The making of the minibody: An engineered β-protein for the display of conformationally constrained peptides

Conformationally constraining selectable peptides onto a suitable scaffold that enables their conformation to be predicted or readily determined by experimental techniques would considerably boost drug discovery process by reducing the gap between the discovery of a peptide lead and the design of a peptidomimetic with a more desirable pharmacological profile. With this in mind, we designed the minibody, a 61-residue β-protein aimed at retaining some desirable features of immunogloblin variable domains, such as tolerance to sequence variability in selected regions of the protein and predictability of main chain conformation of the same regions, based on the ‘canonical structures’ model. To test the ability of the minibody scaffold to support functional sites we also designed a metal binding version of the protein by suitably choosing the sequences of its loops. The minibody was produced both by chemical syntyhesis and expression in E. coli and charactgerized by size exclusion chromatography, UV CD (circular dichroism) spectroscopy and metal binding activity. All our data supported the model, but a more detailed structural characterization of the molecule was impaired by its low soubility. We were able to overcome this problem both by further; mutagenesis of the framework and by addition of a solublizing motif. The minibody is being used to select constrained human IL-6 peptidic ligands from a library displayed on the surface of the f1 bacteriophage.     

First report of Garella musculana (Erschov, 1874) (Lepidoptera: Nolidae) in Italy with insights into its identity

The Asian walnut moth, Garella musculana (Erschov, 1874) (Lepidoptera: Nolidae), is a major pest of walnut. Native to Central Asia, it was found to be invasive in 2008 in Sevastopol (Crimea) and nowadays widespread in Turkey, Bulgaria, Romania and Russia. Here, we account for the finding of G. musculana in NE Italy (Veneto region) in 2021, where adults were found in a light lamp, representing the first record of the Asian walnut moth for this country and Western Europe. Adult specimens were identified morphologically on both external characters and genitalia features. G. musculana larvae and damage were also observed on a plantation of Juglans regia L. (Fagales: Juglandaceae) located in Veneto in October 2021. A COI-barcoding analysis was performed to attain a molecular characterization of our specimens and probate our morphological identification. However, because no sequence of G. musculana was present in major gene databases and the similarity of our sequences with those attributed to Garella ruficirra (Hampson, 1905) (Lepidoptera: Nolidae) made clear that these taxa deserved further scrutiny regarding their specific distinction. Some subtle differences in the male terminalia could be found between them and their vast geographic distributions, but the strong similarity in most features calls for further morphological and genetical insights on a broad set of samples to assess whether they represent two closely related, substantially parapatric species, or a unique, geographically varying entity. Solving this issue may turn out crucial in the identification and proper management of walnut moths of the genus Garella.     

Immunohistochemical localization of epidermal growth factor receptor in leiomyomas from women treated with goserelin depot.

Epidermal growth factor receptors (EGFr) were studied by immunohistochemistry in human myometrium and leiomyomas from women treated with the GnRH agonist (GnRH-a) goserelin. The results were compared with those obtained from women not treated. Vessel cells of leiomyomas and myometrium were always more immunoreactive than fibrocytes and myocites. In fibroids from treated patients the histochemical score (HSCORE) of vessel cells was always significantly lower (p less than 0.001) than in control patients. Our data confirm a role of EGF also in fibroid growth and suggest that, the blood supply reduction associated with the volume reduction of these tumours, consequent to the GnRH-a treatment, could be EGF mediated.     

The effectiveness of flower strips and hedgerows on pest control,pollination services and crop yield: a quantitative synthesis

Floral plantings are promoted to foster ecological intensification of agriculture through provisioning of ecosystem services. However, a comprehensive assessment of the effectiveness of different floral plantings, their characteristics and consequences for crop yield is lacking. Here we quantified the impacts of flower strips and hedgerows on pest control (18 studies) and pollination services (17 studies) in adjacent crops in North America, Europe and New Zealand. Flower strips, but not hedgerows, enhanced pest control services in adjacent fields by 16% on average. However, effects on crop pollination and yield were more variable. Our synthesis identifies several important drivers of variability in effectiveness of plantings: pollination services declined exponentially with distance from plantings, and perennial and older flower strips with higher flowering plant diversity enhanced pollination more effectively. These findings provide promising pathways to optimise floral plantings to more effectively contribute to ecosystem service delivery and ecological intensification of agriculture in the future.     

Biological insights in the pathogenesis of hypermobile Ehlers-Danlos syndrome from proteome profiling of patients' dermal myofibroblasts

Hypermobile Ehlers-Danlos syndrome (hEDS), mainly characterized by generalized joint hypermobility and its complications, minor skin changes, and apparently segregating with an autosomal dominant pattern, is still without a known molecular basis. Hence, its diagnosis is only clinical based on a strict set of criteria defined in the revised EDS nosology. Moreover, the hEDS phenotypic spectrum is wide-ranging and comprises multiple associated signs and symptoms shared with other heritable or acquired connective tissue disorders and chronic inflammatory diseases. In this complex scenario, we previously demonstrated that hEDS patients' skin fibroblasts show phenotypic features of myofibroblasts, widespread extracellular matrix (ECM) disarray, perturbation of ECM-cell contacts, and dysregulated expression of genes involved in connective tissue architecture and related to inflammatory and pain responses. Herein, the cellular proteome of 6 hEDS dermal myofibroblasts was compared to that of 12 control fibroblasts to deepen the knowledge on mechanisms involved in the disease pathogenesis. Qualitative and quantitative differences were assessed based on top-down and bottom-up approaches and some differentially expressed proteins were proofed by biochemical analyses. Proteomics disclosed the differential expression of proteins principally implicated in cytoskeleton organization, energy metabolism and redox balance, proteostasis, and intracellular trafficking. Our findings offer a comprehensive view of dysregulated protein networks and related pathways likely associated with the hEDS pathophysiology. The present results can be regarded as a starting point for future in-depth investigations aimed to decipher the functional impact of potential bioactive molecules for the development of targeted management and therapies.