Astrocytic β-catenin signaling via TCF7L2 regulates synapse development and social behavior

The Wnt/β-catenin pathway contains multiple high-confidence risk genes that are linked to neurodevelopmental disorders, including autism spectrum disorder. However, its ubiquitous roles across brain cell types and developmental stages have made it challenging to define its impact on neural circuit development and behavior. Here, we show that TCF7L2, which is a key transcriptional effector of the Wnt/β-catenin pathway, plays a cell-autonomous role in postnatal astrocyte maturation and impacts adult social behavior. TCF7L2 was the dominant Wnt effector that was expressed in both mouse and human astrocytes, with a peak during astrocyte maturation. The conditional knockout of Tcf7l2 in postnatal astrocytes led to an enlargement of astrocytes with defective tiling and gap junction coupling. These mice also exhibited an increase in the number of cortical excitatory and inhibitory synapses and a marked increase in social interaction by adulthood. These data reveal an astrocytic role for developmental Wnt/β-catenin signaling in restricting excitatory synapse numbers and regulating adult social behavior

On the search for the right definition of heart failure with preserved ejection fraction

The definition of heart failure with preserved ejection fraction (HFpEF) has evolved from a clinically based “diagnosis of exclusion” to definitions focused on objective evidence of diastolic dysfunction and/or elevated left ventricular filling pressures. Despite advances in our understanding of HFpEF pathophysiology and the development of more sophisticated imaging modalities, the diagnosis of HFpEF remains challenging, especially in the chronic setting, given that symptoms are provoked by exertion and diagnostic evaluation is largely conducted at rest. Invasive hemodynamic study, and in particular — invasive exercise testing, is considered the reference method for HFpEF diagnosis. However, its use is limited as opposed to the high number of patients with suspected HFpEF. Thus, diagnostic criteria for HFpEF should be principally based on non-invasive measurements. As no single non-invasive variable can adequately corroborate or refute the diagnosis, different combinations of clinical, echocardiographic, and/or biochemical parameters have been introduced. Recent years have brought an abundance of HFpEF definitions. Here, we present and compare four of them: 1) the 2016 European Society of Cardiology criteria for HFpEF; 2) the 2016 echocardiographic algorithm for diagnosing diastolic dysfunction; 3) the 2018 evidence-based H2FPEF score; and 4) the most recent, 2019 Heart Failure Association HFA-PEFF algorithm. These definitions vary in their approach to diagnosis, as well as sensitivity and specificity. Further studies to validate and compare the diagnostic accuracy of HFpEF definitions are warranted. Nevertheless, it seems that the best HFpEF definition would originate from a randomized clinical trial showing a favorable effect of an intervention on prognosis in HFpEF

Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

Towards a health-aware fault tolerant control of complex systems: A vehicle fleet case

The paper deals with the problem of health-aware fault-tolerant control of a vehicle fleet. In particular, the development process starts with providing the description of the process along with a suitable Internet-of-Things platform, which enables appropriate communication within the vehicle fleet. It also indicates the transportation tasks to the designated drivers and makes it possible to measure their realization times. The second stage pertains to the description of the analytical model of the transportation system, which is obtained with the max-plus algebra. Since the vehicle fleet is composed of heavy duty machines, it is crucial to monitor and analyze the degradation of their selected mechanical components. In particular, the components considered are ball bearings, which are employed in almost every mechanical transportation system. Thus, a fuzzy logic Takagi–Sugeno approach capable of assessing their time-to-failure is proposed. This information is utilized in the last stage, which boils down to health-aware and fault-tolerant control of the vehicle fleet. In particular, it aims at balancing the exploitation of the vehicles in such a way as to maximize they average time-to-failure. Moreover, the fault-tolerance is attained by balancing the use of particular vehicles in such a way as to minimize the effect of possible transportation delays within the system. Finally, the effectiveness of the proposed approach is validated using selected simulation scenarios involving vehicle-based transportation tasks

Linking microbial enzymatic activities and functional diversity of soil around earthworm burrows and casts

