Biology subjects

Smith, T. A.

Publications and source records attributed to Smith, T. A..

3 recordsLinked to original sources

bioRxiv2018

C. elegans germ cells divide and differentiate along a folded epithelium

Knowing how stem cells and their progeny are positioned within their tissues is essential for understanding their regulation. One paradigm for stem cell regulation is the C. elegans germline, which is maintained by a pool of germline stem cells in the distal gonad, in a region known as the progenitor zone. The C. elegans germline is widely used as a stem cell model, but the cellular architecture of the progenitor zone has been unclear. Here we characterize this architecture by creating virtual 3D models of the progenitor zone in both sexes. We show that the progenitor zone in adult hermaphrodites is essentially a folded epithelium. The progenitor zone in males is not folded. Analysis of germ cell division shows that daughter cells are born side-by-side along the surface of the epithelium. Analysis of a key regulator driving differentiation, GLD-1, shows that germ cells in hermaphrodites differentiate along the path of the folded epithelium, with previously described \"steps\" in GLD-1 expression corresponding to germline folds. Our study provides a three-dimensional view of how C. elegans germ cells progress from stem cell to overt differentiation, with critical implications for regulators driving this transition.

developmental biology↗

bioRxiv2017

Simulations for Designing and Interpreting Intervention Trials in Infectious Diseases

Here we urge the adoption of a new paradigm for the design and interpretation of intervention trials in infectious diseases, particularly in emerging infectious disease, that more accurately reflects the dynamics of the transmission process. Interventions in infectious diseases can have indirect effects on those not receiving the intervention as well as direct effects on those receiving the intervention. Combinations of interventions can have complex interactions at the population level. These often cannot be adequately addressed with standard study designs and analytic methods. Simulations can help to accurately represent transmission dynamics in an increasingly complex world which is critical for proper trial design and interpretation. Some ethical aspects of a trial can also be quantified using simulations. After a trial has been conducted, simulations can be used to explore possible explanations for the observed effects. A great deal is to be gained through a multidisciplinary approach that builds collaborations among experts in infectious disease dynamics, epidemiology, statistical science, economics, simulation methods and the conduct of clinical trials.

epidemiology↗

bioRxiv2017

The experience of vivid autobiographical reminiscence is supported by personal semantic representations in the precuneus

Recent studies have suggested that the human posteromedial cortex (PMC), which includes core regions of the default mode network (DMN), plays an important role in episodic memory. Whereas various roles relating to self-relevant processing and memory retrieval have been attributed to different subsystems within this broad network, the nature of representations and the functional roles they support in these brain regions remain unspecified. Here, we describe the whole-brain networks that represent subjective, self-relevant aspects of real-world events during autobiographical recollection. Nine participants wore a device to record images from their lives for a period of two to four weeks (lifelogging phase) and indicated the personally-salient attributes (i.e., personal semantics) of each episode by choosing multiple content tags. Two to four weeks after the lifelogging phase, participants relived their experiences in an fMRI scanner cued by images chosen from their own lives. Representational Similarity Analysis revealed a broad network, including parts of the DMN, that represented personal semantics during autobiographical reminiscence. Furthermore, within this network, the right precuneus represented personally relevant content during vivid recollection but not during non-vivid recollection. The precuneus is a hub within the DMN and has been implicated in metacognitive ability for memory retrieval. Our results suggest a more specific mechanism underlying the phenomenology of vivid reminiscence, supported by personal semantic representations in the precuneus.

neuroscience↗