X-ray quasi-periodic eruptions from two previously quiescent galaxies.

Quasi-periodic eruptions (QPEs) are very-high-amplitude bursts of X-ray radiation recurring every few hours and originating near the central supermassive black holes of galactic nuclei1,2. It is currently unknown what triggers these events, how long they last and how they are connected to the physical properties of the inner accretion flows. Previously, only two such sources were known, found either serendipitously or in archival data1,2, with emission lines in their optical spectra classifying their nuclei as hosting an actively accreting supermassive black hole3,4. Here we report observations of QPEs in two further galaxies, obtained with a blind and systematic search of half of the X-ray sky. The optical spectra of these galaxies show no signature of black hole activity, indicating that a pre-existing accretion flow that is typical of active galactic nuclei is not required to trigger these events. Indeed, the periods, amplitudes and profiles of the QPEs reported here are inconsistent with current models that invoke radiation-pressure-driven instabilities in the accretion disk5-9. Instead, QPEs might be driven by an orbiting compact object. Furthermore, their observed properties require the mass of the secondary object to be much smaller than that of the main body10, and future X-ray observations may constrain possible changes in their period owing to orbital evolution. This model could make QPEs a viable candidate for the electromagnetic counterparts of so-called extreme-mass-ratio inspirals11-13, with considerable implications for multi-messenger astrophysics and cosmology14,15.

Interannual variability in Dinophysis spp. abundance and toxin accumulation in farmed mussels (Perna perna) in a subtropical estuary.

This study evaluated an 8-year dataset (2007 to 2015, except 2008) in the attempt to identify the most susceptible periods for the occurrence of diarrheic shellfish poisoning (DSP) episodes associated with the presence of toxigenic dinoflagellates, Dinophysis spp., in the mussel farming area of Babitonga Bay (southern Brazil). Dinophysis acuminata complex was the most frequent (present in 66% of the samples) and abundant (max. 4100 cells L-1) taxon, followed by D. caudata (14%; max. 640 cells L-1) and D. tripos (0.9%; max. 50 cells L-1). There was a marked onset of the annual rise in Dinophysis spp. abundance during weeks 21-25 (early winter) of each year, followed by a second peak on week 35 (spring). Mussel (Perna perna) samples usually started testing positive in DSP mouse bioassays (MBA) in late winter. Positive results were more frequent in 2007 and 2011 when the mean D. acuminata complex abundance was ~ 500 cells L-1. Although positive DSP-MBA results were observed in only 11% of the samples during the studied period, the toxin okadaic acid (OA) was present in 90% of the analyzed mussels (max. 264 µg kg-1). MBA results were positive when D. acuminata complex cell densities exceed 1200 ± 300 cells L-1, while trace toxin amounts could be detected at cell densities as low as 150 ± 50 cells L-1 (free OA) to 200 ± 100 cells L-1 (conjugated OA). Low salinity and the meteorological conditions triggered by La Niña events were the main factors associated with both Dinophysis abundance and OA accumulation in mussels.

[Pacemaker, defibrillator and co : Perioperative handling of cardiac implantable electronic devices]. / Schrittmacher, Defi & Co : Der perioperative Umgang mit "cardiac implantable electronic devices".

The number of patients treated with cardiac implantable electronic devices (CIED) is continously increasing. Knowledge of the medical indications and technical mode of functioning of these devices is a basic prerequisite for the safe perioperative care of this patient cohort. The CIEDs are subjected to a multitude of disturbing influences in the perioperative setting. This can result in potentially dangerous complications, such as exit block and oversensing. The safe performance of interventions is possible as long as some basic rules are followed. An interdisciplinary approach involving all participating disciplines is necessary in order to adequately deal with the high demands placed on the logistics.

[Pleural effusion cytology of asbestos-associated malignant mesothelioma and lung carcinoma in the diagnosis of occupational diseases by the statutory accident insurance funds]. / Zytopathologische Ergussdiagnostik in der berufsgenossenschaftlichen Begutachtung von Asbest-assoziierten malignen Mesotheliomen und Lungenkarzinomen.