The aim of this work was to evaluate the effect of earthworms (Lumbricidae) on the enzymatic activity and microbial functional diversity in the burrow system (burrow wall 0–3 mm, transitional zone 3–7 mm, bulk soil >20 mm from the burrow wall) and cast aggregates of a loess soil under a pear orchard. The dehydrogenase, β-glucosidase, protease, alkaline phosphomonoesterase, and acid phosphomonoesterase enzymes were assessed using standard methods. The functional diversity (catabolic potential) was assessed using the Average Well Color Development and Richness Index following the community level physiological profiling from Biolog Eco Plates. All measurements were done using soil from each compartment immediately after in situ sampling in spring. The enzymatic activites including dehydrogenase, protease, β-glucosidase and alkaline phosphomonoesterase were appreciably greater in the burrow wall or casts than in bulk soil and transitional zone. Conversely, acid phosphomonoesterase had the largest value in the bulk soil. Average Well Color Development in both the transitional zone and the bulk soil (0.98-0.94 A590nm) were more than eight times higher than in the burrow walls and casts. The lowest richness index in the bulk soil (15 utilized substrates) increased by 86-113% in all the other compartments. The PC1 in principal component analysis (PCA) mainly differentiated the burrow walls and the transitional zone. Utilization of all substrate categories was the lowest in the bulk soil. The PC2 differentiated the casts from the other compartments. The enhanced activity of a majority of the enzymes and increased microbial functional diversity in most earthworm-influenced compartments make the soils less vulnerable to degradation and thus increases the stability of ecologically relevant processes in the orchard ecosystem

Ocena epizootyczna zakażeń Mycobacterium avium spp. paratuberculosis u bydła w Polsce w latach 2011-2020 jako potencjalny czynnik etiologiczny choroby Leśniowskiego-Crohna u ludzi

Background. Mycobacterium avium spp. paratuberculosis (MAP) is a bacterial germ and the etiologic agent in paratuberculosis also known as Johne's disease, a debilitating disease seen in animals. MAP is one of the triggers in the development of Crohn's disease in humans. Therefore the presence of these microorganisms in the environment and their prevalence in farm animals in relation to Crohn's disease is a new area of research. To date, it has not been evaluated in Poland. Material and methods. The materials for this study consisted of 14,468 samples of bovine serum across Poland. Determination of anti-MAP antibody levels was performed using an immunoenzymatic Paratuberculosis Screening Ab Test p/n P07130-5® (IDEXX, Westbrook, Maine 04092, United States). Results. The study consisted of 14,468 samples of bovine serum. Anti-MAP antibodies were identified in 349 cattle sera. Conclusions. Successful paratuberculosis screening programs can lead to a reduction of MAP in animal products. As the role of MAP in Crohn’s disease is not fully understood, future research should be conducted to address this knowledge gap and avoid a potential zoonotic public health problem.Wprowadzenie. Mycobacterium avium spp. paratuberculosis (MAP) zwany także prątkiem Johnego jest czynnikiem etiologicznym paratuberkulozy, wyniszczającej choroby występującej u zwierząt. Jednym z czynników niezbędnych do rozwoju choroby Crohna u ludzi jest obecność MAP, stąd też obecność w środowisku tych drobnoustrojów, a przede wszystkim ocena ich występowania u zwierząt gospodarskich w odniesieniu do choroby Crohna, stanowi nowy obszar badań, nieopisany dotąd w Polsce. Materiał i metody. Materiał do badań stanowiło 14468 bydlęcych surowic pochodzących z terenu całej Polski. Oznaczenie poziomu przeciwciał anty-MAP wykonano przy użyciu immunoenzymatycznego testu Paratuberculosis Screening Ab Test p/n P07130-5® (IDEXX, Westbrook, Maine 04092, United States). Wyniki. W badanej grupie 14468 surowic, przeciwciała anty-MAP potwierdzono u 349 sztuk bydła. Wnioski. Udane programy kontroli paratuberkulozy mogą prowadzić do zmniejszenia występowania MAP w produktach zwierzęcego pochodzenia. W związku z tym, że rola MAP nie jest do końca poznana w chorobie Crohna, przyszłe badania powinny zająć się tymi lukami, aby uniknąć potencjalnego odzwierzęcego problemu zdrowia publicznego