rasiRNAs, DNA damage, and embryonic axis specification.

Drosophila repeat-associated small interfering RNAs (rasiRNAs) have been implicated in retrotransposon and stellate locus silencing. However, mutations in the rasiRNA pathway genes armitage, spindle-E, and aubergine disrupt embryonic axis specification, triggering defects in microtubule organization and localization of osk and grk mRNAs during oogenesis. We show that mutations in mei-41 and mnk, which encode ATR and Chk2 kinases that function in DNA damage signal transduction, dramatically suppress the cytoskeletal and RNA localization defects associated with rasiRNA mutations. In contrast, stellate and retrotransposon silencing are not restored in mei-41 and mnk double mutants. We also find that armitage, aubergine, and spindle-E mutations lead to germ-line-specific accumulation of gamma-H2Av foci, which form at DNA double-strand breaks, and that mutations in armi lead to Chk2-dependent phosphorylation of Vasa, an RNA helicase required for axis specification. The Drosophila rasiRNA pathway thus appears to suppress DNA damage in the germ line, and mutations in this pathway block axis specification by activating an ATR/Chk2-dependent DNA damage response that disrupts microtubule polarization and RNA localization.

A mechanism of separation in electrostatic ion chromatography.

The retention mechanism of electrostatic ion chromatography (EIC) is currently under debate and is the focus of this paper. A comprehensive set of retention data has been obtained on a C18 column coated with the zwitterionic surfactant 3-(N,N-dimethylmyristylammonio)propanesulfonate used with a range of mobile phases in which both the mobile-phase anion and cation have been varied systematically. Electro-osmotic flow measurements were also obtained on fused-silica capillaries coated with the zwitterion (and also some monofunctional surfactants) and were used to evaluate the nature of the surface charge on the layer of adsorbed surfactant in the presence of various background electrolytes. A new retention mechanism for EIC was developed on the basis of these data. This mechanism proposes that equilibration of the bound zwitterions with a mobile phase containing a suitable electrolyte causes the establishment of a charged layer created by the terminal sulfonate groups of the zwitterion, which acts as a Donnan membrane. The magnitude and polarity of the charge on this membrane depends on the nature of the mobile-phase ions. The Donnan membrane exerts weak electrostatic repulsion or attraction effects on analyte anions. A second component of the retention mechanism is chaotropic interaction of the analyte anion with the quaternary ammonium functional group of the zwitterion. This interaction exerts the major effect on the separation selectivity of EIC, such that analyte anions are eluted in order of increasing chaotropic interactions in accordance with the Hofmeister series.

Analysis of inorganic anions by electrostatic ion chromatography using zwitterionic/cationic mixed micelles as the stationary phase.

The inability to separate fluoride, phosphate and sulfate by electrostatic ion chromatography (EIC) was overcome by using an ODS silica column coated with mixed zwitterionic-cationic surfactants as the stationary phase. The best results were obtained using the zwitterionic surfactant, 3-(N,N-dimethylmyristylammonium)-propanesulfonate (C19H41NO3S), and the cationic surfactant, myristyltrimethylammonium, CH3(CH2)13N+(CH3)3, in a 10:1 molar ratio in the column coating solution. With a dilute solution of sodium tetraborate as the eluent the model analyte anions were completely separated in the following elution order: F, HPO42-, SO42-, Cl-, NO2-, Br-, NO3-. The very early elution of phosphate and sulfate is most unusual and is unique to this system. Detection limits better than 1.1 x 10(-4) mM and linear calibration plots up to 7.0 mM were obtained with a suppressed conductivity system.

High prevalence of RET/PTC rearrangements in Ukrainian and Belarussian post-Chernobyl thyroid papillary carcinomas: a strong correlation between RET/PTC3 and the solid-follicular variant.

A sharp increase in the incidence of pediatric thyroid papillary cancer was documented after the Chernobyl power plant explosion. An increased prevalence of rearrangements of the RET protooncogene (RET/PTC rearrangements) has been reported in Belarussian post-Chernobyl papillary carcinomas arising between 1990 and 1995. We analyzed 67 post-Chernobyl pediatric papillary carcinomas arising in 1995-1997 for RET/PTC activation: 28 were from Ukraine and 39 were from Belarus. The study, conducted by a combined immunohistochemistry and RT-PCR approach, demonstrated a high frequency (60.7% of the Ukrainian and 51.3% of the Belarussian cases) of RET/PTC activation. A strong correlation was observed between the solid-follicular subtype of papillary carcinoma and the RET/PTC3 isoform: 19 of the 24 RET/PTC-positive solid-follicular carcinomas harbored a RET/PTC3 rearrangement, whereas only 5 had a RET/PTC1 rearrangement. Taken together these results support the concept that RET/PTC activation plays a central role in the pathogenesis of thyroid papillary carcinomas in both Ukraine and Belarus after the Chernobyl accident.

Overproduction of SecA suppresses the export defect caused by a mutation in the gene encoding the Escherichia coli export chaperone secB.

