Exploring bacterial diversity via a curated and searchable snapshot of archived DNA sequences

The open sharing of genomic data provides an incredibly rich resource for the study of bacterial evolution and function and even anthropogenic activities such as the widespread use of antimicrobials. However, these data consist of genomes assembled with different tools and levels of quality checking, and of large volumes of completely unprocessed raw sequence data. In both cases, considerable computational effort is required before biological questions can be addressed. Here, we assembled and characterised 661,405 bacterial genomes retrieved from the European Nucleotide Archive (ENA) in November of 2018 using a uniform standardised approach. Of these, 311,006 did not previously have an assembly. We produced a searchable COmpact Bit-sliced Signature (COBS) index, facilitating the easy interrogation of the entire dataset for a specific sequence (e.g., gene, mutation, or plasmid). Additional MinHash and pp-sketch indices support genome-wide comparisons and estimations of genomic distance. Combined, this resource will allow data to be easily subset and searched, phylogenetic relationships between genomes to be quickly elucidated, and hypotheses rapidly generated and tested. We believe that this combination of uniform processing and variety of search/filter functionalities will make this a resource of very wide utility. In terms of diversity within the data, a breakdown of the 639,981 high-quality genomes emphasised the uneven species composition of the ENA/public databases, with just 20 of the total 2,336 species making up 90% of the genomes. The overrepresented species tend to be acute/common human pathogens, aligning with research priorities at different levels from individual interests to funding bodies and national and global public health agencies.

This study presents the first uniformly assembled, comprehensively described and searchable dataset of 661,405 bacterial genomes; this resource will empower more scientists to harness the multitude of data in public sequencing archives, but also reveals the biased composition of these archives, with 90% of the data originating from just 20 species.     

Modeling the biocoenose of parasitic diseases using remote sensing and geographic information systems

Application of growing degree day-water budget analysis concepts to snail-borne diseases are reviewed to demonstrate use of the unique thermal-hydrological preferences and limits of tolerance of individual parasite-vector systems to define the environmental niche of disease agents in the landscape by modern geospatial analysis tools.     

Case-control study of fetal microchimerism and breast cancer

Background

Prior pregnancy is known to protect against development of breast cancer. Recent studies have demonstrated that pregnancy has the capacity to establish small numbers of immunologically active fetal-derived cells in the mother, a phenomenon known as fetal microchimerism (FMc). We asked whether presence of FMc, routinely acquired during pregnancy, is a protective factor for breast cancer.

Methodology/Principal Findings

DNA extracts from peripheral blood specimens were obtained from a population-based case-control study of risk factors for breast cancer in women 21 to 45 years old. Specimens were tested with quantitative PCR for presence and concentrations of male DNA presumed to derive from prior pregnancies with a male fetus. Odds ratios (OR) and 95% confidence intervals (CI) were estimated with consideration of multiple established reproductive and environmental risk factors for breast cancer. FMc results were generated on 99 parous women, 54 with primary invasive breast cancer and 45 general population controls. FMc prevalence was 56% (25/45) and 26% (14/54) in controls and cases, respectively. Women harboring FMc were less likely to have had breast cancer (OR = 0.29, 95% CI 0.11–0.83; p = 0.02, adjusting for age, number of children, birth of a son, history of miscarriage, and total DNA tested). In addition, FMc concentrations were higher in controls versus cases (p = 0.01). Median concentrations were 2 (0–78) and 0 (0–374) fetal genomes/10⁶ maternal genomes in controls and cases, respectively.

Conclusions

Results suggest that the enigma of why some parous women are not afforded protection from breast cancer by pregnancy might in part be explained by differences in FMc. Mechanistic studies of FMc-derived protection against breast cancer are warranted.     

Biophysical Factors Influence Methane Fluxes in Subtropical Freshwater Wetlands Using Eddy Covariance Methods

Ecosystems - Wetlands are the largest natural source of methane (CH4); however, the contribution of subtropical wetlands to global CH4 budgets is still unclear due to difficulties in accurately...     

Extending Ethnoprimatology: Human–Alloprimate Relationships in Managed Settings

The majority of studies in ethnoprimatology focus on areas of sympatry where humans and nonhuman primates (hereafter, primates) naturally coexist. We argue that much can be gained by extending the field’s scope to incorporate settings where humans manage most aspects of primates’ lives, such as zoos, laboratories, sanctuaries, and rehabilitation centers (hereafter, managed settings). We suggest that the mixed-methods approach of ethnoprimatology, which facilitates examination of both humans’ and primates’ responses to one another, can reveal not only how humans’ ideas about primates shape management strategies, but also how those management strategies affect primates’ lives. Furthermore, we note that a greater focus on managed settings will strengthen links between ethnoprimatology and primate rights/welfare approaches, and will introduce new questions into discussions of ethics in primatology. For example, managed settings raise questions about when it might be justifiable to restrict primates’ freedom for a “greater good,” and the desirability of making primates’ lives more “natural” even if this would decrease their well-being. Finally, we propose that because ethnoprimatology is premised on challenging false dichotomies between categories of field site—specifically, between “natural” and “unnatural” free-ranging populations—it makes sense for ethnoprimatologists to examine settings in which humans exert considerable control over primates’ lives, given that the distinction between “wild” and “captive” is similarly unclear.     

