A supramolecular carpet formed via self-assembly of bis(4,4'-dihydroxyphenyl) sulfone

Publisher's version/PDFBis(4,4'-dihydroxyphenyl) sulfone 1 exploits its tetrahedrally disposed complementary hydrogen bonding sites to generate a unique doubly interwoven molecular carpet architecture in the solid state

Characterization of the apoptotic response of human leukemia cells to organosulfur compounds

Background: Novel therapeutic agents that selectively induce tumor cell death are urgently needed in the clinical management of cancers. Such agents would constitute effective adjuvant approaches to traditional chemotherapy regimens. Organosulfur compounds (OSCs), such as diallyl disulfide, have demonstrated anti-proliferative effects on cancer cells. We have previously shown that synthesized relatives of dysoxysulfone, a natural OSC derived from the Fijian medicinal plant, Dysoxylum richi, possess tumor-specific antiproliferative effects and are thus promising lead candidates. Methods: Because our structure-activity analyses showed that regions flanking the disulfide bond mediated specificity, we synthesized 18 novel OSCs by structural modification of the most promising dysoxysulfone derivatives. These compounds were tested for anti-proliferative and apoptotic activity in both normal and leukemic cells. Results: Six OSCs exhibited tumor-specific killing, having no effect on normal bone marrow, and are thus candidates for future toxicity studies. We then employed mRNA expression profiling to characterize the mechanisms by which different OSCs induce apoptosis. Using Gene Ontology analysis we show that each OSC altered a unique set of pathways, and that these differences could be partially rationalized from a transcription factor binding site analysis. For example, five compounds altered genes with a large enrichment of p53 binding sites in their promoter regions (p < 0.0001). Conclusions: Taken together, these data establish OSCs derivatized from dysoxysulfone as a novel group of compounds for development as anti-cancer agents

Major issues in the origins of ray‐finned fish ( A ctinopterygii) biodiversity

Ray‐finned fishes ( A ctinopterygii) dominate modern aquatic ecosystems and are represented by over 32000 extant species. The vast majority of living actinopterygians are teleosts; their success is often attributed to a genome duplication event or morphological novelties. The remainder are ‘living fossils’ belonging to a few depauperate lineages with long‐retained ecomorphologies: P olypteriformes (bichirs), H olostei (bowfin and gar) and C hondrostei (paddlefish and sturgeon). Despite over a century of systematic work, the circumstances surrounding the origins of these clades, as well as their basic interrelationships and diagnoses, have been largely mired in uncertainty. Here, I review the systematics and characteristics of these major ray‐finned fish clades, and the early fossil record of A ctinopterygii, in order to gauge the sources of doubt. Recent relaxed molecular clock studies have pushed the origins of actinopterygian crown clades to the mid‐late P alaeozoic [ S ilurian– C arboniferous; 420 to 298 million years ago ( M a)], despite a diagnostic body fossil record extending only to the later M esozoic (251 to 66 M a). This disjunct, recently termed the ‘ T eleost G ap’ (although it affects all crown lineages), is based partly on calibrations from potential P alaeozoic stem‐taxa and thus has been attributed to poor fossil sampling. Actinopterygian fossils of appropriate ages are usually abundant and well preserved, yet long‐term neglect of this record in both taxonomic and systematic studies has exacerbated the gaps and obscured potential synapomorphies. At the moment, it is possible that later P alaeozoic‐age teleost, holostean, chondrostean and/or polypteriform crown taxa sit unrecognized in museum drawers. However, it is equally likely that the ‘ T eleost G ap’ is an artifact of incorrect attributions to extant lineages, overwriting both a post‐ P alaeozoic crown actinopterygian radiation and the ecomorphological diversity of stem‐taxa.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109271/1/brv12086.pd