Correction of ADA-SCID by stem cell gene therapy combined with nonmyeloablative conditioning

Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloablative conditioning. This protocol was used in two patients for whom enzyme replacement therapy was not available, which allowed the effect of gene therapy alone to be evaluated. Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions (including antigen-specific responses), and lower toxic metabolites. Both patients are currently at home and clinically well, with normal growth and development. These results indicate the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID.     

The impact of cellulose fibre surface modification on some physico-chemical properties of the ensuing papers

This review covers both physical and chemical modifications of cellulose fibre surface and their impact on the properties of the ensuing papers. It is not restricted to actual industrial operations, but also deals instead with ongoing research in this area, which appears promising in terms of possible applications to papermaking.     

IgE-Mediated Cross-Reactivity among Leguminous Seed Proteins in Peanut Allergic Children

The immunological cross-reactivity among major protein- and oil-crops, including lupin, lentil, pea, peanut, kidney bean and soybean, has been studied by a combination of in vitro and in vivo experimental approaches: SDS-PAGE separations of legume protein extracts and immuno-blot revelations with 12 peanut-sensitive subjects’ sera, Immuno-CAP and Skin Prick tests on the same subjects. The immuno-blotting data showed a wide range of IgE-binding responses both displayed by one subject towards different plant extracts and among subjects. Differences were both quantitative and qualitative. The prevalent responses of most subjects’ sera were seen with peanut polypeptides, as expected, as well as with various polypeptides of the other legumes, the most recurrent of which were the basic subunits of the 11S globulins. The distribution of in vivo responses generally paralleled those obtained by in vitro approaches with strong responses elicited by peanut, lentil and pea protein extracts, especially by most sensitive subjects, thus providing a consistent overall set of results. In this work, the comparison of various approaches has allowed us to get an overall broad picture of the immunological cross-reactivities among proteins of widely used different seed species and to hypothesize the role of most conserved specific polypeptides.     

Marine-Derived Quorum-Sensing Inhibitory Activities Enhance the Antibacterial Efficacy of Tobramycin against Pseudomonas aeruginosa

Bacterial epiphytes isolated from marine eukaryotes were screened for the production of quorum sensing inhibitory compounds (QSIs). Marine isolate KS8, identified as a Pseudoalteromonas sp., was found to display strong quorum sensing inhibitory (QSI) activity against acyl homoserine lactone (AHL)-based reporter strains Chromobacterium violaceum ATCC 12472 and CV026. KS8 supernatant significantly reduced biofilm biomass during biofilm formation (−63%) and in pre-established, mature P. aeruginosa PAO1 biofilms (−33%). KS8 supernatant also caused a 0.97-log reduction (−89%) and a 2-log reduction (−99%) in PAO1 biofilm viable counts in the biofilm formation assay and the biofilm eradication assay respectively. The crude organic extract of KS8 had a minimum inhibitory concentration (MIC) of 2 mg/mL against PAO1 but no minimum bactericidal concentration (MBC) was observed over the concentration range tested (MBC > 16 mg/mL). Sub-MIC concentrations (1 mg/mL) of KS8 crude organic extract significantly reduced the quorum sensing (QS)-dependent production of both pyoverdin and pyocyanin in P. aeruginosa PAO1 without affecting growth. A combinatorial approach using tobramycin and the crude organic extract at 1 mg/mL against planktonic P. aeruginosa PAO1 was found to increase the efficacy of tobramycin ten-fold, decreasing the MIC from 0.75 to 0.075 µg/mL. These data support the validity of approaches combining conventional antibiotic therapy with non-antibiotic compounds to improve the efficacy of current treatments.     

The mass disruption of Oort cloud comets

We have calculated the number of dormant, nearly isotropic Oort cloud comets in the solar system by (i) combining orbital distribution models with statistical models of dormant comet discoveries by well-defined surveys and (ii) comparing the model results to observations of a population of dormant comets. Dynamical models that assume that comets are not destroyed predict that we should have discovered approximately 100 times more dormant nearly isotropic comets than are actually seen. Thus, as comets evolve inward from the Oort cloud, the majority of them must physically disrupt.     

Structural and technical development in agriculture: An international overview

This study investigates the socio-historical relationships existing between the development of the agricultural structure and the process of technical development. Adopting a political economy posture, it is argued that the development of technical procedures in agriculture has been aimed historically at the maximization of production and productivity. This phenomenon has been generated by the social hegemony of groups interested in the enhancement of accumulation of capital and has been translated into an emphasis on large productive units, which discriminates against small and medium farms. This pattern of development has been legitimized through a social consensus which involves an emphasis on small family producers. This contradiction is embodied in the generation of a dualistic agricultural structure characterized by the prosperity of large farms, the persistence of small farms and the crisis of medium farms and in patterns of overproduction and unavailability of food for the poor segments of society.     

Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior

A common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met), is associated with alterations in brain anatomy and memory, but its relevance to clinical disorders is unclear. We generated a variant BDNF mouse (BDNF(Met/Met)) that reproduces the phenotypic hallmarks in humans with the variant allele. BDNF(Met) was expressed in brain at normal levels, but its secretion from neurons was defective. When placed in stressful settings, BDNF(Met/Met) mice exhibited increased anxiety-related behaviors that were not normalized by the antidepressant, fluoxetine. A variant BDNF may thus play a key role in genetic predispositions to anxiety and depressive disorders.     

Book reviews

Marilyn Holly is an Associate Professor of Philosophy at the University of Florida. Her special interests include political philosophy, ethics and ecology, Jungian thought, and Native American spirituality in its relation to the environment. She is currently at work on a monograph-length piece on the latter topic. She has taught an undergraduate course in ethics and ecology, and plans to do so again. The following essay emerged from her search for a suitable text for such a course.     

Effects of shrimp pond water on phytoplankton: importance of salinity and trophic status of the receiving environment

Aquaculture generates a large load of effluents rich in organic matter and nutrients that may be introduced into the environment. This study aimed to assess in a microcosm experiment, the effect of shrimp pond water mixed with Patos Lagoon estuary water on phytoplankton chlorophyll a and primary production, simulating two salinities. Chlorophyll a, dissolved inorganic nutrients and primary production were measured in two experiments. In Harvest I, salinity of shrimp pond and environment water was similar, and chlorophyll a showed different trends over time, according to the amount of nitrogen available. In Harvest II, with different salinities and high nutrient concentrations in environment water, chlorophyll a levels showed a similar increasing trend over time in all mixtures. Net primary production showed differences among treatments in the first sampling in Harvest I, but not in the second, whereas no differences were observed among treatments in Harvest II. We conclude that shrimp pond effluent can lead to short‐term variations in chlorophyll a and primary production levels, with similar salinities. Salinity differences result in lower chlorophyll a and primary production values than expected according to the nutrient input. Differences in salinity can be an important management strategy to choose the best harvest period.     

Weak effects of habitat type on susceptibility to invasive freshwater species: an Italian case study

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