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At least 469 records · Page 26Linked to original sources
PubMed2006

Ex utero intrapartum treatment (EXIT) for congenital giant ranula.

UNLABELLED: Congenital giant ranula causing life-threatening upper airway obstruction is a rare condition. A well-planned ex utero intrapartum treatment (EXIT) procedure for aspiration and decompression of the cystic lesion is simple, efficacious and effective in securing a patent airway before the fetus is completely delivered, and may prevent lifelong neurodevelopmental complications associated with perinatal asphyxia in such cases. CONCLUSION: EXIT could be a life-saving procedure for congenital giant ranula.

Adult↗
PubMed1993

GLUT2 surface expression and intracellular transport via the constitutive pathway in pancreatic beta cells and insulinoma: evidence for a block in trans-Golgi network exit by brefeldin A.

The biosynthesis, intracellular transport, and surface expression of the beta cell glucose transporter GLUT2 was investigated in isolated islets and insulinoma cells. Using a trypsin sensitivity assay to measure cell surface expression, we determined that: (a) greater than 95% of GLUT2 was expressed on the plasma membrane; (b) GLUT2 did not recycle in intracellular vesicles; and (c) after trypsin treatment, reexpression of the intact transporter occurred with a t1/2 of approximately 7 h. Kinetics of intracellular transport of GLUT2 was investigated in pulse-labeling experiments combined with glycosidase treatment and the trypsin sensitivity assay. We determined that transport from the endoplasmic reticulum to the trans-Golgi network (TGN) occurred with a t1/2 of 15 min and that transport from the TGN to the plasma membrane required a similar half-time. When added at the start of a pulse-labeling experiment, brefeldin A prevented exit of GLUT2 from the endoplasmic reticulum. When the transporter was first accumulated in the TGN during a 15-min period of chase, but not following a low temperature (22 degrees C) incubation, addition of brefeldin A (BFA) prevented subsequent surface expression of the transporter. This indicated that brefeldin A prevented GLUT2 exit from the TGN by acting at a site proximal to the 22 degrees C block. Together, these data demonstrate that GLUT2 surface expression in beta cells is via the constitutive pathway, that transport can be blocked by BFA at two distinct steps and that once on the surface, GLUT2 does not recycle in intracellular vesicles.

Animals↗
PubMed1997

MAP kinase is required for the spindle assembly checkpoint but is dispensable for the normal M phase entry and exit in Xenopus egg cell cycle extracts.

In Xenopus laevis egg cell cycle extracts that mimic early embryonic cell cycles, activation of MAP kinase and MAP kinase kinase occurs in M phase, slightly behind that of maturation promoting factor. To examine the possible role of MAP kinase in the in vitro cell cycle, we depleted the extracts of MAP kinase by using anti-Xenopus MAP kinase antibody. Like in the mock-treated extracts, the periodic activation and deactivation of MPF occurred normally in the MAP kinase-depleted extracts, suggesting that MAP kinase is dispensable for the normal M phase entry and exit in vitro. It has recently been reported that microtubule depolymerization by nocodazole treatment can block exit from mitosis in the extracts if enough sperm nuclei are present, and that the addition of MAP kinase-specific phosphatase MKP-1 overcomes this spindle assembly checkpoint, suggesting the involvement of MAP kinase in the checkpoint signal transduction. We show here that the spindle assembly checkpoint mechanism cannot operate in the MAP kinase-depleted extracts. But, adding recombinant Xenopus MAP kinase to the MAP kinase-depleted extracts restored the spindle assembly checkpoint. These results indicate unambiguously that classical MAP kinase is required for the spindle assembly checkpoint in the cell cycle extracts. In addition, we show that strong activation of MAP kinase by the addition of a constitutively active MAP kinase kinase kinase in the absence of sperm nuclei and nocodazole, induced mitotic arrest in the extracts. Therefore, activation of MAP kinase alone is sufficient for inducing the mitotic arrest in vitro.

Animals↗
PubMed1999

Roles for alpha(2)p24 and COPI in endoplasmic reticulum cargo exit site formation.

