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

A CD19-Anti-ErbB2 scFv Engager Protein Enables CD19-Specific CAR T Cells to Eradicate ErbB2⁺ Solid Cancer

The efficacy of CD19-specific CAR T cells in the treatment of leukemia/lymphoma relies, at least in part, on the unique properties of the particular CAR and the presence of healthy B cells that enhance the target cell lysis and cytokine secretion through repetitive stimulation. Here, we report to apply the same CAR to target solid tumors, such as ErbB2+ carcinoma. CD19 CAR T cells are redirected towards the ErbB2+ cells by a fusion protein that is composed of the herceptin-derived anti-ErbB2 scFv 4D5 linked to the CD19 exodomain. The CD19-4D5scFv engager enabled CD19 CAR T cells to recognize the ErbB2+ cancer cells and to suppress the ErbB2+ tumor growth. The primary killing capacity by the ErbB2-redirected CD19 CAR T cells was as efficient as by the ErbB2 CAR T cells, however, adding CD19+ B cells furthermore reinforced the activation of the CD19 CAR T cells, thereby improving the anti-tumor activities. The ErbB2-redirected CD19 CAR T cells, moreover, showed a 100-fold superior selectivity in targeting cancer cells versus healthy fibroblasts, which was not the case for the ErbB2 CAR T cells. The data demonstrate that the CD19 CAR T cells can be high-jacked by a CD19-scFv engager protein to attack specifically solid cancer, thereby expanding their application beyond the B cell malignancies

A pre-and-post study of an urban renewal program in a socially disadvantaged neighbourhood in Sydney, Australia

Abstract Background Urban renewal programs aim to target both the physical and social environments to improve the social capital, social connectedness, sense of community and economic conditions of residents of the neighbourhoods. We evaluated the impact of an urban renewal program on the health and well-being of residents of a socially disadvantaged community in south-western Sydney, Australia. Methods Pre- and post-urban renewal program surveys were conducted with householders by trained interviewers. The urban renewal program was conducted over 16 months and consisted of internal upgrades (including internal painting; replacement of kitchens, bathrooms and carpets; general maintenance), external upgrades (including property painting; new fencing, carports, letterboxes, concrete driveways, drainage and landscaping), general external maintenance, and social interventions such as community engagement activities, employment initiatives, and building a community meeting place. The questionnaire asked about demographic characteristics, self-reported physical activity, psychological distress, self-rated health, and perceptions of aesthetics, safety and walkability in the neighbourhood. We used the paired chi-square test (McNemars test) to compare paired proportions. A Bonferroni corrected p-value of Results Following the urban renewal program we did not find statistically significant changes in perceptions of aesthetics, safety and walkability in the neighbourhood. However, post-urban renewal, more householders reported there were attractive buildings and homes in their neighbourhood (18% vs 64%), felt that they belonged to the neighbourhood (48% vs 70%), that their area had a reputation for being a safe place (8% vs 27%), that they felt safe walking down their street after dark (52% vs 85%), and that people who came to live in the neighbourhood would be more likely to stay rather than move elsewhere (13% vs 54%). Changes in psychological distress and self-rated health were not statistically significant. Conclusions We found an increase, in the short-term, in the proportion of householders reporting improvements in some aspects of their immediate neighbourhood following the urban renewal program. It will be important to repeat the survey in the future to determine whether these positive changes are sustained.</p