Mosaicism of the UDP-Galactose Transporter SLC35A2 Causes a Congenital Disorder of Glycosylation

Biochemical analysis and whole-exome sequencing identified mutations in the Golgi-localized UDP-galactose transporter SLC35A2 that define an undiagnosed X-linked congenital disorder of glycosylation (CDG) in three unrelated families. Each mutation reduced UDP-galactose transport, leading to galactose-deficient glycoproteins. Two affected males were somatic mosaics, suggesting that a wild-type SLC35A2 allele may be required for survival. In infancy, the commonly used biomarker transferrin showed abnormal glycosylation, but its appearance became normal later in childhood, without any corresponding clinical improvement. This may indicate selection against cells carrying the mutant allele. To detect other individuals with such mutations, we suggest transferrin testing in infancy. Here, we report somatic mosaicism in CDG, and our work stresses the importance of combining both genetic and biochemical diagnoses

Targeting surface nucleolin with a multivalent pseudopeptide delays development of spontaneous melanoma in RET transgenic mice

<p>Abstract</p> <p>Background</p> <p>The importance of cell-surface nucleolin in cancer biology was recently highlighted by studies showing that ligands of nucleolin play critical role in tumorigenesis and angiogenesis. By using a specific antagonist that binds the C-terminal tail of nucleolin, the HB-19 pseudopeptide, we recently reported that HB-19 treatment markedly suppressed the progression of established human breast tumor cell xenografts in the athymic nude mice without apparent toxicity.</p> <p>Methods</p> <p>The <it>in vivo </it>antitumoral action of HB-19 treatment was assessed on the spontaneous development of melanoma in the RET transgenic mouse model. Ten days old RET mice were treated with HB-19 in a prophylactic setting that extended 300 days. In parallel, the molecular basis for the action of HB-19 was investigated on a melanoma cell line (called TIII) derived from a cutaneous nodule of a RET mouse.</p> <p>Results</p> <p>HB-19 treatment of RET mice caused a significant delay in the onset of cutaneous tumors, several-months delay in the incidence of large tumors, a lower frequency of cutaneous nodules, and a reduction of visceral metastatic nodules while displaying no toxicity to normal tissue. Moreover, microvessel density was significantly reduced in tumors recovered from HB-19 treated mice compared to corresponding controls. Studies on the melanoma-derived tumor cells demonstrated that HB-19 treatment of TIII cells could restore contact inhibition, impair anchorage-independent growth, and reduce their tumorigenic potential in mice. Moreover, HB-19 treatment caused selective down regulation of transcripts coding matrix metalloproteinase 2 and 9, and tumor necrosis factor-α in the TIII cells and in melanoma tumors of RET mice.</p> <p>Conclusions</p> <p>Although HB-19 treatment failed to prevent the development of spontaneous melanoma in the RET mice, it delayed for several months the onset and frequency of cutaneous tumors, and exerted a significant inhibitory effect on visceral metastasis. Consequently, HB-19 could provide a novel therapeutic agent by itself or as an adjuvant therapy in association with current therapeutic interventions on a virulent cancer like melanoma.</p

Chemical exploitation of metal contaminated biomass produced in phytoextraction

International audienceThis article describes some aspects of the chemical recovery of the metal contaminated biomass produced in phytoextraction technologies. Taking advantage of the adaptive capacity of certain plants to hyperaccumulate metallic cations in their aerial parts, phytoextraction could be a sustainable way to remediate trace metals pollution. A possible exploitation of the metal contaminated biomass produced in phytoextraction is the direct use of metallic cations derived from plants as Lewis acid catalysts for organic chemistry. These original polymetallic systems serve as heterogeneous catalysts in chemical transformations enabling the synthesis of molecules with high added value. Results for Friedel-Crafts acylations and alkylations are presented in this paper: the acetylation of anisole and benzylation reactions are considered in more detail. The use of mine tailings as catalytic supports is also investigated: it could represent a new integrated outlet for tailings and phytoextraction products. Each step of the process is designed to minimise environmental impacts in accord with the principles of Green Chemistry. The process seeks to be an incentive for the economic development of phytoextraction. As phytoremediation gains momentum, it could also prove a concrete solution to the criticality of non-renewable mineral materials with new sources of zinc, nickel and other metals

