Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.
Prion strains (or variants) are structurally distinct amyloid conformations arising from a single polypeptide sequence. The existence of prion strains has been well documented in mammalian prion diseases. In many cases, prion strains manifest as variation in disease progression and pathology, and in some cases, these prion strains also show distinct biochemical properties. Yet, the underlying basis of prion propagation and the extent of conformational possibilities available to amyloidogenic proteins remain largely undefined. Prion proteins in yeast that are also capable of maintaining multiple self-propagating structures have provided much insight into prion biology. Here, we explore the vast structural diversity of the yeast prion [RNQ+] in Saccharomyces cerevisiae. We screened for the formation of [RNQ+] in vivo, allowing us to calculate the rate of spontaneous formation as ~2.96x10-6, and successfully isolate several different [RNQ+] variants. Through a comprehensive set of biochemical and biological analyses, we show that these prion variants are indeed novel. No individual property or set of properties, including aggregate stability and size, was sufficient to explain the physical basis and range of prion variants and their resulting cellular phenotypes. Furthermore, all of the [RNQ+] variants that we isolated were able to facilitate the de novo formation of the yeast prion [PSI+], an epigenetic determinant of translation termination. This supports the hypothesis that [RNQ+] acts as a functional amyloid in regulating the formation of [PSI+] to produce phenotypic diversity within a yeast population and promote adaptation. Collectively, this work shows the broad spectrum of available amyloid conformations, and thereby expands the foundation for studying the complex factors that interact to regulate the propagation of distinct aggregate structures.
Identifying early risk factors for childhood obesity is critical, as weight in infancy and early childhood tracks to later periods. Continued bottle use - primarily from excess milk intake - is emerging as a potential risk factor for early childhood overweight. Over three fourths of US infants drink from bottles beyond the recommended weaning age of 12 months, and two thirds of UK infants use a bottle at 18 months. This paper is divided into three parts. Part 1 reviews the literature on beverage intake, weight and bottle use in young children. Part II describes pilot data on milk bottle use and weight in 12-60-month-olds, collected prior to a randomized controlled (RCT) trial of a bottle-weaning intervention. Median daily milk bottle consumption at 12 months was 5.0 (interquartile range = 3-6). Among 12-36-month-olds, current users were significantly more likely to be >95th% weight-for-height (19% vs. 0%, P < 0.02), and more were >85% weight-for-height (27% vs. 11%, P < 0.11), vs. non-users. In contrast, current bottle use was not associated with either overweight or obesity in 37-60-month-olds. Part III describes the RCT, begun in fall 2008. It is enrolling 464 parent/12-month-old dyads from a nutrition assistance programme for low-income families. Children's bottle use, anthropometrics, dietary intake and nutrient density (via 24 h recall) are assessed quarterly through 24 months of age. For the intervention, site nutritionists employ a project-developed, visually attractive flip chart. An observational study nested within the RCT will describe dietary changes during this period of feeding transitions.
In treated and untreated children alike, adiposity is a significant predictor of liver fat content. This relationship was altered by low vitamin D level. These results suggest a modifiable pathway to hepatic steatosis. Further research is needed to test the hypothesis that children with high adiposity and low vitamin D have particularly increased risks for the development of fatty liver.
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