Discovery and replication of microRNAs for breast cancer risk using genome-wide profiling

Genome-wide miRNA expression may be useful for predicting breast cancer risk and/or for the early detection of breast cancer

Site and Strain-Specific Variation in Gut Microbiota Profiles and Metabolism in Experimental Mice

The gastrointestinal tract microbiota (GTM) of mammals is a complex microbial consortium, the composition and activities of which influences mucosal development, immunity, nutrition and drug metabolism. It remains unclear whether the composition of the dominant GTM is conserved within animals of the same strain and whether stable GTMs are selected for by host-specific factors or dictated by environmental variables.The GTM composition of six highly inbred, genetically distinct strains of mouse (C3H, C57, GFEC, CD1, CBA nu/nu and SCID) was profiled using eubacterial -specific PCR-DGGE and quantitative PCR of feces. Animals exhibited strain-specific fecal eubacterial profiles that were highly stable (c. >95% concordance over 26 months for C57). Analyses of mice that had been relocated before and after maturity indicated marked, reproducible changes in fecal consortia and that occurred only in young animals. Implantation of a female BDF1 mouse with genetically distinct (C57 and Agoutie) embryos produced highly similar GTM profiles (c. 95% concordance) between mother and offspring, regardless of offspring strain, which was also reflected in urinary metabolite profiles. Marked institution-specific GTM profiles were apparent in C3H mice raised in two different research institutions.Strain-specific data were suggestive of genetic determination of the composition and activities of intestinal symbiotic consortia. However, relocation studies and uterine implantation demonstrated the dominance of environmental influences on the GTM. This was manifested in large variations between isogenic adult mice reared in different research institutions

Recent shifts in the genomic ancestry of Mexican Americans may alter the genetic architecture of biomedical traits

People in the Americas represent a diverse continuum of populations with varying degrees of admixture among African, European, and Amerindigenous ancestries. In the United States, populations with non-European ancestry remain understudied, and thus little is known about the genetic architecture of phenotypic variation in these populations. Using genotype data from the Hispanic Community Health Study/Study of Latinos, we find that Amerindigenous ancestry increased by an average of ~20% spanning 1940s-1990s in Mexican Americans. These patterns result from complex interactions between several population and cultural factors which shaped patterns of genetic variation and influenced the genetic architecture of complex traits in Mexican Americans. We show for height how polygenic risk scores based on summary statistics from a European-based genome-wide association study perform poorly in Mexican Americans. Our findings reveal temporal changes in population structure within Hispanics/Latinos that may influence biomedical traits, demonstrating a need to improve our understanding of admixed populations

Ebola virus, but not Marburg virus, replicates efficiently and without required adaptation in snake cells.

Ebola virus (EBOV) disease is a viral hemorrhagic fever with a high case-fatality rate in humans. This disease is caused by four members of the filoviral genus Ebolavirus, including EBOV. The natural hosts reservoirs of ebolaviruses remain to be identified. Glycoprotein 2 of reptarenaviruses, known to infect only boa constrictors and pythons, is similar in sequence and structure to ebolaviral glycoprotein 2, suggesting that EBOV may be able to infect reptilian cells. Therefore, we serially passaged EBOV and a distantly related filovirus, Marburg virus (MARV), in boa constrictor JK cells and characterized viral infection/replication and mutational frequency by confocal imaging and sequencing. We observed that EBOV efficiently infected and replicated in JK cells, but MARV did not. In contrast to most cell lines, EBOV-infected JK cells did not result in an obvious cytopathic effect. Surprisingly, genomic characterization of serial-passaged EBOV in JK cells revealed that genomic adaptation was not required for infection. Deep sequencing coverage (>10,000×) demonstrated the existence of only a single nonsynonymous variant (EBOV glycoprotein precursor pre-GP T544I) of unknown significance within the viral population that exhibited a shift in frequency of at least 10 per cent over six serial passages. In summary, we present the first reptilian cell line that replicates a filovirus at high titers, and for the first time demonstrate a filovirus genus-specific restriction to MARV in a cell line. Our data suggest the possibility that there may be differences between the natural host spectra of ebolaviruses and marburgviruses

Ebola virus, but not Marburg virus, replicates efficiently and without required adaptation in snake cells.

Ebola virus (EBOV) disease is a viral hemorrhagic fever with a high case-fatality rate in humans. This disease is caused by four members of the filoviral genus Ebolavirus, including EBOV. The natural hosts reservoirs of ebolaviruses remain to be identified. Glycoprotein 2 of reptarenaviruses, known to infect only boa constrictors and pythons, is similar in sequence and structure to ebolaviral glycoprotein 2, suggesting that EBOV may be able to infect reptilian cells. Therefore, we serially passaged EBOV and a distantly related filovirus, Marburg virus (MARV), in boa constrictor JK cells and characterized viral infection/replication and mutational frequency by confocal imaging and sequencing. We observed that EBOV efficiently infected and replicated in JK cells, but MARV did not. In contrast to most cell lines, EBOV-infected JK cells did not result in an obvious cytopathic effect. Surprisingly, genomic characterization of serial-passaged EBOV in JK cells revealed that genomic adaptation was not required for infection. Deep sequencing coverage (>10,000×) demonstrated the existence of only a single nonsynonymous variant (EBOV glycoprotein precursor pre-GP T544I) of unknown significance within the viral population that exhibited a shift in frequency of at least 10 per cent over six serial passages. In summary, we present the first reptilian cell line that replicates a filovirus at high titers, and for the first time demonstrate a filovirus genus-specific restriction to MARV in a cell line. Our data suggest the possibility that there may be differences between the natural host spectra of ebolaviruses and marburgviruses

Reactivity and regulation of motor responses in cocaine-exposed infants

Effects of prenatal exposure to cocaine on the reactivity and regulation of the motor system of 825 four-month-old infants enrolled in the Maternal Lifestyle Study were examined. Videotaped assessments of 338 cocaine-exposed (CE) infants and 487 non-exposed comparison infants were coded by examiners masked to exposure status. Exposure status was determined by meconium assay and maternal self-report of prenatal cocaine use. Infants were presented with a series of 17 visual, auditory and tactile stimuli for 30-second each. Intensity and latency of limb movement responses on a subset of items were analyzed to test the following hypotheses: CE infants are more active in general; CE infants exhibit increased movement levels for a larger proportion of time in response to stimulation; the motor systems of CE infants are more reactive to stimulation (e.g., shorter latencies to respond); and CE infants are poorer regulators of the motor system. Results CE infants were not more active in general and data do not indicate a more highly reactive motor system. However, CE infants exhibited increased movement levels for a larger proportion of time in response to stimulation. Additional analysis of movement exhibited during three tactile items found increased movement lability in CE infants and different patterns of responding, suggesting that the effects of prenatal cocaine exposure on the motor system may vary by context. Covariate effects for tobacco, alcohol, and marijuana are also reported