The chemical exploitation of nickel phytoextraction: An environmental, ecologic and economic opportunity for New Caledonia

Herein, we explore the outlines of an innovative method based on the chemical recovery of metal-rich biomass produced in phytoextraction technologies. Taking advantage of the adaptive capacity of some New Caledonian plants to hyperaccumulate Ni2+ cations in their aerial parts, this technique is based on the direct use of metals derived from plants as "Lewis acid" catalysts in organic chemistry. Metallic cations contained in New Caledonian nickel hyperaccumulators are recovered through a simple cost-effective process and serve the preparation of heterogeneous catalysts used in synthetic transformations allowing access to molecules with high added-value. The design of all processes is in line with the principles of green chemistry; it is adapted to the new economic constraints; it offers a new relevant outlet for metal-rich biomass; and it represents an altemative to non-renewable mineral materials

Mining in New Caledonia : environmental stakes and restoration opportunities

New Caledonia is a widely recognised marine and terrestrial biodiversity hot spot. However, this unique environment is under increasing anthropogenic pressure. Major threats are related to land cover change and include fire, urban sprawling and mining. Resulting habitat loss and fragmentation end up in serious erosion of the local biodiversity. Mining is of particular concern due to its economic significance for the island. Open cast mines were exploited there since 1873, and scraping out soil to access ores wipes out flora. Resulting perturbations on water flows and dramatic soil erosion lead to metal-rich sediment transport downstream into rivers and the lagoon. Conflicting environmental and economic aspects of mining are discussed in this paper. However, mining practices are also improving, and where impacts are inescapable ecological restoration is now considered. Past and ongoing experiences in the restoration of New Caledonian terrestrial ecosystems are presented and discussed here. Economic use of the local floristic diversity could also promote conservation and restoration, while providing alternative incomes. In this regard, Ecocatalysis, an innovative approach to make use of metal hyperaccumulating plants, is of particular interest

Salmonellosis with Salmonella typhi murium in the foal

Les auteurs décrivent l’apparition de foyers importants de Salmonel lose équine en France en 1981, provoquant la mort de jeunes poulains de 1 à 3 mois et quelques avortements sur les juments. Le portage par les animaux adultes apparemment sains est important. Cette épidémie de Salmonelloses est due à Salmonella typhimurium V. Copenhague, si cette salmonelle appartient à un biotype particulier (biotype b) connu, elle appartient par contre à un lyzotype encore inconnu en France. Cette salmonelle a d’autre part la particularité d’être multirésistante aux antibiotiques et, de ce fait, les auteurs attirent l’attention des vété rinaires, éleveurs et médecins en leur demandant une grande vigilance et une certaine prudence concernant des traitements intempestifs et « aveu gles » avec des antibiotiques.The authors describe some outbreaks of equine salmonellosis which occured in France during 1981, inducing the death of 1 to 3 months old foals and some abortions on the mares. This epizooty was due to Salmonella typhimurium v. Copenhagen, this salmonella belongs to a special biotype (biotype b) already known but to a lysotype still un know in France. This salmonella has also the characteristic of being multiresistant to antibiotics and the authors draw the attention of the veterinarians, breeders, and physicians on this fact and ask hem to be vigilant and cautions toward the use of «blind» treatements with antibiotics

Characterization by PIV of the Effect of Vortex Generators in a Transonic Separated Flow

The present study is aimed to analyse the effect of passive vortex generators in a transonic interaction between a shock-wave and a turbulent boundary layer in a channel flow at Mach number M = 1.45. Control of the boundary layer detachment downstream of the shock is obtained thanks to momentum transfer given by passive control devices, mechanical vortex generators (VG), located upstream of the shock and distributed in the spanwise direction. The channel\u92s lower wall is equipped with a contour profile - a bump - allowing flow separation. Two-component PIV velocity measurements are performed using the iterative gradient-based cross-correlation algorithm FOLKI-SPIV developed at ONERA. The evolution of the bulk flow and of the separated bubble due to the shock-wave boundary layer interaction is accurately quantified. Changes in the turbulent behaviour are also analysed thanks to the fluctuating fields. Comparisons with the already known flow without control give an appraisal of the effectiveness of such devices