The Arabidopsis PILZ group genes encode tubulin-folding cofactor orthologs required for cell division but not cell growth

Plant microtubules are organized into specific cell cycle-dependent arrays that have been implicated in diverse cellular processes, including cell division and organized cell expansion. Mutations in four Arabidopsis genes collectively called the PILZ group result in lethal embryos that consist of one or a few grossly enlarged cells. The mutant embryos lack microtubules but not actin filaments. Whereas the cytokinesis-specific syntaxin KNOLLE is not localized properly, trafficking of the putative auxin efflux carrier PIN1 to the plasma membrane is normal. The four PILZ group genes were isolated by map-based cloning and are shown to encode orthologs of mammalian tubulin-folding cofactors (TFCs) C, D, and E, and associated small G-protein Arl2 that mediate the formation of alpha/beta-tubulin heterodimers in vitro. The TFC C ortholog, PORCINO, was detected in cytosolic protein complexes and did not colocalize with microtubules. Another gene with a related, although weaker, embryo-lethal phenotype, KIESEL, was shown to encode a TFC A ortholog. Our genetic ablation of microtubules shows their requirement in cell division and vesicle trafficking during cytokinesis, whereas cell growth is mediated by microtubule-independent vesicle trafficking to the plasma membrane during interphase.     

DicomWorks: Software for Reviewing DICOM Studies and Promoting Low-cost Teleradiology

DicomWorks is freeware software for reading and working on medical images [digital imaging and communication in medicine (DICOM)]. It was jointly developed by two research laboratories, with the feedback of more than 35,000 registered users throughout the world who provided information to guide its development. We detail their occupations (50% radiologists, 20% engineers, 9% medical physicists, 7% cardiologists, 6% neurologists, and 8% others), geographic origins, and main interests in the software. The viewer’s interface is similar to that of a picture archiving and communication system viewing station. It provides basic but efficient tools for opening DICOM images and reviewing and exporting them to teaching files or digital presentations. E-mail, FTP, or DICOM protocols are supported for transmitting images through a local network or the Internet. Thanks to its wide compatibility, a localized (15 languages) and user-friendly interface, and its opened architecture, DicomWorks helps quick development of non proprietary, low-cost image review or teleradiology solutions in developed and emerging countries.     

Dietary and lifestyle correlates of plasma insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3): the multiethnic cohort.

High circulating concentration of insulin-like growth factor-I (IGF-I) and low circulating concentration of IGF binding protein-3 (IGFBP-3) have been associated with increased risk for breast, prostate, and colorectal cancers. Building on previous work in the Multiethnic Cohort (MEC) showing significant differences in IGF-I levels across racial/ethnic groups, we investigated which lifestyle and dietary factors are associated with levels of IGF-I and IGFBP-3 in a random sample of 1,000 MEC participants, which included Native Hawaiian, African American, Japanese, Latino, and White men and women. Crude analyses confirmed the existence of differences in protein levels with race/ethnicity, sex, age, and body size. Reproductive, physical activity, smoking, and diet variables had less consistent effects. In multivariate analyses, IGF-I levels were lower and IGFBP-3 were higher in females versus males. IGF-I and IGFBP-3 declined with increasing age in both genders. Women in the highest quartile of body mass index showed depressed IGF-I and IGFBP-3 levels; in men, height was significantly positively associated with both proteins. In women, alcohol was directly associated with IGFBP-3. Both proteins were lowest among female Latinos. IGF-I was highest among female African Americans. In men, IGFBP-3 was lowest among African Americans. Overall, although these factors were statistically significant determinants of IGF-related protein levels, they did not explain much of the variation in these levels. A positive correlation was found between IGF-I levels (ng/mL) and colon cancer incidence rates (per 100,000) within the MEC by race/ethnicity for both sexes but not for either breast or prostate cancer.     

Association of breast cancer risk loci with breast cancer survival

The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over‐all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta‐analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1‐rs3817198 was significantly associated with improved OS (HR_per‐allele=0.70; 95% CI: 0.58–0.85; p_trend = 2.84 × 10^?4; HR_{heterozygotes} = 0.71; 95% CI: 0.55–0.92; HR_homozygotes = 0.48; 95% CI: 0.31–0.76; p_2DF = 1.45 × 10^?3). In silico, the C allele of LSP1‐rs3817198 was predicted to increase expression of the tumor suppressor cyclin‐dependent kinase inhibitor 1C (CDKN1C). In the meta‐analysis, TNRC9‐rs3803662 was significantly associated with increased death hazard (HR_META =1.09; 95% CI: 1.04–1.15; p_trend = 6.6 × 10^?4; HR_{heterozygotes} = 0.96 95% CI: 0.90–1.03; HR_homozygotes = 1.21; 95% CI: 1.09–1.35; p_2DF=1.25 × 10^?4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1‐rs3817198 and TNRC9‐rs3803662.     

Hydrophobicity of Lipid-Conjugated siRNAs Predicts Productive Loading to Small Extracellular Vesicles

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Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles

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