The rhesus macaque (Macaca mulatta) is an abundant primate species that diverged from the ancestors of Homo sapiens about 25 million years ago. Because they are genetically and physiologically similar to humans, rhesus monkeys are the most widely used nonhuman primate in basic and applied biomedical research. We determined the genome sequence of an Indian-origin Macaca mulatta female and compared the data with chimpanzees and humans to reveal the structure of ancestral primate genomes and to identify evidence for positive selection and lineagespecific expansions and contractions of gene families. A comparison of sequences from individual animals was used to investigate their underlying genetic diversity. The complete description of the macaque genome blueprint enhances the utility of this animal model for biomedical research and improves our understanding of the basic biology of the species.

Breast cancer is a leading cause of cancer-death among women, where the clinicopathological features of tumors are used to prognosticate and guide therapy. DNA copy number alterations (CNAs), which occur frequently in breast cancer and define key pathogenetic events, are also potentially useful prognostic or predictive factors. Here, we report a genome-wide array-based comparative genomic hybridization (array CGH) survey of CNAs in 89 breast tumors from a patient cohort with locally advanced disease. Statistical analysis links distinct cytoband loci harboring CNAs to specific clinicopathological parameters, including tumor grade, estrogen receptor status, presence of TP53 mutation, and overall survival. Notably, distinct spectra of CNAs also underlie the different subtypes of breast cancer recently defined by expression-profiling, implying these subtypes develop along distinct genetic pathways. In addition, higher numbers of gains/losses are associated with the "basal-like" tumor subtype, while high-level DNA amplification is more frequent in "luminal-B" subtype tumors, suggesting also that distinct mechanisms of genomic instability might underlie their pathogenesis. The identified CNAs may provide a basis for improved patient prognostication, as well as a starting point to define important genes to further our understanding of the pathobiology of breast cancer. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat

Dr. Young H. Kim obtained a BS and MS at Yonsei University, Korea, then a Ph.D. at The Weizmann Institute of Science, Israel, with Dr. E. Gil-Av in the subject of chiral recognition. After postdoctoral work with Prof. D. Cram at UCLA working on the stereoselective synthesis and cavitands, he moved to the DuPont CR&D in 1984. Since then, he has started to get involved in polymer research, and has been working on hyperbranched dendritic polymers, aromatic polyamides, and chemical modification of polymers, polyurethane chemistry.ABSTRACT: It has been about 10 years since the first intentional preparation of hyperbranched polymer was disclosed. Hyperbranched polymers, as well as dendrimers, may find utilities in the areas where the structural uniqueness of these polymers gives merit. There has been much progress in the structural understanding and the methods of synthesis of these polymers. However, functional understanding and utility of these polymers are still in infancy. Better understanding on physical properties of these polymers, such as solubility and miscibility of these polymers in solvents or with polymers, and functional group dependency to the thermal relaxation process are needed for further development of the subject.

Highly branched polyphenylenes were synthesized from AB2 type monomers, e.g., 3,5dibromophenylboronic acid (1A) and 3,5-dihalophenyl Grignard reagents (IB and 2). Monomers 1 and 2 were polymerized by Pd(0) and Ni(II) catalyzed aryl-aryl coupling reactions, respectively. Polymers obtained from 1 had molecular weights in the 5000-35 000 range with polydispersities less than 1.5. They are thermally stable to 550 aC and soluble in many organic solvents. 13C NMR indicates about 70% branching efficiency. A Tt at 236 °C was observed, but the polymer was brittle and did not form films. The melt viscosity of polystyrene was reduced, and the modulus was improved as a bromo functional hyperbranched polymer was added. The bromo polymer was metalated with butyllithium. The resulting lithio polymer reacted with various electrophiles to provide polymers with other end groups which control solubility as well as thermal properties. Some of these derivatives were used as multifunctional initiators to prepare star polymers, for example, via ring-opening polymerization of propiolactone and anionic polymerization of methyl methacrylate.