Pleural effusion often represents the first clinical symptom of lung carcinoma and malignant mesothelioma. As pleural punctation is performed quite early in the diagnostic procedure, effusion cytology frequently gives the first evidence about the presence of tumour cells and tumor histogenesis. In this study, we report on seven cases which were evaluated in our institution for the Employers' Liability Insurance Association, based solely on cytology findings.The mean age of the seven patients with a given long-term asbestos exposure during their working life was 81.7 years. On average eight smears per patient were investigated. In addition to routine cytology, immunocytochemistry, DNA image cytometry, AgNOR-analysis and fluorescence in situ hybridization were applied in a case-specific way. The results were interpreted against the clinical and occupational history of the respective patient.Definitive diagnosis could be made in six cases. In three of them, the diagnosis of malignant mesothelioma was made. Two cases were diagnosed as malignant effusion due to metastatic lung cancer. In one case, cells of high-grade Non-Hodgkin's lymphoma (NHL) were diagnosed and a malignant mesothelioma was excluded. In the last case, malignant mesothelioma could not be diagnosed unequivocally by cytology. In all seven cases, our interpretation was accepted by Employers' Liability Insurance Association. The five mesothelioma or lung cancer cases were accepted as asbestos-associated occupational disease, while the NHL case was rejected. In the last case, malignant mesothelioma was diagnosed later by autopsy, and the case was retroactively accepted as occupational disease.Cytology-based tumor diagnosis including adjuvant methods is a useful and reliable approach in cases of asbestos-associated tumours. Acceptance of occupational disease on the basis of cytological diagnoses even by the Employers' Liability Insurance Association helps avoid invasive pleural or lung biopsies in cases with an unequivocally positive effusion cytology of lung cancer or malignant mesothelioma.

17-year follow-up of the rough-blasted threaded Weill cup in uncemented total hip arthroplasty.

INTRODUCTION: For uncemented hip arthroplasty, various cup designs are available. The threaded Weill acetabular component (Weill cup; Zimmer, Winterthur, Switzerland) has been used for more than 20 years, with poor results of the smooth threaded design. Our study was intended to assess the 17-year outcome of the rough-blasted option of the threaded Weill cup. MATERIALS AND METHODS: Between 1987 and 1988, a series of 86 rough-blasted threaded Weill cups were implanted in combination with the CLS Spotorno stem (Zimmer Ltd, Germany) The patients' mean age at the time of surgery was 50 years (range 19-67 years). 67 out of 86 hips (78%) were available for a follow-up at a mean of 17 years (range 16-18 years). Radiographs were available from 55 out of 63 unrevised hips (87%) and analyzed for radiolucency and PE wear. RESULTS: Two out of 86 cups (3%) were revised due to aseptic loosening and another two cups (3%) were awaiting revision for the same reason. Ten patients (10 cups, 12%) were lost to follow-up, and nine patients with nine cups (11%) had deceased without radiographic signs of cup failure. Cup survival with "revision or awaiting revision" as endpoint was 86% (95% CI 75-92%). No deep infections occurred, and no polyethylene insert was exchanged. The Harris hip score was excellent in 37 out of 67 clinically examined hips (55%), good in 18 hips (26%), satisfactory in 5 hips (8%) and moderate or poor in 5 hips (8%) and 2 hips (3%), respectively. CONCLUSION: The rough-blasted threaded Weill cup provides a good long-term performance in cementless total hip arthroplasty. The results compare favourably to the smooth threaded cup design.

Pneumorrhachis following cervical spine surgery.

A 66-year-old man experienced symptomatic pneumorrhachis (air within the spinal canal) following a cervical laminoplasty for the excision of meningioma. Following an uneventful intraoperative course, he suffered a fluctuating hemiparesis of varying severity. Urgent imaging demonstrated extradural and intradural air in the spinal canal. Treatment with supplemental oxygen and dexamethasone was commenced, and the patient's symptoms improved over a period of three days with full resolution at six weeks. Pneumorrhachis can be avoided by allowing air to escape from the spinal canal through positioning, and displacement with irrigation fluid at the time of wound closure. However, if pneumorrhachis does occur, oxygen therapy, positioning of the patient to mitigate the gravitational effect of the air bubbles and supportive treatment are the central elements of management. Other possible causes of neurological deficit should be ruled out. This is particularly important as treatment options for some differential diagnoses can potentially cause harm if started based on clinical impression alone, for example, re-exploration for suspected haematoma. Only a small number of previous reports have described symptomatic pneumorrhachis as a complication of spinal surgery. This patient was successfully managed with conservative measures following the exclusion of other spinal cord pathologies.

Retention of amylase in the secretory granules of parotid gland after extensive release of Ca++ by ionophore A-23187.

The effect of the ionophore A-23187 was tested on isolated secretory granules of rat parotid gland. The ionophore caused extensive release of calcium from the granules without effecting release of amylase or other secretory proteins. It is therefore concluded that the role of calcium in the granules is probably not that of a stabilizing agent.

