The Angiomotins – From discovery to function

Angiomotins were originally identified as angiostatin binding proteins and implicated in the regulation of endothelial cell migration. Recent studies have shed light on the role of Angiomotins and other members of the Motin protein family in epithelial cells and in pathways directly linked to the pathogenesis of cancer. In particular, Motins have been shown to play a role in signaling pathways regulated by small G-proteins and the Hippo–YAP pathway. In this review the role of the Motin protein family in these signaling pathways will be described and open questions will be discussed.     

Urocortin – From Parkinson's disease to the skeleton

Urocortin (Ucn 1), a 40 amino acid long peptide related to corticotropin releasing factor (CRF) was discovered 19 years ago, based on its sequence homology to the parent molecule. Its existence was inferred in the CNS because of anatomical and pharmacological discrepancies between CRF and its two receptor subtypes. Although originally found in the brain, where it has opposing actions to CRF and therefore confers stress-coping mechanisms, Ucn 1 has subsequently been found throughout the periphery including heart, lung, skin, and immune cells. It is now well established that this small peptide is involved in a multitude of physiological and pathophysiological processes, due to its receptor subtype distribution and promiscuity in second messenger signalling pathways. As a result of extensive studies in this field, there are now well over one thousand peer reviewed publications involving Ucn 1. In this review, we intend to highlight some of the less well known actions of Ucn 1 and in particular its role in neuronal cell protection and maintenance of the skeletal system, both by conventional methods of reviewing the literature and using bioinformatics, to highlight further associations between Ucn 1 and disease conditions. Understanding how Ucn 1 works in these tissues, will help to unravel its role in normal and pathophysiological processes. This would ultimately allow the generation of putative medical interventions for the alleviation of important diseases such as Parkinson's disease, arthritis, and osteoporosis.     

From septicemia to sepsis 3.0 – from Ignaz Semmelweis to Louis Pasteur

Sepsis remains a contemporary threat, and its frequency remains high amongst an aging population. Its definition has been regularly revisited, but the impact of the translational research studying it remains very modest compared to the results seen after the introduction of hygiene and the use of antibiotics. In the past, the main forms of sepsis were hospital gangrene (also known as nosocomial fever or putrid fever) that affected the wounded, and puerperal fever that affected women shortly after delivery. In 1858, Armand Trousseau stated that these two pathologies were identical. Lucrezia Borgia, who died in 1519, is undoubtedly the most famous woman to die from puerperal fever. The notion of sepsis as a real epidemic was deplored. For decades doctors remained deaf to the recommendations of their clairvoyant colleagues who advocated for the use of hygienic measures. It was as early as 1795 that Alexander Gordon (UK) and later in 1843, Oliver Holmes (USA), called for the use of hygienic practices. In 1847, Ignaz Semmelweis, a Hungarian physician, provided an irrefutable demonstration of the importance of hygiene in the prevention of contamination by the hands of the practitioners. But Ignaz Semmelweis' life was a tragedy, his fight against the medical nomenklatura was a tragedy, and his death was a tragedy! Nowadays, Ignaz Semmelweis is receiving the honor that he deserves, but never received during his life. Carl Mayrhofer, Victor Feltz, and Léon Coze were the first to associate the presence of bacteria with sepsis. These observations were confirmed by Louis Pasteur who, thanks to his prestige, had a great influence on how to undertake measures to prevent infections. He inspired Joseph Lister who reduced mortality associated with surgery, particularly amputation, by utilizing antiseptic methods.     

Abiotic Stress Tolerance： From Gene Discovery in Model Organisms to Crop Improvement

Productive and sustainable agriculture necessitates growing plants in sub-optimal environments with less input of precious resources such as fresh water. For a better understanding and rapid improvement of abiotic stress tolerance, it is important to link physiological and biochemical work to molecular studies in genetically tractable model organisms. With the use of several technologies for the discovery of stress tolerance genes and their appropriate alleles, transgenic approaches to improving stress tolerance in crops remarkably parallels breeding principles with a greatly expanded germplasm base and will succeed eventually.     

