Pathophysiological Mechanisms of Cardiac Dysfunction in Transgenic Mice with Viral Myocarditis.

Viral myocarditis is pathologically associated with RNA viruses such as coxsackievirus B3 (CVB3), or more recently, with SARS-CoV-2, but despite intensive research, clinically proven treatment is limited. Here, by use of a transgenic mouse strain (TG) containing a CVB3ΔVP0 genome we unravel virus-mediated cardiac pathophysiological processes in vivo and in vitro. Cardiac function, pathologic ECG alterations, calcium homeostasis, intracellular organization and gene expression were significantly altered in transgenic mice.

Genotoxic effects of particulate matter on larvae of a common and widespread butterfly along an urbanization gradient.

Biodiversity is currently declining worldwide. Several threats have been identified such as habitat loss and climate change. It is unknown if and how air pollution can work in addition or in synergy to these threats, contributing to the decline of current species and/or local extinction.

Cabbage butterfly as bioindicator species to investigate the genotoxic effects of PM.

Atmospheric pollution poses a serious threat to environment and human health, and particulate matter (PM) is one of the major contributors. Biological effects induced by PM are investigated through in vitro assays using cells and by in vivo tests with laboratory model animals. However, also the estimation of adverse effects of pollutants, including airborne ones, on wild animals, such as insects, is an essential component of environmental risk assessment.

Intermediate Hair Follicles from Patients with Female Pattern Hair Loss Are Associated with Nutrient Insufficiency and a Quiescent Metabolic Phenotype.

Female pattern hair loss (FPHL) is a non-scarring alopecia resulting from the progressive conversion of the terminal (t) scalp hair follicles (HFs) into intermediate/miniaturized (i/m) HFs. Although data supporting nutrient deficiency in FPHL HFs are lacking, therapeutic strategies are often associated with nutritional supplementation. Here, we show by metabolic analysis that selected nutrients important for hair growth such as essential amino acids and vitamins are indeed decreased in affected iHFs compared to tHFs in FPHL scalp skin, confirming nutrient insufficiency.

Peroxisome proliferator-activated receptor-γ signalling protects hair follicle stem cells from chemotherapy-induced apoptosis and epithelial-mesenchymal transition.

Background: Permanent chemotherapy-induced alopecia (pCIA), for which preventive interventions remain limited, can manifest with scarring. While the underlying pathomechanisms of pCIA are unclear, depletion of epithelial hair follicle (HF) stem cells (eHFSCs) is likely to play a role.

Objectives: To explore the hypothesis that, besides apoptosis, eHFSCs undergo pathological epithelial-mesenchymal transition (EMT) in pCIA, thus explaining the scarring phenotype.

Zerynthia polyxena Locally Monophagous on Aristolochia pallida in the Susa Valley.

In insect-plant biology, oviposition choices and larval development on different host plants are crucial factors to be investigated. To design conservation strategies for protected Lepidoptera, which are overall oligophagous but locally monophagous, it is important to understand which host plant species is locally preferred. We thus investigated oviposition choices and larval development of the protected butterfly Zerynthia polyxena in controlled laboratory conditions, using three possible host plant species which are present in the Piedmont region: Aristolochia pallida, A.

The first versatile human iPSC-based model of ectopic virus induction allows new insights in RNA-virus disease.

A detailed description of pathophysiological effects that viruses exert on their host is still challenging. For the first time, we report a highly controllable viral expression model based on an iPS-cell line from a healthy human donor. The established viral model system enables a dose-dependent and highly localized RNA-virus expression in a fully controllable environment, giving rise for new applications for the scientific community.

Human Wound Healing Ex Vivo Model with Focus on Molecular Markers.

Wound healing is a complex, multifactorial process that is divided in sequential and overlapping phases in order to restore the skin barrier. For the study of wound healing, different in vivo, in vitro, and ex vivo models have been used in the past. Here we describe in detail the methodology of the human skin punch-in-a-punch ex vivo wound healing model.

Experimentally Induced Epithelial-Mesenchymal Transition of Human Hair Follicle Stem Cells as a Model of Scarring Alopecia Ex Vivo.

Primary cicatricial alopecia is characterized by a permanent "scarring" alopecia. This condition is characterized by the irreversible loss of hair follicles (HF) as a result of apoptosis and epithelial-mesenchymal transition (EMT) of epithelial stem cells localized in the HF bulge.We here report the procedure for experimentally induced EMT in healthy human epidermal stem cells (eSCs) using full-length HF organ culture ex vivo.

Cardiogenic programming of human pluripotent stem cells by dose-controlled activation of EOMES.

Master cell fate determinants are thought to induce specific cell lineages in gastrulation by orchestrating entire gene programs. The T-box transcription factor EOMES (eomesodermin) is crucially required for the development of the heart-yet it is equally important for endoderm specification suggesting that it may act in a context-dependent manner. Here, we define an unrecognized interplay between EOMES and the WNT signaling pathway in controlling cardiac induction by using loss and gain-of-function approaches in human embryonic stem cells.