Rapid release of the zymogen granule protein by osmium tetroxide and its retention during fixation by glutaraldehyde.

Fixation by osmium tetroxide and glutaraldehyde of zymogen granules isolated from rat parotid and pancreas was investigated. Protein determinations showed that osmium tetroxide caused rapid release of most of the soluble protein of the granule during fixation in buffered isotonic sucrose. Such granules when examined in the electron microscope after shadow casting appeared quite flat, indicating that most of the contents had indeed been removed. Numerous damaged membranes of the granules were also observed. In contrast, zymogen granules fixed by glutaraldehyde and shadow cast essentially retained the spherical shape and the protein contents. The application of the shadow-casting technique in quantitative studies on the protein content of zymogen granules is discussed.

Secretion of old versus new exportable protein in rat parotid slics. Control by neurotransmitters.

The possibility that old and new secretory granules do not mix and that older exportable protein can be secreted preferentially was tested on parotid gland in vitro. Slices from fasted animals were pulse labeled for 3 min with L-[3H]leucine. Subcellular fractionstion showed that after 1 90-min chase period, the formation of new labeled secretory granules was mostly completed. The ratio of label in secretory granules to label in microsomes increased 250-fold during the period 5--90 min postpulse. After the 90-min chase, a submaximal rate of secretion was initiated by adding a low concentration of isoproterenol to the slices. Preferential secretion of old unlabeled exportable protein was evident from the finding that the percent of total amylase secreted was 3.5-fold greater than the percent of labeled protein secreted. Preferential secretion of old unlabeled exportable amylase was undiminished even when the chase period before addition of isoproterenol was extended to 240 min. Such long chase incubations were still meaningful due to the fact that the spontaneous rat of amylase release and radioactive protein release from the slices was negligibly low. A high isoproterenol concentration added to the slices after a 90-min chase produced the following results. An initial phase of preferential secretion of old unlabeled protein was soon replaced by secretion of a random mixture of new and old exportable protein. Electron micrographs indicated that high rates of secretion involved sequential fusion of secretory granules so that the lumen extended deep into the cell where the new labeled granules were presumably located. At low rates of secretion, the lumen showed no such deep extensions. Experiments were also conducted on slices from glands which had been largely depleted of old granules by prior injection of isoproterenol into the animals. Secretion of labeled protein from such slices stopped with the export of 80% of the labeled protein. This finding indicates that about 20% of the radioactive protein is cellular nonexportable protein and that the slices are capable of exporting the entire amount of secretory protein which was symthesized in vitrol. In addition to the beta-adrenergic receptor which mediates protein secretion, the parotid acinar cell also possesses an alpha-adrenergic and a cholinergic receptor both of which cause K+ release, vacuole formation, and water secretion. Activation of either of the latter two receptors in conjunction with the beta-adrenergic receptor increased randomization of the protein secreted. It is concluded that in the rat parotid acinar cell there is little spontaneous mixing between old granules near the luminal cell membrane and new granules coming up behind from the Golgi complex. The neurotransmitters which induce secretion produce the observed randomization.

Dynamic changes in the ultrastructure of the acinar cell of the rat parotid gland during the secretory cycle.

Synchronization of the secretory cycle in vivo was obtained by injecting isoprenaline as an inducer of secretion. A quantitative correlation between enzyme release, its subsequent reaccumulation, and the sequence of ultrastructural changes was found. At the ultrastructural level secretion was paralleled by depletion of zymogen granules through fusion of the granule membrane with the lumen membrane and discharge of the content. Each zymogen granule membrane, once connected with the lumen, acted as a lumen membrane. Fusion was thus sequential and resulted in a dramatic enlargement of the lumen space. During the entire process the passage between the lumen and the intercellular space remained blocked by the tight junctions, as shown by their impenetrability to ferritin. Reduction of the lumen size following enzyme discharge seemed to be achieved by withdrawal of lumen membrane in the form of small smooth vesicles which appeared mostly in the apical part of the cell. At the same time, the cell retracted towards the lumen, the whole process being completed within 2 hr from onset of secretion. Disappearance of the smooth vesicle followed, concomitant with formation of many condensing vacuoles and appearance of mature zymogen granules. The fate of the zymogen granule membrane, including its fusion with the lumen membrane, resorption in the form of small smooth vesicles, and its eventual reutilization mediated by the Golgi system, is discussed.

