Publications

Therapeutic breakthroughs have transformed HIV into an illness that is routinized within the clinic. It is unclear, however, how these breakthroughs shape the lives of newly infected adolescents who are beginning to receive what will be life-long care and treatment. The reframing of HIV as no longer exceptional influences the lived experience of urban adolescents, whose futures must shift to incorporate expectations that they live a full life with HIV. They must now manage the clinical demands of a chronic and infectious disease, while navigating the transition from adolescence to a 'normal' adulthood, which, for some, means completing education, findings jobs, and building careers. Drawing on ethnographic research conducted in Baltimore, Maryland, I examine the tensions adolescents face as their experiences with HIV conflict with policy makers and researchers' reframing of HIV as a disease like any other.

The nematode Caenorhabditis elegans has served as a fruitful setting for cell death research for over three decades. A conserved pathway of four genes, egl-1/BH3-only, ced-9/Bcl-2, ced-4/Apaf-1, and ced-3/caspase, coordinates most developmental cell deaths in C. elegans. However, other cell death forms, programmed and pathological, have also been described in this animal. Some of these share morphological and/or molecular similarities with the canonical apoptotic pathway, while others do not. Indeed, recent studies suggest the existence of an entirely novel mode of programmed developmental cell destruction that may also be conserved beyond nematodes. Here, we review evidence for these noncanonical pathways. We propose that different cell death modalities can function as backup mechanisms for apoptosis, or as tailor-made programs that allow specific dying cells to be efficiently cleared from the animal.

PURPOSE OF REVIEW

Despite the progress toward understanding the molecular pathogenesis of rheumatoid arthritis (RA), its cause remains elusive. Genes are important but rather insufficient to explain the majority of RA cases. This review describes the novel data supporting the microbiome and its interactions with the human host as potential en('in')vironmental factors in RA pathogenesis.

RECENT FINDINGS

Animal models of inflammatory arthritis have shown that the presence of bacteria in mucosal surfaces is sufficient to alter local and systemic host immune responses and elicit joint inflammation. Human RA studies have focused on three mucosal sites: the gut, the gingiva, and the respiratory tree. The oral microbiome, and specifically Porphyromonas gingivalis, has long been implicated. Novel sequencing technologies have allowed investigations into the role of the gut microbiome in the development of autoimmune arthritis. Most recently, the pulmonary parenchyma has also been described as yet another possible mucosal site of initiation of autoimmunity in RA.

SUMMARY

Emerging data implicate the microbiome in RA pathogenesis. Mucosal sites exposed to a high load of bacterial antigens--such as the periodontium, lung, and gut--may represent the initial site of autoimmune generation. If validated, these findings could lead to the discovery of potential biomarkers and therapeutic approaches in the preclinical and clinical phases of RA.