scholarly journals Multigram synthesis of an orthogonally protected pentasaccharide for use as glycan precursor in a Shigella flexneri 3a conjugate vaccine: application to a ready-for-conjugation decasaccharide

2021 ◽  
Author(s):  
Johan Cornil ◽  
Zhaoyu Hu ◽  
Marion Bouchet ◽  
Laurence A. MULARD
Keyword(s):  
Conjugate Vaccine ◽  
Large Scale ◽  
Shigella Flexneri ◽  
Bioactive Molecules

The rapidly growing interest for carbohydrate-based bioactive molecules calls for strategies enabling appropriate design and large scale delivery of the glycan moiety. Here, we described a robust and high-yielding chemical...

Increased risk of invasive pneumococcal disease in haematological and solid-organ malignancies

2010 ◽  
Vol 138 (12) ◽  
pp. 1804-1810 ◽  
Author(s):  
A. WONG ◽  
T. J. MARRIE ◽  
S. GARG ◽  
J. D. KELLNER ◽  
G. J. TYRRELL ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Large Scale ◽  
Adult Population ◽  
Retrospective Chart Review ◽  
Polysaccharide Vaccine ◽  
Solid Organ ◽  
Pneumococcal Polysaccharide Vaccine ◽  
Increased Risk

SUMMARYLarge-scale population-based studies have reported a significant increase in invasive pneumococcal disease (IPD) in those with underlying haematological or solid-organ malignancy, but limited condition-specific data are available on rates of IPD in the adult population. A retrospective chart review of all patients with IPD (identified prospectively) in the province of Alberta, Canada (population ~3·3 million) was conducted from 2000 to 2004 to study the epidemiology of IPD. Rates of IPD in patients with various haematological and solid-organ malignancies were determined by obtaining the number of these patients at risk from the provincial cancer registry. Compared to the attack rate of IPD in the adult population aged ⩾18 years (11·0 cases/100 000 per year, 95% CI 10·44–11·65), there were significantly increased rates of IPD in those with lung cancer (143·6 cases/100 000 per year, OR 13·4, 95% CI 9·3–19·4, P<0·001) and multiple myeloma (673·9 cases/100 000 per year, OR 62·8, 95% CI 39·6–99·8, P<0·001). More modestly increased rates of IPD were found in those with chronic lymphocytic leukaemia, acute myeloid leukaemia, acute lymphoblastic leukaemia, and Hodgkin's and non-Hodgkin's lymphoma. There was an increased prevalence of serotype 6A in those with these underlying malignancies, but no other serotypes predominated. Fifty-three percent (48/83) of cases were caused by serotypes in the investigational 13-valent pneumococcal conjugate vaccine (PCV13), and 57/83 (69%) of the cases were caused by serotypes in the 23-valent pneumococcal polysaccharide vaccine (PPV23). The incidence of IPD in adults with certain haematological and solid-organ malignancies is significantly greater than the overall adult population. Such patients should be routinely given pneumococcal polysaccharide vaccine; this population could also be targeted for an expanded valency conjugate vaccine.

scholarly journals MEMO: Mass Spectrometry-based Sample Vectorization to Explore Chemodiverse Datasets

2021 ◽  
Author(s):  
Arnaud Gaudry ◽  
Florian Huber ◽  
Louis-Felix Nothias ◽  
Sylvian Cretton ◽  
Marcel Kaiser ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Large Scale ◽  
State Of The Art ◽  
Mass Spectrometric ◽  
Bioactive Molecules ◽  
Computational Time ◽  
Mass Spectral ◽  
Experimental Variation ◽  
Alignment Step ◽  
Feature Alignment

