Remarks on the extension of the Ricci flow

We present two new conditions to extend the Ricci flow on a compact manifold over a finite time, which are improvements of some known extension theorems.Comment: 9 pages, to appear in Journal of Geometric Analysi

Animal Toxicity of Hairpin Pyrrole-Imidazole Polyamides Varies with the Turn Unit

A hairpin pyrrole-imidazole polyamide (1) targeted to the androgen receptor consensus half-site was found to exert antitumor effects against prostate cancer xenografts. A previous animal study showed that 1, which has a chiral amine at the α-position of the γ-aminobutyric acid turn (γ-turn), did not exhibit toxicity at doses less than 10 mg/kg. In the same study, a polyamide with an acetamide at the β-position of the γ-turn resulted in animal morbidity at 2.3 mg/kg. To identify structural motifs that cause animal toxicity, we synthesized polyamides 1–4 with variations at the α- and β-positions in the γ-turn. Weight loss, histopathology, and serum chemistry were analyzed in mice post-treatment. While serum concentration was similar for all four polyamides after injection, dose-limiting liver toxicity was only observed for three polyamides. Polyamide 3, with an α-acetamide, caused no significant evidence of rodent toxicity and retains activity against LNCaP xenografts

Targeting Medium-Chain Acyl-CoA Dehydrogenase for Glioblastoma

View full abstracthttps://openworks.mdanderson.org/leading-edge/1041/thumbnail.jp

ANKRD26 and Its Interacting Partners TRIO, GPS2, HMMR and DIPA Regulate Adipogenesis in 3T3-L1 Cells

Partial inactivation of the Ankyrin repeat domain 26 (Ankrd26) gene causes obesity and diabetes in mice and increases spontaneous and induced adipogenesis in mouse embryonic fibroblasts. However, it is not yet known how the Ankrd26 protein carries out its biological functions. We identified by yeast two-hybrid and immunoprecipitation assays the triple functional domain protein (TRIO), the G protein pathway suppressor 2 (GPS2), the delta-interacting protein A (DIPA) and the hyaluronan-mediated motility receptor (HMMR) as ANKRD26 interacting partners. Adipogenesis of 3T3-L1 cells was increased by selective down-regulation of Ankrd26, Trio, Gps2, Hmmr and Dipa. Furthermore, GPS2 and DIPA, which are normally located in the nucleus, were translocated to the cytoplasm, when the C-terminus of ANKRD26 was introduced into these cells. These findings provide biochemical evidence that ANKRD26, TRIO, GPS2 and HMMR are novel and important regulators of adipogenisis and identify new targets for the modulation of adipogenesis

Genome-Wide Association Analyses Identify SPOCK as a Key Novel Gene Underlying Age at Menarche

For females, menarche is a most significant physiological event. Age at menarche (AAM) is a trait with high genetic determination and is associated with major complex diseases in women. However, specific genes for AAM variation are largely unknown. To identify genetic factors underlying AAM variation, a genome-wide association study (GWAS) examining about 380,000 SNPs was conducted in 477 Caucasian women. A follow-up replication study was performed to validate our major GWAS findings using two independent Caucasian cohorts with 854 siblings and 762 unrelated subjects, respectively, and one Chinese cohort of 1,387 unrelated subjects—all females. Our GWAS identified a novel gene, SPOCK (Sparc/Osteonectin, CWCV, and Kazal-like domains proteoglycan), which had seven SNPs associated with AAM with genome-wide false discovery rate (FDR) q<0.05. Six most significant SNPs of the gene were selected for validation in three independent replication cohorts. All of the six SNPs were replicated in at least one cohort. In particular, SNPs rs13357391 and rs1859345 were replicated both within and across different ethnic groups in all three cohorts, with p values of 5.09×10−3 and 4.37×10−3, respectively, in the Chinese cohort and combined p values (obtained by Fisher's method) of 5.19×10−5 and 1.02×10−4, respectively, in all three replication cohorts. Interestingly, SPOCK can inhibit activation of MMP-2 (matrix metalloproteinase-2), a key factor promoting endometrial menstrual breakdown and onset of menstrual bleeding. Our findings, together with the functional relevance, strongly supported that the SPOCK gene underlies variation of AAM

Immobilization, Trapping, and Anion Exchange of Perrhenate Ion Using Copper-Based Tripodal Complexes

We describe a multidentate tripodal ligand in which three pendant arms carrying di(2-picolyl)amine units are linked to the ortho positions of a tris(o-xylyl) scaffold, providing N(CH[subscript 2]-o-C[subscript 6]H[subscript 4]CH[subscript 2]N(CH2py)[subscript 2])[subscript 3] (L). Reaction of L with CuCl[subscript 2] in the presence of hexafluorophosphate anion afforded blue cubes of [(CuCl)[subscript 3]L](PF[subscript 6])[subscript 3]·5H[subscript 2]O (1). Crystallographic studies of 1 revealed that the three symmetry-related arms each coordinate a {Cu[superscript II]Cl} unit, and two molecules of 1 are connected to one another through a Cu(μ-Cl)[subscript 2]Cu bridge, extending the molecular structure to form a two-dimensional (2-D) layer. These 2-D layers pack in an ABCABC... fashion with PF[subscript 6]– anions located in between. Reaction of 1 with a stoichiometric amount of perrhenate ion afforded blue plates of [(CuCl)[subscript 3]L](PF[subscript 6])(ReO[subscript 4])[subscript 2]·3H[subscript 2]O (2). Compound 2 has the same lattice structure as 1, but the tricopper unit backbone now traps one ReO[subscript 4]– anion through Coulombic interactions. In addition, three molecules of 2 are bridged by a perrhenate ion, forming a Cu[subscript 3](μ[superscript 3]-ReO[subscript 4]) cluster, to give a different 2-D structure displaying a rare tridentate bridging ReO[subscript 4]– mode. Thus, in addition to classic perrhenate trapping through weak Coulombic interactions, 2 represents an exceptional example in which the ReO[subscript 4]– anion is immobilized in an extended framework through tight covalent interactions. The interlamellar PF[subscript 6]– anions in 1 can be exchanged with other anions including perrhenate, perchlorate, or periodate. The structural similarity between perrhenate and pertechnetate makes these materials of potential interest for pertechnetate trapping

Deep Sequencing of Small RNAs in Tomato for Virus and Viroid Identification and Strain Differentiation

Small RNAs (sRNA), including microRNAs (miRNA) and small interfering RNAs (siRNA), are produced abundantly in plants and animals and function in regulating gene expression or in defense against virus or viroid infection. Analysis of siRNA profiles upon virus infection in plant may allow for virus identification, strain differentiation, and de novo assembly of virus genomes. In the present study, four suspected virus-infected tomato samples collected in the U.S. and Mexico were used for sRNA library construction and deep sequencing. Each library generated between 5–7 million sRNA reads, of which more than 90% were from the tomato genome. Upon in-silico subtraction of the tomato sRNAs, the remaining highly enriched, virus-like siRNA pools were assembled with or without reference virus or viroid genomes. A complete genome was assembled for Potato spindle tuber viroid (PSTVd) using siRNA alone. In addition, a near complete virus genome (98%) also was assembled for Pepino mosaic virus (PepMV). A common mixed infection of two strains of PepMV (EU and US1), which shared 82% of genome nucleotide sequence identity, also could be differentially assembled into their respective genomes. Using de novo assembly, a novel potyvirus with less than 60% overall genome nucleotide sequence identity to other known viruses was discovered and its full genome sequence obtained. Taken together, these data suggest that the sRNA deep sequencing technology will likely become an efficient and powerful generic tool for virus identification in plants and animals