Revised roles of ISL1 in a hES cell-based model of human heart chamber specification.

The transcription factor ISL1 is thought to be key for conveying the multipotent and proliferative properties of cardiac precursor cells. Here, we investigate its function upon cardiac induction of human embryonic stem cells. We find that ISL1 does not stabilize the transient cardiac precursor cell state but rather serves to accelerate cardiomyocyte differentiation.

Dung beetles as drivers of ecosystem multifunctionality: Are response and effect traits interwoven?

Rapid biodiversity loss has emphasized the need to understand how biodiversity affects the provisioning of ecological functions. Of particular interest are species and communities with versatile impacts on multiple parts of the environment, linking processes in the biosphere, lithosphere, and atmosphere to human interests in the anthroposphere (in this case, cattle farming). In this study, we examine the role of a specific group of insects - beetles feeding on cattle dung - on multiple ecological functions spanning these spheres (dung removal, soil nutrient content and greenhouse gas emissions).

Adrenergic Stress Protection of Human iPS Cell-Derived Cardiomyocytes by Fast K7.1 Recycling.

The fight-or-flight response (FFR), a physiological acute stress reaction, involves positive chronotropic and inotropic effects on heart muscle cells mediated through β-adrenoceptor activation. Increased systolic calcium is required to enable stronger heart contractions whereas elevated potassium currents are to limit the duration of the action potentials and prevent arrhythmia. The latter effect is accomplished by an increased functional activity of the K7.

Cardiac Subtype-Specific Modeling of K1.5 Ion Channel Deficiency Using Human Pluripotent Stem Cells.

The ultrarapid delayed rectifier K current (I), mediated by K1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying gene have been shown to cause hereditary forms of atrial fibrillation (AF).

Greenhouse gas emissions from dung pats vary with dung beetle species and with assemblage composition.

Cattle farming is a major source of greenhouse gases (GHGs). Recent research suggests that GHG fluxes from dung pats could be affected by biotic interactions involving dung beetles. Whether and how these effects vary among beetle species and with assemblage composition is yet to be established.

Generation and cardiac subtype-specific differentiation of PITX2-deficient human iPS cell lines for exploring familial atrial fibrillation.

Loss-of-function mutations in the PITX2 transcription factor gene have been shown to cause familial atrial fibrillation (AF). To potentially model aspects of AF and unravel PITX2-regulated downstream genes for drug target discovery, we here report the generation of integration-free PITX2-deficient hiPS cell lines. We also show that both PITX2 knockout hiPS cells and isogenic wild-type controls can selectively be differentiated into human atrial cardiomyocytes, to potentially uncover differentially expressed gene sets between these groups.

From iPSC towards cardiac tissue-a road under construction.

The possibility to generate induced pluripotent stem cells (iPSC) opens the way to generate virtually all cell types of our human body. In combination with modern gene editing techniques like CRISPR/CAS, a new set of powerful tools becomes available for life science. Scientific fields like genotype and cell type-specific pharmacology, disease modeling, stem cell biology, and developmental biology have been dramatically fostered and their faces have been changed.

The Natural Plant Product Rottlerin Activates Kv7.1/KCNE1 Channels.

Background/aims: Acquired as well as inherited channelopathies are disorders that are caused by altered ion channel function. A family of channels whose malfunction is associated with different channelopathies is the Kv7 K+ channel family; and restoration of normal Kv7 channel function by small molecule modulators is a promising approach for treatment of these often fatal diseases.

Methods: Here, we show the modulation of Kv7 channels by the natural compound Rottlerin heterologously expressed in Xenopus laevis oocytes and on iPSC cardiomyocytes overexpressing Kv7.

Functional high-resolution time-course expression analysis of human embryonic stem cells undergoing cardiac induction.

Cardiac induction of human embryonic stem cells (hESCs) is a process bearing increasing medical relevance, yet it is poorly understood from a developmental biology perspective. Anticipated technological progress in deriving stably expandable cardiac precursor cells or in advancing cardiac subtype specification protocols will likely require deeper insights into this fascinating system. Recent improvements in controlling hESC differentiation now enable a near-homogeneous induction of the cardiac lineage.

Human Lineage-Specific Transcriptional Regulation through GA-Binding Protein Transcription Factor Alpha (GABPa).

A substantial fraction of phenotypic differences between closely related species are likely caused by differences in gene regulation. While this has already been postulated over 30 years ago, only few examples of evolutionary changes in gene regulation have been verified. Here, we identified and investigated binding sites of the transcription factor GA-binding protein alpha (GABPa) aiming to discover cis-regulatory adaptations on the human lineage.