PRODUCTIVE INFECTION OF ISOLATED HUMAN ALVEOLAR MACROPHAGES BY RESPIRATORY SYNCYTIAL VIRUS

Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract disease in children and individuals with cell-mediated immunodeficiencies. Airway epithelial cells may be infected with RSV, but it is unknown whether other cells within the lung permit viral replication. We studied whether human alveolar macrophages supported RSV replication in vitro. Alveolar macrophages exposed to RSV demonstrated expression of RSV fusion gene, which increased in a time-dependent manner and correlated with RSV protein expression. RSV-exposed alveolar macrophages produced and released infectious virus into supernatants for at least 25 d after infection. Viral production per alveolar macrophage declined from 0.053 plaque-forming units (pfu)/cell at 24 h after infection to 0.003 pfu/cell by 10 d after infection and then gradually increased. The capability of alveolar macrophages to support prolonged RSV replication may have a role in the pulmonary response to RSV infection

Emergence of a High-Plasticity Cell State during Lung Cancer Evolution.

Tumor evolution from a single cell into a malignant, heterogeneous tissue remains poorly understood. Here, we profile single-cell transcriptomes of genetically engineered mouse lung tumors at seven stages, from pre-neoplastic hyperplasia to adenocarcinoma. The diversity of transcriptional states increases over time and is reproducible across tumors and mice. Cancer cells progressively adopt alternate lineage identities, computationally predicted to be mediated through a common transitional, high-plasticity cell state (HPCS). Accordingly, HPCS cells prospectively isolated from mouse tumors and human patient-derived xenografts display high capacity for differentiation and proliferation. The HPCS program is associated with poor survival across human cancers and demonstrates chemoresistance in mice. Our study reveals a central principle underpinning intra-tumoral heterogeneity and motivates therapeutic targeting of the HPCS.This work was supported by the Transcend Program and Janssen Pharmaceuticals, the Howard Hughes Medical Institute, and, in part, by the NIH/NCI Cancer Center Support Grants P30-CA08748 (MSKCC) and P30-CA14051 (Koch Institute). T.T. is supported by American Cancer Society, Rita Allen, Josie Robertson Scholar, and V Foundation Scholarships and the American Association for Cancer Research Next Generation Transformative Research Award; the American Lung Association; the Stanley and Fiona Druckenmiller Center for Lung Cancer Research; and NCI-CA187317. T.J. is supported by NCI-PO1CA42063. A.R. is supported by the Klarman Cell Observatory. J.E.C is supported by the MSK T32 Investigational Cancer Therapeutics Training Program Grant (NIH MSK ICTTP T32-CA009207). P.P.M. is supported by NCI-CA196405. L.M. is supported by The Alan and Sandra Gerry Foundation. We acknowledge the use of the Integrated Genomics Operation Core, funded by CCSG P30-CA08748, Cycle for Survival, and the Marie-Josée and Henry R. Kravis Center for Molecular Oncology at MSKCC; the Flow Cytometry and Histology Core Facilities at the Swanson Biotechnology Center at the Koch Institute; and the MIT Bio-Micro Center. A.R., T.J.and A.A. are Howard Hughes Medical Institute Investigators; T.J. is a David H. Koch Professor of Biology, and a Daniel K. Ludwig Scholar

The Strange Case of Yugoslav Feminism: Feminism and Socialism in ‘the East’

The text counters the prevailing idea that there was no feminism in the socialist Eastern bloc, carefully presenting a peculiar case of Yugoslav feminism which grew out of socialist political and cultural framework. Yugoslavia was the country where the organization of the singular feminist event in the Eastern world, the conference “Comrade Woman – The New Approach?” (1978), took place. The text traces the ideas on emancipation and liberation which appeared in Yugoslav scientific and literary journals, immediately after the “Comrade Woman” and until the late 1980s, before the proclaimed fall of the Iron Curtain. The written material is grouped into three sections, according to how the so called woman’s question was elaborated. By re-reading this material, the text examines if feminism was legitimized within the dominant socialist discourse, or whether it was purely translated as something externally Western. The aim of the text is to describe how scholars and activists portrayed emancipation and liberation at that very time: to see if they negotiated or failed to negotiate Western definitions and Eastern realities. In that sense, given material is not used to simply reinforce or refute the claim that feminism was an imported Western (i.e. capitalist) product that had no place interfering with the development. of socialism. It also urges us to re-consider the common knowledges we have, in order to see how they become situated as commo