Concomitant synthesis of membrane protein and exportable protein of the secretory granule in rat parotid gland.

After enzyme secretion the membrane of the secretory granule, which had been fused to the cell membrane, was resorbed into the cell. Experiments were therefore carried out to test whether formation of new secretory granules involves reutilization of the resorbed membrane or synthesis of a new membrane, de novo, from amino acids. Incorporation of amino acids-(14)C into proteins of various cell fractions was measured in vivo, 30, 120, and. 300 min after labeling. At all times the specific radioactivity of the secretory granule membrane was about equal to that of the granule's exportable content. At 120 and 300 min the specific radioactivity of the granule membrane and of the granule content was much higher than that of any other subcellular fraction. It is therefore concluded that the protein of the membrane is synthesized de novo concomitantly with the exportable protein. The proteins of the granule membrane could be distinguished from those of the granule content by gel electrophoresis. All major bands were labeled proportionately to their staining intensity. The amino acid composition of the secretory granule membrane was markedly different from that of the granule's content and also from that of the mitochondrial membrane. The granule membrane showed a high proline content, 30 moles/100 moles amino acids. The analyses show that the radioactivity of the granule membrane is indeed inherent in its proteins and is not due to contamination by other fractions. The possibility is considered that the exportable protein leaves the endoplasmic reticulum already enveloped by the newly synthesized membrane.

Message transmission: receptor controlled adenylate cyclase system.

The adenylate cyclase system is composed of an activating hormone or neurotransmitter (H), its receptor (R), the guanosine triphosphate (GTP) binding protein (Gs), and the catalytic unit (C). The activation of the receptor R involves a transient change in conformation, from a loose binding of the neurotransmitter H to an extremely tight interaction, termed locking. The system is regulated in the activation steps and also by three deactivation processes. A guanosine triphosphatase activity is built into the Gs protein so that the active GsGTP has only a limited lifetime during which it is able to activate C. In addition, the continued occupation of R by H causes desensitization of R. Finally, there are inhibitory receptors, such as alpha-adrenergic and opiate receptors, which inhibit the adenylate cyclase by way of a specific GTP binding protein (Gi). Yet to be determined are the conformational transformations of pure R on binding of an agonist or a partial agonist; the genes that code for the many different receptors that activate the adenylate cyclase, and the possibility that the G components interact with systems in the cell other than the adenylate cyclase.

Potassium ion release and enzyme secretion: adrenergic regulation by alpha- and beta-receptors.

Epinephrine caused amylase secretion and K(+) release in rat parotid slices. Propranolol, which blocks beta-receptors, inhibited amylase secretion; phentolamine, which blocks alpha-receptors, inhibited K(+) release. Since enzyme secretion was associated with fusion of secretory granules to the cell membrane and K(+) release was associated with vacuole formation, it could be shown that both alpha- and beta-receptors are present in the same exocrine cell. The findings appear to exclude cyclic 3',5'-adenosine monophosphate as an intermediate in the alpha-receptor response.

Non-parallel transport of membrane proteins and content proteins during assembly of the secretory granule in rat parotid gland.

The insertion of newly synthesized protein molecules into the membrane of the secretory granule of the rat parotid gland was studied by in vivo labeling with [3-H]-proline and [3-H]leucine. 2 h after the injection of the amino acid into the rat, the membrane fraction isolated from the secretory granules was found to be highly labeled with proline but only slightly labeled with leucine. The ratio of proline label in the granule membrane to that in the granule's secretory content was roughly equivalent to the ratio of total proline in the proteins of these two fractions. In contrast the ratio of leucine label in the membrane to that in the secretory content was much less than would be expected from the relative amount of leucine in both fractions. Separation of the proteins of the granule membrane by gel electrophoresis in presence of sodium dodecylsulfate showed that a considerable amount of these proteins was unlabeled. The labeled proteins could be selectively extracted from the membrane by 0.15 M Nacl solution or by dilute buffer at pH 4.5. These extracted proteins were found to contain a high proportion of proline residues and a negligible amount of leucine residues. In the extract proline constituted 36 mole % of the total amino acids. Proline plus glycine plus glutamic acid constituted more than 80 mole % and leucine constituted about 1 mole% of the total amino acids. Further analyses by gel electrophoresis in presence of sodium dodecylsulfate showed that the fractions of secretory granule membrane and secretory granule content are relatively free of contamination by proteins from other subcellular structures. It is suggested that the proteins which will constitute the mature secretory granule are transported to the site of final assembly by two pathways. The proline-rich proteins are transported to the site of assembly in close coordination with all the exportable proteins. The other membrane proteins arrive by a different pathway. Two alternative mechanisms are suggested to explain the finding that a considerable part of the membrane proteins are not labeled. I. The pathway of the intracellular transport of the unlabeled membrane proteins is similar to that of the secretory proteins but the newly synthesized membrane protein molecules are diluted in a large intermediate pool--the GOLgi complex. II. The proteins that did not get labeled are derived by a process of reutilization, from membranes of granules which have previously discharged their content in the process of secretion.

