Genome sequence and cell biological toolbox of the highly regenerative, coenocytic green feather alga Bryopsis.

Green feather algae (Bryopsidales) undergo a unique life cycle in which a single cell repeatedly executes nuclear division without cytokinesis, resulting in the development of a thallus (>100 mm) with characteristic morphology called coenocyte. Bryopsis is a representative coenocytic alga that has exceptionally high regeneration ability: extruded cytoplasm aggregates rapidly in seawater, leading to the formation of protoplasts. However, the genetic basis of the unique cell biology of Bryopsis remains poorly understood. Here, we present a high-quality assembly and annotation of the nuclear genome of Bryopsis sp. (90.7 Mbp, 27 contigs, N50 = 6.7 Mbp, 14 034 protein-coding genes). Comparative genomic analyses indicate that the genes encoding BPL-1/Bryohealin, the aggregation-promoting lectin, are heavily duplicated in Bryopsis, whereas homologous genes are absent in other ulvophyceans, suggesting the basis of regeneration capability of Bryopsis. Bryopsis sp. possesses >30 kinesins but only a single myosin, which differs from other green algae that have multiple types of myosin genes. Consistent with this biased motor toolkit, we observed that the bidirectional motility of chloroplasts in the cytoplasm was dependent on microtubules but not actin in Bryopsis sp. Most genes required for cytokinesis in plants are present in Bryopsis, including those in the SNARE or kinesin superfamily. Nevertheless, a kinesin crucial for cytokinesis initiation in plants (NACK/Kinesin-7II) is hardly expressed in the coenocytic part of the thallus, possibly underlying the lack of cytokinesis in this portion. The present genome sequence lays the foundation for experimental biology in coenocytic macroalgae.

Comparison of adaptive statistical iterative and filtered back projection reconstruction techniques in quantifying coronary calcium.

BACKGROUND: Adaptive statistical iterative reconstruction (ASIR) has been used to reduce radiation dose in cardiac computed tomography. However, change of image parameters by ASIR as compared to filtered back projection (FBP) may influence quantification of coronary calcium. OBJECTIVE: To investigate the influence of ASIR on calcium quantification in comparison to FBP. METHODS: In 352 patients, CT images were reconstructed using FBP alone, FBP combined with ASIR 30%, 50%, 70%, and ASIR 100% based on the same raw data. Image noise, plaque density, Agatston scores and calcium volumes were compared among the techniques. RESULTS: Image noise, Agatston score, and calcium volume decreased significantly with ASIR compared to FBP (each P < 0.001). Use of ASIR reduced Agatston score by 10.5% to 31.0%. In calcified plaques both of patients and a phantom, ASIR decreased maximum CT values and calcified plaque size. CONCLUSION: In comparison to FBP, adaptive statistical iterative reconstruction (ASIR) may significantly decrease Agatston scores and calcium volumes.

Evaluation of perivalvular infectious ventricular pseudoaneurysm by ECG-gated cardiac computed tomography: 2 case reports.

Left ventricular (LV) pseudoaneurysm is a serious complication of periannular extension of infective endocarditis (IE). Because pseudoaneurysm carries a high risk of rupture, its detection and evaluation are crucial for patient management and surgical planning. We report 2 cases with LV pseudoaneurysms, one near the aortic valve and the other near the mitral valve, which were caused by IE and treated successfully. In both cases, cardiac multidetector-row computed tomography enabled detection of the LV pseudoaneurysm and a detailed demonstration of its anatomic relationship with surrounding structures, which helped guide surgical planning.

Telomerase inhibitors identified by a forward chemical genetics approach using a yeast strain with shortened telomere length.

Telomerase has been proposed as a selective target for cancer chemotherapy. We established a forward chemical genetics approach using a yeast strain with shortened telomere length. Since this strain rapidly enters cell senescence in the absence of active telomerase, compounds that induce selective growth defects against telomere-shortened yeast could be candidates for drugs acting on telomeres and telomerase. We screened our microbial products library and identified three structurally unrelated antibiotics, chrolactomycin, UCS1025A, and radicicol, as active compounds. Detailed analysis showed that chrolactomycin inhibited human telomerase in a cell-free assay as well as in a cellular assay. Long-term culture of cancer cells with chrolactomycin revealed population-doubling-dependent antiproliferative activity accompanied by telomere shortening. These results suggest that chrolactomycin is a telomerase inhibitor, and that the yeast-based assay is useful for discovering the small molecules acting on human telomerase.

Synthesis and antitumor activity of novel O-carbamoylmethyloxime derivatives of radicicol.

Radicicol (1), a macrocyclic antifungal antibiotic, is the lead compound of a novel class of heat shock protein 90 (Hsp90) inhibitors that result in the inhibition or degradation of Hsp90-associated proteins, such as v-src and Raf-1 kinases. New O-carbamoylmethyloxime derivatives of 1 were synthesized and evaluated for their in vitro antiproliferative activities against v-src- and K-ras-transformed cells and for their inhibitory activity against v-src tyrosine kinase. O-(Piperidinocarbonyl)methyloxime 9b, one of the most potent of these derivatives, exhibited more potent antiproliferative activity than 1 and its hydroxime KF25706 (2) and had an IC(50) of 25 nM for the inhibition of v-src kinase activity. Compound 9b was also found to decrease the Raf-1 protein level of KNRK5.2 cells. Furthermore, compound 9b exhibited significant antitumor activity when tested against MX-1 and A431 xenografts in nude mice.

UCS1025A and B, new antitumor antibiotics from the fungus Acremonium species.

[structure: see text] UCS1025A and B, novel pentacyclic polyketides with an unprecedented furopyrrolizidine skeleton, were isolated from the fungus Acremonium sp. KY4917. The structures and stereochemistry were elucidated by a combination of two-dimensional NMR and X-ray crystallographic analysis. UCS1025A showed unique chemical equilibria involving three tautomeric isomers and exhibited antimicrobial activity and antiproliferative activity against human tumor cell lines.

Halohydrin and oxime derivatives of radicicol: synthesis and antitumor activities.

Novel halohydrin and oxime derivatives of radicicol (1) were prepared and evaluated for their v-src tyrosine kinase inhibitory, antiproliferative, and antitumor activities. Some of the resulting derivatives showed significantly improved antitumor activities than those of 1 in vitro as tested in a cell proliferation assay and in vivo using sc-inoculated human breast carcinoma and epidermoid tumor models. Design and synthesis of radicicol-based novel affinity probes are also described.