Metabolic Investigation and Auxiliary Enzyme Modelization of the Pyrrocidine Pathway Allow Rationalization of Paracyclophane-Decahydrofluorene Formation.

Fungal paracyclophane-decahydrofluorene-containing natural products are complex polycyclic metabolites derived from similar hybrid PKS-NRPS pathways. Herein we studied the biosynthesis of pyrrocidines, one representative of this family, by gene inactivation in the producer coupled to thorough metabolic analysis and molecular modeling of key enzymes. We characterized nine pyrrocidines and analogues as well as in mutants a variety of accumulating metabolites with new structures including rare -decalin, cytochalasan, and fused 6/15/5 macrocycles.

Additional Sarasinosides from the Marine Sponge Collected from the Bismarck Sea.

In our continuing efforts to describe the biological and chemical diversity of sponges from Kimbe Bay, Papua New Guinea, the known 30-norlanostane saponin sarasinoside C () was identified along with six new analogues named sarasinosides C, C, C, C, C, and C (-) from the sponge . The structures of the new compounds were elucidated by analysis of 1D and 2D NMR and HRMS data, as well as comparison with literature data. All new compounds are characterized by the same tetraose moiety, β-d-Xyl-(1→6)-β-d-GlcNAc-(1→2)-[β-d-GalNAc-(1→4)]-β-d-Xyl, as described previously for sarasinoside C, but differed in their aglycone moieties.

Seed fungal endophytes as biostimulants and biocontrol agents to improve seed performance.

Seed germination is a major determinant of plant development and final yield establishment but strongly reliant on the plant's abiotic and biotic environment. In the context of global climate change, classical approaches to improve seed germination under challenging environments through selection and use of synthetic pesticides reached their limits. A currently underexplored way is to exploit the beneficial impact of the microorganisms associated with plants.

Dual-AAV vector-mediated expression of improves vestibular function in a mouse model of Usher syndrome 1B.

Usher syndrome is the most common cause of deafness-blindness in the world. Usher syndrome type 1B (USH1B) is associated with mutations in . Patients with USH1B experience deafness, blindness, and vestibular dysfunction.

Optimization of Capillary-Based Western Blotting for MYO7A.

Myosin VIIA (MYO7A)-associated Usher syndrome type 1B (USH1B) is a severe disorder that impacts the auditory, vestibular, and visual systems of affected patients. Due to the large size (~7.5 kb) of the MYO7A coding sequence, we have designed a dual adeno-associated virus (AAV) vector-based approach for the treatment of USH1B-related vision loss.

Development of an AAV-CRISPR-Cas9-based treatment for dominant cone-rod dystrophy 6.

Cone-rod dystrophy 6 (CORD6) is caused by gain-of-function mutations in the gene, which encodes retinal guanylate cyclase-1 (RetGC1). There are currently no treatments available for this autosomal dominant disease, which is characterized by severe, early-onset visual impairment. The purpose of our study was to develop an adeno-associated virus (AAV)-CRISPR-Cas9-based approach referred to as "ablate and replace" and evaluate its therapeutic potential in mouse models of CORD6.

Antifungal mono- and dimeric nitrogenous bisabolene derivatives from a sponge in the order Bubarida from Futuna Islands.

An abundant sponge of the order Bubarida was selected for further chemical investigation following biological and chemical screening of sponges collected from Futuna Islands in the Indo-Pacific. Ten new nitrogenous bisabolene derivatives were isolated and identified: the monomeric theonellin formamide analogues named bubaridins A-F (1-6) with unusual oxidised linear chains, and the first isocyanide/formamide dimeric and cyclised bisabolenes 7-9. The structure elucidation of these nitrogenous bisabolenes involved HRESIMS, NMR, and ECD analyses, and the chiral compounds were found to be racemates.

Evaluation and Impact of ASPIRE: An Interactive Tobacco Prevention Curriculum among University Students in India.

Online education approach provides innovative opportunities for engaging youths. Web-based, multimedia smoking prevention programs have been tested in high-income countries; however, efficacy of such programs is not well-investigated in low- and middle-income countries. The aim of this study was to evaluate the impact of A Smoking Prevention Interactive Experience (ASPIRE), an interactive tobacco prevention curriculum, among university students in India.

Mobile Text Messaging for Tobacco Risk Communication Among Young Adult Community College Students: Randomized Trial of Project Debunk.

Background: The use of new and emerging tobacco products (NETPs) and conventional tobacco products (CTPs) has been linked to several alarming medical conditions among young adults (YAs). Considering that 96% of YAs own mobile phones, SMS text messaging may be an effective strategy for tobacco risk communication.

Objective: Project Debunk is a community-based randomized trial aiming to identify specific types of messages that effectively improve perceived NETP and CTP risk among YAs in community colleges.

Nebulosins: Trisubstituted Thiolane Natural Products from the Northeastern Atlantic Annelid .

Using both multi-informative molecular network and score-based approaches as prioritization strategies, the Northeastern Atlantic marine terebellid was selected for in-depth chemical investigation. A family of 16 new metabolites named nebulosins was isolated and structurally characterized from extensive analyses of HRMS/MS and NMR spectroscopic data. Nebulosins feature an unprecedented highly substituted thiolane ring leading to up to four contiguous chiral centers.

Futunamine, a Pyrrole-Imidazole Alkaloid from the Sponge aff. Collected off the Futuna Islands.

The chemical investigation of the sponge aff. collected around Futuna Islands in the Pacific Ocean led to the isolation of three new dimeric pyrrole 2-aminoimidazole alkaloids (PIAs). Futunamine () features an unprecedented pyrrolo[1,2-]imidazole core, while two other new dimeric PIAs were identified as analogues of palau'amine.

