Local and Regional Dynamics of Native Maize Seed Lot Use by Small-Scale Producers and Their Impact on Transgene Presence in Three Mexican States.

Mexico harbors over 50% of maize's genetic diversity in the Americas. Native maize varieties are actively managed by small-scale producers within a diverse array of cultivation systems. Seed lot use, exchange and admixture has consequences for the in situ conservation of such varieties. Here we analyze native maize seed management dynamics from 906 small-scale producers surveyed in three Mexican states: Mexico City, Oaxaca and Chiapas. Furthermore, we analyze how their management practices can relate to transgene presence, which was experimentally documented for maize samples associated with the applied surveys. Through a data mining approach, we investigated which practices might be related with a higher probability of transgene presence. The variables found to have a strong spatial association with transgene presence were: for Mexico City, maize producers with larger parcels; for Oaxaca, producer's age (43-46 years) and the sale of seed; for Chiapas, the use of agricultural machinery and younger producers (37-43 years). Additionally, transgene presence and frequency within the socioeconomic regions of Oaxaca and Chiapas was analyzed. In Oaxaca, higher transgene frequencies occurred in regions where transgene presence had been previously reported. In Chiapas, the border regions with Guatemala as well as a region where reproduction of improved seed takes place, the highest proportion of positive samples were found. A detailed mapping of regional seed markets and seed exchange sites together with deployment of national and local biosecurity measures, could help prevent the further spread of transgenes into native maize varieties, as well as improve conservation efforts.

Compensatory mutations rescue the virus replicative capacity of VIRIP-resistant HIV-1.

VIRIP has been identified as a highly specific natural inhibitor of HIV-1 that blocks HIV-1 gp41-dependent fusion by interacting with the gp41 fusion peptide. Two analogues of VIRIP (VIR-353 and VIR-576) with a few amino acid changes increase its antiretroviral potency by two orders of magnitude in cell culture. VIR-576 has been shown effective in a phase I/II clinical trial. Resistance to VIRIP and its analogue VIR-353 were generated after long-term passage in cell culture suggesting a high genetic barrier to resistance. Mutations conferring resistance to VIRIP and VIR-353 significantly reduced virus fitness. However, accumulation of additional mutations rescued the replication capacity of the virus while retaining resistance to VIR-353 and full sensitivity to T20. Combinations of VIR-353 and T20 had an additive effect on the inhibition of wild type HIV-1 replication, but only a single agent was active when combinations were tested against T20-resistant HIV-1, suggesting that both gp41 peptides do not interfere with each other in their binding to gp41. Our results provide additional support to the development of a new class of antiretroviral agents targeting gp41-dependent fusion.

Diarylpyrimidine-dihydrobenzyloxopyrimidine hybrids: new, wide-spectrum anti-HIV-1 agents active at (sub)-nanomolar level.

Here, we describe a novel small series of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that combine peculiar structural features of diarylpyrimidines (DAPYs) and dihydro-alkoxy-benzyl-oxopyrimidines (DABOs). These DAPY-DABO hybrids (1-4) showed a characteristic SAR profile and a nanomolar anti-HIV-1 activity at both enzymatic and cellular level. In particular, the two compounds 4d and 2d, with a (sub)nanomolar activity against wild-type and clinically relevant HIV-1 mutant strains, were selected as lead compounds for next optimization studies.

ADS-J1 inhibits HIV-1 entry by interacting with gp120 and does not block fusion-active gp41 core formation.

We had shown that virus resistance to ADS-J1 was associated with amino acid changes in the envelope glycoprotein, mostly located in the gp120 coding region. Time-of-addition and endocytic virus transfer assays clearly demonstrated that ADS-J1 behaved as a gp120 inhibitor. ADS-J1-resistant virus was cross-resistant to the polyanion dextran sulfate, and recombination of gp120 recovered only the ADS-J1-resistant phenotype. In summary, ADS-J1 blocks an early step of virus entry that appears to be driven by gp120 alone.

The xipotl mutant of Arabidopsis reveals a critical role for phospholipid metabolism in root system development and epidermal cell integrity.

Phosphocholine (PCho) is an essential metabolite for plant development because it is the precursor for the biosynthesis of phosphatidylcholine, which is the major lipid component in plant cell membranes. The main step in PCho biosynthesis in Arabidopsis thaliana is the triple, sequential N-methylation of phosphoethanolamine, catalyzed by S-adenosyl-l-methionine:phosphoethanolamine N-methyltransferase (PEAMT). In screenings performed to isolate Arabidopsis mutants with altered root system architecture, a T-DNA mutagenized line showing remarkable alterations in root development was isolated. At the seedling stage, the mutant phenotype is characterized by a short primary root, a high number of lateral roots, and short epidermal cells with aberrant morphology. Genetic and biochemical characterization of this mutant showed that the T-DNA was inserted at the At3g18000 locus (XIPOTL1), which encodes PEAMT (XIPOTL1). Further analyses revealed that inhibition of PCho biosynthesis in xpl1 mutants not only alters several root developmental traits but also induces cell death in root epidermal cells. Epidermal cell death could be reversed by phosphatidic acid treatment. Taken together, our results suggest that molecules produced downstream of the PCho biosynthesis pathway play key roles in root development and act as signals for cell integrity.