Shaping of human germline IgH repertoires revealed by deep sequencing.

To understand better how selection processes balance the benefits of Ig repertoire diversity with the risks of autoreactivity and nonfunctionality of highly variable IgH CDR3s, we collected millions of rearranged germline IgH CDR3 sequences by deep sequencing of DNA from mature human naive B cells purified from four individuals and analyzed the data with computational methods. Long HCDR3 regions, often components of HIV-neutralizing Abs, appear to derive not only from incorporation of long D genes and insertion of large N regions but also by usage of multiple D gene segments in tandem. However, comparison of productive and out-of-frame IgH rearrangements revealed a selection bias against long HCDR3 loops, suggesting these may be disproportionately either poorly functional or autoreactive. Our data suggest that developmental selection removes HCDR3 loops containing patches of hydrophobicity, which are commonly found in some auto-antibodies, and at least 69% of the initial productive IgH rearrangements are removed from the repertoire during B cell development. Additionally, we have demonstrated the potential utility of this new technology for vaccine development with the identification in all four individuals of related candidate germline IgH precursors of the HIV-neutralizing Ab 4E10.

Agile methods in biomedical software development: a multi-site experience report.

BACKGROUND: Agile is an iterative approach to software development that relies on strong collaboration and automation to keep pace with dynamic environments. We have successfully used agile development approaches to create and maintain biomedical software, including software for bioinformatics. This paper reports on a qualitative study of our experiences using these methods. RESULTS: We have found that agile methods are well suited to the exploratory and iterative nature of scientific inquiry. They provide a robust framework for reproducing scientific results and for developing clinical support systems. The agile development approach also provides a model for collaboration between software engineers and researchers. We present our experience using agile methodologies in projects at six different biomedical software development organizations. The organizations include academic, commercial and government development teams, and included both bioinformatics and clinical support applications. We found that agile practices were a match for the needs of our biomedical projects and contributed to the success of our organizations. CONCLUSION: We found that the agile development approach was a good fit for our organizations, and that these practices should be applicable and valuable to other biomedical software development efforts. Although we found differences in how agile methods were used, we were also able to identify a set of core practices that were common to all of the groups, and that could be a focus for others seeking to adopt these methods.

Anatomical Variations of the Transverse-Sigmoid Sinus Junction: Implications for Endovascular Treatment of Idiopathic Intracranial Hypertension.

Venous sinus pathology can result in multiple pathological diseases, including idiopathic intracranial hypertension (IIH). There remains a paucity of information on anatomical luminal variations of the major venous sinuses which may contribute to the etiology of certain disease states. Thirty-six transverse and sigmoid sinuses were removed following dissection of 19 unfixed cadaveric heads. Sinuses were opened longitudinally to study luminal variations. A semiquantitative classification system was developed to assess septations and blind pouches. Seventy-nine percent of cadavers had a luminal anatomical variation. Forty-four percent and 42% of sinuses dissected had occurrence of a septations or blind pouches, respectively. Thirty percent of septations and 25% of pouches were classified as large. Incidence of anatomical variations was not statistically significant between cadaver gender or sinus laterality. Luminal variations are present in the transverse and sigmoid sinuses at rates higher than expected. This study is the first to report the presence of blind pouches in the luminal wall of transverse and sigmoid sinuses. These variations can have clinical importance to the endovascular surgeon and may also contribute to the pathophysiological etiology of venous sinus diseases. Anat Rec, 299:1037-1042, 2016. © 2016 Wiley Periodicals, Inc.