A two-step reconstitution system for the generation of ER cargo exit sites from starting ER-derived low density microsomes (LDMs; 1.17 g/cc) is described. The first step is mediated by the hydrolysis of Mg(2+)ATP and Mg(2+)GTP, leading to the formation of a transitional ER (tER) with the soluble cargo albumin, transferrin, and the ER-to-Golgi recycling membrane proteins alpha(2)p24 and p58 (ERGIC-53, ER-Golgi intermediate compartment protein) enriched therein. Upon further incubation (step two) with cytosol and mixed nucleotides, interconnecting smooth ER tubules within tER transforms into vesicular tubular clusters (VTCs). The cytosolic domain of alpha(2)p24 and cytosolic COPI coatomer affect VTC formation. This is deduced from the effect of antibodies to the COOH-terminal tail of alpha(2)p24, but not of antibodies to the COOH-terminal tail of calnexin on this reconstitution, as well as the demonstrated recruitment of COPI coatomer to VTCs, its augmentation by GTPgammaS, inhibition by Brefeldin A (BFA), or depletion of beta-COP from cytosol. Therefore, the p24 family member, alpha(2)p24, and its cytosolic coat ligand, COPI coatomer, play a role in the de novo formation of VTCs and the generation of ER cargo exit sites.

Adenosine Triphosphate↗
PubMed2002

The Saccharomyces cerevisiae Mob2p-Cbk1p kinase complex promotes polarized growth and acts with the mitotic exit network to facilitate daughter cell-specific localization of Ace2p transcription factor.

The Saccharomyces cerevisiae mitotic exit network (MEN) is a conserved signaling network that coordinates events associated with the M to G1 transition. We investigated the function of two S. cerevisiae proteins related to the MEN proteins Mob1p and Dbf2p kinase. Previous work indicates that cells lacking the Dbf2p-related protein Cbk1p fail to sustain polarized growth during early bud morphogenesis and mating projection formation (Bidlingmaier, S., E.L. Weiss, C. Seidel, D.G. Drubin, and M. Snyder. 2001. Mol. Cell. Biol. 21:2449-2462). Cbk1p is also required for Ace2p-dependent transcription of genes involved in mother/daughter separation after cytokinesis. Here we show that the Mob1p-related protein Mob2p physically associates with Cbk1p kinase throughout the cell cycle and is required for full Cbk1p kinase activity, which is periodically activated during polarized growth and mitosis. Both Mob2p and Cbk1p localize interdependently to the bud cortex during polarized growth and to the bud neck and daughter cell nucleus during late mitosis. We found that Ace2p is restricted to daughter cell nuclei via a novel mechanism requiring Mob2p, Cbk1p, and a functional nuclear export pathway. Furthermore, nuclear localization of Mob2p and Ace2p does not occur in mob1-77 or cdc14-1 mutants, which are defective in MEN signaling, even when cell cycle arrest is bypassed. Collectively, these data indicate that Mob2p-Cbk1p functions to (a) maintain polarized cell growth, (b) prevent the nuclear export of Ace2p from the daughter cell nucleus after mitotic exit, and (c) coordinate Ace2p-dependent transcription with MEN activation. These findings may implicate related proteins in linking the regulation of cell morphology and cell cycle transitions with cell fate determination and development.

Active Transport, Cell Nucleus↗
PubMed2003

Budding yeast PAK kinases regulate mitotic exit by two different mechanisms.

We report the characterization of the dominant-negative CLA4t allele of the budding yeast CLA4 gene, encoding a member of the p21-activated kinase (PAK) family of protein kinases, which, together with its homologue STE20, plays an essential role in promoting budding and cytokinesis. Overproduction of the Cla4t protein likely inhibits both endogenous Cla4 and Ste20 and causes a delay in the onset of anaphase that correlates with inactivation of Cdc20/anaphase-promoting complex (APC)-dependent proteolysis of both the cyclinB Clb2 and securin. Although the precise mechanism of APC inhibition by Cla4t remains to be elucidated, our results suggest that Cla4 and Ste20 may regulate the first wave of cyclinB proteolysis mediated by Cdc20/APC, which has been shown to be crucial for activation of the mitotic exit network (MEN). We show that the Cdk1-inhibitory kinase Swe1 is required for the Cla4t-dependent delay in cell cycle progression, suggesting that it might be required to prevent full Cdc20/APC and MEN activation. In addition, inhibition of PAK kinases by Cla4t prevents mitotic exit also by a Swe1-independent mechanism impinging directly on the MEN activator Tem1.

Anaphase↗
PubMed2006

Disappearance of the budding yeast Bub2-Bfa1 complex from the mother-bound spindle pole contributes to mitotic exit.