In natural products research, chemodiverse extracts coming from multiple organisms are explored for novel bioactive molecules, sometimes over extended periods. Samples are usually analyzed by liquid chromatography coupled with fragmentation mass spectrometry to acquire informative mass spectral ensembles. Such data is then exploited to establish relationships among analytes or samples (e.g. via molecular networking) and annotate metabolites. However, the comparison of samples profiled in different batches is challenging with current metabolomics methods. Indeed, the experimental variation - changes in chromatographical or mass spectrometric conditions - often hinders the direct comparison of the profiled samples. Here we introduce MEMO - MS2 BasEd SaMple VectOrization - a method allowing to cluster large amounts of chemodiverse samples based on their LC-MS/MS profiles in a retention time agnostic manner. This method is particularly suited for heterogeneous and chemodiverse sample sets. MEMO demonstrated similar clustering performance as state-of-the-art metrics taking into account fragmentation spectra. More importantly, such performance was achieved without the requirement of a prior feature alignment step and in a significantly shorter computational time. MEMO thus allows the comparison of vast ensembles of samples, even when analyzed over long periods of time, and on different chromatographic or mass spectrometry platforms. This new addition to the computational metabolomics toolbox should drastically expand the scope of large-scale comparative analysis.

scholarly journals Omeprazole Promotes Chloride Exclusion and Induces Salt Tolerance in Greenhouse Basil

Agronomy ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 355 ◽  
Author(s):  
Petronia Carillo ◽  
Pasqualina Woodrow ◽  
Giampaolo Raimondi ◽  
Christophe El-Nakhel ◽  
Antonio Pannico ◽  
...  
Keyword(s):  
Salt Tolerance ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Benzimidazole Derivative ◽  
Ion Homeostasis ◽  
Chloride Concentration ◽  
Co2 Assimilation ◽  
Stomatal Resistance ◽  
Bioactive Molecules ◽  
Proton Pumps

The role of small bioactive molecules (<500 Da) in mechanisms improving resource use efficiency in plants under stress conditions draws increasing interest. One such molecule is omeprazole (OMP), a benzimidazole derivative and inhibitor of animal proton pumps shown to improve nitrate uptake and exclusion of toxic ions, especially of chloride from the cytosol of salt-stressed leaves. Currently, OMP was applied as substrate drench at two rates (0 or 10 μM) on hydroponic basil (Ocimum basilicum L. cv. Genovese) grown under decreasing NO3−:Cl− ratio (80:20, 60:40, 40:60, or 20:80). Chloride concentration and stomatal resistance increased while transpiration, net CO2 assimilation rate and beneficial ions (NO3−, PO43−, and SO42−) decreased with reduced NO3−:Cl− ratio under the 0 μM OMP treatment. The negative effects of chloride were not only mitigated by the 10 μM OMP application in all treatments, with the exception of 20:80 NO3−:Cl−, but plant growth at 80:20, 60:40, and 40:60 NO3−:Cl− ratios receiving OMP application showed maximum fresh yield (+13%, 24%, and 22%, respectively), shoot (+10%, 25%, and 21%, respectively) and root (+32%, 76%, and 75%, respectively) biomass compared to the corresponding untreated treatments. OMP was not directly involved in ion homeostasis and compartmentalization of vacuolar or apoplastic chloride. However, it was active in limiting chloride loading into the shoot, as manifested by the lower chloride concentration in the 80:20, 60:40, and 40:60 NO3−:Cl− treatments compared to the respective controls (−41%, −37%, and −24%), favoring instead that of nitrate and potassium while also boosting photosynthetic activity. Despite its unequivocally beneficial effect on plants, the large-scale application of OMP is currently limited by the molecule’s high cost. However, further studies are warranted to unravel the molecular mechanisms of OMP-induced reduction of chloride loading to shoot and improved salt tolerance.

scholarly journals Evaluation of Vaccine Safety After the First Public Sector Introduction of Typhoid Conjugate Vaccine—Navi Mumbai, India, 2018

