Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.

Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells

Human pluripotent stem cell-derived organoids and their potential to reduce the use of animal models in research

Efficient and reproducible generation of tissue-specific organoids from Human Pluripotent Stem Cells (hPSCs) represents one of the key tools for reducing the use of animals in research. STEMCELL Technologies is committed to optimizing workflows that efficiently support the generation and maintenance of multiple types of organoid cultures derived from hPSCs.</jats:p

Data-driven Fault Detection and Diagnosis for HVAC water chillers

Faulty operations of Heating, Ventilation and Air Conditioning (HVAC) chiller systems can lead to discomfort for the users, energy wastage, system unreliability and shorter equipment life. Faults need to be early diagnosed to prevent further deterioration of the system behaviour and energy losses. Since it is not a common practice to collect historical data regarding unforeseen phenomena and abnormal behaviours for HVAC installations, in this paper, a semi-supervised data-driven approach is employed for fault detection and isolation that makes no use of a priori knowledge about abnormal phenomena. The proposed method exploits Principal Component Analysis (PCA) to distinguish anomalies from normal operation variability and a reconstruction-based contribution approach to isolate variables related to faults. The diagnosis task is then tackled by means of a decision table that associates the influence of faults to certain characteristic features. The Fault Detection and Diagnosis (FDD) algorithm performance is assessed by exploiting experimental datasets from two types of water chiller systems

Leveraging demand flexibility by exploiting prosumer response to price signals in microgrids

The diffusion of distributed energy resources in distribution networks requires new approaches to exploit the users' capabilities of providing ancillary services. Of particular interest will be the coordination of microgrids operating as an aggregate of demand and supply units. This work reports a model predictive control (MPC) application in microgrids for the efficient energy management of energy storage systems and photovoltaic units. The MPC minimizes the economic cost of aggregate prosumers into a prediction horizon by forecasting generation and absorption profiles. The MPC is compared in realistic conditions with a heuristic strategy that acts in a instant manner, without taking into account signals prediction. The work aims at investigating the effect that different types of energy tariffs have in enhancing the end-users' flexibility, based on three examples of currently applied tariffs, comparing the two storage control modes. The MPC always achieves a better solution than the heuristic approach in all considered scenarios from the cost minimization point of view, with an improvement that is amplified by increasing the energy price variations between peak and off-peak periods. Furthermore, the MPC approach provides a cost saving when compared to the case considering a microgrid endowed with only photovoltaic units, in which no storage is installed. Findings in this work confirm that storage units better perform when some knowledge of future demand and supply trends is provided, ensuring an economic cost saving and an important service for the overall community

Organoid culture systems: Products supporting one of the biggest revolutions in biological research

Organoids are stem cell-derived structures that are generated in three-dimensional tissue culture. They are unique since they exhibit a high degree of self-organization and differentiation, and thus recapitulate many of the features of the tissues from which they were derived. Because of this, organoids are now firmly established as an essential tool in medical research, and have the potential to drastically reduce the number of animals required for experimentation.</jats:p

MOLECULAR AND SEROLOGICAL DIVERSITY OF NEISSERIA MENINGITIDIS CARRIER STRAINS ISOLATED FROM ITALIAN STUDENTS AGED 14-22 YEARS.

Neisseria meningitidis is an obligate human commensal that commonly colonizes the oropharyngeal mucosa. Carriage is age dependent and very common in young adults. The relationships between carriage and invasive disease are not completely understood. In this work, we performed a longitudinal carrier study in adolescents and young adults (173 subjects). Overall, 32 subjects (18.5%) had results that were positive for meningococcal carriage in at least one visit (average monthly carriage rate, 12.1%). Only five subjects tested positive at all four visits. All meningococcal isolates were characterized by molecular and serological techniques. Multilocus sequence typing, PorA typing, and sequencing of the 4CMenB vaccine antigens were used to assess strain diversity. The majority of positive subjects were colonized by capsule null (34.4%) and capsular group B strains (28.1%), accounting for 23.5% and 29.4% of the total number of isolates, respectively. The fHbp and nhba genes were present in all isolates, while the nadA gene was present in 5% of the isolates. The genetic variability of the 4CMenB vaccine antigens in this collection was relatively high compared with that of other disease-causing strain panels. Indications about the persistence of the carriage state were limited to the time span of the study. All strains isolated from the same subject were identical or cumulated minor changes over time. The expression levels and antigenicities of the 4CMenB vaccine antigens in each strain were analyzed by the meningococcal antigen typing system (MATS), which revealed that expression can change over time in the same individual. Future analysis of antigen variability and expression in carrier strains after the introduction of the MenB vaccine will allow for a definition of its impact on nasopharyngeal/oropharyngeal carriage