ABSTRACT
Animal longevity is a function of global vital organ functionality and, consequently, a complex polygenic trait. Yet, monogenic regulators controlling overall or organ-specific ageing exist, owing their conservation to their function in growth and development. Here, by using pathway analysis combined with wet-biology methods on several dynamic timelines, we identified Hnf1a as a novel master regulator of the maturation and ageing in the adult pancreatic islet during the first year of life. Conditional transgenic mice bearing suboptimal levels of this transcription factor in the pancreatic islets displayed age-dependent changes, with a profile echoing precocious maturation. Additionally, the comparative pathway analysis revealed a link between Hnf1a age-dependent regulation and immune signaling, which was confirmed in the ageing timeline of an overly immunodeficient mouse model. Last, the global proteome analysis of human islets spanning three decades of life largely backed the age-specific regulation observed in mice. Collectively, our results suggest a novel role of Hnf1a as a monogenic regulator of the maturation and ageing process in the pancreatic islet via a direct or indirect regulatory loop with immune signaling.
ABSTRACT
The Synthetic Aperture Real-time Ultrasound System (SARUS) for acquiring and processing synthetic aperture (SA) data for research purposes is described. The specifications and design of the system are detailed, along with its performance for SA, nonlinear, and 3-D flow estimation imaging. SARUS acquires individual channel data simultaneously for up to 1024 transducer elements for a couple of heart beats, and is capable of transmitting any kind of excitation. The 64 boards in the system house 16 transmit and 16 receive channels each, where sampled channel data can be stored in 2 GB of RAM and processed using five field-programmable gate arrays (FPGAs). The fully parametric focusing unit calculates delays and apodization values in real time in 3-D space and can produce 350 million complex samples per channel per second for full non-recursive synthetic aperture B-mode imaging at roughly 30 high-resolution images/s. Both RF element data and beamformed data can be stored in the system for later storage and processing. The stored data can be transferred in parallel using the system's sixty-four 1-Gbit Ethernet interfaces at a theoretical rate of 3.2 GB/s to a 144-core Linux cluster.
