Joseph K. Hwang

The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin

Insulin stimulates glucose transport by promoting exocytosis of the glucose transporter Glut4 (refs 1, 2). The dynamic processes involved in the trafficking of Glut4-containing vesicles, and in their targeting, docking and fusion at the plasma membrane, as well as the signalling processes that govern these events, are not well understood. We recently described tyrosine-phosphorylation events restricted to subdomains of the plasma membrane that result in activation of the G protein TC10 (refs 3, 4). Here we show that TC10 interacts with one of the components of the exocyst complex, Exo70. Exo70 translocates to the plasma membrane in response to insulin through the activation of TC10, where it assembles a multiprotein complex that includes Sec6 and Sec8. Overexpression of an Exo70 mutant blocked insulin-stimulated glucose uptake, but not the trafficking of Glut4 to the plasma membrane. However, this mutant did block the extracellular exposure of the Glut4 protein. So, the exocyst might have a crucial role in the targeting of the Glut4 vesicle to the plasma membrane, perhaps directing the vesicle to the precise site of fusion.

Progenitor cell maintenance requires numb and numblike during mouse neurogenesis

Neurons in most regions of the mammalian nervous system are generated over an extended period of time during development. Maintaining sufficient numbers of progenitors over the course of neurogenesis is essential to ensure that neural cells are produced in correct numbers and diverse types. The underlying molecular mechanisms, like those governing stem-cell self-renewal in general, remain poorly understood. We report here that mouse numb and numblike (Nbl), two highly conserved homologues of Drosophila numb, play redundant but critical roles in maintaining neural progenitor cells during embryogenesis, by allowing their progenies to choose progenitor over neuronal fates. In Nbl mutant embryos also conditionally mutant for mouse numb in the nervous system, early neurons emerge in the expected spatial and temporal pattern, but at the expense of progenitor cells, leading to a nearly complete depletion of dividing cells shortly after the onset of neurogenesis. Our findings show that a shared molecular mechanism, with mouse Numb and Nbl as key components, governs the self-renewal of all neural progenitor cells, regardless of their lineage or regional identities.

Nuclear spin relaxation by intermolecular magnetic dipole coupling in the gas phase. 129Xe in oxygen

The nuclear spin relaxation times (T1) of 129Xe in xenon–O2 gas mixtures have been measured as a function of temperature and density at different magnetic fields. This system is used to characterize the intermolecular dipolar relaxation of nuclear spins in the gas phase. An empirical Boltzmann‐averaged collision cross section associated with the collision‐induced transitions between 129Xe nuclear spin states is obtained as a function of temperature.

Mycoplasma, Ureaplasma, and Adverse Pregnancy Outcomes: A Fresh Look

Recent work on the Molicutes that associate with genital tract tissues focuses on four species that may be of interest in potential maternal, fetal, and neonatal infection and in contributing to adverse pregnancy outcomes. Mycoplasma hominis and Ureaplasma urealyticum have historically been the subject of attention, but Mycoplasma genitalis which causes male urethritis in addition to colonizing the female genital tract and the division of Ureaplasma into two species, urealyticum and parvum, has also added new taxonomic clarity. The role of these genital tract inhabitants in infection during pregnancy and their ability to invade and infect placental and fetal tissue is discussed. In particular, the role of some of these organisms in prematurity may be mechanistically related to their ability to induce inflammatory cytokines, thereby triggering pathways leading to preterm labor. A review of this intensifying exploration of the mycoplasmas in relation to pregnancy yields several questions which will be important to examine in future research.

Pseudoaneurysm of the uterine artery.

BACKGROUND Preexisting aneurysms in several arterial locations have been associated with an increased risk of rupture in pregnancy. We report a rare case of uterine artery pseudoaneurysm that presented during the puerperium. CASE A 31-year-old woman had moderate suprapubic pain on postpartum day 8. The diagnosis of uterine artery aneurysm was made by duplex Doppler sonography and confirmed by arteriography. It was successfully treated by embolization of the left uterine artery. CONCLUSION In a rare case of pseudoaneurysm of the uterine artery, the complications of pregnancy-related aneurysmal rupture were prevented by prompt sonographic diagnosis and embolization therapy.

