Multi-omic detection of <i>Mycobacterium leprae</i> in archaeological human dental calculus

Mineralized dental plaque (calculus) has proven to be an excellent source of ancient biomolecules. Here we present a Mycobacterium leprae genome (6.6-fold), the causative agent of leprosy, recovered via shotgun sequencing of sixteenth-century human dental calculus from an individual from Trondheim, Norway. When phylogenetically placed, this genome falls in branch 3I among the diversity of other contemporary ancient strains from Northern Europe. Moreover, ancient mycobacterial peptides were retrieved via mass spectrometry-based proteomics, further validating the presence of the pathogen. Mycobacterium leprae can readily be detected in the oral cavity and associated mucosal membranes, which likely contributed to it being incorporated into this individual's dental calculus. This individual showed some possible, but not definitive, evidence of skeletal lesions associated with early-stage leprosy. This study is the first known example of successful multi-omics retrieval of M. leprae from archaeological dental calculus. Furthermore, we offer new insights into dental calculus as an alternative sample source to bones or teeth for detecting and molecularly characterizing M. leprae in individuals from the archaeological record.publishedVersio

Paneth cell - rich regions separated by a cluster of Lgr5+ cells initiate crypt fission in the intestinal stem cell niche

The crypts of the intestinal epithelium house the stem cells that ensure the continual renewal of the epithelial cells that line the intestinal tract. Crypt number increases by a process called crypt fission, the division of a single crypt into two daughter crypts. Fission drives normal tissue growth and maintenance. Correspondingly, it becomes less frequent in adulthood. Importantly, fission is reactivated to drive adenoma growth. The mechanisms governing fission are poorly understood. However, only by knowing how normal fission operates can cancer-associated changes be elucidated. We studied normal fission in tissue in three dimensions using high-resolution imaging and used intestinal organoids to identify underlying mechanisms. We discovered that both the number and relative position of Paneth cells and Lgr5+ cells are important for fission. Furthermore, the higher stiffness and increased adhesion of Paneth cells are involved in determining the site of fission. Formation of a cluster of Lgr5+ cells between at least two Paneth-cell-rich domains establishes the site for the upward invagination that initiates fission

Cardiac resynchronization therapy guided by cardiovascular magnetic resonance

Cardiac resynchronization therapy (CRT) is an established treatment for patients with symptomatic heart failure, severely impaired left ventricular (LV) systolic dysfunction and a wide (> 120 ms) complex. As with any other treatment, the response to CRT is variable. The degree of pre-implant mechanical dyssynchrony, scar burden and scar localization to the vicinity of the LV pacing stimulus are known to influence response and outcome. In addition to its recognized role in the assessment of LV structure and function as well as myocardial scar, cardiovascular magnetic resonance (CMR) can be used to quantify global and regional LV dyssynchrony. This review focuses on the role of CMR in the assessment of patients undergoing CRT, with emphasis on risk stratification and LV lead deployment

Heterochromatin Protein 1 (HP1) Proteins Do Not Drive Pericentromeric Cohesin Enrichment in Human Cells

Sister chromatid cohesion mediated by cohesin is essential for accurate chromosome segregation. Classical studies suggest that heterochromatin promotes cohesion, but whether this happens through regulation of cohesin remains to be determined. Heterochromatin protein 1 (HP1) is a major component of heterochromatin. In fission yeast, the HP1 homologue Swi6 interacts with cohesin and is required for proper targeting and/or stabilization of cohesin at the centromeric region. To test whether this pathway is conserved in human cells, we have examined the behavior of cohesin in cells in which the levels of HP1 alpha, beta or gamma (the three HP1 proteins present in mammalian organisms) have been reduced by siRNA. We have also studied the consequences of treating human cells with drugs that change the histone modification profile of heterochromatin and thereby affect HP1 localization. Our results show no evidence for a requirement of HP1 proteins for either loading of bulk cohesin onto chromatin in interphase or retention of cohesin at pericentric heterochromatin in mitosis. However, depletion of HP1gamma leads to defects in mitotic progression

The aesthetics of ritual--contested identities and conflicting performances in the Iraqi Shi’a diaspora: Ritual, performance and identity change

What are the processes through which identity change takes place at the individual and collective level? How might a focus on embodied religious performance and ritual contribute to understandings of such identity change? Through an ethnographic analysis of the Muharram rituals of Iraqi Shi’is in London, I take religious rites as a starting point from which to theorise a performative theory of identity change to highlight the role of ritual and performance in shaping changing notions of identity at both the individual and collective level. Such a project necessarily engages both with processes of identity change and with the paradox of identity/difference, particularly the ways in which articulations of subjective identity are ontologically dependent on an external ‘other’. Ultimately, I argue that paying close critical attention to the performative and (re)iterative processes of micro-level identificatory practices allows a more nuanced understanding of the mechanisms through which identity change comes to take effect, both at the level of individual subjectivity and that of collective social belonging

Fragmented realities: The ‘sectarianisation’of space among Iraqi Shias in London

How do the spaces we inhabit shape our lived experiences? And how do those lived experiences in turn come to shape and influence our political subjectivity? Such questions are rendered all the more important in studies of migrant or diaspora populations who, by definition, conduct their daily lives in spaces and places that were initially alien to them. The way in which migrants interact with the spaces around them can tell us much about the social, political, and religious engagements they invest in, as well as the very real way in which they experience their local milieu. Through a detailed study of Iraqi Shiis living in London, specifically in the north-western borough of Brent, this article will seek to trace the ways in which religious institutions have carved up the physical and social landscape of north-west London in ways that have enduring effect on the communities with which they engage. The increasing diversification of different religious establishments, I argue, has led to a fragmentation of the city-as-lived, in which the vast majority of practising Iraqi Shiis engage with only small isolated pockets of the urban environment on a daily basis. Moreover, the growing number of specifically Shia schools, charities, mosques, community centres and other such institutions has resulted in what I call a ‘sectarianisation’ of space in Brent, in which individuals hailing from different branches of Islam inhabit different spaces within the city despite often living within metres of each other. Drawing on a mixture of interviews, participant observation, and mapping techniques, I bring together theory and practice in order to sketch out the ways migrant lives can come to be localised in certain spaces, and what that can ultimately mean in terms of their political subjectivity and engagement