Untargeted Metabolomics Approach Using UHPLC-HRMS to Unravel the Impact of Fermentation on Color and Phenolic Composition of Rosé Wines.

Color is a major quality trait of rosé wines due to their packaging in clear glass bottles. This color is due to the presence of phenolic pigments extracted from grapes to wines and products of reactions taking place during the wine-making process. This study focuses on changes occurring during the alcoholic fermentation of Syrah, Grenache and Cinsault musts, which were conducted at laboratory (250 mL) and pilot (100 L) scales.

Sexually transmitted infections on the border between Brazil and French Guiana.

Purpose: The border between the State of Amapa, Brazil, and French Guiana is mostly primary forest. In the Oyapock basin, socioeconomic circumstances have fueled sex work, gold mining and the circulation of sexually transmitted infections. Given the lack of comprehensive data on this border area, we describe the different sexually transmitted infections along the Brazil/French Guiana border and the testing and care activity.

Multi-method study of the impact of fermentation on the polyphenol composition and color of Grenache, Cinsault, and Syrah rosé wines.

Rosé wines show large color diversity, due to different phenolic pigment compositions. However, the mechanisms responsible for such diversity are poorly understood. The present work aimed at investigating the impact of fermentation on the color and composition of rosé wines made from Grenache, Cinsault, and Syrah grapes.

Sexually transmitted infections on the border between Suriname and French Guiana: A scoping review.

Purpose: The Maroni basin -delineating the border between Suriname and French Guiana- presents sociocultural, geographical and economic circumstances that have been conducive to the circulation of sexually transmitted infections and to delays in diagnosis and care. Given the scarcity of published data, we aimed to describe different sexually transmitted infections along the Maroni and to gain a broader understanding of the epidemiologic situation.

Methods: We conducted a scoping review of the efforts to approach the problem of sexually transmitted infections in this complex border area.

Semirational bioengineering of AAV vectors with increased potency and specificity for systemic gene therapy of muscle disorders.

Bioengineering of viral vectors for therapeutic gene delivery is a pivotal strategy to reduce doses, facilitate manufacturing, and improve efficacy and patient safety. Here, we engineered myotropic adeno-associated viral (AAV) vectors via a semirational, combinatorial approach that merges AAV capsid and peptide library screens. We first identified shuffled AAVs with increased specificity in the murine skeletal muscle, diaphragm, and heart, concurrent with liver detargeting.

Elucidating the Color of Rosé Wines Using Polyphenol-Targeted Metabolomics.

The color of rosé wines is extremely diverse and a key element in their marketing. It is due to the presence of anthocyanins and of additional pigments derived from them and from other wine constituents. To explore the pigment composition and determine its links with color, 268 commercial rosé wines were analysed.

A novel therapeutic strategy for skeletal disorders: Proof of concept of gene therapy for X-linked hypophosphatemia.

Adeno-associated virus (AAV) vectors are a well-established gene transfer approach for rare genetic diseases. Nonetheless, some tissues, such as bone, remain refractory to AAV. X-linked hypophosphatemia (XLH) is a rare skeletal disorder associated with increased levels of fibroblast growth factor 23 (FGF23), resulting in skeletal deformities and short stature.

IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies.

Neutralizing antibodies to adeno-associated virus (AAV) vectors are highly prevalent in humans, and block liver transduction and vector readministration; thus, they represent a major limitation to in vivo gene therapy. Strategies aimed at overcoming anti-AAV antibodies are being studied, which often involve immunosuppression and are not efficient in removing pre-existing antibodies. Imlifidase (IdeS) is an endopeptidase able to degrade circulating IgG that is currently being tested in transplant patients.

Separation and isolation of major polyphenols from maritime pine (Pinus pinaster) knots by two-step centrifugal partition chromatography monitored by LC-MS and NMR spectroscopy.

Pine knots are a rich source of lignans, flavonoids, and stilbenes. These bioactive compounds are widely known for their roles to combat human disorders but also to protect plants against pathogens. In order to gain knowledge inside their potential activities, a suitable isolation and purification of these high-added value compounds is required.

Capsid-specific removal of circulating antibodies to adeno-associated virus vectors.

Neutralizing antibodies directed against adeno-associated virus (AAV) are commonly found in humans. In seropositive subjects, vector administration is not feasible as antibodies neutralize AAV vectors even at low titers. Consequently, a relatively large proportion of humans is excluded from enrollment in clinical trials and, similarly, vector redosing is not feasible because of development of high-titer antibodies following AAV vector administration.

Peptides derived from the C-terminal domain of HIV-1 Viral Protein R in lipid bilayers: Structure, membrane positioning and gene delivery.

Viral protein R (Vpr) is a small accessory protein of 96 amino acids that is present in Human and simian immunodeficiency viruses. Among the very different properties that Vpr possesses we can find cell penetrating capabilities. Based on this and on its capacity to interact with nucleic acids we previously investigated the DNA transfection properties of Vpr and subfragments thereof.

Erratum: Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction.

[This corrects the article DOI: 10.1016/j.omtm.

Induction of tumor-specific CTL responses using the C-terminal fragment of Viral protein R as cell penetrating peptide.

The discovery of tumor-associated antigens recognized by T lymphocytes opens the possibility of vaccinating cancer patients with defined antigens. However, one of the major limitation of peptide-based vaccines is the low immunogenicity of antigenic peptides. Interestingly, if these epitopes are directly delivered into the cytoplasm of antigen presenting cells, they can be efficiently presented via the direct MHC class I presentation pathway.

