The knowledge of the history of a subject stimulates understanding. As we study how other people have made scientific breakthroughs, we develop the breadth of imagination that would inspire us to make new discoveries of our own. This perspective certainly applies to the teaching of genetics as hallmarked by the pea experiments of Mendel. Common questions students have in reading Mendel's paper for the first time is how it compares to other botanical, agricultural, and biological texts from the early and mid-nineteenth centuries; and, more precisely, how Mendel's approach to, and terminology for debating, topics of heredity compare to those of his contemporaries? Unfortunately, textbooks are often unavailing in answering such questions. It is very common to find an introduction about heredity in genetic textbooks covering Mendel without mentions of preceding breeding experiments carried out in his alma mater. This does not help students to understand how Mendel came to ask the questions he did, why he did, or why he planned his pea studies the way he did. Furthermore, the standard textbook "sketch" of genetics does not allow students to consider how discoveries could have been framed and inspired so differently in various parts of the world within a single historical time. In our review we provide an extended overview bridging this gap by showing how different streams of ideas lead to the eventual foundation of particulate inheritance as a scientific discipline. We close our narrative with investigations on the origins of animal and plant breeding in Central Europe prior to Mendel in Kőszeg and Brno, where vigorous debates touched on basic issues of heredity from the early eighteenth-century eventually reaching a pinnacle coining the basic questions: What is inherited and how is it passed on from one generation to another?

SARS-CoV-2 infection could cause severe acute respiratory syndrome, largely attributed to dysregulated immune activation and extensive lung tissue damage. However, the underlying mechanisms are not fully understood. Here, we reported that viral infection could induce syncytia formation within cells expressing ACE2 and the SARS-CoV-2 spike protein, leading to the production of micronuclei with an average rate of about 4 per syncytium (> 93%). Remarkably, these micronuclei were manifested with a high level of activation of both DNA damage response and cGAS-STING signaling, as indicated by micronucleus translocation of γH2Ax and cGAS, and upregulation of their respective downstream target genes. Since activation of these signaling pathways were known to be associated with cellular catastrophe and aberrant immune activation, these findings help explain the pathological effects of SARS-CoV-2 infection at cellular and molecular levels, and provide novel potential targets for COVID-19 therapy.

Skeletal muscle has an extraordinary regenerative capacity reflecting the rapid activation and effective differentiation of muscle stem cells (MuSCs). In the course of muscle regeneration, MuSCs are reprogrammed by immune cells. In turn, MuSCs confer immune cells anti-inflammatory properties to resolve inflammation and facilitate tissue repair. Indeed, MuSCs can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory ability, including effects primed by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). At the molecular level, the tryptophan metabolites, kynurenine or kynurenic acid, produced by indoleamine 2,3-dioxygenase (IDO), augment the expression of TNF-stimulated gene 6 (TSG6) through the activation of the aryl hydrocarbon receptor (AHR). In addition, insulin growth factor 2 (IGF2) produced by MuSCs can endow maturing macrophages oxidative phosphorylation (OXPHOS)-dependent anti-inflammatory functions. Herein, we summarize the current understanding of the immunomodulatory characteristics of MuSCs and the issues related to their potential applications in pathological conditions, including COVID-19.

Periosteum is a thin membrane covering bone surfaces and consists of two layers: outer fibrous layer and inner cambium layer. Simple appearance of periosteum has belied its own complexity as a composite structure for physical bone protection, mechano-sensor for sensing mechanical loading, reservoir of biochemical molecules for initiating cascade signaling, niche of osteogenic cells for bone formation and repair, and "umbilical cord" for nourishing bone tissue. Periosteum-derived cells (PDCs) have stem cell attributes: self-renewal (no signs of senescence until 80 population doublings) and multipotency (differentiate into fibroblasts, osteoblasts, chondrocytes, adipocytes and skeletal myocytes). In this review, we summarized the currently available knowledge about periosteum and with special references to antler-lineage periostea, and demonstrated that although periosteum is a type of simple tissue in appearance, with multiple faces in functions; antler-lineage periostea add another dimension to the properties of somatic periostea: capable of initiation of ectopic organ formation upon transplantation and full mammalian organ regeneration when interacted with the covering skin. Very recently, we have translated this finding into other mammals, i.e. successfully induced partial regeneration of the amputated rat legs. We believe further refinement along this line would greatly benefit human health.

BACKGROUND: Human bone marrow-derived mesenchymal stem cells (hBMSCs) are the primary source of osteoblasts in vivo. Emerging literatures have unveiled that circular RNAs (circRNAs) are actively drawn in the osteogenic differentiation of mesenchymal stem cells (MSCs). This research mainly illuminated the role of circ_0067680 as well as its regulatory mechanism in osteoblastic differentiation. METHODS: In this study, RT-qPCR was to measure the expression of circ_0067680. Functional assays were implemented to assess the role of circ_0067680 in osteogenic differentiation. Besides, RNA pull down, RIP and luciferase reporter assays were carried out to investigate the regulatory mechanism of circ_0067680. RESULTS: Circ_0067680, which derived from its host gene divergent protein kinase domain 2A (C3orf58), was up-regulated during osteogenic differentiation of hBMSCs. Besides, circ_0067680 deficiency impeded the osteoblastic differentiation of hBMSCs. Moreover, circ_0067680 served as a ceRNA via sequestering miR-4429 to regulate the expression of catenin beta 1 (CTNNB1), thereby activating the Wnt/β-catenin signaling pathway. CONCLUSION: Circ_0067680 accelerated hBMSCs osteogenic differentiation by the miR-4429/CTNNB1/Wnt/β-catenin signaling, which might be used as a potential biomarker for osteoblastic differentiation.

The interaction between proteins is a fundamental event for cellular life that is generally mediated by specialized protein domains or modules. PDZ domains are the largest class of protein-protein interaction modules, involved in several cellular pathways such as signal transduction, cell-cell junctions, cell polarity and adhesion, and protein trafficking. Because of that, dysregulation of PDZ domain function often causes the onset of pathologies, thus making this family of domains an interesting pharmaceutical target. In this review article we provide an overview of the structural and functional features of PDZ domains and their involvement in the cellular and molecular pathways at the basis of different human pathologies. We also discuss some of the strategies that have been developed with the final goal to hijack or inhibit the interaction of PDZ domains with their ligands. Because of the generally low binding selectivity of PDZ domain and the scarce efficiency of small molecules in inhibiting PDZ binding, this task resulted particularly difficult to pursue and still demands increasing experimental efforts in order to become completely feasible and successful in vivo.