Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin, and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics, and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analyzed the largest cohort and set of distinct, clinically relevant body habitats to date. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families, and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology, and translational applications of the human microbiome.
A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies—a whole-genome assembly and a regional chromosome assembly—were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional ∼12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.
A variety of microbial communities and their genes (microbiome) exist throughout the human body, playing fundamental roles in human health and disease. The NIH funded Human Microbiome Project (HMP) Consortium has established a population-scale framework which catalyzed significant development of metagenomic protocols resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 to 18 body sites up to three times, which to date, have generated 5,177 microbial taxonomic profiles from 16S rRNA genes and over 3.5 Tb of metagenomic sequence. In parallel, approximately 800 human-associated reference genomes have been sequenced. Collectively, these data represent the largest resource to date describing the abundance and variety of the human microbiome, while providing a platform for current and future studies.
Background: Most eukaryotic genomes include a substantial repeat-rich fraction termed heterochromatin, which is concentrated in centric and telomeric regions. The repetitive nature of heterochromatic sequence makes it difficult to assemble and analyze. To better understand the heterochromatic component of the Drosophila melanogaster genome, we characterized and annotated portions of a whole-genome shotgun sequence assembly.
Brazilian strains of T. gondii differ from lineages in North America and Europe; these differences may underlie severe ocular disease.
Do experiences with nature – from wilderness backpacking to plants in a preschool, to a wetland lesson on frogs—promote learning? Until recently, claims outstripped evidence on this question. But the field has matured, not only substantiating previously unwarranted claims but deepening our understanding of the cause-and-effect relationship between nature and learning. Hundreds of studies now bear on this question, and converging evidence strongly suggests that experiences of nature boost academic learning, personal development, and environmental stewardship. This brief integrative review summarizes recent advances and the current state of our understanding. The research on personal development and environmental stewardship is compelling although not quantitative. Report after report – from independent observers as well as participants themselves – indicate shifts in perseverance, problem solving, critical thinking, leadership, teamwork, and resilience. Similarly, over fifty studies point to nature playing a key role in the development of pro-environmental behavior, particularly by fostering an emotional connection to nature. In academic contexts, nature-based instruction outperforms traditional instruction. The evidence here is particularly strong, including experimental evidence; evidence across a wide range of samples and instructional approaches; outcomes such as standardized test scores and graduation rates; and evidence for specific explanatory mechanisms and active ingredients. Nature may promote learning by improving learners’ attention, levels of stress, self-discipline, interest and enjoyment in learning, and physical activity and fitness. Nature also appears to provide a calmer, quieter, safer context for learning; a warmer, more cooperative context for learning; and a combination of “loose parts” and autonomy that fosters developmentally beneficial forms of play. It is time to take nature seriously as a resource for learning – particularly for students not effectively reached by traditional instruction.
Since Ernest Boyer's landmark 1990 report, Scholarship Reconsidered: Priorities of the Professoriate, leaders in higher education, including academic medicine, have advocated that faculty members apply their expertise in new and creative ways in partnership with communities. Such community engagement can take many forms, including community-based teaching, research, clinical care, and service. There continues to be a gap, however, between the rhetoric of this idea and the reality of how promotion and tenure actually work in health professions schools. The Commission on Community-Engaged Scholarship in the Health Professions was established in October 2003 with funding from the W.K. Kellogg Foundation to take a leadership role in creating a more supportive culture and reward system for community-engaged faculty in the nation's health professions schools. The authors prepared this article to inform the commission's deliberations and to stimulate discussion among educators in the health professions. The authors define the work that faculty engage in with communities, consider whether all work by faculty in community-based settings is actually scholarship, and propose a framework for documenting and assessing community-engaged scholarship for promotion and tenure decisions. They conclude with recommendations for change in academic health centers and health professions schools.
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