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Collagen type II-induced arthritis is a CD4(+) T-cell-dependent chronic inflammation in susceptible DBA/1 mice and represents an animal model of human rheumatoid arthritis. We found that development of this condition, and even established disease, are inhibited by an agonistic anti-4-1BB monoclonal antibody. Anti-4-1BB suppressed serum antibodies to collagen type II and CD4(+) T-cell recall responses to collagen type II. Crosslinking of 4-1BB evoked an antigen-specific, active suppression mechanism that differed from the results of blocking the interaction between 4-1BB and its ligand, 4-1BBL. Anti-4-1BB monoclonal antibodies induced massive, antigen-dependent clonal expansion of CD11c(+)CD8(+) T cells and accumulation of indoleamine 2,3-dioxygenase in CD11b(+) monocytes and CD11c(+) dendritic cells. Both anti-interferon-gamma and 1-methyltryptophan, a pharmacological inhibitor of indoleamine 2,3-dioxygenase, reversed the anti-4-1BB effect. We conclude that the suppression of collagen-induced arthritis was caused by an expansion of new CD11c(+)CD8(+) T cells, and that interferon-gamma produced by these cells suppresses antigen-specific CD4(+) T cells through an indoleamine 2,3-dioxygenase-dependent mechanism.

The widespread application of computed tomography (CT) in different clinical situations has increased the detection of intussusception, particularly non-lead point intussusception, which tends to be transient. Consequently, determining the clinical significance of intussusception seen at CT poses a diagnostic challenge. Patients with intussusception may or may not be symptomatic, and symptoms can be acute, intermittent, or chronic, making clinical diagnosis difficult. In most cases, radiologists can readily make the correct diagnosis of intestinal intussusception by noting the typical bowel-within-bowel appearance at abdominal CT. However, the CT findings that help differentiate between lead point and non-lead point intussusception have not been well studied. Nevertheless, although there is considerable overlap of CT findings, when a lead mass is seen at CT as a separate and distinct entity vis-à-vis edematous bowel, it can be considered a reliable indicator of a lead point intussusception. Differentiating between lead point and non-lead point intussusception is important in determining the appropriate treatment and has the potential to reduce the prevalence of unnecessary surgery.

BackgroundPromoter hypermethylation coupled with loss of heterozygosity at the same locus results in loss of gene function in many tumor cells. The “rules” governing which genes are methylated during the pathogenesis of individual cancers, how specific methylation profiles are initially established, or what determines tumor type-specific methylation are unknown. However, DNA methylation markers that are highly specific and sensitive for common tumors would be useful for the early detection of cancer, and those required for the malignant phenotype would identify pathways important as therapeutic targets.Methods and FindingsIn an effort to identify new cancer-specific methylation markers, we employed a high-throughput global expression profiling approach in lung cancer cells. We identified 132 genes that have 5′ CpG islands, are induced from undetectable levels by 5-aza-2′-deoxycytidine in multiple non-small cell lung cancer cell lines, and are expressed in immortalized human bronchial epithelial cells. As expected, these genes were also expressed in normal lung, but often not in companion primary lung cancers. Methylation analysis of a subset (45/132) of these promoter regions in primary lung cancer (n = 20) and adjacent nonmalignant tissue (n = 20) showed that 31 genes had acquired methylation in the tumors, but did not show methylation in normal lung or peripheral blood cells. We studied the eight most frequently and specifically methylated genes from our lung cancer dataset in breast cancer (n = 37), colon cancer (n = 24), and prostate cancer (n = 24) along with counterpart nonmalignant tissues. We found that seven loci were frequently methylated in both breast and lung cancers, with four showing extensive methylation in all four epithelial tumors.ConclusionsBy using a systematic biological screen we identified multiple genes that are methylated with high penetrance in primary lung, breast, colon, and prostate cancers. The cross-tumor methylation pattern we observed for these novel markers suggests that we have identified a partial promoter hypermethylation signature for these common malignancies. These data suggest that while tumors in different tissues vary substantially with respect to gene expression, there may be commonalities in their promoter methylation profiles that represent targets for early detection screening or therapeutic intervention.