Budding yeast spindle position checkpoint is engaged by misoriented spindles and prevents mitotic exit by inhibiting the G protein Tem1 through the GTPase-activating protein (GAP) Bub2/Bfa1. Bub2 and Bfa1 are found on both duplicated spindle pole bodies until anaphase onset, when they disappear from the mother-bound spindle pole under unperturbed conditions. In contrast, when spindles are misoriented they remain symmetrically localized at both SPBs. Thus, symmetric localization of Bub2/Bfa1 might lead to inhibition of Tem1, which is also present at SPBs. Consistent with this hypothesis, we show that a Bub2 version symmetrically localized on both SPBs throughout the cell cycle prevents mitotic exit in mutant backgrounds that partially impair it. This effect is Bfa1 dependent and can be suppressed by high Tem1 levels. Bub2 removal from the mother-bound SPB requires its GAP activity, which in contrast appears to be dispensable for Tem1 inhibition. Moreover, it correlates with the passage of one spindle pole through the bud neck because it needs septin ring formation and bud neck kinases.

Alleles↗
PubMedDate not supplied

Thermoregulation in juvenile red kangaroos (Macropus rufus) after pouch exit: higher metabolism and evaporative water requirements.

The population dynamics of red kangaroos (Macropus rufus) in the Australian arid zone is tightly linked with environmental factors, which partly operate via the survival of juvenile animals. A crucial stage is the young-at-foot (YAF) stage when kangaroos permanently exit the pouch. We have examined the thermal biology of YAF red kangaroos during ages from permanent pouch exit until weaning. Over a wide range of environmental temperatures (ambient temperature [T(a)] -5 degrees to 45 degrees C), YAF red kangaroos had a mass-specific metabolism that was generally twice that of adults, considerably higher than would be expected for an adult marsupial of their body size. The total energy requirements of YAF red kangaroos were 60%-70% of those of adult females, which were three times their size. Over the same range in T(a), YAF red kangaroos also had total evaporative water losses equal to those of adult females. At the highest T(a) (45 degrees C), differences were noted in patterns of dry heat loss (dry conductance) between YAF red kangaroos and adult females, which may partially explain the relatively high levels of evaporative cooling by YAF. By weaning age, young kangaroos showed little change in their basal energy and water requirements (at T(a) 25 degrees C) but did show reduced mass-specific costs in terms of energy and water use at extremes of T(a) (-5 degrees and 45 degrees C, respectively). In their arid environment, typified by unpredictable rainfall and extremes of T(a), young red kangaroos may need to remain close to water points, which, in turn, may restrict their ability to find the high-quality forage needed to meet their high energy demands.

Adaptation, Physiological↗
PubMed2005

Carbohydrate- and conformation-dependent cargo capture for ER-exit.

Some secretory proteins leave the endoplasmic reticulum (ER) by a receptor-mediated cargo capture mechanism, but the signals required for the cargo-receptor interaction are largely unknown. Here, we describe a novel targeting motif that is composed of a high-mannose type oligosaccharide intimately associated with a surface-exposed peptide beta-hairpin loop. The motif accounts for lectin ERGIC-53-assisted ER-export of the lyososomal enzyme procathepsin Z. The second oligosaccharide chain of procathepsin Z exhibits no binding activity for ERGIC-53, illustrating the selective lectin properties of ERGIC-53. Our data suggest that the conformation-based motif is only present in fully folded procathepsin Z and that its recognition by ERGIC-53 reflects a quality control mechanism that acts complementary to the primary folding machinery in the ER. A similar oligosaccharide/beta-hairpin loop structure is present in cathepsin C, another cargo of ERGIC-53, suggesting the general nature of this ER-exit signal. To our knowledge this is the first documentation of an ER-exit signal in soluble cargo in conjunction with its decoding by a transport receptor.

Amino Acid Motifs↗
PubMed2005

GMx33 associates with the trans-Golgi matrix in a dynamic manner and sorts within tubules exiting the Golgi.

The trans-Golgi matrix consists of a group of proteins dynamically associated with the trans-Golgi and thought to be involved in anterograde and retrograde Golgi traffic, as well as interactions with the cytoskeleton and maintenance of the Golgi structure. GMx33 is localized to the cytoplasmic face of the trans-Golgi and is also present in a large cytoplasmic pool. Here we demonstrate that GMx33 is dynamically associated with the trans-Golgi matrix, associating and dissociating with the Golgi in seconds. GMx33 can be locked onto the trans-Golgi matrix by GTPgammaS, indicating that its association is regulated in a GTP-dependent manner like several other Golgi matrix proteins. Using live-cell imaging we show that GMx33 exits the Golgi associated with tubules and within these tubules GMx33 segregates from transmembrane proteins followed by fragmentation of the tubules into smaller tubules and vesicles. Within vesicles produced by an in vitro budding reaction, GMx33 remains segregated in a matrixlike tail region that sometimes contains Golgin-245. This trans-matrix often links a few vesicles together. Together these data suggest that GMx33 is a member of the trans-Golgi matrix and offer clues regarding the role of the trans-Golgi matrix in sorting and exit from the Golgi.

