A Photoprotein in Mouse Embryonic Stem Cells Measures Ca2+ Mobilization in Cells and in Animals

Exogenous expression of pharmacological targets in transformed cell lines has been the traditional platform for high throughput screening of small molecules. However, exogenous expression in these cells is limited by aberrant dosage, or its toxicity, the potential lack of interaction partners, and alterations to physiology due to transformation itself. Instead, primary cells or cells differentiated from precursors are more physiological, but less amenable to exogenous expression of reporter systems. To overcome this challenge, we stably expressed c-Photina, a Ca2+-sensitive photoprotein, driven by a ubiquitous promoter in a mouse embryonic stem (mES) cell line. The same embryonic stem cell line was also used to generate a transgenic mouse that expresses c-Photina in most tissues. We show here that these cells and mice provide an efficient source of primary cells, cells differentiated from mES cells, including cardiomyocytes, neurons, astrocytes, macrophages, endothelial cells, pancreatic islet cells, stably and robustly expressing c-Photina, and may be exploited for miniaturized high throughput screening. Moreover, we provide evidence that the transgenic mice may be suitable for ex-vivo bioimaging studies in both cells and tissues

Телемедицина: перспективы развития

Необходимость развития в условиях цифровой экономики такого направления как телемедицина кажется необходимостью, однако существует противоречие между существующими проблемами в системе организации здравоохранения Российской Федерации и возможностями доступности к услугам телемедицины. Анализ показал, что данное направление востребовано, необходимо, существует ряд сервисов, предлагающих услуги по телемедицине, однако нормативно-правовая база не позволяет в полной мере организовать полноценную работу по предоставлению телемедицинских услуг, в том числе, бесплатных

Forms of Understanding of XAI-Explanations

Explainability has become an important topic in computer science and artificial intelligence, leading to a subfield called Explainable Artificial Intelligence (XAI). The goal of providing or seeking explanations is to achieve (better) 'understanding' on the part of the explainee. However, what it means to 'understand' is still not clearly defined, and the concept itself is rarely the subject of scientific investigation. This conceptual article aims to present a model of forms of understanding in the context of XAI and beyond. From an interdisciplinary perspective bringing together computer science, linguistics, sociology, and psychology, a definition of understanding and its forms, assessment, and dynamics during the process of giving everyday explanations are explored. Two types of understanding are considered as possible outcomes of explanations, namely enabledness, 'knowing how' to do or decide something, and comprehension, 'knowing that' -- both in different degrees (from shallow to deep). Explanations regularly start with shallow understanding in a specific domain and can lead to deep comprehension and enabledness of the explanandum, which we see as a prerequisite for human users to gain agency. In this process, the increase of comprehension and enabledness are highly interdependent. Against the background of this systematization, special challenges of understanding in XAI are discussed

A potassium channel agonist protects hearing function and promotes outer hair cell survival in a mouse model for age-related hearing loss

Abstract Age-related hearing loss (ARHL) is the most common sensory impairment mainly caused by degeneration of sensory hair cells in the cochlea with no causal medical treatment available. Auditory function and sensory hair cell survival critically depend on the Kv7.4 (KCNQ4) channel, a voltage-gated potassium channel expressed in outer hair cells (OHCs), with its impaired function or reduced activity previously associated with ARHL. Here, we investigated the effect of a potent small-molecule Kv7.4 agonist on ARHL in the senescence-accelerated mouse prone 8 (SAMP8) model. For the first time in vivo, we show that Kv7.4 activation can significantly reduce age-related threshold shifts of auditory brainstem responses as well as OHC loss in the SAMP8 model. Pharmacological activation of Kv7.4 thus holds great potential as a therapeutic approach for ARHL as well as other hearing impairments related to Kv7.4 function