Syntaxin 16 is a master recruitment factor for cytokinesis

Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively. However, it is not clear how either of these complexes is targeted to the midbody and whether their delivery is coordinated. The trafficking of membrane vesicles between different intracellular organelles involves the formation of soluble N-ethylmalei­mide–sensitive factor attachment protein receptor (SNARE) complexes. Although membrane traffic is known to play an important role in cytokinesis, the contribution and identity of intracellular SNAREs to cytokinesis remain unclear. Here we demonstrate that syntaxin 16 is a key regulator of cytokinesis, as it is required for recruitment of both recycling endosome–associated Exocyst and ESCRT machinery during late telophase, and therefore that these two distinct facets of cytokinesis are inextricably linked

Adjuvant breast cancer chemotherapy during late-trimester pregnancy: not quite a standard of care

<p>Abstract</p> <p>Background</p> <p>Diagnosis of breast cancer during pregnancy was formerly considered an indication for abortion. The pendulum has since swung to the other extreme, with most reviews now rejecting termination while endorsing immediate anthracycline-based therapy for any pregnant patient beyond the first trimester. To assess the evidence for this radical change in thinking, a review of relevant studies in the fields of breast cancer chemotherapy, pregnancy, and drug safety was conducted.</p> <p>Discussion</p> <p>Accumulating evidence for the short-term safety of anthracycline-based chemotherapy during late-trimester pregnancy represents a clear advance over the traditional norm of therapeutic abortion. Nonetheless, the emerging orthodoxy favoring routine chemotherapy during gestation should continue to be questioned on several grounds: (1) the assumed difference in maternal survival accruing from chemotherapy administered earlier – i.e., during pregnancy, rather than after delivery – has not been quantified; (2) the added survival benefit of adjuvant cytotoxic therapy prescribed within the hormone-rich milieu of pregnancy remains presumptive, particularly for ER-positive disease; (3) the maternal survival benefit associated with modified adjuvant regimens (e.g., weekly schedules, omission of taxanes, etc.) has not been proven equivalent to standard (e.g., post-delivery) regimens; and (4) the long-term transplacental and transgenerational hazards of late-trimester chemotherapy are unknown.</p> <p>Summary</p> <p>Although an incrementally increased risk of cancer-specific mortality is impossible to exclude, mothers who place a high priority on the lifelong well-being of their progeny may be informed that deferring optimal chemotherapy until after delivery is still an option to consider, especially in ER-positive, node-negative and/or last-trimester disease.</p

Sorting of GLUT4 into its insulin-sensitive store requires the Sec1/Munc18 protein mVps45

Insulin stimulates glucose transport in fat and muscle cells by regulating delivery of the facilitative glucose transporter, glucose transporter isoform 4 (GLUT4), to the plasma membrane. In the absence of insulin, GLUT4 is sequestered away from the general recycling endosomal pathway into specialized vesicles, referred to as GLUT4-storage vesicles. Understanding the sorting of GLUT4 into this store is a major challenge. Here we examine the role of the Sec1/Munc18 protein mVps45 in GLUT4 trafficking. We show that mVps45 is up-regulated upon differentiation of 3T3-L1 fibroblasts into adipocytes and is expressed at stoichiometric levels with its cognate target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor, syntaxin 16. Depletion of mVps45 in 3T3-L1 adipocytes results in decreased GLUT4 levels and impaired insulin-stimulated glucose transport. Using sub-cellular fractionation and an in vitro assay for GLUT4-storage vesicle formation, we show that mVps45 is required to correctly traffic GLUT4 into this compartment. Collectively our data reveal a crucial role for mVps45 in the delivery of GLUT4 into its specialized, insulin-regulated compartment

Understanding racial differences in health-related quality of life in a population-based cohort of breast cancer survivors

PURPOSE: Although racial disparities in health-related quality of life (HRQOL) among women with breast cancer (BC) are well documented, less is known about HRQOL changes over time among women of different races. Our objective was to assess racial differences in HRQOL during active treatment and survivorship phases of BC care. METHODS: We used data from the third phase of the Carolina Breast Cancer Study (CBCS-III). CBCS-III enrolled 3,000 women in North Carolina aged 20-74 years diagnosed with BC between 2008 and 2013. HRQOL assessments occurred 5- and 25-months post-diagnosis, representing distinct phases of care. HRQOL measures included the Functional Assessment of Cancer Therapy for BC and Functional Assessment of Chronic Illness Therapy for Spiritual Well-Being. Analysis of covariance models were employed to assess racial differences in changes in HRQOL. RESULTS: The cohort included 2,142 Non-Hispanic White (n=1,105) and Black women (n=1,037) who completed both HRQOL assessments. During active treatment, Whites reported physical and functional scores 2-2.5 points higher than Blacks (p<0.0001). Spiritual HRQOL was 2.1 points higher for Blacks (p<0.0001). During survivorship, differences persisted. After adjusting for demographic, socioeconomic, tumor and treatment characteristics, physical and functional HRQOL gaps narrowed, but spiritual HRQOL gaps widened. CONCLUSIONS: Racial differences in physical and functional HRQOL during active treatment and survivorship may be largely mediated by socioeconomic factors. However, our results suggest that among Black women, spiritual HRQOL is well supported throughout the BC care continuum. These results inform opportunities for improving the quality and equity of supportive services for women with BC