Novel AAV44.9-Based Vectors Display Exceptional Characteristics for Retinal Gene Therapy.

The majority of inherited retinal diseases (IRDs) are caused by mutations in genes expressed in photoreceptors (PRs). The ideal vector to address these conditions is one that transduces PRs in large areas of retina with the smallest volume/lowest titer possible, and efficiently transduces foveal cones, the cells responsible for acute, daylight vision that are often the only remaining area of functional retina in IRDs. The purpose of our study was to evaluate the retinal tropism and potency of a novel capsid, AAV44.

Fluorescent Cholangiography in Laparoscopic Cholecystectomy and the Use in Pediatric Patients.

Common bile duct (CBD) injury is one of the most serious complications of laparoscopic cholecystectomy and carries an incidence of 0.3%-0.7%.

Cytotoxic and Anti-Inflammatory Effects of -Kaurane Derivatives Isolated from the Alpine Plant .

This paper reports the isolation and structural characterization of four new -kaurane derivatives from the Lamiaceae plant . Planar structures and relative configurations were determined using both mass spectrometry and nuclear magnetic resonance (1D and 2D). Absolute configurations were determined by comparing experimental and theoretical electronic circular dichroism spectra.

Pilot study to inform young adults about the risks of electronic cigarettes through text messaging.

Introduction: Young adults are rapidly adopting electronic cigarette (e-cigarette) use. The popularity of e-cigarettes among young people can be attributed to heavy industry advertising and misleading health claims. Data indicate that young e-cigarette users who have never used conventional cigarettes may transition toward smoking combustible cigarettes.

A Novel Mouse Model of USH1B Reveals Auditory and Visual System Haploinsufficiencies.

Usher's syndrome is the most common combined blindness-deafness disorder with USH1B, caused by mutations in , resulting in the most severe phenotype. The existence of numerous, naturally occurring mice harboring variable mutations on different genetic backgrounds has complicated the characterization of MYO7A knockout (KO) and heterozygote mice. We generated a novel MYO7A KO mouse ( ) that is easily genotyped, maintained, and confirmed to be null for MYO7A in both the eye and inner ear.

Revealing users' experience and social interaction outcomes following a web-based smoking prevention intervention for adolescents: A qualitative study.

Background: Tobacco smoking remains a public health problem among adolescents in the United States. While Web-based interventions for smoking prevention have been successful at the individual level, there is still an urgent need to understand their engagement capabilities and their effects at the social level. In the current study, we aimed to (1) learn about adolescents' subjective experience with a Web-based program called a smoking prevention interactive experience (ASPIRE), (2) obtain suggestions for improvement in ASPIRE content, (3) identify psychological outcomes of ASPIRE, and (4) explore outcomes of social interaction.

Bromotryptamine and Bromotyramine Derivatives from the Tropical Southwestern Pacific Sponge .

So far, the Futuna Islands located in the Central Indo-Pacific Ocean have not been inventoried for their diversity in marine sponges and associated chemical diversity. As part of the Tara Pacific expedition, the first chemical investigation of the sponge collected around the Futuna Islands yielded 18 brominated alkaloids: seven new bromotryptamine derivatives - and one new bromotyramine derivative together with 10 known metabolites of both families -. Their structures were deduced from extensive analyses of nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) data.

Structure Revision of Microginins 674 and 690 from the Cultured Cyanobacterium Microcystis aeruginosa.

The structures of the commercially available microginins 674 and 690 isolated from a cultured strain of Microcystis aeruginosa and only recently characterized have been revisited. Using NMR and HRMS/MS data, an inversion of two amino acids, N-methylmethionine and tyrosine, in the structure of these metabolites is unambiguously demonstrated. These results highlight the importance of careful examination of spectroscopic data for the proposition of structures of natural products, especially when they are of commercial value.

Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from .

species are the producers of the marine toxins ciguatoxins and maitotoxins which cause worldwide human intoxications recognized as Ciguatera Fish Poisoning. A deep chemical investigation of a cultured strain of , collected in the Caribbean Sea, led to the identification of a structural homologue of the recently described gambierone isolated from the same strain. The structure was elucidated mainly by comparison of NMR and MS data with those of gambierone and ascertained by 2D NMR data analyses.

Trends in hospital length of stay and 30-day morbidity in pediatric patients undergoing laparoscopic ileocecal resection, 2012-2016.

Purpose: To examine postoperative length of stay (LOS), hospital readmission, and 30-day complications in pediatric patients undergoing laparoscopic ileocecal resection in a contemporary cohort.

Methods: Retrospective review of the American College of Surgeons National Surgery Quality Improvement Project, Pediatric (NSQIP-P) 2012-2016 participant user files for patients <19 years old who underwent laparoscopic ileocecal resection. Mean postoperative LOS, hospital readmission and both wound-specific and composite complications were calculated and compared by year of operation.

Treasures from the Deep: Characellides as Anti-Inflammatory Lipoglycotripeptides from the Sponge Characella pachastrelloides.

The chemical investigation of marine invertebrates from the deep Northeastern Atlantic revealed new lipoglycotripeptides named characellides isolated from the tetractinellid sponge Characella pachastrelloides. This new family of natural products features a central tripeptide linked to a rare sugar unit and a long alkyl chain ending with a 2,3-dimethyltetrahydropyran. The configurations of all 13 chiral centers were determined by extensive use of NMR data and circular dichroism spectra combined with calculations.