Identifying Natural Products (NPs) as potential UPR inhibitors for crop protection

As far as the future of agriculture is concerned, one major challenge will be to face an expected increase in health risks due to pesticides together with a lower efficiency of crop treatments. Therefore it is today necessary to develop new strategies to enhance the effectiveness and sustainability of current control methods. The so-called “Alternaria Leaf Spot“ is a common disease of crucifers caused by the fungal pathogen Alternaria brassicicola which affects different crops including cabbage, kale, Brussels sprout, cauliflower and broccoli. Indole phytoalexins camalexin and brassinin play in planta a key role in crop protection against this necrotrophic agent. However it has been shown that mutants become phytoalexin-resistant by activating at least three signaling pathways named as Cell Wall Integrity (CWI), High Osmolarity Glycerol (HOG) and Unfolded Protein Response (UPR) [1,2]. The latter is particularly involved in the fungus protection against phytoalexins since UPR deficient avirulent mutants of A. brassicicola appear as hypersensitive to camalexin and brassinin [3]. Since very few UPR inhibitors such as the synthetic STF-083010 [4] are known we decided to develop an original screening assay, detecting the production of a HAC1 fluorescence-induced protein, i.e. a transcriptional activator involved in the UPR pathway, in Saccharomyces cerevisiae cultures (Figure 1). The preliminary screening of an in-house NPs library [c.a. 70 compounds (polyphenols, terpenoids and alkaloids)] clearly revealed aescin (Aesculus hippocastanum)] as a potential UPR inhibitor

Intracerebral delivery of the M2 polarizing cytokine interleukin 13 using mesenchymal stem cell implants in a model of temporal lobe epilepsy in mice

OBJECTIVES: Neuroinflammation plays a critical role in the pathophysiology of mesial temporal lobe epilepsy. We aimed to evaluate whether intracerebral transplantation of interleukin 13-producing mesenchymal stem cells (IL-13 MSCs) induces an M2 microglia/macrophage activation phenotype in the hippocampus with an epileptogenic insult, thereby providing a neuroprotective environment with reduced epileptogenesis. METHODS: Genetically engineered syngeneic IL-13 MSCs or vehicle was injected within the hippocampus 1 week before the intrahippocampal kainic acid-induced status epilepticus (SE) in C57BL/6J mice. Neuroinflammation was evaluated at disease onset as well as during the chronic epilepsy period (9 weeks). In addition, continuous video-electroencephalography (EEG) (vEEG) monitoring was obtained during the chronic epilepsy period (between 6 and 9 weeks after SE). RESULTS: Evaluation of vEEG recordings suggested that IL-13 MSC grafts did not affect the severity and duration of SE or the seizure burden during the chronic epilepsy period, when compared to the vehicle treated SE mice. An M2-activation phenotype was induced in microglia/macrophages that infiltrated the -13 MSC graft site, as evidenced by the arginase1 expression at the graft site at both the 2-week and 9-week time-points. However, M2-activated immune cells were rarely observed outside the graft site and, accordingly, the neuroinflammatory response or cell loss related to SE induction was not altered by IL-13 MSC grafting. Moreover, an increase in the proportion of F4/80+ cells was observed in the IL-13 MSC group compared to the controls. SIGNIFICANCE: Our data suggest that MSC-based IL-13 delivery to induce M2 glial activation does not provide any neuroprotective or disease-modifying effects in a mouse model of epilepsy. Moreover, use of cell grafting to deliver bioactive compounds for modulating neuroinflammation may have confounding effects in disease pathology of epilepsy due to the additional immune response generated by the grafted cells

P.C. Hoofts Mengelwerken : ten deele nooit tevooren gedrukt : nu op veele plaatsen verbetert en vermeerdert.

Includes indexes.Added engraved title-page by Abraham Blooteling after Gérard Lairesse; engraved title vignette (printer's device) by Gilliam van der Gouwen after Joseph Mulder; 30 copper engravings of emblems (possibly by Christof Le Blon) first published in Hooft's Emblemata amatoria.Errata: p. [1] at end; final page blank.Signatures: a-d⁴ A-5D⁴ 5E².Henrik de Gróóte : zyn leven en bedryf -- Rampzaaligheden der verheffinge van den huize Medicis -- Brieven -- Vertaalingen -- Toonneelspeelen -- Minnezinnebeelden, verscheide gedichten zangen, en sonnetten.Landwehr, J. Emblem and fable books (3rd ed.)Mode of access: Internet.Bound in old vellum; ornament stamped in blind on front and rear boards; gilt red leather label on spine; edges sprinkled red

Iohannis de Brunes I.C. Emblemata, of, Zinne-werck : voorghestelt in beelden, ghedichten en breeder uijt-legginghen, tot uijt-druckinghe en verbeteringhe van verscheijden feijlen onser eeuwe.

Engraved t.p. Fifty-one emblematic engravings by Christof Le Blon, Johann Gelle, Willem van de Passe, Albert Poel and Jan Gerrits Swelinck, all after Adriaen van de Venne; see Landwehr. Woodcut head-pieces, initials (some historiated).Colophon: Tot Middelburgh, Ghedruckt by Hans vander Hellen, anno MDCXXIV.1st ed. See Landwehr.Landwehr, J. Emblem books in the Low Countries,Mode of access: Internet.Binding, c. 2: later vellum, page edges red, 2 spine labels. Bookplate of Mexborough, and a 2nd bookplate with a scorpion and initials W R H J (Wynne Rice Hugh Jeudwine).Binding, c. 1: violet paper, three-quarter vellum. Large ogival-lobed blind stamp on spine and adjacent boards