Wood and roots of major grapevine cultivars and rootstocks: A comparative analysis of stilbenes by UHPLC-DAD-MS/MS and NMR.

Introduction: Grapevine wood and roots are by-products obtained during vineyard management. This plentiful biomass is known to be rich in stilbenes and can be used as a source of high-value compounds as well as active natural extracts. However, the stilbenes in grapevine wood and roots from different cultivars and rootstocks remain to be characterized.

AAV Gene Transfer with Tandem Promoter Design Prevents Anti-transgene Immunity and Provides Persistent Efficacy in Neonate Pompe Mice.

Hepatocyte-restricted, AAV-mediated gene transfer is being used to provide sustained, tolerogenic transgene expression in gene therapy. However, given the episomal status of the AAV genome, this approach cannot be applied to pediatric disorders when hepatocyte proliferation may result in significant loss of therapeutic efficacy over time. In addition, many multi-systemic diseases require widespread expression of the therapeutic transgene that, when provided with ubiquitous or tissue-specific non-hepatic promoters, often results in anti-transgene immunity.

Exposure to wild-type AAV drives distinct capsid immunity profiles in humans.

Recombinant adeno-associated virus (AAV) vectors have been broadly adopted as a gene delivery tool in clinical trials, owing to their high efficiency of transduction of several host tissues and their low immunogenicity. However, a considerable proportion of the population is naturally exposed to the WT virus from which AAV vectors are derived, which leads to the acquisition of immunological memory that can directly determine the outcome of gene transfer. Here, we show that prior exposure to AAV drives distinct capsid immunity profiles in healthy subjects.

Antigen-selective modulation of AAV immunogenicity with tolerogenic rapamycin nanoparticles enables successful vector re-administration.

Gene therapy mediated by recombinant adeno-associated virus (AAV) vectors is a promising treatment for systemic monogenic diseases. However, vector immunogenicity represents a major limitation to gene transfer with AAV vectors, particularly for vector re-administration. Here, we demonstrate that synthetic vaccine particles encapsulating rapamycin (SVP[Rapa]), co-administered with AAV vectors, prevents the induction of anti-capsid humoral and cell-mediated responses.

Influence of Pre-existing Anti-capsid Neutralizing and Binding Antibodies on AAV Vector Transduction.

Pre-existing immunity to adeno-associated virus (AAV) is highly prevalent in humans and can profoundly impact transduction efficiency. Despite the relevance to AAV-mediated gene transfer, relatively little is known about the fate of AAV vectors in the presence of neutralizing antibodies (NAbs). Similarly, the effect of binding antibodies (BAbs), with no detectable neutralizing activity, on AAV transduction is ill defined.

Prevalence and long-term monitoring of humoral immunity against adeno-associated virus in Duchenne Muscular Dystrophy patients.

Adeno-associated virus (AAV) vectors are promising candidates for gene therapy and have been explored as gene delivery vehicles in the treatment of Duchenne Muscular Dystrophy (DMD). Recent studies showed compelling evidence of therapeutic efficacy in large animal models following the intravenous delivery of AAV vectors expressing truncated forms of dystrophin. However, to translate these results to humans, careful assessment of the prevalence of anti-AAV neutralizing antibodies (NAbs) is needed, as presence of preexisting NABs to AAV in serum have been associated with a drastic diminution of vector transduction.

Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase.

Glycogen storage disease type II or Pompe disease is a severe neuromuscular disorder caused by mutations in the lysosomal enzyme, acid α-glucosidase (GAA), which result in pathological accumulation of glycogen throughout the body. Enzyme replacement therapy is available for Pompe disease; however, it has limited efficacy, has high immunogenicity, and fails to correct pathological glycogen accumulation in nervous tissue and skeletal muscle. Using bioinformatics analysis and protein engineering, we developed transgenes encoding GAA that could be expressed and secreted by hepatocytes.

Bioengineered AAV Capsids with Combined High Human Liver Transduction In Vivo and Unique Humoral Seroreactivity.

Existing recombinant adeno-associated virus (rAAV) serotypes for delivering in vivo gene therapy treatments for human liver diseases have not yielded combined high-level human hepatocyte transduction and favorable humoral neutralization properties in diverse patient groups. Yet, these combined properties are important for therapeutic efficacy. To bioengineer capsids that exhibit both unique seroreactivity profiles and functionally transduce human hepatocytes at therapeutically relevant levels, we performed multiplexed sequential directed evolution screens using diverse capsid libraries in both primary human hepatocytes in vivo and with pooled human sera from thousands of patients.

Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction.

Pompe disease results from acid α-glucosidase (GAA) deficiency, and enzyme replacement therapy (ERT) with recombinant human (rh) GAA has clinical benefits, although its limitations include the short half-life of GAA and the formation of antibody responses. The present study compared the efficacy of ERT against gene transfer with an adeno-associated viral (AAV) vector containing a liver-specific promoter. GAA knockout (KO) mice were administered either a weekly injection of rhGAA (20 mg/kg) or a single injection of AAV2/8-LSPhGAA (8 × 10 vector genomes [vg]/kg).

The absorption enhancer sodium deoxycholate promotes high gene transfer in skeletal muscles.

Gene delivery to skeletal muscle is a promising strategy for the treatment of muscle disorders and for the systemic secretion of therapeutic proteins. In addition, muscle is an attractive target tissue because it is easily accessible. However, very few synthetic vectors proved capable of surpassing naked DNA mediated muscle gene transfer.