Progesterone Interactions with the Cervix: Translational Implications for Term and Preterm Birth

The uterine cervix plays a vital role in maintaining pregnancy and an equally important role in allowing parturition to occur. Progesterone, either endogenously produced or supplied exogenously, supports the function of the cervix in sustaining intrauterine pregnancy, and the withdrawal of progesterone, either through natural processes or pharmacologic intervention, leads to delivery which underscores the importance of the progesterones biological activities manifest in normal gestation and pregnancy that ends prematurely. Research crossing many scientific disciplines has demonstrated that progesterone is a pleotropic compound that affects the cervix through cytoplasmic and membrane receptors with profound effects on cellular and molecular functions that influence inflammatory cascades and extracellular matrix, both of which have consequences for parturition. Beyond the local cell and molecular biology of progesterone, it has systemic effects of relevance to pregnancy as well. This paper examines the biology of the cervix from its gross to cellular structure and biological activities of its cell and molecular processes that may be affected by progesterone. The implications of these processes for preterm birth are explored, and direction of current research is in relation to translational medicine implications for diagnostic, prognostic, and therapeutic approaches to threatened preterm birth.

A recombinogenic targeting method to modify large-inserts for cis-regulatory analysis in transgenic mice: construction and expression of a 100-kb, zebrafish Hoxa-11b-lacZ reporter gene

Abstract The identification of cis-sequences responsible for spatiotemporal patterns of gene expression often requires the functional analysis of large genomic regions. In this study a 100-kb zebrafish Hoxa-11b-lacZ reporter gene was constructed and expressed in transgenic mice. PAC clone 10-O19, containing a portion of the zebrafish HoxA-b cluster, was captured into the yeast-bacterial shuttle vector, pPAC-ResQ, by recombinogenic targeting. A lacZ reporter gene was then inserted in-frame into exon 1 of the zfHoxa-11b locus by a second round of recombinogenic targeting. Expression of the zfHoxa-11b-lacZ reporter gene in 10.5 d.p.f. transgenic mouse embryos was observed only in the posterior portion of the A-P axis, in the paraxial mesoderm, neural tube, and somites. These findings demonstrate the utility of recombinogenic targeting for the modification and expression of large inserts captured from P1/PAC clones.

Cross sections for the anisotropic interaction of NNO with various molecules

Cross sections for the relaxation of the rotational angular momentum vector of the NNO molecule on collision with CO, Ar, CO2, NNO, Kr, CF4, and Xe, have been measured by 15N spin relaxation in 15N15NO molecules. The relaxation times of the two nuclei are in a ratio 1.86, independent of density, collision partner, or temperature. Except for Ar and CO, the cross sections are larger than the hard sphere cross sections and their temperature dependences range from T−0.8 to T−1.0.

19F nuclear spin relaxation by intermolecular magnetic dipole coupling. CF4 and SiF4 in oxygen gas

The 19F spin relaxation in CF4 in oxygen gas and in SiF4 in oxygen gas has been measured as a function of density, temperature, and magnetic field. The spin–rotation (intramolecular) and the nuclear spin dipole–electron spin dipole interactions (intermolecular) are the dominant mechanisms. The field dependence of the dipolar relaxation rates is characterized for CF4–O2 and SiF4–O2, and compared with those for other spherical top‐O2 systems. Agreement of theoretical estimates with the observed field dependence is satisfactory. The temperature dependences of the collision efficiencies for the CF4–O2 and SiF4–O2 intermolecular relaxation have been determined. The magnitudes are found to be roughly three times that for hard spheres.

Sonographic prenatal diagnosis of congenital Marfan syndrome

Congenital Marfan syndrome is a rare and severe disease of the newborn, causing devastating and often fatal effects on the cardiovascular, pulmonary, and musculoskeletal systems. Familial mutations of FBN1 have been studied and identified in Marfan syndrome, but the congenital variant is often due to de novo mutations, limiting the diagnostic capabilities of genetic screening. Ultrasound is essential for early diagnosis and management, yet few cases of sonographic diagnosis have been cited in the literature. This report outlines one such case of congenital Marfan syndrome diagnosed at 24week ultrasound. Further detailed reports should aim to improve screening, diagnosis, and treatment of congenital Marfan syndrome to advance options in family planning and disease management.