Derivation of Inhibitory Peptides to Target the Cardiac Troponin C–I Interaction as Potential Therapeutics for Heart Failure

The Ca²⁺-sensitive cardiac troponin (cTn) is a hetero-trimer complex consisting of three subunits cTnC, cTnI, and cTnT, which has been recognized as an important biomarker and a potential target of cardiovascular diseases. Previously, several small-molecule agents such as levosimendan and pimobendan have been successfully developed to target this protein for the treatment of heart failure. Here, instead of small-molecule chemical drugs, we purposed rational derivation of self-inhibitory peptides as potential biologic disruptors of cTnC–cTnI interaction from the interaction complex interface. In the procedure, the crystal structure of cTn trimer was examined in detail using bioinformatics approach, from which a peptide-mediated interaction between the N-terminal domain of cTnC and the switch region of cTnI was identified. The switch is a 19-mer peptide segment Swt that contains a structured helical core capped by a short N-terminal tripeptide and a disordered C-terminal tail. Structural and energetic analysis revealed that the Swt peptide binds independently to cTnC N-terminal domain, which can be stripped from the intact cTnI subunit to interact effectively with cTnC. Further investigations found that truncation of two N-terminal residues and five C-terminal residues of the full-length Swt peptide, resulting in a shortened version namely Swt-ΔN2ΔC5 peptide, would not cause substantial loss in its binding potency to cTnC. The computational finding was then confirmed by using fluorescence-based affinity assays; the Swt and Swt-ΔN2ΔC5 peptides was experimentally measured to have a moderately high affinity to the recombinant protein of human cTnC N-terminal domain with K _d values at micromolar level. The Swt and Swt-ΔN2ΔC5 are considered as inhibitory peptides that can be further optimized and modified to obtain high-affinity disruptors of cTnI–cTnC interaction.     

RANKL/RANK – From bone physiology to breast cancer

RANK and its ligand RANKL are key molecules in bone metabolism and are critically involved in pathologic bone disorders. Deregulation of the RANK/RANKL system is for example a main reason for the development of postmenopausal osteoporosis, which affects millions of women worldwide. Another essential function of RANK and RANKL is the development of a functional lactating mammary gland during pregnancy. Sex hormones, in particular progesterone, induce RANKL expression resulting in proliferation of mammary epithelial cells. Moreover, RANK and RANKL have been shown to regulate mammary epithelial stem cells. RANK and RANKL were also identified as critical mechanism in the development of hormone-induced breast cancer and metastatic spread to bone. In this review, we will focus on the various RANK/RANKL functions ranging from bone physiology, immune regulation, and initiation of breast cancer.     

From symbolism to information? – Decoding the gene code

‘Information’ and ‘code’ originated as technical terms within linguistics and information theory but are now widely used in genetics and developmental biology. Against this background, it is examined if coded information distinguishes genes from other information carriers, i.e., whether there are genetic words or sentences by virtue of the genetic code, and, if so, whether they have any semantic content. It is concluded that there is no genetic language with semantic content, but that the genetic code still enables unique language-like modes of transmission and interpretation of causal information.     

Thelazia callipaeda in Slovakia – From sporadic cases to endemic areas

Spirurid nematode Thelazia callipaeda, transmitted by the fruit fly Phortica variegata, is a causative agent of an ocular parasitic disease called also canine thelaziosis. Dogs, cats, and wild canids are considered the primary definitive hosts for the parasite, but humans may also serve as aberrant definitive hosts. For long decades the geographic range of T. callipaeda was strictly limited to the territory of Asia, but after the year 2000, the parasite began to spread rapidly through Europe. The first autochthonous infections of dogs and foxes in Slovakia were recorded in 2016. In the present study, the results of a whole-area surveillance for canine thelaziosis are reported. Altogether, 142 cases of infection caused by T. callipaeda were diagnosed by veterinarians in dogs between 2016 and the first quarter of 2021, and two cases of feline thelaziosis were recorded. The majority of the dogs showed mild ocular signs manifested by conjunctivitis; 8.5% of them suffered from more serious mucopurulent discharge, and in two dogs corneal ulceration was recorded. The screening revealed increasing trends in the occurrence of canine thelaziosis from both a temporal and spatial point of view and unambiguously confirms the endemic status of T. callipaeda in Slovakia with the prospect of its further expansion.