Adenosine Triphosphate↗
PubMed2005

Overexpression of p27 Kip 1, probability of cell cycle exit, and laminar destination of neocortical neurons.

Neocortical projection neurons arise from a pseudostratified ventricular epithelium (PVE) from embryonic day 11 (E11) to E17 in mice. The sequence of neuron origin is systematically related to mechanisms that specify neuronal class properties including laminar fate destination. Thus, the neurons to be assembled into the deeper layers are the earliest generated, while those to be assembled into superficial layers are the later generated neurons. The sequence of neuron origin also correlates with the probability of cell cycle exit (Q) and the duration of G1-phase of the cell cycle (T(G1)) in the PVE. Both Q and T(G1) increase as neuronogenesis proceeds. We test the hypothesis that mechanisms regulating specification of neuronal laminar destination, Q and T(G1) are coordinately regulated. We find that overexpression of p27(Kip1) in the PVE from E12 to E14 increases Q but not T(G1) and that the increased Q is associated with a commensurate increase in the proportion of exiting cells that is directed to superficial layers. We conclude that mechanisms that govern specification of neocortical neuronal laminar destination are coordinately regulated with mechanisms that regulate Q and are independent of mechanisms regulatory to cell cycle duration. Moreover, they operate prior to postproliferative mechanisms necessary to neocortical laminar assembly.

Algorithms↗
PubMed1998

The polo-like kinase Plx1 is required for M phase exit and destruction of mitotic regulators in Xenopus egg extracts.

Polo-like kinases (Plks), named after the Drosophila gene product polo, have been implicated in the regulation of multiple aspects of mitotic progression, including the activation of the Cdc25 phosphatase, bipolar spindle formation and cytokinesis. Genetic analyses performed in yeast and Drosophila suggest a function for Plks at late stages of mitosis, but biochemical data to support such a function in vertebrate organisms are lacking. Here we have taken advantage of Xenopus egg extracts for exploring the function of Plx1, a Xenopus Plk, during the cell cycle transition from M phase to interphase (I phase). We found that the addition of a catalytically inactive Plx1 mutant to M phase-arrested egg extracts blocked their Ca2+-induced release into interphase. Concomitantly, the proteolytic destruction of several targets of the anaphase-promoting complex and the inactivation of the Cdc2 protein kinase (Cdk1) were prevented. Moreover, the M to I phase transition could be abolished by immunodepletion of Plx1, but was restored upon the addition of recombinant Plx1. These results demonstrate that the exit of egg extracts from M phase arrest requires active Plx1, and they strongly suggest an important role for Plx1 in the activation of the proteolytic machinery that controls the exit from mitosis.

Anaphase-Promoting Complex-Cyclosome↗
PubMed2001

cdc42 regulates the exit of apical and basolateral proteins from the trans-Golgi network.

It is well established that Rho-GTPases regulate vesicle fusion and fission events at the plasma membrane through their modulatory role on the cortical actin cytoskeleton. In contrast, their effects on intracellular transport processes and actin pools are less clear. It was recently shown that cdc42 associates with the Golgi apparatus in an ARF-dependent manner, similarly to coat proteins involved in vesicle formation and to several actin-binding proteins. We report here that mutants of cdc42 inhibited the exit of basolateral proteins from the trans-Golgi network (TGN), while stimulating the exit of an apical marker, in two different transport assays. This regulation may result from modulation of the actin cytoskeleton, as GTPase-deficient cdc42 depleted a perinuclear actin pool that rapidly exchanges with exogenous fluorescent actin.

Actin Cytoskeleton↗
PubMed1997

The Swi5 transcription factor of Saccharomyces cerevisiae has a role in exit from mitosis through induction of the cdk-inhibitor Sic1 in telophase.

