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The effects of two land-use-related contaminants, DDT and polychlorinated biphenyls (PCBs), were investigated as endpoints at 5, 10, and 20 ppb. Animals were either environmentally exposed (10 ppb) or exposed to a pharmacological challenge (5 ppb) on an AD/cholesterol diet. Both DDT and PCB exposures affected development in a dose-dependent fashion. The toxic effects of DDT and PCB were in the reverse order of potency for eggs, larvae, and juveniles. A developmental threshold for DDT and PCB can be established at 5 and 10 ppb, respectively, for eggs, larvae, and juveniles. The severity of the toxic effects of DDT and PCB increased when developmental time was extended. The results from the intraspecific comparison of populations of newt from different land-use types were qualitatively similar to the intraspecific toxicity results. Mean levels of DDT and PCB in the egg were 0.0024 and 0.068 ppb, respectively, for nongrazing compared with 0.0007 and 0.08 ppb for grazing populations. When these levels of pollutants were administered to eggs, the concentration-response relationships were similar. Although the magnitude of the effects of a toxicant depends on the nature of the toxicological response, the effects of DDT and PCB were of a comparable order in all life-history stages of the newt.A novel RUNX1 gene deletion in a patient with acute myeloid leukemia.
RUNX1 is a member of the runt domain transcription factor family, which has important functions in hematopoietic differentiation. RUNX1 translocations are reported in almost all acute myeloid leukemia (AML) cases; however, inactivation of RUNX1 through deletions is rare. Here, we report a deletion spanning exons 4-8 (nt 500-1000)

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The design and synthesis of novel 4-benzyl piperazine (BZP) derivatives 1-32 are described as dual 5-hydroxytryptamine(1A) (5-HT(1A)) receptor and D(1) dopamine receptor (DA) antagonists. The pharmacological studies were carried out on agonist radioligand [125I]DOI in the 5-HT(1A) receptor and antagonist radioligand [(3)H]SCH23390 in the DA D(1) receptor assays. The majority of the synthesized compounds exhibited good affinity for both the receptors. Some of the derivatives such as compound 6c, 12b, 14b, 17d, 18e, 20d, 25a and 26d showed comparable or better selectivity for 5-HT(1A) receptor than previously reported compounds. The representative compounds 14b and 26d exhibited selectivity for 5-HT(1A) receptor over DA D(1) receptor, when tested in vivo using male BALB/c mice (20 mg/kg p.o.).define([], function() {

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