The proteins of the content of the secretory granules of the rat parotid gland.

The proteins of the secretory granules of the rat parotid gland were characterized by sodium dodecylsulfate gel electrophoresis, by chromatography of [3-H]proline-labeled proteins on DEAE-cellulose and by amino acid analysis. Sodium dodecylsulfate gel electrophoresis of the secretory granule content showed five principal proteins and a limited number of minor components. Only two of the principal bands could be identified as known secretory enzymes of the parotid gland. One was identified as the alpha-amylase and one as deoxyribonuclease. Peroxidase and ribonuclease form minor portions of the secretory proteins. The other three major proteins constitute, together, about 60% by weight, of the secretory granule content proteins. Of these, one which represents more than 30% of the total granule protein was found to contain uniquely high amounts of leucine residues (21 mole%). Another one of these principal proteins was relatively rich in cysteine residues (7 mole%). The fifth principal protein was found to contain high amounts of proline (28 mole%) glutamic acid (17 mole%) and glycine (18 mole%) residues. Its amino acid composition was very similar to that of the proline-se granules. This protein, however, differed from the "membranous" proline-rich proteins by several criteria. Two minor glycoproteins of the secretory granule content were also found to be rich in proline residues (37 mole%). As with the other proline-rich proteins of the granule, they contained no sulphur-containing amino acids, stained faintly pink with Coomassie Blue and were underestimated by the Lowry method. They differ however, from all the other proline-rich proteins of the granule by having a significantly higher content of threonine, less glycine (9 mole%) and much less glutamic acid (3 mole%). Of the principal proteins, only the deoxyribonuclease and the half-cystine-rich proteins were positively stained by periodic acid Schiff staining. The possible functions of the leucine-rich, the half cystine-rich and the various proline-rich proteins are discussed.

Factors influencing the difference between maternal and cord blood lead.

AIMS: To determine the factors that affect why some infants receive higher exposures relative to the mother's body burden than do others. METHODS: A total of 159 mother-infant pairs from a cohort of women receiving prenatal care at Magee-Womens Hospital in Pittsburgh, PA from 1992 to 1995 provided blood samples at delivery for lead determination. The difference between cord and maternal blood lead concentration (PbB) and a dichotomous variable indicator of higher cord than maternal PbB, were examined as indicators of relative transfer. Women were interviewed twice during the pregnancy about lifestyle, medical history, calcium nutrition, and physical activity. RESULTS: Higher blood pressure was associated with relatively greater cord compared with maternal PbB, as was maternal alcohol use. Sickle cell trait and higher haemoglobin were associated with a lower cord relative to maternal blood lead PbB. No association was seen with smoking, physical exertion, or calcium consumption. CONCLUSION: While reduction in maternal exposure will reduce fetal exposure, it may also be possible to mitigate infant lead exposure by reducing transfer from the pregnant woman. Interventions aimed at reducing blood pressure and alcohol consumption during pregnancy may be useful in this regard.

Lipid requirements for reconstitution of the delipidated beta-adrenergic receptor and the regulatory protein.

The role of lipids in the interaction of the beta-adrenergic receptor (R) with the regulatory protein (Gs) was investigated. Solubilized preparations of R and of Gs from turkey erythrocytes were delipidated by gel filtration. They were subsequently combined and reconstituted by the addition of various lipids. When reconstitution was carried out in the presence of soybean lipids, Gs could be fully activated via R by addition of hormone plus GTP gamma S. In contrast, purified phospholipids or a phospholipid fraction from soybean failed to produce an active system. Fractionation of soybean lipids revealed that acetone-soluble neutral lipids are essential for the reconstitution of a hormone responsive system. The acetone fraction could be replaced by specific neutral lipids such as alpha-tocopherol or cholesteryl arachidonate while a mixture of phosphatidylethanolamine, -choline and -serine satisfied the phospholipid requirement of the system.