Deactivation of the B cyclin kinase (Cdc28/Clb) drives the telophase to G1 cell cycle transition. Here we investigate one of the control pathways than contributes to kinase deactivation, involving the cell cycle-regulated production of the cdk inhibition Sic1. We show that the cell cycle timing of SIC1 expression depends on the transcription factor Swi5, and that Swi5-dependent SIC1 expression begins during telophase. In contrast to Swi5, the related transcription factor Ace2, which can also induce SIC1 expression, is not active during telophase. The functional consequence of Swi5-regulated SIC1 expression in vivo is that both sic1 delta and swi5 delta strains have identical mitotic exit-related phenotypes. First, both are synthetically lethal with dbj2 delta, resulting in cell cycle arrest in telophase. Second, both are hypersensitive to overexpression of the B cyclin CLB2. Thus Swi5-dependent activation of the SIC1 gene contributes to the deactivation of the B cyclin kinase, and hence exit from mitosis.

CDC28 Protein Kinase, S cerevisiae↗
PubMed1997

Pathways to labor force exit: work transitions and work instability.

The purpose of this study is to examine alternative pathways to labor force exit among older men. Based on the life course perspective, we distinguish between crisp exits from the labor force, which are characterized as being unidirectional, and blurred transition patterns, which include repeated exists, entrances, and unemployment spells. Using longitudinal data from the 1984 Survey of Income and Program Participation, we find that one-quarter of the sample of men aged 55 to 74 at first interview experienced at least one transition in labor force status over a 28-month observation period. Fewer than half of these can be characterized as crisp exists from the labor force. Our multivariate analysis suggests that blurred transition patterns are likely part of an effort to maintain economic status in later life.

Age Factors↗
PubMed2000

Pathways to retirement: patterns of labor force participation and labor market exit among the pre-retirement population by race, Hispanic origin, and sex.

OBJECTIVES: This study examines the pre-retirement labor force participation behavior of Black, White, and Hispanic men and women to determine how patterns of labor market exit differ among groups. METHODS: We combine data from the first and second waves of the Health and Retirement Study and apply multinomial logit regression techniques to model labor force status in the first wave of the HRS and change over time. RESULTS: Black, Hispanic, and female elderly persons experience more involuntary job separation in the years immediately prior to retirement, and the resulting periods of joblessness often eventuate in "retirement" or labor force withdrawal. Minority disadvantage in human capital, health, and employment characteristics accounts for a large part of racial and ethnic differences in labor force withdrawal. Nevertheless, Black men and Hispanic women experience more involuntary labor market exits than Whites with similar socioeconomic and demographic characteristics. DISCUSSION: Workers most vulnerable to labor market difficulties during their youth confront formidable obstacles maintaining their desired level of labor force attachment as they approach their golden years. This has significant policy implications for the contours of gender and race/ethnic inequality among elderly persons, particularly as life expectancy and the size of the minority elderly population continue to increase.

Black or African American↗
PubMed2000

Outpatient CAPD catheter salvage for persistent exit-site/tunnel infection.

BACKGROUND: Partial replantation (i.e. replacement of the extraperitoneal portion of the catheter with creation of a new subcutaneous tunnel) has been suggested to avoid catheter removal in patients with persistent exit-site/tunnel infection (ESTI). However, published experience with this technique is limited. METHODS: Partial replantation was performed on an outpatient basis under local anesthesia for seven patients with persistent ESTI of >3 months duration. All patients resumed CAPD immediately following surgery. RESULTS: One patient had dialysate leakage less than 1 week after surgery that required catheter removal. The other patients had no complications and mean catheter survival following surgery was 7. 7 months (range 3.5-13 months). There was no recurrence of ESTI after surgery, although two patients presented with exit-site infection unrelated to the initial episode (i.e. different organism, long latency). Three other patients presented with episodes of peritonitis unrelated to surgery (i.e. delay >1 month) or ESTI (i.e. different organism). CONCLUSIONS: Partial replantation allows significant prolongation of catheter survival without major complications or interruption of CAPD. This novel procedure appears to be an appropriate alternative to catheter removal for the management of persistent ESTI. However, further studies are needed to prospectively compare partial replantation with catheter removal.

Aged↗
PubMed2003

Probation foster care as an outcome for children exiting child welfare foster care.

Little research has been done to help us understand what happens to children who exit child welfare foster care for reasons other than emancipation. Almost no research exists to help us understand out-of-home placement supervised by other providers of children's social services such as juvenile probation or mental health. This study examined school-age children who entered out-of-home placement supervised by probation departments after they left child welfare foster or group care. Instability in child welfare placements significantly increased the risk of a transition to probation foster care. Among the children exiting child welfare placements, those who had entered their first spell in care at ages 12 through 14 or were first removed because of sexual abuse or neglect were at greater risk of probation out-of-home placement. Implications for social work policy and services are discussed.

Adolescent↗