Surface modifications based on the cyanobacterial siderophore anachelin: from structure to functional biomaterials design

This review describes the design, synthesis and evaluation of novel catechol based anchors for surface modification. The anachelin chromophore, the catecholate fragment of the siderophore anachelin from the cyanobacterium Anabaena cylindrica, allows for the immobilization of polyethylene glycol (PEG) on titania and glass surfaces thus rendering them protein resistant and antifouling. It is proposed that catecholate siderophores constitute a class of natural products useful for surface modification similar to dihydroxyphenylalanine and dopamine derived compounds found in mussel adhesive proteins. Second-generation dopamine derivatives featuring a quaternary ammonium group were found to be equally efficient in generating antifouling surfaces. The anachelin chromophore, merged via a PEG linker to the glycopeptide antibiotic vancomycin, allowed for the generation of antimicrobial surfaces through an operationally simple dip-and-rinse procedure. This approach offers an option for the prevention of nosocomial infections through antimicrobial implants, catheters and stents. Consequences for the mild generation of functional biomaterials are discussed and novel strategies for the immobilization of complex natural products, proteins and DNA on surfaces are presente

Characterization of Wild Corsican Hops and Assessment of the Performances of German Hops in Corsican Environmental Conditions through a Multidisciplinary Approach

Hops (Humulus lupulus L.) is a species that grows spontaneously in Corsica, but the characterization of this species in this territory has not yet been investigated. The main objectives of this study are to explore the features of wild hops from Corsica and to determine the effect of the island terroir on some cultivars in the first year of growth. A multidisciplinary approach consisting of the genetic analysis, morphological comparison and chemical characterization of essential oils was carried out on four wild Corsican hops and three hop cultivars grown in Tettnang, Germany and Corsica, France. The morphological and GC-MS analysis of Corsican wild hops, set cluster coastal samples apart from the one far from the coast. This dissimilarity is supported by the SSR analysis by two of the three coastal accessions. The genetics demonstrate a proximity between the European noble cultivar Tettnanger and the mountain Corsican wild hop from Corte. The morphological comparison between German hops cultivated in Tettnang and in Corsican soil, and the GC-MS characterization of their essential oils’ chemical profiles, show different features between year 0 and year +1 for each sample. This multidisciplinary approach highlights an acclimatization of hop cultivars to the Corsican terroir one year after planting

Surface modifications based on the cyanobacterial siderophore anachelin: from structure to functional biomaterials design

This review describes the design, synthesis and evaluation of novel catechol based anchors for surface modification. The anachelin chromophore, the catecholate fragment of the siderophore anachelin from the cyanobacterium Anabaena cylindrica, allows for the immobilization of polyethylene glycol (PEG) on titania and glass surfaces thus rendering them protein resistant and antifouling. It is proposed that catecholate siderophores constitute a class of natural products useful for surface modification similar to dihydroxyphenylalanine and dopamine derived compounds found in mussel adhesive proteins. Second-generation dopamine derivatives featuring a quaternary ammonium group were found to be equally efficient in generating antifouling surfaces. The anachelin chromophore, merged via a PEG linker to the glycopeptide antibiotic vancomycin, allowed for the generation of antimicrobial surfaces through an operationally simple dip-and-rinse procedure. This approach offers an option for the prevention of nosocomial infections through antimicrobial implants, catheters and stents. Consequences for the mild generation of functional biomaterials are discussed and novel strategies for the immobilization of complex natural products, proteins and DNA on surfaces are presented

Protein-Resistant Surfaces through Mild Dopamine Surface Functionalization

The synthesis and evaluation of new dopamine-based catechol anchors coupled to poly(ethylene glycol) (PEG) for surface modification of TiO2 are reported. Dopamine is modified by dimethylamine-methylene or trimethylammonium- methylene groups, and the preparation of mPEG-Glu didopamine polymer 11 is presented. All these PEG polymers allow stable adlayers on TiO2 to be generated through mild dip-and-rinse procedures, as evaluated both by variable angle spectroscopic ellipsometry and X-ray photoelectron spectroscopy. The resulting surfaces substantially reduced protein adsorption upon exposure to full human serum

