People and Things on the Move: Domestic Material Culture, Poverty and Mobility in Victorian London

© 2016, The Author(s). The development of what Mayne and Lawrence (Urban History 26: 325–48, 1999) termed “ethnographic” approaches to studying nineteenth-century households and urban communities has gathered momentum in recent years. As such research agendas have taken hold and been applied to new contexts, so critiques, methodological developments, and new intellectual and theoretical currents, have provided opportunities to enhance and develop approaches. This article contributes to this on-going process. Drawing upon household archaeological research on Limehouse, a poor neighborhood in Victorian London, and inspired by the theoretical insights provided by the “new mobilities paradigm,” it aims to place “mobility” as a central and enabling intellectual framework for understanding the relationships between people, place, and poverty. Poor communities in nineteenth-century cities were undeniably mobile and transient. Historians and archaeologists have often regarded this mobility as an obstacle to studying everyday life in such contexts. However, examining temporal routines and geographical movements across a variety of time frames and geographical scales, this article argues that mobility is actually key to understanding urban life and an important mechanism for interpreting the fragmented material and documentary traces left by poor households in the nineteenth-century metropolis.We are grateful to the UK’s Arts and Humanities Research Council who funded the research upon which this paper is based (Grant Reference AH/E002285/1): ‘Living in Victorian London: Towards a Material History of Everyday Domestic Life in the Nineteenth-Century Metropolis

MDA-5 Recognition of a Murine Norovirus

Noroviruses are important human pathogens responsible for most cases of viral epidemic gastroenteritis worldwide. Murine norovirus-1 (MNV-1) is one of several murine noroviruses isolated from research mouse facilities and has been used as a model of human norovirus infection. MNV-1 infection has been shown to require components of innate and adaptive immunity for clearance; however, the initial host protein that recognizes MNV-1 infection is unknown. Because noroviruses are RNA viruses, we investigated whether MDA5 and TLR3, cellular sensors that recognize dsRNA, are important for the host response to MNV-1. We demonstrate that MDA5−/− dendritic cells(DC) have a defect in cytokine response to MNV-1. In addition, MNV-1 replicates to higher levels in MDA5−/− DCs as well as in MDA5−/− mice in vivo. Interestingly, TLR3−/− DCs do not have a defect in vitro, but TLR3−/− mice have a slight increase in viral titers. This is the first demonstration of an innate immune sensor for norovirus and shows that MDA5 is required for the control of MNV-1 infection. Knowledge of the host response to MNV-1 may provide keys for prevention and treatment of the human disease

Primary care multidisciplinary teams in practice: a qualitative study.

BACKGROUND: Current recommendations for strengthening the US healthcare system consider restructuring primary care into multidisciplinary teams as vital to improving quality and efficiency. Yet, approaches to the selection of team designs remain unclear. This project describes current primary care team designs, primary care professionals' perceptions of ideal team designs, and perceived facilitating factors and barriers to implementing ideal team-based care. METHODS: Qualitative study of 44 health care professionals at 6 primary care practices in North Carolina using focus group discussions and surveys. Data was analyzed using framework content analysis. RESULTS: Practices used a variety of multidisciplinary team designs with the specific design being influenced by the social and policy context in which practices were embedded. Practices overwhelmingly located barriers to adopting ideal multidisciplinary teams as being outside of their individual practices and outside of their control. Participants viewed internal organizational contexts as the major facilitators of multidisciplinary primary care teams. The majority of practices described their ideal team design as including a social worker to meet the needs of socially complex patients. CONCLUSIONS: Primary care multidisciplinary team designs vary across practices, shaped in part by contextual factors perceived as barriers outside of the practices' control. Facilitating factors within practices provide a culture of support to team members, but they are insufficient to overcome the perceived barriers. The common desire to add social workers to care teams reflects practices' struggles to meet the complex demands of patients and external agencies. Government or organizational policies should avoid one-size-fits-all approaches to multidisciplinary care teams, and instead allow primary care practices to adapt to their specific contextual circumstances.American Academy of Family Physicians Foundation’s Joint Grant Award Program [#G1401JG

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

Fluorescent amino acids as versatile building blocks for chemical biology

Fluorophores have transformed the way we study biological systems, enabling non-invasive studies in cells and intact organisms, which increase our understanding of complex processes at the molecular level. Fluorescent amino acids have become an essential chemical tool because they can be used to construct fluorescent macromolecules, such as peptides and proteins, without disrupting their native biomolecular properties. Fluorescent and fluorogenic amino acids with unique photophysical properties have been designed for tracking protein–protein interactions in situ or imaging nanoscopic events in real time with high spatial resolution. In this Review, we discuss advances in the design and synthesis of fluorescent amino acids and how they have contributed to the field of chemical biology in the past 10 years. Important areas of research that we review include novel methodologies to synthesize building blocks with tunable spectral properties, their integration into peptide and protein scaffolds using site-specific genetic encoding and bioorthogonal approaches, and their application to design novel artificial proteins, as well as to investigate biological processes in cells by means of optical imaging. [Figure not available: see fulltext.]

Processing of DNA for nonhomologous end-joining by cell-free extract

In mammalian cells, nonhomologous end-joining (NHEJ) repairs DNA double-strand breaks created by ionizing radiation and V(D)J recombination. We have developed a cell-free system capable of processing and joining noncompatible DNA ends. The system had key features of NHEJ in vivo, including dependence on Ku, DNA-PKcs, and XRCC4/Ligase4. The NHEJ reaction had striking properties. Processing of noncompatible ends involved polymerase and nuclease activities that often stabilized the alignment of opposing ends by base pairing. To achieve this, polymerase activity efficiently synthesized DNA across discontinuities in the template strand, and nuclease activity removed a limited number of nucleotides back to regions of microhomology. Processing was suppressed for DNA ends that could be ligated directly, biasing the reaction to preserve DNA sequence and maintain genomic integrity. DNA sequence internal to the ends influenced the spectrum of processing events for noncompatible ends. Furthermore, internal DNA sequence strongly influenced joining efficiency, even in the absence of processing. These results support a model in which DNA-PKcs plays a central role in regulating the processing of ends for NHEJ