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.     

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.     

Facteurs pronostiques en insémination avec sperme de donneur : suivi rétrospectif d’une cohorte de 188 patientes

ObjectivesImproving our practice by a constant evaluation is essential in the field of donor semen insemination (DI). Our center examined the prognosis factors for DI success in order to standardize patient treatment options.Patients and methodsWe retrospectively analysed all couples referred for DI from January 2000 till December 2010.ResultsWe analysed 551 cycles among 188 patients. Pregnancy rate by stimulation cycle was 19,8% with birth rate of 16.7%. The rate of pregnancy was improved till the fourth trial then plateau. On a patient-based analysis, success factors were age (P = 0.04), previous successful DSI (P = 0.02), and no previous failure of an ICSI-C (P = 0.035). On a cycle-based analysis, success factors were the number of follicles greater than 15 mm (P = 0.04) and than 18 mm (P = 0.001). The percentage of 68.1 patients obtained a child by IVF-D after a failed DI.ConclusionThere are two predictive factors for DI success: the age of the patient and the number of mature follicles. It seems accurate to referred patients to IVF-D after four unsuccessful cycles of DSI. This recommendation may be adapted according to patient's age and hormonal evaluation.     

Les médecins traitants devant le défi du dépistage et de la prise en charge de l’endométriose : résultats d’une enquête

ObjectiveTo evaluate the knowledge of general practitioners concerning the endometriosis diagnostic and care.Population and methodsSurvey enrolling 100 general practitioners of the 76th Seine Maritime French department (region of Upper Normandy) who usually perform gynaecological follow up, asked to answer an irreversible 36 item step-by-step questionnaire.ResultsAmong them, 44% perform more than one gynaecological consultation each week. They were 63% to feel ill at ease in the diagnosis and follow up of women presenting with endometriosis. One half of physicians could not cite three main symptoms of the disease out of dysmenorrhea, dyspareunia, chronic pelvic pain and infertility. Only 38% of general practitioners perform a clinical gynaecological examination when they suspect the endometriosis, and 28% of them recommended MRI to confirm the diagnosis. They are 24% to refer the patient without delay, but only 52% to the universitary hospital, which is the tertiary regional referral center, while 68% of them refer to a fellow practicing in a private facility. They were 64% to believe that therapeutic amenorrhea is on the bottom of the medical therapy. General practitioners were more likely to accurately answer the questionnaire when they attended gynaecological advanced courses during previous 5 years and when they followed up more than three patients previously managed for endometriosis.Discussion and conclusionGeneral practitioners’ knowledge about endometriosis is limited, with possible direct consequences on the delay of the diagnosis. The attendance of gynaecological advanced courses and the exchange of information between gynaecologic surgeons and general practitioners who follow up the patients appear to be two-way to improve the accuracy of the answers to the questionnaire.     

Hématome infecté du cul-de-sac de Douglas : une complication spécifique de la chirurgie de l’endométriose profonde postérieure du fond vaginal

ObjectiveSurgical management of deep pelvic endometriosis may be responsible for various complications, such as infected pelvic haematic collection of the Douglas pouch. The aim of this study is to describe this unfavourable outcome and to estimate its frequency in the series of women managed by our team.Patients and methodsRetrospective study enrolling 163 women undergoing surgical removal of deep posterior endometriosis involving the vagina, from January 2008 to September 2011. We indentified women presenting with postoperative fever associated with computed tomographic findings suggesting an abscess of the Douglas pouch. Women characteristics, complication's management and outcomes were analysed in each case.ResultsTen patients presented an inflammatory syndrome associated to hypothetical Douglas pouch abscess, revealed 6 days postoperatively on average. All women reported increasing pelvic pain, fever higher than 38.5 °C, increased level of leucocytes and C reactive protein, and liquid collection of the Douglas pouch. Surgical management was carried out in nine women, revealing a pelvic collection of cloudy haematic liquid. Various bacteria were identified in six cases out of nine, suggesting liquid contamination through vagina opening. Postoperative outcome were immediately favourable.Discussion and conclusionInflammatory syndrome associated with infected haematic collection of the Douglas pouch is a postoperative complication of the surgical removal of deep endometriosis involving the posterior vagina. Surgical removal of the haematic collection allows rapid and definitive favourable outcomes.     

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

1. Download high-res image (121KB)
2. Download full-size image

     

Optimized Cholesterol-siRNA Chemistry Improves Productive Loading onto Extracellular Vesicles

1. Download high-res image (101KB)
2. Download full-size image