Moderate beta-cell ablation triggers synergic compensatory mechanisms even in the absence of overt metabolic disruption.

Regeneration, the ability to replace injured tissues and organs, is a phenomenon commonly associated with lower vertebrates but is also observed in mammals, in specific tissues. In this study, we investigated the regenerative potential of pancreatic islets following moderate beta-cell loss in mice. Using a rapid model of moderate ablation, we observed a compensatory response characterized by transient inflammation and proliferation signatures, ultimately leading to the recovery of beta-cell identity and function. Interestingly, this proliferative response occurred independently of inflammation, as demonstrated in ablated immunodeficient mice. Furthermore, exposure to high-fat diet stimulated beta-cell proliferation but negatively impacted beta-cell function. In contrast, an equivalent slower ablation model revealed a delayed but similar proliferative response, suggesting proliferation as a common regenerative response. However, high-fat diet failed to promote proliferation in this model, indicating a differential response to metabolic stressors. Overall, our findings shed light on the complex interplay between beta-cell loss, inflammation, and stress in modulating pancreatic islet regeneration. Understanding these mechanisms could pave the way for novel therapeutic strategies based on beta-cell proliferation.

The age-dependent regulation of pancreatic islet landscape is fueled by a HNF1a-immune signaling loop.

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.

SARUS: A Synthetic Aperture Real-time Ultrasound System.

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.