2021 ◽  
Author(s):  
Ashley T Longley ◽  
Kashmira Date ◽  
Stephen P Luby ◽  
Pankaj Bhatnagar ◽  
Adwoa D Bentsi-Enchill ◽  
...  
Keyword(s):  
Public Sector ◽  
Adverse Events ◽  
Conjugate Vaccine ◽  
Surveillance System ◽  
Large Scale ◽  
Safety Evaluation ◽  
Vaccine Safety ◽  
World Health ◽  
Post Vaccination ◽  
Health Organization

Abstract Background In December 2017, the World Health Organization (WHO) prequalified the first typhoid conjugate vaccine (TCV) (Typbar-TCV). While no safety concerns were identified in pre- and post-licensure studies, WHO’s Global Advisory Committee on Vaccine Safety recommended robust safety evaluation with large-scale TCV introductions. During July–August 2018, the Navi Mumbai Municipal Corporation (NMMC) launched the world’s first public sector TCV introduction. Per administrative reports, 113,420 children 9 months–14 years old received TCV. Methods We evaluated adverse events following immunization (AEFI) using passive and active surveillance via 1) reports from the passive NMMC AEFI surveillance system, 2) telephone interviews with 5% of caregivers of vaccine recipients 48 hours and 7 days post-vaccination, and 3) chart abstraction for adverse events of special interest (AESI) among patients admitted to 5 hospitals using the Brighton Collaboration criteria followed by ascertainment of vaccination status. Results We identified 222/113,420 (0.2%) AEFI through the NMMC AEFI surveillance system: 211 (0.19%) minor, 2 (0.002%) severe, and 9 (0.008%) serious. At 48 hours post-vaccination, 1,852/5,605 (33%) caregivers reported one or more AEFI, including injection site pain (n=1,452, 26%), swelling (n=419, 7.5%), and fever (n=416, 7.4%). Of the 4,728 interviews completed at 7 days post-vaccination, the most reported AEFI included fever (n=200, 4%), pain (n=52, 1%), and headache (n=42, 1%). Among 525 hospitalized children diagnosed with an AESI, 60 were vaccinated; no AESI were causally associated with TCV. Conclusions No unexpected safety signals were identified with TCV introduction. This provides further reassurance for the large-scale use of Typbar-TCV among children 9 months–14 years old.

scholarly journals Bioactivity and Delivery Strategies of Phytochemical Compounds in Bone Tissue Regeneration

2021 ◽  
Vol 11 (11) ◽  
pp. 5122
Author(s):  
Anna Valentino ◽  
Francesca Di Cristo ◽  
Michela Bosetti ◽  
Amal Amaghnouje ◽  
Dalila Bousta ◽  
...  
Keyword(s):  
Side Effects ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Large Scale ◽  
Stability Limit ◽  
Cost Effective ◽  
Biological Properties ◽  
Delivery Systems ◽  
Bioactive Molecules ◽  
Bone Tissue Regeneration

Plant-derived secondary metabolites represent a reservoir of phytochemicals for regenerative medicine application because of their varied assortment of biological properties including anti-oxidant, anti-inflammatory, antibacterial, and tissue remodeling properties. In addition, bioactive phytochemicals can be easily available, are often more cost-effective in large-scale industrialization, and can be better tolerated compared to conventional treatments mitigating the long-lasting side effects of synthetic compounds. Unfortunately, their poor bioavailability and lack of long-term stability limit their clinical impact. Nanotechnology-based delivery systems can overcome these limitations increasing bioactive molecules’ local effectiveness with reduction of the possible side effects on healthy bone. This review explores new and promising strategies in the area of delivery systems with particular emphasis on solutions that enhance bioavailability and/or health effects of plant-derived phytochemicals such as resveratrol, quercetin, epigallocatechin-3-gallate, and curcumin in bone tissue regeneration.

scholarly journals Future Directions for Meningitis Surveillance and Vaccine Evaluation in the Meningitis Belt of Sub-Saharan Africa