Furoquinoline alkaloids of Ertela (Monnieria) trifolia (L.) Kuntze from the Suriname rainforest

7-(2'-Hydroxy-3'-chloroprenyloxy)-4,8-dimethoxyfuroquinoline (1) and 6-(2'-hydroxy-3'-chloroprenyloxy)-4,7-dimethoxyfuroquinoline (2), together with ten known compounds, have been isolated from the aerial parts of Ertela (Monnieria) trifolia (L.) Kuntze. All the isolates were tested for antiproliferative activity against the A2780 human ovarian cancer cell line.     

A Frailty‐Model‐Based Approach to Estimating the Age‐Dependent Penetrance Function of Candidate Genes Using Population‐Based Case‐Control Study Designs: An Application to Data on the BRCA1 Gene

Summary The population‐based case–control study design is perhaps one of, if not the most, commonly used designs for investigating the genetic and environmental contributions to disease risk in epidemiological studies. Ages at onset and disease status of family members are routinely and systematically collected from the participants in this design. Considering age at onset in relatives as an outcome, this article is focused on using the family history information to obtain the hazard function, i.e., age‐dependent penetrance function, of candidate genes from case–control studies. A frailty‐model‐based approach is proposed to accommodate the shared risk among family members that is not accounted for by observed risk factors. This approach is further extended to accommodate missing genotypes in family members and a two‐phase case–control sampling design. Simulation results show that the proposed method performs well in realistic settings. Finally, a population‐based two‐phase case–control breast cancer study of the BRCA1 gene is used to illustrate the method.     

Centrosome attachment to the C. elegans male pronucleus is dependent on the surface area of the nuclear envelope

A close association must be maintained between the male pronucleus and the centrosomes during pronuclear migration. In C. elegans, simultaneous depletion of inner nuclear membrane LEM proteins EMR-1 and LEM-2, depletion of the nuclear lamina proteins LMN-1 or BAF-1, or the depletion of nuclear import components leads to embryonic lethality with small pronuclei. Here, a novel centrosome detachment phenotype in C. elegans zygotes is described. Zygotes with defects in the nuclear envelope had small pronuclei with a single centrosome detached from the male pronucleus. ZYG-12, SUN-1, and LIS-1, which function at the nuclear envelope with dynein to attach centrosomes, were observed at normal concentrations on the nuclear envelope of pronuclei with detached centrosomes. Analysis of time-lapse images showed that as mutant pronuclei grew in surface area, they captured detached centrosomes. Larger tetraploid or smaller histone::mCherry pronuclei suppressed or enhanced the centrosome detachment phenotype respectively. In embryos fertilized with anucleated sperm, only one centrosome was captured by small female pronuclei, suggesting the mechanism of capture is dependent on the surface area of the outer nuclear membrane available to interact with aster microtubules. We propose that the limiting factor for centrosome attachment to the surface of abnormally small pronuclei is dynein.     

Evidence that DNA (cytosine-5) methyltransferase regulates synaptic plasticity in the hippocampus

DNA (cytosine-5) methylation represents one of the most widely used mechanisms of enduring cellular memory. Stable patterns of DNA methylation are established during development, resulting in creation of persisting cellular phenotypes. There is growing evidence that the nervous system has co-opted a number of cellular mechanisms used during development to subserve the formation of long term memory. In this study, we examined the role DNA (cytosine-5) methyltransferase (DNMT) activity might play in regulating the induction of synaptic plasticity. We found that the DNA within promoters for reelin and brain-derived neurotrophic factor, genes implicated in the induction of synaptic plasticity in the adult hippocampus, exhibited rapid and dramatic changes in cytosine methylation when DNMT activity was inhibited. Moreover, zebularine and 5-aza-2-deoxycytidine, inhibitors of DNMT activity, blocked the induction of long term potentiation at Schaffer collateral synapses. Activation of protein kinase C in the hippocampus decreased reelin promoter methylation and increased DNMT3A gene expression. Interestingly, DNMT activity is required for protein kinase C-induced increases in histone H3 acetylation. Considered together, these results suggest that DNMT activity is dynamically regulated in the adult nervous system and that DNMT may play a role in regulating the induction of synaptic plasticity in the mature CNS.