A novel HDAC inhibitor with a hydroxy-pyrimidine scaffold

Histone deacetylases (HDACs) are enzymes involved in many important biological functions. They have been linked to a variety of cancers, psychiatric disorders, and other diseases. Since small molecules can serve as probes to study the relevant biological roles of HDACs, novel scaffolds are necessary to develop more efficient, selective drug candidates. Screening libraries of molecules may yield structurally diverse probes that bind these enzymes and modulate their functions in cells. Here we report a small molecule with a novel hydroxy-pyrimidine scaffold that inhibits multiple HDAC enzymes and modulates acetylation levels in cells. Analogs were synthesized in an effort to evaluate structure-activity relationships.     

Clustering heterochromatin: Sir3 promotes telomere clustering independently of silencing in yeast

A general feature of the nucleus is the organization of repetitive deoxyribonucleic acid sequences in clusters concentrating silencing factors. In budding yeast, we investigated how telomeres cluster in perinuclear foci associated with the silencing complex Sir2-Sir3-Sir4 and found that Sir3 is limiting for telomere clustering. Sir3 overexpression triggers the grouping of telomeric foci into larger foci that relocalize to the nuclear interior and correlate with more stable silencing in subtelomeric regions. Furthermore, we show that Sir3's ability to mediate telomere clustering can be separated from its role in silencing. Indeed, nonacetylable Sir3, which is unable to spread into subtelomeric regions, can mediate telomere clustering independently of Sir2-Sir4 as long as it is targeted to telomeres by the Rap1 protein. Thus, arrays of Sir3 binding sites at telomeres appeared as the sole requirement to promote trans-interactions between telomeres. We propose that similar mechanisms involving proteins able to oligomerize account for long-range interactions that impact genomic functions in many organisms.     

A New Insight into Allelopathic Effects of <Emphasis Type="Italic">Alexandrium minutum</Emphasis> on Photosynthesis and Respiration of the Diatom <Emphasis Type="Italic">Chaetoceros neogracile</Emphasis> Revealed by Photosynthetic-performance Analysis and Flow Cytometry

The allelopathic effects of Alexandrium minutum, a toxic dinoflagellate, on the diatom Chaetoceros neogracile were evaluated using unialgal cultures evaluated by flow cytometry (FCM) and photosynthetic-performance analysis. Using FCM, we demonstrated that red chlorophyll fluorescence, relative cell size (Forward scatter of blue laser light, FSC) and cell complexity (Side scatter, 90°-angle scatter of blue laser light, SSC) significantly and rapidly decreased in C. neogracile cells exposed to A. minutum. Cells of C. neogracile exposed to A. minutum had fewer active photosynthetic reaction centers and sharply decreased photosynthetic efficiency. These effects were intensified with advancing A. minutum batch culture age and cell density. The supernatant of A. minutum contained the majority of the putative allelopathic compounds, and the biological activity of these compounds remained active less than 9 h after release. This paper describes for the first time specific effects of allelochemicals produced by A. minutum on the photosynthetic apparatus of microalgal target cells. The biochemical composition of A. minutum allelopathic agents, however, remains unknown and still needs to be investigated.     

Relative contribution of seed phosphorus reserves and exogenous phosphorus uptake to maize (Zea mays L.) nutrition during early growth stages

Adequate phosphorus (P) nutrition during early stages is critical for maize growth. Our objective was to evaluate the relative contribution of seed P reserves and exogenous P to maize nutrition during early growth stages. Seedlings were grown with labeled nutrient solution (³²P). Seedlings were harvested periodically over the course of the three-week study. Initially, 87% and 77% of the total C and N in seeds were located in the endosperm, whereas 86% of seed P was located in the scutellum as phytate. Up to the 7th day after sowing, 96% of phytate was hydrolyzed. Hydrolyzed forms of P were temporarily stored in the seed before being translocated to growing organs, suggesting that the hydrolysis of phytate was not a limiting step for P supply to seedlings. Significant P uptake by roots was observed from the 5th day after sowing on. Both sources of P supplied roots and leaves, with a slightly higher proportion of P from seed reserves going to leaves rather than to roots. Of total seed P, 60% and 92% was exported towards newly growing seedlings till 7th and 17th days after sowing and ceased to be a significant source of P for growth thereafter. We conclude that although both P supply processes overlap in time, seed P was the main P source during early growth stages.     

Impact of past climatic and recent anthropogenic factors on wild yam genetic diversity

Forests of the Dahomey Gap are considered as refugia for many species. They play a crucial role in providing ecosystem services in an area devoid of forests. However, the impact of the way they are managed on the biodiversity they host has barely been investigated. Wild yams existing in these forests play a crucial role in maintaining the genetic diversity of cultivated yams. Indeed, studies of farmer practices have shown that, by way of ennoblement, wild yams collected and selected in the forests and old fallow areas are integrated into the cultivated pool. However, the genetic structure of wild yams is poorly understood. Using nine microsatellite loci, we investigated the population genetics of Dioscorea praehensilis in five forests in Benin, involving different management strategies and bioclimatic areas. Populations of D. praehensilis were strongly differentiated, consistent with an ancient separation of the forests. While the D. praehensilis population in a holly forest was undergoing mutation and drift equilibrium, the population collected from the most conserved forest was in a bottleneck. Moreover, in two forests with different management strategies, accessions from other forests were found, resulting from the displacement of yams following farmer migrations. No isolation by distance was detected, but a differentiation was found between populations of the Sudano-Guinean climate and the Guineo-Congolian climate. Our findings suggest differentiation due to forest isolations under past climatic conditions and more recent tuber flow through anthropogenic impacts.