Genome sequencing of large numbers of individuals promises to advance the understanding, treatment, and prevention of human diseases, among other applications. We describe a genome sequencing platform that achieves efficient imaging and low reagent consumption with combinatorial probe anchor ligation chemistry to independently assay each base from patterned nanoarrays of self-assembling DNA nanoballs. We sequenced three human genomes with this platform, generating an average of 45- to 87-fold coverage per genome and identifying 3.2 to 4.5 million sequence variants per genome. Validation of one genome data set demonstrates a sequence accuracy of about 1 false variant per 100 kilobases. The high accuracy, affordable cost of $4400 for sequencing consumables, and scalability of this platform enable complete human genome sequencing for the detection of rare variants in large-scale genetic studies.

Although small, the international evidence base suggests that screening with the Alcohol Use Disorders Identification Test or Alcohol Use Disorders Identification Test-C and brief interventions for primary care patients with chronic medical conditions, delivered by nurses or other providers, are effective for identifying unhealthy substance use and associated with healthy behaviours and improved outcomes. Lacking are studies screening for illicit drug use, and using single-item screening tools, which could be especially helpful for frontline primary care providers including nurses.

Tissue invasion and metastasis are leading causes of death among cancer patients due to cells escaping from the primary tumor and invading distant sites. To better understand these phenomena and develop efficient therapeutic regimens against different types of malignancies, there is a need for exclusive cellular and molecular examination of migrating cells. In this study, aggressive brain cancer cells, G55, migrating through confined microchannels were directly extracted and used for subsequent proteomic analysis via Western Blot and/or immunostaining quantification. The method was based on an engineered Polydimethylsiloxane microchannel platform that facilitated the exclusive extraction of migrating cells and their contents while preventing non-migrating (or proliferatingdenoted as 2D) cell contamination. The migrating cells in physical confinement of the microchannels were exclusively examined for their protein expression. They were found with increased expression of Vimentin, approximately 2.5-fold higher than 2D cells. On the other hand, the migrating cells showed significantly decreased β3-Tubulin and Met signal compared to 2D cells. The differences in biomarker expression between migrating cells and non-migrating cells revealed by this study provided an insight into key features of cancer invasion and metastasis. The successful outcome of this research suggests improved targets for ceasing different types of malignancies. REVISED

This study examined social processes of support, goal direction, provision of role models, and involvement in rewarding activities to explain benefits of participating in Al-Anon, a 12-step mutual-help program for people concerned about another person’s substance use. Newcomers to Al-Anon were studied at baseline and 6 months later, when they were identified as having sustained attendance or dropped out. Among newcomers, and among established Al-Anon members (“oldtimers”), we also used number of Al-Anon meetings attended during follow-up to indicate extent of participation. Social processes significantly mediated between newcomers’ attendance status as sustained (versus dropped out) and outcomes of Al-Anon in the domains of life context (e.g., better quality of life, better able to handle problems due to the drinker), improved positive symptoms (more self-esteem, more hopeful), and decreased negative symptoms (e.g., less abuse, less depressed). Social processes also significantly mediated between newcomers’ number of meetings and outcomes. However, among oldtimers, Al-Anon attendance was not associated with outcomes, so the potential mediating role of social processes could not be examined, but social processes were associated with outcomes. Findings add to the growing body of work identifying mechanisms by which 12-step groups are effective, by showing that bonding, goal direction, and access to peers in recovery and rewarding pursuits help to explain associations between sustained Al-Anon participation among newcomers and improvements on key concerns of Al-Anon attendees. Al-Anon is free of charge and widely available, making it a potentially cost-effective public health resource in helping to alleviate negative consequences of concern about another’s addiction.

Phage display libraries are widely used as tools for identifying, dissecting and optimizing ligands. Development of a simple method to access greater library diversities could expedite and expand the technique. This paper reports progress toward harnessing the naturally occurring diversity generating retroelement used by Bordetella bronchiseptica bacteriophage to alter its tail-fiber protein. Mutagenesis and testing identified four sites amenable to the insertion of <19-residue heterologous peptides within the variable region. Such sites allow auto-generation of peptide libraries surrounded by a scaffold with additional variations. The resultant self-made phage libraries were used successfully for selections targeting anti-FLAG antibody, immobilized metal affinity chromatography microtiter plates and HIV-1 gp41. The reported experiments demonstrate the utility of the major tropism determinant protein of B.bronchiseptica as a natural scaffold for diverse, phage-constructed libraries with heterologous self-made phage libraries.