The Lsm2-8 complex determines nuclear localization of the spliceosomal U6 snRNA

Lsm proteins are ubiquitous, multifunctional proteins that are involved in the processing and/or turnover of many, if not all, RNAs in eukaryotes. They generally interact only transiently with their substrate RNAs, in keeping with their likely roles as RNA chaperones. The spliceosomal U6 snRNA is an exception, being stably associated with the Lsm2-8 complex. The U6 snRNA is generally considered to be intrinsically nuclear but the mechanism of its nuclear retention has not been demonstrated, although La protein has been implicated. We show here that the complete Lsm2-8 complex is required for nuclear accumulation of U6 snRNA in yeast. Therefore, just as Sm proteins effect nuclear localization of the other spliceosomal snRNPs, the Lsm proteins mediate U6 snRNP localization except that nuclear retention is the likely mechanism for the U6 snRNP. La protein, which binds only transiently to the nascent U6 transcript, has a smaller, apparently indirect, effect on U6 localization that is compatible with its proposed role as a chaperone in facilitating U6 snRNP assembly

Entrepreneurship during the Covid-19 Pandemic: A global study of entrepreneurs' challenges, resilience, and well-being

Summary: Small and medium-sized enterprises (SMEs including the self-employed) account for 90% of businesses globally and provide 70% of employment worldwide. These businesses, typically entrepreneur led, are threatened by the Covid-19 pandemic, meaning that millions of jobs are at risk. This report presents insights from a global study conducted during the pandemic in 2020. We surveyed over 5,000 entrepreneurs in 23 countries that represent 3/4 of the world’s economic output. Most entrepreneurs faced significant challenges threatening the survival of their businesses. We also see resilience in how entrepreneurs navigated the crisis through being agile, adaptive, and exploring new opportunities, utilizing government support, giving back to society, and even harbouring growth ambitions beyond the pandemic. Entrepreneurs’ mental well-being dropped by 12% in the pandemic presenting another threat to their businesses. We chart stressors and well-being resources including social support and self-care strategies that entrepreneurs engaged to stay productive. We close the report (1) by reflecting on five trends for the post-Covid economy and formulate actionable policy recommendations of how entrepreneurs and SMEs can be supported in light of these trends (digitalisation; ‘local’ focus, inclusive business models, developing personal and business resilience), and (2) offer five practical steps for entrepreneurs to protect their well-being

Yeast Npi3/Bro1 is involved in ubiquitin-dependent control of permease trafficking

AbstractThe membrane traffic and stability of the general amino acid permease Gap1 of Saccharomyces cerevisiae are under nitrogen control. Addition of a preferential nitrogen source such as ammonium to cells growing on a poor nitrogen source induces internalization of the permease and its subsequent degradation in the vacuole. This down-regulation requires ubiquitination of Gap1 through a process involving ubiquitin ligase Npi1/Rsp5, ubiquitin hydrolase Npi2/Doa4, and Bul1/2, two Npi1/Rsp5 interacting proteins. Here we report that yet another protein, Npi3, is involved in the regulation of Gap1 trafficking. We show that Npi3 is required for NH4+-induced down-regulation of Gap1, and particularly for efficient ubiquitination of the permease. Npi3 plays a pleiotropic role in permease down-regulation, since it is also involved in ubiquitination and stress-induced down-regulation of the uracil permease Fur4 and in glucose-induced degradation of hexose transporters Hxt6/7. We further provide evidence that Npi3 is required for direct vacuolar sorting of neosynthesized Gap1 permease as it occurs in npr1 mutant cells. NPI3 is identical to BRO1, a gene encoding a protein of unknown biochemical function and recently proposed to be involved in protein turnover. Npi3/Bro1 homologues include fungal proteins required for proteolytic cleavage of zinc finger proteins and the mouse Aip1 protein involved in apoptosis. We propose that proteins of the Npi3/Bro1 family, including homologues from higher species, may play a conserved role in ubiquitin-dependent control of membrane protein trafficking

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN