416 research outputs found
Structural insights into crista junction formation by the Mic60-Mic19 complex
Mitochondrial cristae membranes are the oxidative phosphorylation sites in cells. Crista junctions (CJs) form the highly curved neck regions of cristae and are thought to function as selective entry gates into the cristae space. Little is known about how CJs are generated and maintained. We show that the central coiled-coil (CC) domain of the mitochondrial contact site and cristae organizing system subunit Mic60 forms an elongated, bow tie–shaped tetrameric assembly. Mic19 promotes Mic60 tetramerization via a conserved interface between the Mic60 mitofilin and Mic19 CHCH (CC-helix-CC-helix) domains. Dimerization of mitofilin domains exposes a crescent-shaped membrane-binding site with convex curvature tailored to interact with the curved CJ neck. Our study suggests that the Mic60-Mic19 subcomplex traverses CJs as a molecular strut, thereby controlling CJ architecture and function
What is multidisciplinary cancer care like in practice? a protocol for a mixed-method study to characterise ambulatory oncology services in the Australian public sector
© 2019 Author(s). Introduction An understanding of the real-world provision of oncology outpatient services can help maintain service quality in the face of escalating demand and tight budgets, by informing the design of interventions that improve the effectiveness or efficiency of provision. The aims of this study are threefold. First, to develop an understanding of cancer services in outpatient clinics by characterising the organisation and practice of multidisciplinary care (MDC). Second, to explore the key areas of: (a) clinical decision-making and (b) engagement with patients' supportive needs. Third, to identify barriers to, and facilitators of, the delivery of quality care in these settings. Methods and analysis A suite of mixed-methods studies will be implemented at six hospitals providing cancer outpatient clinics, with a staged roll-out. In Stage One, we will examine policies, use unstructured observations and undertake interviews with key health professionals to characterise the organisation and delivery of MDC. In Stage Two, observations of practice will continue, to deepen our understanding, and to inform two focused studies. The first will explore decision-making practices and the second will examine how staff engage with patients' needs; both studies involve interviews, to complement observation. As part of the study of supportive care, we will examine the implications of an introduction of patient-reported measures (PRMs) into care, adding surveys to interviews before and after PRMs roll-out. Data analysis will account for site-specific and cross-site issues using an adapted Qualitative Rapid Appraisal, Rigorous Analysis approach. Quantitative data from clinician surveys will be statistically analysed and triangulated with the related qualitative study findings. Ethics and dissemination Ethical approval was granted by South Eastern Sydney Local Health District Human Research Ethics Committee (no. 18/207). Findings will be shared with participating hospitals and widely disseminated through publications and presentations
Structural insights into crista junction formation by the Mic60-Mic19 complex
Mitochondrial cristae membranes are the oxidative phosphorylation sites in cells. Crista junctions (CJs) form the highly curved neck regions of cristae and are thought to function as selective entry gates into the cristae space. Little is known about how CJs are generated and maintained. We show that the central coiled-coil (CC) domain of the mitochondrial contact site and cristae organizing system subunit Mic60 forms an elongated, bow tie–shaped tetrameric assembly. Mic19 promotes Mic60 tetramerization via a conserved interface between the Mic60 mitofilin and Mic19 CHCH (CC-helix-CC-helix) domains. Dimerization of mitofilin domains exposes a crescent-shaped membrane-binding site with convex curvature tailored to interact with the curved CJ neck. Our study suggests that the Mic60-Mic19 subcomplex traverses CJs as a molecular strut, thereby controlling CJ architecture and function
Deterministic and stochastic descriptions of gene expression dynamics
A key goal of systems biology is the predictive mathematical description of
gene regulatory circuits. Different approaches are used such as deterministic
and stochastic models, models that describe cell growth and division explicitly
or implicitly etc. Here we consider simple systems of unregulated
(constitutive) gene expression and compare different mathematical descriptions
systematically to obtain insight into the errors that are introduced by various
common approximations such as describing cell growth and division by an
effective protein degradation term. In particular, we show that the population
average of protein content of a cell exhibits a subtle dependence on the
dynamics of growth and division, the specific model for volume growth and the
age structure of the population. Nevertheless, the error made by models with
implicit cell growth and division is quite small. Furthermore, we compare
various models that are partially stochastic to investigate the impact of
different sources of (intrinsic) noise. This comparison indicates that
different sources of noise (protein synthesis, partitioning in cell division)
contribute comparable amounts of noise if protein synthesis is not or only
weakly bursty. If protein synthesis is very bursty, the burstiness is the
dominant noise source, independent of other details of the model. Finally, we
discuss two sources of extrinsic noise: cell-to-cell variations in protein
content due to cells being at different stages in the division cycles, which we
show to be small (for the protein concentration and, surprisingly, also for the
protein copy number per cell) and fluctuations in the growth rate, which can
have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012
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