sizes and food tables. Information on admissions to hospital was obtained from the Danish National Patient Registry and diagnoses of hypertensive, cerebrovascular and ischaemic heart disease were used to define the outcome: cardiovascular disease. During the follow-up period 263 events of cardiovascular disease were identified. Overall, there was no association between cardiovascular disease and fish intake, confidence intervals for effect estimates in the different fish intake groups were wide, overlapped and for all but one they encompassed unity. Restricting the analysis to women who had reported the same fish intake in a questionnaire in gestation week 30 did not alter these findings. In conclusion, our data from a prospective cohort of relatively young and initially healthy women from Aarhus linked with information from registries could not substantiate a protective effect of fish intake against cardiovascular disease.     

HPV E6/E7 mRNA testing is more specific than cytology in post-colposcopy follow-up of women with negative cervical biopsy

Background

In Norway, women with negative or low-grade cervical biopsies (normal/CIN1) are followed up after six months in order to decide on further follow-up or recall for screening at three-year intervals. A high specificity and positive predictive value (PPV) of the triage test is important to avoid unnecessary diagnostic and therapeutic procedures whereas a low risk of high-grade disease among triage negative women assures safety.

Materials and Methods

At the University Hospital of North Norway, cytology and the HPV mRNA test PreTect HPV-Proofer, detecting E6/E7 mRNA from HPV types 16, 18, 31, 33 and 45, are used in post-colposcopy follow-up of women with negative or low-grade biopsy. In this study, women with negative biopsy after high grade cytology (ASC-H/HSIL) and/or positive HPV mRNA test in the period 2005–2009 were included (n = 520). Histologically confirmed cervical intraepithelial neoplasia of grade 2 or worse (CIN2+) was used as study endpoint.

Results

Of 520 women with negative or low-grade biopsy, 124 women (23.8%) had CIN2+ in follow-up biopsy. The sensitivity and specificity of the HPV mRNA test were 89.1% (95% CI, 80.1–98.1) and 92.5% (95% CI, 88.2–96.7), respectively. The ratios of sensitivity, specificity and PPV of HPV mRNA testing compared to repeat cytology for finding CIN2+ was 1.05 (95% CI: 0.92–1.21), 1.21 (95% CI: 1.12–1.32), and 1.49 (95% CI: 1.20–1.86), respectively. The PPV of mRNA was 77.3% (95% CI, 59.8–94.8) in women aged 40 or older.

Conclusion

Women with negative cervical biopsy require follow-up before resumption of routine screening. Post-colposcopy HPV mRNA testing was as sensitive but more specific than post-colposcopy cytology. In addition, the HPV mRNA test showed higher PPV. A positive mRNA test post-colposcopy could justify treatment in women above 40 years.