2019 ◽  
Vol 220 (Supplement_4) ◽  
pp. S279-S285 ◽  
Author(s):  
Ryan T Novak ◽  
Olivier Ronveaux ◽  
André F Bita ◽  
Honoré Flavien Aké ◽  
Fernanda C Lessa ◽  
...  
Keyword(s):  
Conjugate Vaccine ◽  
Large Scale ◽  
Public Health Problem ◽  
Study Data ◽  
Sub Saharan Africa ◽  
Laboratory Diagnostics ◽  
Meningitis Belt ◽  
Significant Public Health ◽  
Sub Saharan ◽  
The Impact

Abstract In sub-Saharan Africa, bacterial meningitis remains a significant public health problem, especially in the countries of the meningitis belt, where Neisseria meningitidis serogroup A historically caused large-scale epidemics. In 2014, MenAfriNet was established as a consortium of partners supporting strategic implementation of case-based meningitis surveillance to monitor meningitis epidemiology and impact of meningococcal serogroup A conjugate vaccine (MACV). MenAfriNet improved data quality through use of standardized tools, procedures, and laboratory diagnostics. MenAfriNet surveillance and study data provided evidence of ongoing MACV impact, characterized the burden of non-serogroup A meningococcal disease (including the emergence of a new epidemic clone of serogroup C), and documented the impact of pneumococcal conjugate vaccine. New vaccines and schedules have been proposed for future implementation to address the remaining burden of meningitis. To support the goals of “Defeating Meningitis by 2030,” MenAfriNet will continue to strengthen surveillance and support research and modeling to monitor the impact of these programs on meningitis burden in sub-Saharan Africa.

scholarly journals Plant Milking Technology—An Innovative and Sustainable Process to Produce Highly Active Extracts from Plant Roots

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4162
Author(s):  
Hanane Chajra ◽  
Aleksander Salwinski ◽  
Agnès Guillaumin ◽  
Benoit Mignard ◽  
Paul Hannewald ◽  
...  
Keyword(s):  
Large Scale ◽  
Morus Alba ◽  
Bioactive Molecules ◽  
Plant Roots ◽  
Efficient Production ◽  
Root Extract ◽  
Nitrogen Deprivation ◽  
Active Ingredients ◽  
Prenylated Flavonoids

We have used an original technology (Plant Milking Technology) based on aeroponic cultivation of plants associated with the gentle recovery of active ingredients from roots. Extraction of bioactive molecules was achieved by soaking the roots, still attached to the living plants, into a nontoxic solvent for a 2 h period. This nondestructive recovery process allows using the same root biomass for successive harvesting dates, in a recyclable way. We have applied this technology to Morus alba L. (mulberry tree), an emblematic tree of the Traditional Chinese Medicine (TCM). Trees were aeroponically grown in large-scale devices (100 m2) and were submitted to nitrogen deprivation to increase the content in active molecules (prenylated flavonoids). The Plant Milking technology applied to Morus alba L. allowed to produce an extract enriched in prenylated compounds (18-fold increase when compared to commercial root extract). Prenylated flavonoids (moracenin A and B, kuwanon C, wittiorumin F, morusin) presented a high affinity for the aged-associated collagenase enzyme, which was confirmed by activity inhibition. In accordance, M. alba extract presents efficient properties to regulate the skin matrisome, which is critical during skin aging. The benefits have been especially confirmed in vivo on wrinkle reduction, in a clinical study that involved aged women. Plant Milking technology is an optimal solution to produce active ingredients from plant roots, including trees, that meet both customer expectations around sustainability, as well as the need for an efficient production system for biotechnologists.

scholarly journals Chemically-Induced Production of Anti-Inflammatory Molecules in Microalgae

