Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Determining crystal structures through crowdsourcing and coursework

We show here that computer game players can build high-quality crystal structures. Introduction of a new feature into the computer game Foldit allows players to build and real-space refine structures into electron density maps. To assess the usefulness of this feature, we held a crystallographic model-building competition between trained crystallographers, undergraduate students, Foldit players and automatic model-building algorithms. After removal of disordered residues, a team of Foldit players achieved the most accurate structure. Analysing the target protein of the competition, YPL067C, uncovered a new family of histidine triad proteins apparently involved in the prevention of amyloid toxicity. From this study, we conclude that crystallographers can utilize crowdsourcing to interpret electron density information and to produce structure solutions of the highest quality

STEP IN: Supporting Together Exercise and Play and Improving Nutrition; a Feasibility Study of Parent-Led Group Sessions and Fitness Trackers to Improve Family Healthy Lifestyle Behaviors in a Low-Income, Predominantly Black Population

Background: Pediatric obesity is prevalent and challenging to treat. Although family-centered behavioral management is the gold standard, many families face structural inequities to its access and efficacy. Identifying ways to manage pediatric obesity within primary care is needed. Methods: This feasibility study included three sequential trials of peer-led group sessions occurring biweekly or monthly between 3/2016 and 2/2017. Parent–child dyads were recruited from a large academic primary care clinic via mailed invitations, prioritizing patients living in local zip codes of historical disinvestment. Eligible patients were 6 to 12 years with a body mass index ≥85th percentile, with parent and child interest in making healthy lifestyle changes, and English speaking. Results: 27 dyads participated, 77% were non-Hispanic Black. Retention and attendance rates were highest in the initial four-session biweekly pilot (100%, 0 dropouts), high in the full six-session biweekly cohort (83%, 1 dropout), and moderate in the monthly cohort (62.7%, 4 dropouts). Families reported high satisfaction with the sessions (4.75/5). Qualitative comments suggested social connections had motivated behavior change in some families. Conclusion: Parent-led group sessions for pediatric weight management show promise in engaging families. A future large trial is needed to assess behavior change and anthropometric outcomes

Change in CD25 expression on B and CD4+ T cells negatively correlates with viral load.

<p>PBMCs were cultured overnight with or without anti-CD3 stimulation. Change in CD25 or CD86 expression was determined by subtracting the frequency of expression before stimulation from the frequency of expression after stimulation. (<b>A</b>) Representative plots of CD25 expression on CD4+ T cells and B cells with (bottom) and without (top) anti-CD3 stimulation. CD4+ T cell population shown is CD3+CD4+CD19- and B cell population shown is CD3-CD4-CD19+. (<b>B</b>-<b>D</b>) Change in expression of CD25 on CD4+ T cells (r= -.53; p= .056) (B), CD25 on B cells (r= -.63; p= .018) (C), and CD86 on B cells (r= -.44; p= .11) (D) correlates negatively with viral load. </p

Magnitude of B cell responses to inactivated HIV-1 inversely correlates with viral load.

<p>(<b>A</b>) Expression of CD86 on B cells after stimulation of PBMC with HIV-1 MN control (left column) or HIV-1 MN (right column). Shown are representative plots from one individual (subject 10071).. (<b>B</b>) PBMCs from 21 HIV-infected individuals (closed circles) and 7 HIV-negative control subjects (open circles) were incubated with inactivated HIV-1 MN, and changes in CD86 expression on B cells were measured. Change was calculated by subtracting the frequency of CD86 expression from stimulation with the HIV-1 MN control (containing no HIV proteins) from stimulation with HIV-1 MN. CD86 expression on B cells in response to HIV-antigen in HIV infected individuals is negatively correlated with viral load (r= -.6; p= .006). Correlation statistics are only applied to HIV-infected individuals and do not include data from uninfected subjects. </p

PD-1 blockade improves B cell responses to stimulation with inactivated HIV-1.

<p>PBMCs were cultured overnight with or without anti-PD-1 and stimulated with inactivated HIV-1 MN protein. Change in response to MN stimulation was calculated by subtracting stimulation with MN control protein from stimulation with HIV-1 MN protein (p= .003).</p