SecB is a cytosolic protein required for rapid and efficient export of particular periplasmic and outer membrane proteins in Escherichia coli. SecB promotes export by stabilizing newly synthesized precursor proteins in a nonnative conformation and by targeting the precursors to the inner membrane. Biochemical studies suggest that SecB facilitates precursor targeting by binding to the SecA protein, a component of the membrane-embedded translocation apparatus. To gain more insight into the functional interaction of SecB and SecA, in vivo, mutations in the secA locus that compensate for the export defect caused by the secB missense mutation secBL75Q were isolated. Two suppressors were isolated, both of which led to the overproduction of wild-type SecA protein. In vivo studies demonstrated that the SecBL75Q mutant protein releases precursor proteins at a lower rate than does wild-type SecB. Increasing the level of SecA protein in the cell was found to reverse this slow-release defect, indicating that overproduction of SecA stimulates the turnover of SecBL75Q-precursor complexes. These findings lend additional support to the proposed pathway for precursor targeting in which SecB promotes targeting to the translocation apparatus by binding to the SecA protein.

Effects of electrical stimulation on lymphatic flow and limb volume in the rat.

BACKGROUND AND PURPOSE: The mechanism by which electrical stimulation affects edema has not been elucidated. The purpose of this study was to determine whether subcontraction high-voltage stimulation (SC-HVS) (ie, electrical stimulation that did not elicit a visible contraction) applied to the right hind limbs of rats would (1) alter the rate of lymphatic uptake of injected albumin labeled with Evans blue dye (AL-EBD) and (2) affect experimentally induced edema. SUBJECTS AND METHODS: The paws of 28 anesthetized Sprague-Dawley rats (mean weight = 263 g, SD = 48 g) were injected with AL-EBD. The experimental group (n = 13) received 1 hour of SC-HVS, and the control group (n = 15) received sham treatment consisting of the same treatment administered to the experimental group but without the SC-HVS. Blood samples and volume measurements were obtained at intervals over a 7-hour period. RESULTS: Analysis of variance and post hoc testing indicated that higher amounts of AL-EBD were taken up by the lymph of the experimental group animals as compared with the control group animals at each time period following the treatment. The experimental group's AL-EBD reached significance immediately after treatment, whereas the control group required an additional 4 hours. There was no significant reduction in limb volume in either group. CONCLUSION AND DISCUSSION: The SC-HVS significantly increased the uptake of AL-EBD by lymphatic vessels, but it did not cause a significant decrease in the induced edema. The results of this study indicate that SC-HVS has the potential to reduce edema by increasing lymphatic uptake of proteins.

Experience with external cephalic version and selective vaginal breech delivery in private practice.

OBJECTIVE: The purpose of this study was to decrease the rate of cesarean delivery for breech presentation through use of a protocol that calls for external cephalic version and selected vaginal delivery of the infant in breech position. STUDY DESIGN: I offered external cephalic version to patients whose fetuses were in the breech position beyond 36 weeks' gestation and who were not in active labor. Patients in active labor were included in the review if they agreed to a trial of labor. RESULTS: Sixty-five deliveries were included in this review. The success rate of the version procedure was 53%. Among patients in whom version was successful 28% required cesarean delivery. Of those remaining breech fetuses believed to be candidates for vaginal delivery, 80% were successfully delivered vaginally. The overall vaginal delivery rate was 31 of 65 deliveries, or 48%. CONCLUSION: Protocols that call for external cephalic version with vaginal delivery of selected fetuses in breech presentation that either do not respond to or are not candidates for version can be used in the private practice setting. Such protocols should result in a decreased number of cesarean sections.

Aneurysmal subarachnoid hemorrhage: neurosurgical frontiers and nursing challenges.

Despite increases in survival beyond the initial hemorrhage, the devastating consequences of subarachnoid hemorrhage persist. Ruptured intracranial aneurysms are the most likely cause of subarachnoid hemorrhage, with morbidity and mortality rates approaching 75%. Complications arising from aneurysmal subarachnoid hemorrhage include rebleeding, delayed cerebral ischemia, hydrocephalus, hypothalamic dysfunction, and seizure activity. In order to positively influence outcome after subarachnoid hemorrhage, preservation of an adequate cerebral blood flow and prevention of secondary aneurysmal rupture is essential. This article reviews aneurysmal subarachnoid hemorrhage, relating the management of complications to currently accepted treatment strategies.

Cerebral angioplasty: a new treatment for vasospasm secondary to subarachnoid hemorrhage.

The potential benefit of cerebral angioplasty for patients with delayed cerebral ischemia secondary to vasospasm is promising. Cerebral angioplasty has the potential for positively affecting patient outcome and quality of life. Further, cerebral angioplasty may lead to a reduction in long-term care needs for patients who experience severe cerebral vasospasm from an aneurysmal subarachnoid hemorrhage. The challenge to the neuroscience nurse begins with the early detection of neurological changes signaling the onset of progressive delayed cerebral ischemia despite conventional therapies for vasospasm. The nurse's sagacious management of neurologic, hemodynamic and pulmonary status and the ongoing support of the patient and family throughout the angioplasty procedure is crucial to a positive outcome.