Marine Drugs ◽  
2018 ◽  
Vol 16 (12) ◽  
pp. 478 ◽  
Author(s):  
Zaida Montero-Lobato ◽  
María Vázquez ◽  
Francisco Navarro ◽  
Juan Fuentes ◽  
Elisabeth Bermejo ◽  
...  
Keyword(s):  
Production Process ◽  
Large Scale ◽  
Algal Species ◽  
Algal Growth ◽  
Production Costs ◽  
Bioactive Molecules ◽  
Chemically Induced ◽  
Anti Inflammatory ◽  
Valuable Compounds ◽  
Inflammatory Molecules

Microalgae have been widely recognized as a valuable source of natural, bioactive molecules that can benefit human health. Some molecules of commercial value synthesized by the microalgal metabolism have been proven to display anti-inflammatory activity, including the carotenoids lutein and astaxanthin, the fatty acids EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), and sulphated polysaccharides. These molecules can accumulate to a certain extent in a diversity of microalgae species. A production process could become commercially feasible if the productivity is high and the overall production process costs are minimized. The productivity of anti-inflammatory molecules depends on each algal species and the cultivation conditions, the latter being mostly related to nutrient starvation and/or extremes of temperature and/or light intensity. Furthermore, novel bioprocess tools have been reported which might improve the biosynthesis yields and productivity of those target molecules and reduce production costs simultaneously. Such novel tools include the use of chemical triggers or enhancers to improve algal growth and/or accumulation of bioactive molecules, the algal growth in foam and the surfactant-mediated extraction of valuable compounds. Taken together, the recent findings suggest that the combined use of novel bioprocess strategies could improve the technical efficiency and commercial feasibility of valuable microalgal bioproducts production, particularly anti-inflammatory compounds, in large scale processes.

Harvest date and variability in lipid bioactive compounds in Pistacia atlantica

2021 ◽  
pp. 1-18
Author(s):  
Mebarka Imane Benguechoua ◽  
Madjda Benguechoua ◽  
Nadhir Gourine ◽  
Artur M. S. Silva ◽  
Mokhtar Saidi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Antioxidant Activity ◽  
Large Scale ◽  
Unsaturated Fatty Acids ◽  
Antioxidant Activities ◽  
Essential Fatty Acids ◽  
Saturated Fatty Acids ◽  
Growth Period ◽  
Bioactive Molecules ◽  
Pistacia Atlantica

BACKGROUND: The present work stands as an endeavor to uncover the ideal harvesting time of leaves in which they exhibits the maximum contents of bioactive molecules such as essential fatty acids, tocopherols and carotenoids. METHODS: A large scale investigation was carried out for the leaves of Pistacia atlantica involving a large number of populations collected over a period of four months during the growing season. The antioxidant activity was evaluated using both DPPH and β-carotene assays. The chemical percentage variability of the fatty acids was investigated using statistical analysis methods (Agglomerative Hierarchical Clustering “AHC”, also cited as CAH). OBJECTIVE: During the growth period, the effects of harvesting date on the total contents of lipids, tocopherols, carotenoids, fatty acids composition and also the antioxidant activities of the lipids were investigated. RESULTS: The content of myristic acid and other saturated fatty acids increased during leaf development, while linoleic, linolenic acids and unsaturated fatty acids decreased. The highest percentages of both linolenic C18:3 (27.25±5.92%) and linoleic acids C18:2 (17.68±3.80%) were obtained for the month of May at the first stage of leaves development (young leaves), but higher percentage levels of C18:1, were obtained for both consecutive months of August & September (28.83±6.50%; 27.79±8.63%, respectively) at intermediate developing stage. The lipids, tocopherols, carotenoids contents and the saturated and unsaturated fatty acids were dependent on the harvest time. The antioxidant activity showed higher powers at the first developing stage (May). Two main clusters and two sub-clusters of the fatty acids were distinguished and were also depending clearly on the period of the collection. CONCLUSIONS: The results showed that the FAs were dependent on the period of collection of the leaves. The main result of this study illustrate the nutritional potential (richness in MUFA such as C18:1, 2, 3) of the oil of P. atlantica leaves, which can provide opportunities for rational exploitation in the food industries or for medicinal purposes.

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